Sulfamoyl benzamide derivatives and methods of their use

US 20060079557A1
Filed: 10/13/2005
Published: 04/13/2006
Est. Priority Date: 10/13/2004
Status: Active Grant

First Claim

Patent Images

1. A compound of formula I′

;

View all claims

1 Assignment

Timeline View

Assignment View

0 Petitions

Accused Products

Abstract

Novel sulfamoyl benzamide compounds, pharmaceutical compositions containing the sulfamoyl benzamide compounds, and methods of their pharmaceutical use are disclosed. In certain embodiments, the sulfamoyl benzamide compounds are agonists and/or modulating ligands of cannabinoid receptors and may be useful, inter alia, for treating and/or preventing pain, gastrointestinal disorders, inflammation, auto-immune diseases, ischemic conditions, immune-related disorders, hypertension, neurological disorders, and neurodegenerative diseases, for providing cardioprotection against ischemic and reperfusion effects, for inducing apoptosis in malignant cells, for inhibiting mechanical hyperalgesia associated with nerve injury, and as an appetite stimulant.

Citations

272 Claims

1. A compound of formula I′
- ;
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 43, 44, 131)
- - 2. A compound according to claim 1, wherein R¹is alkyl, F, Cl, or Br.
  - 3. A compound according to claim 2, wherein R¹is alkyl.
  - 4. A compound according to claim 3, wherein R¹is C_1-6alkyl.
  - 5. A compound according to claim 4, wherein R¹is C_1-3alkyl.
  - 6. A compound according to claim 2, wherein R¹is F, Cl, or Br.
  - 7. A compound according to claim 6, wherein R¹is Br.
  - 8. A compound according to claim 1, wherein R²and R³are each independently alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroaralkyl, or taken together with the nitrogen atom to which they are attached, R²and R³form a 3- to 8-membered heterocycloalkyl ring, wherein 1 or 2 of the heterocycloalkyl ring carbon atoms independently may each be optionally replaced by —
    - O—
      
      , —
      
      S—
      
      , —
      
      N(R⁹)—
      
      , —
      
      N(R¹⁰)—
      
      C(═
      
      O)—
      
      , or —
      
      C(═
      
      O)—
      
      N(R¹⁰)—
      
      .
  - 9. A compound according to claim 8, wherein at least one of R²and R³is independently cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroaralkyl, or taken together with the nitrogen atom to which they are attached, R²and R³form a 3- to 8-membered heterocycloalkyl ring, wherein 1 or 2 of the heterocycloalkyl ring carbon atoms independently are optionally replaced by —
    - O—
      
      , —
      
      S—
      
      , —
      
      N(R⁹)—
      
      , —
      
      N(R¹⁰)—
      
      C(═
      
      O)—
      
      , or —
      
      C(═
      
      O)—
      
      N(R¹⁰)—
      
      .
  - 10. A compound according to claim 9, wherein at least one of R²and R³is aralkyl.
  - 11. A compound according to claim 10, wherein at least one of R²and R³is benzyl.
  - 12. A compound according to claim 8, wherein R²and R³, taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocycloalkyl ring, wherein one of the heterocycloalkyl ring carbon atoms is optionally replaced by —
    - O—
      
      , —
      
      S—
      
      , —
      
      N(R⁹)—
      
      , —
      
      N(R¹⁰)—
      
      C(═
      
      O)—
      
      , or —
      
      C(═
      
      O)—
      
      N(R¹⁰)—
      
      .
  - 13. A compound according to claim 12, wherein R²and R³, taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocycloalkyl ring, wherein one of the heterocycloalkyl ring carbon atoms is replaced by —
    - O—
      
      , —
      
      S—
      
      , —
      
      N(R⁹)—
      
      , —
      
      N(R¹⁰)—
      
      C(═
      
      O)—
      
      , or —
      
      C(═
      
      O)—
      
      N(R¹⁰)—
      
      .
  - 14. A compound according to claim 13, wherein R²and R³, taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocycloalkyl ring, wherein one of the heterocycloalkyl ring carbon atoms is replaced by —
    - O—
      
      , —
      
      S—
      
      , or —
      
      N(R⁹)—
      
      .
  - 15. A compound according to claim 1, wherein R⁴is H.
  - 16. A compound according to claim 1, wherein r is 0, 1 or 2.
  - 17. A compound according to claim 16, wherein r is 0 or 1.
  - 18. A compound according to claim 17, wherein r is 0.
  - 19. A compound according to claim 1, wherein R^aand R^bare each H.
  - 20. A compound according to claim 19, wherein r is 1.
  - 21. A compound according to claim 1, wherein R^cis H.
  - 22. A compound according to claim 1, wherein R^cis alkyl.
  - 23. A compound according to claim 22, wherein R^dand R^etaken together with the carbon atom to which they are attached form a monocyclic carbocyclic ring.
  - 24. A compound according to claim 1, wherein R^dand R^e, taken together with the carbon atom to which they are attached, form a 3- to 12-membered carbocyclic ring, wherein the carbocyclic ring is substituted with 0-5 groups each independently selected from C_1-4alkyl and C_1-4alkoxyl.
  - 25. A compound according to claim 24, wherein the carbocyclic ring is bicycloalkyl or tricycloalkyl.
  - 26. A compound according to claim 25, wherein the carbocyclic ring is bicycloalkyl.
  - 27. A compound according to claim 26, wherein the bicycloalkyl ring is substituted with 1-3 C_1-4alkyl groups.
  - 28. A compound according to claim 1, wherein R⁵is:
  - 29. A compound according to claim 1, wherein R⁶and R⁷are each independently H, F, Cl, or Br.
  - 30. A compound according to claim 29, wherein R⁶and R⁷are each H.
  - 31. A compound according to claim 1, wherein when R⁶, R⁷, or R⁸is alkyl, said alkyl is independently substituted with one or more fluorine atoms.
  - 32. A compound according to claim 31, wherein when R⁶, R⁷, or R⁸is alkyl, said alkyl is perfluorinated.
  - 33. A compound according to claim 1, wherein R⁸is H.
  - 34. A compound according to claim 1 wherein R¹¹is alkyl.
  - 35. A compound according to claim 1 of formula II:
  - 36. A compound according to claim 35, wherein:
    - R²³and R²³are each independently alkyl or aralkyl, or R²and R³, when taken together with the nitrogen atom to which they are attached, form a 5- or 6-membered heterocycloalkyl ring, wherein one of the heterocycloalkyl ring carbon atoms is replaced by —
      
      O—
      
      .
  - 37. A compound according to claim 36, wherein R^dand R^e, taken together with the carbon atom to which they are attached form a bicycloalkyl or tricycloalkyl ring.
  - 38. A compound according to claim 37, wherein r is 0 or 1.
  - 39. A compound according to claim 37, wherein R^a, R^b, and R^care each H.
  - 40. A compound according to claim 1, wherein the compound is selected from the group consisting of:
    - 4-chloro-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      4-bromo-N-(6,6-dimethylbicyclo[3.1.1]hept-2-ylmethyl)-3-(piperidine-1-sulfonyl)-benzamide;
      
      3-(N-benzyl-N-methylsulfamoyl)-4-bromo-N-(6,6-dimethylbicyclo[3.1.1]hept-2-ylmethyl)-benzamide;
      
      4-bromo-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      4-isopropyl-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      3-(piperidine-1-sulfonyl)-N,S-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(piperidine-1-sulfonyl)-N,R-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(N-benzyl-N-methylsulfamoyl)-4-bromo-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      4-[2-methyl-5-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl-carbamoyl)-benzenesulfonyl]-piperazine-1-carboxylic acid tert-butyl ester;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N,S-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N,R-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      2-(piperidine-1-sulfonyl)-biphenyl-4-carboxylic acid (1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-amide;
      
      {4-[2-methyl-5-(1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl-carbamoyl)-benzene-sulfonyl]-piperazin-1-yl}-acetic acid methyl ester;
      
      4-[2-methyl-5-(1,3,3-trimethylbicyclo[2.2.1]hept-2ylcarbamoyl)-benzenesulfonyl]-piperazine-1-carboxylic acid ethylamide;
      
      4-methyl-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(4-acetyl-piperazine-1-sulfonyl)-4-bromo-N-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      3-(4-methanesulfonyl-piperazine-1-sulfonyl)-4-methyl-N-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      4-methyl-3-(piperazine-1-sulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]hept-2-yl)-benzamide; and
      
      a pharmaceutically acceptable salt thereof.
  - 41. A compound according to claim 1, wherein the compound is selected from the group consisting of:
    - 4-chloro-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      4-bromo-N-(6,6-dimethylbicyclo[3.1.1]hept-2-ylmethyl)-3-(piperidine-1-sulfonyl)-benzamide;
      
      3-(N-benzyl-N-methylsulfamoyl)-4-bromo-N-(6,6-dimethylbicyclo[3.1.1]hept-2-yl-methyl)-benzamide;
      
      4-bromo-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      4-isopropyl-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      3-(piperidine-1-sulfonyl)-N,S-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(piperidine-1-sulfonyl)-N,R-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(N-benzyl-N-methylsulfamoyl)-4-bromo-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      4-[2-methyl-5-(1,3,3-trimethylbicyclo[2.2.1]hept-2-ylcarbamoyl)-benzenesulfonyl]-piperazine-1-carboxylic acid tert-butyl ester;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N,S-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N,R-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      2-(piperidine-1-sulfonyl)-biphenyl-4-carboxylic acid (1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-amide;
      
      {4-[2-methyl-5-(1,3,3-trimethylbicyclo[2.2.1]hept-2-ylcarbamoyl)-benzene-sulfonyl]-piperazin-1-yl}-acetic acid methyl ester;
      
      4-[2-methyl-5-(1,3,3-trimethylbicyclo[2.2.1]hept-2ylcarbamoyl)-benzenesulfonyl]-piperazine-1-carboxylic acid ethylamide;
      
      3-(4-methanesulfonyl-piperazine-1-sulfonyl)-4-methyl-N-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide; and
      
      a pharmaceutically acceptable salt thereof.
  - 43. A compound according to claim 1, wherein the compound is selected from the group consisting of:
    - 4-chloro-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(benzyl-methyl-sulfamoyl)-4-bromo-N-(6,6-dimethylbicyclo[3.1.1]hept-2-yl-methyl)-benzamide;
      
      4-bromo-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      4-isopropyl-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      4-methyl-3-(piperidine-1-sulfonyl)-N,R-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(benzyl-methyl-sulfamoyl)-4-bromo-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N,S-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N,R-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      2-(piperidine-1-sulfonyl)-biphenyl-4-carboxylic acid (1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-amide; and
      
      a pharmaceutically acceptable salt thereof.
  - 44. A compound according to claim 1, wherein the compound is selected from the group consisting of:
    - 4-chloro-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(benzyl-methyl-sulfamoyl)-4-bromo-N-(6,6-dimethylbicyclo[3.1.1]hept-2-yl-methyl)-benzamide;
      
      4-bromo-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(benzyl-methyl-sulfamoyl)-4-bromo-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N,S-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide; and
      
      a pharmaceutically acceptable salt thereof.
  - 131. A pharmaceutical composition according to claim 1-30, wherein the analgesic is a COX2 inhibitor, aspirin, acetaminophen, ibuprophen, or naproxen, or a mixture thereof.

42. A compound selected from the group consisting of:
- 4-bromo-N-(2,2-dimethylpropyl)-3-(piperidine-1-sulfonyl)-benzamide;
  
  3-(N-benzyl-N-methylsulfamoyl)-4-bromo-N-(2,2-dimethylpropyl)-benzamide;
  
  3-(N-benzyl-N-methylsulfamoyl)-4-bromo-N-isobutyl-benzamide;
  
  4-chloro-N-(2,2-dimethylpropyl)-3-(piperidine-1-sulfonyl)-benzamide;
  
  N-(2,2-dimethylpropyl)-4-methyl-3-(piperidine-1-sulfonyl)-benzamide;
  
  4-bromo-N-(2,2-dimethylpropyl)-3-(pyrrolidine-1-sulfonyl)-benzamide; and
  
  a pharmaceutically acceptable salt thereof.

45. A compound of formula III:
- View Dependent Claims (46, 47, 48)
- - 46. A compound according to claim 45, wherein the compound is selected from the group consisting of:
    - N-benzyl-2-chloro-4-fluoro-5-(morpholine-4-sulfonyl)-benzamide;
      
      3-(N-benzyl-N-methylsulfamoyl)-4-bromo-N-pyridin-3-yl-methyl-benzamide;
      
      4-bromo-N-(3-methoxybenzyl)-3-(piperidine-1-sulfonyl)-benzamide;
      
      4-bromo-N-(3-methoxybenzyl)-3-(pyrrolidine-1-sulfonyl)-benzamide;
      
      N-benzyl-4-bromo-3-(pyrrolidine-1-sulfonyl)-benzamide;
      
      N-benzyl-4-bromo-N-methyl-3-(morpholine-4-sulfonyl)-benzamide; and
      
      a pharmaceutically acceptable salt thereof.
  - 47. A compound according to claim 46, wherein the compound is N-benzyl-2-chloro-4-fluoro-5-(morpholine-4-sulfonyl)-benzamide.
  - 48. A compound according to claim 45, wherein the compound is N-benzyl-5-(N-benzyl-N-methylsulfamoyl)-2-chloro-4-fluoro-N-methylbenzamide.

49. A pharmaceutical composition, comprising:
- a pharmaceutically acceptable carrier; and
  
  a compound of formula Ia;
  
  wherein;
  
  R¹is H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroaralkyl, F, Cl, or Br;
  
  R²and R³are each independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroaralkyl, provided that at least one of R²and R³is other than H;
  
  or R²and R³when taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocycloalkyl ring, wherein 1 or 2 of the heterocycloalkyl ring carbon atoms independently may each be optionally replaced by —
  
  O—
  
  , —
  
  S—
  
  , —
  
  N(R⁹)—
  
  , —
  
  N(R¹⁰)—
  
  C(═
  
  O)—
  
  , or —
  
  C(═
  
  O)—
  
  N(R¹⁰)—
  
  ;
  
  R⁴is H or alkyl;
  
  R⁵is;
  
  each R^a, R^b, R^c, R^d, and R^eare each independently H or alkyl;
  
  or R^dand R^etaken together with the carbon atom to which they are attached form a carbocyclic ring;
  
  R⁶, R⁷, and R⁸are each independently H, F, Cl, Br, or alkyl;
  
  R⁹is H, alkyl, aryl, —
  
  C(═
  
  O)—
  
  R¹¹, —
  
  C(═
  
  O)—
  
  OR¹¹, —
  
  [C(R¹¹)(R¹¹)]_s—
  
  C(═
  
  O)—
  
  OR¹¹, —
  
  SO₂R¹¹, or —
  
  C(═
  
  O)N(R¹¹)R¹¹;
  
  R¹⁰is H, alkyl, or aryl;
  
  each R¹¹is independently H or alkyl;
  
  r is 0, 1, 2, or 3; and
  
  s is 1, 2, 3, or 4;
  
  provided that;
  
  (1) when R^dand R^etaken together with the carbon atom to which they are attached form a monocyclic carbocyclic ring, then R^cis alkyl or the monocyclic carbocyclic ring is an alkylcycloalkyl ring;
  
  (2) at least two of R^c, R^d, and R^eare other than H; and
  
  (3) when R¹is methyl or bromo, R², R⁴, R⁶, R⁷, and R⁸are each H, and R³is methyl, then R⁵is other than but-2-yl, pent-2-yl, hex-2-yl, hept-2-yl, 1,1,1-dimethyleth-1-yl, 1-dimethylprop-1-yl, 1,1-dimethylbut-1-yl, or 1,1-dimethylpent-1-yl;
  
  or a pharmaceutically acceptable salt thereof.
- View Dependent Claims (50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61)
- - 50. A pharmaceutical composition of claim 49, wherein when R^dand R^eare taken together with the carbon atom to which they are attached to form a monocyclic carbocyclic ring, then R^cis alkyl.
  - 51. A pharmaceutical composition of claim 49, wherein the compound of formula Ia is selected from the group consisting of:
    - 4-bromo-N-(2,2-dimethyl-propyl)-3-(piperidine-1-sulfonyl)-benzamide;
      
      4-chloro-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(N-benzyl-N-methylsulfamoyl)-4-bromo-N-(2,2-dimethylpropyl)-benzamide;
      
      4-bromo-N-(6,6-dimethyl-bicyclo[3.1.1]hept-2-yl-methyl)-3-(piperidine-1-sulfonyl)-benzamide;
      
      3-(N-benzyl-N-methylsulfamoyl)-4-bromo-N-(6,6-dimethyl-bicyclo[3.1.1]hept-2-yl-methyl)-benzamide;
      
      3-(N-benzyl-N-methylsulfamoyl)-4-bromo-N-isobutyl-benzamide;
      
      4-bromo-3-(piperidine-1-sulfonyl)-N-(1,3,3-tri-methylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      4-isopropyl-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethyl-bicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      3-(piperidine-1-sulfonyl)-N,S-(1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(piperidine-1-sulfonyl)-N,R-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(N-benzyl-N-methylsulfamoyl)-4-bromo-N-(1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl)-benzamide;
      
      4-[2-methyl-5-(1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl-carbamoyl)-benzenesulfonyl]-piperazine-1-carboxylic acid tert-butyl ester;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N,S-(1,3,3-trimethyl-bicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N,R-(1,3,3-trimethyl-bicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      2-(piperidine-1-sulfonyl)-biphenyl-4-carboxylic acid (1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl)-amide;
      
      {4-[2-methyl-5-(1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl-carbamoyl)-benzene-sulfonyl]-piperazin-1-yl}-acetic acid methyl ester;
      
      4-[2-methyl-5-(1,3,3-trimethyl-bicyclo[2.2.1]hept-2yl-carbamoyl)-benzenesulfonyl]-piperazine-1-carboxylic acid ethylamide;
      
      4-chloro-N-(2,2-dimethylpropyl)-3-(piperidine-1-sulfonyl)-benzamide;
      
      N-(2,2-dimethyl-propyl)-4-methyl-3-(piperidine-1-sulfonyl)-benzamide;
      
      4-bromo-N-(2,2-dimethylpropyl)-3-(pyrrolidine-1-sulfonyl)-benzamide;
      
      4-methyl-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(4-acetyl-piperazine-1-sulfonyl)-4-bromo-N-(1,3,3-trimethyl-bicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      4-methyl-3-(piperazine-1-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(4-methanesulfonyl-piperazine-1-sulfonyl)-4-methyl-N-(1,3,3-tri-methyl-bicyclo[2.2.1]-hept-2-yl)-benzamide; and
      
      a pharmaceutically acceptable salt thereof.
  - 52. A pharmaceutical composition according to claim 49, further comprising at least one cannabinoid.
  - 53. A pharmaceutical composition according to claim 52, wherein the cannabinoid is Δ
    - ⁹-tetrahydrocannabinol or cannabidiol.
  - 54. A pharmaceutical composition according to claim 49, further comprising at least one opioid.
  - 55. A pharmaceutical composition according to claim 54, wherein said opioid is selected from the group consisting of alfentanil, buprenorphine, butorphanol, codeine, dezocine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, levorphanol, loperamide, meperidine (pethidine), methadone, morphine, nalbuphine, oxycodone, oxymorphone, pentazocine, propiram, propoxyphene, sufentanil and tramadol, and mixtures thereof.
  - 56. A pharmaceutical composition according to claim 49, further comprising at least one analgesic.
  - 57. A pharmaceutical composition according to claim 56, wherein the analgesic is a COX2 inhibitor, aspirin, acetaminophen, ibuprophen, or naproxen, or a mixture thereof.
  - 58. A pharmaceutical composition according to claim 49, further comprising at least one agent selected from the group consisting of an anti-seizure agent, an anti-depressant, an NMDA receptor antagonist, an ion channel antagonist, a nicotinic receptor agonist, and an anti-Parkinson'"'"'s agent.
  - 59. A pharmaceutical composition according to claim 58 wherein said anti-seizure agent is carbamazepine, gabapentin, lamotrigine, or phenyloin, or a mixture thereof.
  - 60. A pharmaceutical composition according to claim 58 wherein said anti-depressant is amitryptiline.
  - 61. A pharmaceutical composition according to claim 58, wherein said anti-Parkinson'"'"'s agent is deprenyl, amantadine, levodopa, or carbidopa, or a mixture thereof.

62. A method of binding cannabinoid receptors in a patient in need thereof, comprising the step of:
- administering to said patient an effective amount of a compound of formula Ia;
  
  wherein;
  
  R¹is H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroaralkyl, F, Cl, or Br;
  
  R²and R³are each independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroaralkyl, provided that at least one of R²and R³is other than H;
  
  or R²and R³when taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocycloalkyl ring, wherein 1 or 2 of the heterocycloalkyl ring carbon atoms independently may each be optionally replaced by —
  
  O—
  
  , —
  
  S—
  
  , —
  
  N(R⁹)—
  
  , —
  
  N(R¹⁰)—
  
  C(═
  
  O)—
  
  , or —
  
  C(═
  
  O)—
  
  N(R¹⁰)—
  
  ;
  
  R⁴is H or alkyl;
  
  R⁵is;
  
  each R^a, R^b, R^c, R^d, and R^eis independently H or alkyl;
  
  or R^dand R^etaken together with the carbon atom to which they are attached form a carbocyclic ring;
  
  R⁶, R⁷, and R⁸are each independently H, F, Cl, Br, or alkyl;
  
  R⁹is H, alkyl, aryl, —
  
  C(═
  
  O)—
  
  R¹¹, —
  
  C(═
  
  O)—
  
  OR¹¹, —
  
  [C(R¹¹)(R¹¹)]_s—
  
  C(═
  
  O)—
  
  OR¹¹, —
  
  SO₂R¹¹, or —
  
  C(═
  
  O)N(R¹¹)R¹¹;
  
  R¹⁰is H, alkyl, or aryl;
  
  each R¹¹is independently H or alkyl;
  
  r is 0, 1, 2, or 3; and
  
  s is 1, 2, 3, or 4;
  
  provided that;
  
  (1) when R^dand R^etaken together with the carbon atom to which they are attached form a monocyclic carbocyclic ring, then R^cis alkyl or the monocyclic carbocyclic ring is an alkylcycloalkyl ring; and
  
  (2) at least two of R^c, R^d, and R^eare other than H;
  
  or a pharmaceutically acceptable salt thereof.
- View Dependent Claims (63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123)
- - 63. A method according to claim 62, wherein when R^dand R^eare taken together with the carbon atom to which they are attached to form a monocyclic carbocyclic ring, then R^cis alkyl.
  - 64. A method of claim 62, wherein the compound of formula Ia is selected from the group consisting of:
    - 4-bromo-N-(2,2-dimethyl-propyl)-3-(piperidine-1-sulfonyl)-benzamide;
      
      4-chloro-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(N-benzyl-N-methylsulfamoyl)-4-bromo-N-(2,2-dimethylpropyl)-benzamide;
      
      4-bromo-N-(6,6-dimethyl-bicyclo[3.1.1]hept-2-yl-methyl)-3-(piperidine-1-sulfonyl)-benzamide;
      
      3-(N-benzyl-N-methylsulfamoyl)-4-bromo-N-(6,6-dimethyl-bicyclo[3.1.1]hept-2-yl-methyl)-benzamide;
      
      3-(N-benzyl-N-methylsulfamoyl)-4-bromo-N-isobutyl-benzamide;
      
      4-bromo-3-(piperidine-1-sulfonyl)-N-(1,3,3-tri-methylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      4-isopropyl-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethyl-bicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      3-(piperidine-1-sulfonyl)-N,S-(1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(piperidine-1-sulfonyl)-N,R-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(N-benzyl-N-methylsulfamoyl)-4-bromo-N-(1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl)-benzamide;
      
      4-[2-methyl-5-(1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl-carbamoyl)-benzenesulfonyl]-piperazine-1-carboxylic acid tert-butyl ester;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N,S-(1,3,3-trimethyl-bicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N,R-(1,3,3-trimethyl-bicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      2-(piperidine-1-sulfonyl)-biphenyl-4-carboxylic acid (1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl)-amide;
      
      {4-[2-methyl-5-(1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl-carbamoyl)-benzene-sulfonyl]-piperazin-1-yl}-acetic acid methyl ester;
      
      4-[2-methyl-5-(1,3,3-trimethyl-bicyclo[2.2.1]hept-2yl-carbamoyl)-benzenesulfonyl]-piperazine-1-carboxylic acid ethylamide;
      
      4-chloro-N-(2,2-dimethylpropyl)-3-(piperidine-1-sulfonyl)-benzamide;
      
      N-(2,2-dimethyl-propyl)-4-methyl-3-(piperidine-1-sulfonyl)-benzamide;
      
      4-bromo-N-(2,2-dimethylpropyl)-3-(pyrrolidine-1-sulfonyl)-benzamide;
      
      4-methyl-3-(piperidine-1-sulfonyl)-N-(1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(a-Acetyl-piperazine-1-sulfonyl)-4-bromo-N-(1,3,3-trimethyl-bicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      4-methyl-3-(piperazine-1-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      3-(4-methanesulfonyl-piperazine-1-sulfonyl)-4-methyl-N-(1,3,3-tri-methyl-bicyclo[2.2.1]-hept-2-yl)-benzamide; and
      
      a pharmaceutically acceptable salt thereof.
  - 65. A method according to claim 62, wherein the cannabinoid receptors are selected from the group consisting of CB1 and CB2 cannabinoid receptors.
  - 66. A method according to claim 65, wherein the cannabinoid receptors are located in the central nervous system.
  - 67. A method according to claim 62, wherein the cannabinoid receptors are located peripherally to the central nervous system.
  - 68. A method according to claim 65, wherein the compound selectively binds the CB2 cannabinoid receptors relative to the CB1 receptors.
  - 69. A method according to claim 62, wherein the binding agonizes the activity of the cannabinoid receptors.
  - 70. A method according to claim 62, wherein the binding antagonizes the activity of the cannabinoid receptors.
  - 71. A method according to claim 62, wherein the binding inversely agonizes the activity of the cannabinoid receptors.
  - 72. A method according to claim 62, further comprising administering to said patient an effective amount of at least one cannabinoid.
  - 73. A method according to claim 72, wherein said cannabinoid is Δ
    - ⁹-tetrahydrocannabinol or cannabidiol.
  - 74. A method according to claim 62, further comprising administering to said patient an effective amount of at least one opioid.
  - 75. A method according to claim 74, wherein said opioid is selected from alfentanil, buprenorphine, butorphanol, codeine, dezocine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, levorphanol, loperamide, meperidine (pethidine), methadone, morphine, nalbuphine, oxycodone, oxymorphone, pentazocine, propiram, propoxyphene, sufentanil and tramadol, and a mixture thereof.
  - 76. A method according to claim 62 which is for the treatment of a disease or disorder selected from the group consisting of a gastrointestinal disorder, inflammation, an auto-immune disease, an immune-related disorder, pain, hypertension, a neurodegenerative disease, a neurological disorder, and a combination thereof.
  - 77. A method of claim 76, wherein the compound of formula Ia is other than:
  - 78. A method according to claim 62 which is for providing cardioprotection against ischemic or reperfusion effects, inhibiting mechanical hyperalgesia associated with nerve injury, inducing apoptosis in malignant cells, modulating appetite, or a combination thereof.
  - 79. A method of claim 78, wherein the compound of formula Ia is other than:
  - 80. A method according to claim 76 which is for the treatment of pain.
  - 81. A method according to claim 80, further comprising administering to said patient at least one cannabinoid.
  - 82. A method according to claim 80, wherein said pain is inflammatory pain, neuropathic pain, visceral pain, surgical pain, post-surgical pain, cancer related pain or a combination thereof.
  - 83. A method according to claim 82, for treating pain, further comprising administering to said patient codeine, carbamazepine, gabapentin, lamotrigine, phenyloin, amitryptiline, an NMDA receptor antagonist, an ion channel antagonist, a nicotinic receptor agonist, or a mixture thereof.
  - 84. A method according to claim 76, which is for the treatment of a gastrointestinal disorder.
  - 85. A method according to claim 84, wherein the gastrointestinal disorder is nausea, vomiting, loss of appetite, cachexia, diarrhea, inflammatory bowel disease, irritable bowel syndrome or a combination thereof.
  - 86. A method according to claim 76, which is for the treatment of an auto-immune disease.
  - 87. A method according to claim 86, wherein the auto-immune disease is multiple sclerosis, rheumatoid arthritis, psoriasis, Crohn'"'"'s disease, systemic lupus erythematosus, myasthenia gravis, diabetes mellitus type I, osteoporosis, or a combination thereof.
  - 88. A method according to claim 62, which is for the treatment of an ischemic condition.
  - 89. A method according to claim 88, wherein said ischemic condition is renal ischemia, cerebral stroke, cerebral ischemia, or a combination thereof.
  - 90. A method according to claim 76, which is for the treatment of a neurological disorder.
  - 91. A method according to claim 90, wherein said
  - 92. A method according to claim 76, which is for the treatment of an immune-related disorder.
  - 93. A method according to claim 92, wherein said immune-related disorder is asthma, chronic pulmonary obstructive disorder, emphysema, bronchitis, allergy, tissue rejection in organ transplants, celiac disease, Sjö
    - gren'"'"'s syndrome, or a combination thereof.
  - 94. A method according to claim 77, which is for the treatment of neurodegenerative disease.
  - 95. A method according to claim 94, wherein said neurodegenerative disease is Parkinson'"'"'s disease, Alzheimer'"'"'s disease, Huntington'"'"'s disease, amyotrophic lateral sclerosis, or a combination thereof.
  - 96. A method according to claim 94, further comprising administering to said patient deprenyl, amantadine, levodopa, or carbidopa.
  - 97. A method according to claim 78, which is for providing cardioprotection against ischemic or reperfusion effects.
  - 98. A method according to claim 97, wherein the ischemic or reperfusion effect is arrhythmia or hypertension.
  - 99. A method according to claim 78, which is for inducing apoptosis in malignant cells.
  - 100. A method according to claim 99, wherein the apoptosis occurs in vitro.
  - 101. A method according to claim 99, wherein the apoptosis occurs in vivo.
  - 102. A method according to claim 78, which is for the treatment of pain.
  - 103. A method according to claim 102, further comprising administering to said patient at least one cannabinoid.
  - 104. A method according to claim 102, wherein said pain is inflammatory pain, neuropathic pain, visceral pain, surgical pain, post-surgical pain, cancer related pain or a combination thereof.
  - 105. A method according to claim 104, for treating pain, further comprising administering to said patient codeine, carbamazepine, gabapentin, lamotrigine, phenyloin, amitryptiline, an NMDA receptor antagonist, an ion channel antagonist, a nicotinic receptor agonist, or a mixture thereof.
  - 106. A method according to claim 77, which is for the treatment of a gastrointestinal disorder.
  - 107. A method according to claim 106, wherein the gastrointestinal disorder is nausea, vomiting, loss of appetite, cachexia, diarrhea, inflammatory bowel disease, irritable bowel syndrome or combination thereof.
  - 108. A method according to claim 77, which is for the treatment of an auto-immune disease.
  - 109. A method according to claim 108, wherein the auto-immune disease is multiple sclerosis, rheumatoid arthritis, psoriasis, Crohn'"'"'s disease, systemic lupus erythematosus, myasthenia gravis, diabetes mellitus type I, osteoporosis, or a combination thereof.
  - 110. A method according to claim 88 wherein the compound of formula Ia administered is other than:
  - 111. A method according to claim 110, wherein said ischemic condition is renal ischemia, cerebral stroke, cerebral ischemia, or a combination thereof.
  - 112. A method according to claim 77, which is for the treatment of a neurological disorder.
  - 113. A method according to claim 112, wherein said neurological disorder is stroke, migraine, cluster headache, or combination thereof.
  - 114. A method according to claim 77, which is for the treatment of an immune-related disorder.
  - 115. A method according to claim 114, wherein said immune-related disorder is asthma, chronic pulmonary obstructive disorder, emphysema, bronchitis, allergy, tissue rejection in organ transplants, celiac disease, Sjö
    - gren'"'"'s syndrome, or a combination thereof.
  - 116. A method according to claim 77, which is for the treatment of neurodegenerative disease.
  - 117. A method according to claim 116, wherein said neurodegenerative disease is Parkinson'"'"'s disease, Alzheimer'"'"'s disease, Huntington'"'"'s disease, amyotrophic lateral sclerosis, or combination thereof.
  - 118. A method according to claim 116, further comprising administering to said patient deprenyl, amantadine, levodopa, or carbidopa.
  - 119. A method according to claim 79, which is for providing cardioprotection against ischemic or reperfusion effects.
  - 120. A method according to claim 119, wherein the ischemic or reperfusion effect is arrhythmia or hypertension.
  - 121. A method according to claim 79, which is for inducing apoptosis in malignant cells.
  - 122. A method according to claim 121, wherein the apoptosis occurs in vitro.
  - 123. A method according to claim 121, wherein the apoptosis occurs in vivo.

124. A pharmaceutical composition, comprising:
- a pharmaceutically acceptable carrier; and
  
  a compound of formula III;
  
  wherein;
  
  R^1ais F, Cl or Br;
  
  R^2ais methyl;
  
  R^3ais benzyl;
  
  or R^2aand R^3awhen taken together with the nitrogen atom to which they are attached, form a morpholine, piperidine or pyrrolidine ring;
  
  R^4ais H or methyl;
  
  R^5ais benzyl, 3-methoxybenzyl, or pyrid-3-yl methyl; and
  
  R^7ais H, F, Cl or Br;
  
  or a pharmaceutically acceptable salt thereof.
- View Dependent Claims (125, 126, 127, 128, 129, 130, 132, 133, 134, 135)
- - 125. A pharmaceutical composition of claim 124, wherein the compound of formula III is selected from the group consisting of:
    - N-benzyl-4-bromo-3-(morpholine-4-sulfonyl)-benzamide;
      
      N-benzyl-2-chloro-4-fluoro-5-(morpholine-4-sulfonyl)-benzamide;
      
      3-(N-benzyl-N-methylsulfamoyl)-4-bromo-N-pyridin-3-yl-methylbenzamide;
      
      4-bromo-N-(3-methoxybenzyl)-3-(piperidine-1-sulfonyl)-benzamide;
      
      4-bromo-N-(3-methoxybenzyl)-3-(pyrrolidine-1-sulfonyl)-benzamide;
      
      N-benzyl-4-bromo-3-(pyrrolidine-1-sulfonyl)-benzamide;
      
      N-benzyl-4-bromo-3-(piperidine-1-sulfonyl)-benzamide, N-benzyl-4-bromo-N-methyl-3-(morpholine-4-sulfonyl)-benzamide; and
      
      a pharmaceutically acceptable salt thereof.
  - 126. A pharmaceutical composition according to claim 124, further comprising at least one cannabinoid.
  - 127. A pharmaceutical composition according to claim 126, wherein the cannabinoid is Δ
    - ⁹-tetrahydrocannabinol or cannabidiol.
  - 128. A pharmaceutical composition according to claim 124, further comprising at least one opioid.
  - 129. A pharmaceutical composition according to claim 128, wherein said opioid is selected from the group consisting of alfentanil, buprenorphine, butorphanol, codeine, dezocine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, levorphanol, loperamide, meperidine (pethidine), methadone, morphine, nalbuphine, oxycodone, oxymorphone, pentazocine, propiram, propoxyphene, sufentanil and tramadol, and mixtures thereof.
  - 130. A pharmaceutical composition according to claim 124, further comprising at least one analgesic.
  - 132. A pharmaceutical composition according to claim 124, further comprising at least one agent selected from the group consisting of an anti-seizure agent, an anti-depressant, an NMDA receptor antagonist, an ion channel antagonist, a nicotinic receptor agonist, and an anti-Parkinson'"'"'s agent.
  - 133. A pharmaceutical composition according to claim 132 wherein said anti-seizure agent is carbamazepine, gabapentin, lamotrigine, or phenyloin, or a mixture thereof.
  - 134. A pharmaceutical composition according to claim 132 wherein said anti-depressant is amitryptiline.
  - 135. A pharmaceutical composition according to claim 134, wherein said antiParkinson'"'"'s agent is deprenyl, amantadine, levodopa, or carbidopa, or a mixture thereof.

136. A method of binding cannabinoid receptors in a patient in need thereof, comprising the step of:
- administering to a patient in need thereof, an effective amount of a compound of formula III;
  
  wherein;
  
  R^1ais F, Cl or Br;
  
  R^2ais methyl;
  
  R^3ais benzyl;
  
  or R^2aand R^3awhen taken together with the nitrogen atom to which they are attached, form a morpholine, piperidine or pyrrolidine ring;
  
  R^4ais H or methyl;
  
  R^5ais benzyl, 3-methoxybenzyl, or pyrid-3-yl methyl; and
  
  R^7ais H, F, Cl or Br;
  
  or a pharmaceutically acceptable salt thereof.
- View Dependent Claims (137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172)
- - 137. A method of claim 136, wherein the compound of formula III is selected from the group consisting of:
    - N-benzyl-4-bromo-3-(morpholine-4-sulfonyl)-benzamide;
      
      N-benzyl-2-chloro-4-fluoro-5-(morpholine-4-sulfonyl)-benzamide;
      
      3-(N-benzyl-N-methylsulfamoyl)-4-bromo-N-pyridin-3-yl-methylbenzamide;
      
      4-bromo-N-(3-methoxybenzyl)-3-(piperidine-1-sulfonyl)-benzamide;
      
      4-bromo-N-(3-methoxybenzyl)-3-(pyrrolidine-1-sulfonyl)-benzamide;
      
      N-benzyl-4-bromo-3-(pyrrolidine-1-sulfonyl)-benzamide;
      
      N-benzyl-4-bromo-3-(piperidine-1-sulfonyl)-benzamide, N-benzyl-4-bromo-N-methyl-3-(morpholine-4-sulfonyl)-benzamide; and
      
      a pharmaceutically acceptable salt thereof.
  - 138. A method according to claim 136, wherein the cannabinoid receptors are selected from the group consisting of CB1 and CB2 cannabinoid receptors.
  - 139. A method according to claim 138, wherein the cannabinoid receptors are located in the central nervous system.
  - 140. A method according to claim 136, wherein the cannabinoid receptors are located peripherally to the central nervous system.
  - 141. A method according to claim 140, wherein the compound selectively binds the CB2 cannabinoid receptors relative to the CB1 receptors.
  - 142. A method according to claim 136, wherein the binding agonizes the activity of the cannabinoid receptors.
  - 143. A method according to claim 136, wherein the binding antagonizes the activity of the cannabinoid receptors.
  - 144. A method according to claim 136, wherein the binding inversely agonizes the activity of the cannabinoid receptors.
  - 145. A method according to claim 136, further comprising administering to said patient an effective amount of at least one cannabinoid.
  - 146. A method according to claim 145, wherein said cannabinoid is Δ
    - ⁹-tetrahydrocannabinol or cannabidiol.
  - 147. A method according to claim 136, further comprising administering to said patient an effective amount of at least one opioid.
  - 148. A method according to claim 147, wherein said opioid is selected from alfentanil, buprenorphine, butorphanol, codeine, dezocine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, levorphanol, loperamide, meperidine (pethidine), methadone, morphine, nalbuphine, oxycodone, oxymorphone, pentazocine, propiram, propoxyphene, sufentanil and tramadol, and mixtures thereof.
  - 149. A method according to claim 136 which is for the treatment of a disease or disorder selected from the group consisting of a gastrointestinal disorder, inflammation, an auto-immune disease, an immune-related disorder, pain, hypertension, a neurodegenerative disease, a neurological disorder, and combinations thereof.
  - 150. A method according to claim 136 which is for providing cardioprotection against ischemic or reperfusion effects, inhibiting mechanical hyperalgesia associated with nerve injury, inducing apoptosis in malignant cells, modulating appetite, or combination thereof.
  - 151. A method according to claim 149, which is for the treatment of pain.
  - 152. A method according to claim 151, further comprising administering to said patient at least one cannabinoid.
  - 153. A method according to claim 151, wherein said pain is inflammatory pain, neuropathic pain, visceral pain, surgical pain, post-surgical pain, cancer related pain or a combination thereof.
  - 154. A method according to claim 153, for treating pain, further comprising administering to said patient codeine, carbamazepine, gabapentin, lamotrigine, phenyloin, amitryptiline, an NMDA receptor antagonist, an ion channel antagonist, a nicotinic receptor agonist, or a mixture thereof.
  - 155. A method according to claim 149, which is for the treatment of a gastrointestinal disorder.
  - 156. A method according to claim 155, wherein the gastrointestinal disorder is nausea, vomiting, loss of appetite, cachexia, diarrhea, inflammatory bowel disease, irritable bowel syndrome or combination thereof.
  - 157. A method according to claim 149, which is for the treatment of an auto-immune disease.
  - 158. A method according to claim 157, wherein the auto-immune disease is multiple sclerosis, rheumatoid arthritis, psoriasis, Crohn'"'"'s disease, systemic lupus erythematosus, myasthenia gravis, diabetes mellitus type I, osteoporosis, or a combination thereof.
  - 159. A method according to claim 136, which is for the treatment of an ischemic condition.
  - 160. A method according to claim 159, wherein said ischemic condition is renal ischemia, cerebral stroke, cerebral ischemia, or a combination thereof.
  - 161. A method according to claim 149, which is for the treatment of a neurological disorder.
  - 162. A method according to claim 161, wherein said neurological disorder is stroke, migraine, cluster headache, or combination thereof.
  - 163. A method according to claim 149, which is for the treatment of an immune-related disorder.
  - 164. A method according to claim 163, wherein said immune-related disorder is asthma, chronic pulmonary obstructive disorder, emphysema, bronchitis, allergy, tissue rejection in organ transplants, celiac disease, Sjö
    - gren'"'"'s syndrome, or a combination thereof.
  - 165. A method according to claim 149, which is for the treatment of neurodegenerative disease.
  - 166. A method according to claim 165, wherein said neurodegenerative disease is Parkinson'"'"'s disease, Alzheimer'"'"'s disease, Huntington'"'"'s disease, amyotrophic lateral sclerosis, or combination thereof.
  - 167. A method according to claim 165, further comprising administering to said patient deprenyl, amantadine, levodopa, or carbidopa.
  - 168. A method according to claim 150, which is for providing cardioprotection against ischemic or reperfusion effects.
  - 169. A method according to claim 168, wherein the ischemic or reperfusion effect is arrhythmia or hypertension.
  - 170. A method according to claim 150, which is for inducing apoptosis in malignant cells.
  - 171. A method according to claim 170, wherein the apoptosis occurs in vitro.
  - 172. A method according to claim 170, wherein the apoptosis occurs in vivo.

173. A compound of formula IV:
- View Dependent Claims (174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 217, 218, 219, 220, 221)
- - 174. A compound according to claim 173, wherein R¹is alkyl, F, Cl, or Br.
  - 175. A compound according to claim 174, wherein R¹is alkyl.
  - 176. A compound according to claim 175, wherein R¹is C_1-6alkyl.
  - 177. A compound according to claim 176, wherein R¹is C_1-3alkyl.
  - 178. A compound according to claim 174, wherein R¹is F or Br.
  - 179. A compound according to claim 178, wherein R¹is Br.
  - 180. A compound according to claim 173, wherein R²and R³are each independently alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroaralkyl, or taken together with the nitrogen atom to which they are attached, R²and R³form a 3- to 8-membered heterocycloalkyl ring, wherein 1 or 2 of the heterocycloalkyl ring carbon atoms independently may each be optionally replaced by —
    - O—
      
      , —
      
      S—
      
      , —
      
      N(R⁹)—
      
      , —
      
      N(R¹⁰)—
      
      C(═
      
      O)—
      
      , or —
      
      C(═
      
      O)—
      
      N(R¹⁰)—
      
      .
  - 181. A compound according to claim 180, wherein at least one of R²and R³is independently cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroaralkyl, or taken together with the nitrogen atom to which they are attached, R²and R³form a 3- to 8-membered heterocycloalkyl ring, wherein 1 or 2 of the heterocycloalkyl ring carbon atoms independently are optionally replaced by —
    - O—
      
      , —
      
      S—
      
      , —
      
      N(R⁹)—
      
      , —
      
      N(R¹⁰)—
      
      C(═
      
      O)—
      
      , or —
      
      C(═
      
      O)—
      
      N(R¹⁰)—
      
      .
  - 182. A compound according to claim 180, wherein at least one of R²and R³is aralkyl.
  - 183. A compound according to claim 181, wherein at least one of R²and R³is benzyl.
  - 184. A compound according to claim 180, wherein R²and R³, taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocycloalkyl ring, wherein one of the heterocycloalkyl ring carbon atoms is optionally replaced by —
    - O—
      
      or —
      
      N(R⁹)—
      
      .
  - 185. A compound according to claim 183, wherein R²and R³, taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocycloalkyl ring, wherein one of the heterocycloalkyl ring carbon atoms is replaced by —
    - O—
      
      or —
      
      N(R⁹).
  - 186. A compound according to claim 180, wherein R²and R³, taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocycloalkyl ring, wherein one of the heterocycloalkyl ring carbon atoms is replaced by —
    - O—
      
      , —
      
      S—
      
      , or —
      
      N(R⁹)—
      
      .
  - 187. A compound according to claim 186, wherein R²and R³, taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocycloalkyl ring which is optionally substituted with at least one substituent selected from the group consisting of alkyl, alkoxyl, halo, N,N-dialkylaminocarbonyl, alkoxycarbonyl, and hydroxyl.
  - 188. A compound according to claim 187, wherein R²and R³, taken together with the nitrogen atom to which they are attached, form morpholin-4-yl, pyrrolidin-1-yl, 1,3-dihydroisoindol-2-yl, 3,4-dihydro-2H-quinolin-1-yl, octahydroquinolin-1-yl, 2,6-dimethylmorpholin-1-yl, 3,5-dimethylpiperidin-1-yl, 2-methylpiperidin-1-yl, 4-hydroxypiperidin-1-yl, 3-N,N-diethylaminocarbonylpiperidin-1-yl, 3-fluoropiperidin-1-yl, 3-hydroxypyrrolidin-1-yl, 3-ethoxycarbonylpiperidin-1-yl, or 3-N,N-diethylaminocarbonylpyrrolidin-1-yl.
  - 189. A compound according to claim 173, wherein R⁴is H.
  - 190. A compound according to claim 173, wherein r is 0, 1 or 2.
  - 191. A compound according to claim 190, wherein r is 0 or 1.
  - 192. A compound according to claim 191, wherein r is 0.
  - 193. A compound according to claim 173, wherein R^ais H and R^bis H or alkyl.
  - 194. A compound according to claim 193, wherein r is 1.
  - 195. A compound according to claim 173, wherein R^cis H.
  - 196. A compound according to claim 173, wherein R^cis alkyl.
  - 197. A compound according to claim 173, wherein R^dand R^eare each alkyl.
  - 198. A compound according to claim 173, wherein R^dand R^e, taken together with the carbon atom to which they are attached, form a 3- to 12-membered carbocyclic ring, wherein the carbocyclic ring is substituted with 0-5 groups each independently selected from C_1-4alkyl, hydroxyl, and C_1-4alkoxyl.
  - 199. A compound according to claim 198, wherein the carbocyclic ring is bicycloalkyl or tricycloalkyl.
  - 200. A compound according to claim 199, wherein the carbocyclic ring is bicycloalkyl.
  - 201. A compound according to claim 200, wherein the bicycloalkyl ring is substituted with 1-3 alkyl groups, each selected independently.
  - 202. A compound according to claim 173, wherein R⁵is:
  - 203. A compound according to claim 173, wherein R^c, R^d, and R^e, taken together with the carbon atom to which they are attached, form a bicycloalkyl or tricycloalkyl ring.
  - 204. A compound according to claim 203, wherein the bicycloalkyl or tricycloalkyl ring is substituted with 1-3 groups selected independently from alkyl, alkoxyl, or hydroxyl.
  - 205. A compound according to claim 173, wherein R⁶and R⁷are each independently H, F, Cl, or Br.
  - 206. A compound according to claim 203, wherein R⁶and R⁷are each H.
  - 207. A compound according to claim 173, wherein R⁸is H.
  - 208. A compound according to claim 173 of formula V:
  - 209. A compound according to claim 208, wherein:
    - R²and R³are each independently alkyl or aralkyl, or R²and R³, when taken together with the nitrogen atom to which they are attached, form a 5- or 6-membered heterocycloalkyl ring, wherein one of the heterocycloalkyl ring carbon atoms is replaced by —
      
      O—
      
      ; and
      
      R^dand R^e, taken together with the carbon atom to which they are attached form a carbocyclic ring.
  - 210. A compound according to claim 209, wherein R^dand R^e, taken together with the carbon atom to which they are attached form a bicycloalkyl or tricycloalkyl ring.
  - 211. A compound according to claim 208, wherein:
    - R²and R³are each independently alkyl or aralkyl, or R²and R³, when taken together with the nitrogen atom to which they are attached, form a 5- or 6-membered heterocycloalkyl ring, wherein one of the heterocycloalkyl ring carbon atoms is replaced by —
      
      O—
      
      ; and
      
      R^c, R^d, and R^e, taken together with the carbon atom to which they are attached, form a bicycloalkyl or tricycloalkyl ring.
  - 212. A compound according to claim 211, wherein the bicycloalkyl or tricycloalkyl ring is substituted with 1-3 groups selected independently from alkyl, alkoxyl, or hydroxyl.
  - 213. A compound according to claim 210, wherein r is 0 or 1.
  - 214. A compound according to claim 210, wherein R^a, R^b, and R^care each H.
  - 215. A compound according to claim 173, selected from the group consisting of:
    - N-adamantan-2-yl-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      N-(1-adamantan-1-ylethyl)-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N-(1,7,7-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      N-bicyclo-[2.2.1]hept-2-yl-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      N-[1-(3-hydroxy-adamantan-1-yl)-ethyl]-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      4-methyl-3-(1,3-dihydroisoindole-2-sulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      N-bicyclo-[2.2.1]hept-2-yl-3-(1,3-dihydroisoindole-2-sulfonyl)-4-methylbenzamide;
      
      3-(1,3-dihydroisoindole-2-sulfonyl)-4-methyl-N-(1,7,7-trimethylbicyclo-[2.2.1]hept-2-yl)-benzamide;
      
      3-(1,3-dihydroisoindole-2-sulfonyl)-N-[1-(3-hydroxyadamantan-1-yl)-ethyl]-4-methylbenzamide;
      
      N-adamantan-2-yl-3-(3,4-dihydro-2H-quinoline-1-sulfonyl)-4,5-dimethylbenzamide;
      
      N-(1-adamantan-1-ylethyl)-3-(3,4-dihydro-2H-quinoline-1-sulfonyl)-4,5-dimethylbenzamide;
      
      3-(3,4-dihydroquinolin-1 (2H)-ylsulfonyl)-4,5-dimethyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      N-adamantan-2-yl-3,4-dimethyl-5-(octahydroquinoline-1-sulfonyl)-benzamide;
      
      N-(1-adamantan-1-ylethyl)-3,4-dimethyl-5-(octahydroquinoline-1-sulfonyl)-benzamide;
      
      3,4-dimethyl-5-(octahydroquinolin-1 (2H)-ylsulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)benzamide;
      
      N-adamantan-2-yl-3-(2,6-dimethylmorpholine-4-sulfonyl)-4-methylbenzamide;
      
      N-(1-adamantan-1-ylethyl)-3-(2,6-dimethylmorpholine-4-sulfonyl)-4-methylbenzamide;
      
      3-(2,6-dimethylmorpholinosulfonyl)-4-methyl-N-(1,3,3-trimethylbicylo-[2.2.1]heptan-2-yl)-benzamide;
      
      N-adamantan-2-yl-3-(2,6-dimethylmorpholine-4-sulfonyl)-4,5-dimethylbenzamide;
      
      N-(1-adamantan-1-ylethyl)-3-(2,6-dimethylmorpholine-4-sulfonyl)-4,5-dimethylbenzamide;
      
      3-(2,6-dimethylmorpholinosulfonyl)-4,5-dimethyl-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      N-adamantan-2-yl-5-(N-benzyl-N-methylsulfamoyl)-2-chloro-4-fluoro-benzamide;
      
      N-(1-adamantan-1-ylethyl)-5-(N-benzyl-N-methylsulfamoyl)-2-chloro-4-fluorobenzamide;
      
      5-(N-benzyl-N-methylsulfamoyl)-2-chloro-4-fluoro-N-(1,3,3-trimethylbicyclo[2.2.1]-heptan-2-yl)benzamide;
      
      3,4-dimethyl-5-(morpholinosulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      N-((6,6-dimethylbicyclo-[3.1.1]-heptan-2-yl)methyl)-3,4-dimethyl-5-(morpholinosulfonyl)-benzamide;
      
      N-(1-adamantan-1-ylethyl)-5-(morpholinosulfonyl)-4,5-dimethylbenzamide;
      
      3-(N-benzyl-N-methyl-sulfamoyl)-4,5-dimethyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)benzamide;
      
      3-(N-benzyl-N-methyl-sulfamoyl)-N-((6,6-dimethylbicyclo-[3.1.1]-heptan-2-yl)methyl)-4,5-dimethylbenzamide;
      
      N-(1-adamantan-1-ylethyl)-5-(N-benzyl-N-methyl-sulfamoyl)-4,5-dimethylbenzamide;
      
      1-(2,3-dimethyl-5-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-ylcarbamoyl)-phenylsulfonyl)-N,N-diethylpiperidine-3-carboxamide;
      
      3-(azetidin-1-ylsulfonyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      3-(3-hydroxypyrrolidin-1-ylsulfonyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      3-(3-hydroxypyrrolidin-1-ylsulfonyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)benzamide;
      
      3-(4-hydroxypiperidin-1-ylsulfonyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      N,N-diethyl-1-(2-methyl-5-(1,3,3-trimethylbicylo-[2.2.1]heptan-2-ylcarbamoyl)-phenylsulfonyl)-piperidine-3-carboxamide;
      
      3-(N-(2-methoxyethyl)-N-methylsulfamoyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      N,N-diethyl-1-(2-methyl-5-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-ylcarbamoyl)-phenylsulfonyl)-pyrrolidine-3-carboxamide;
      
      N-(1-adamantan-1-ylmethyl)-5-(morpholinosulfonyl)-2-chloro-4-fluorobenzamide;
      
      4-methyl-3-(morpholinosulfonyl)-N-(2,6,6-trimethylbicyclo-[3.1.1]-heptan-3-yl)-benzamide;
      
      4-methyl-3-(morpholinosulfonyl)-N-(2,6,6-trimethylbicyclo-[3.1.1]heptan-3-yl)-benzamide;
      
      4-ethyl-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      4-isopropyl-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicylo[2.2.1]hept-2-yl)-benzamide;
      
      4-propyl-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)-benzamide;
      
      4-(3-methoxypropyl)-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]hept-2-yl)-benzamide;
      
      5-methyl-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      4,6-dimethyl-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]hept-2-yl)-benzamide;
      
      3-(N,N-dimethylsulfamoyl-4-bromo-N-(1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      4-bromo-3-(N-methylsulfamoyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      4-bromo-3-(N-phenylsulfamoyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      4-bromo-3-(morpholinosulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      4-bromo-3-(3-fluoropiperidin-1-ylsulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      4-bromo-3-(pyrrolidin-1-ylsulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      4-bromo-3-(3,5-dimethylpiperidin-1-ylsulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      4-bromo-3-(2,6-dimethylmorpholinosulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      ethyl 1-(2-bromo-5-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl-carbamoyl)-phenylsulfonyl)-piperidine-3-carboxylate;
      
      4-bromo-N-((6,6-dimethylbicyclo-[3.1.1]-heptan-2-yl)methyl)-3-(N-((6,6-dimethylbicyclo[3.1.1]heptan-3-yl)methyl)sulfamoyl)-benzamide;
      
      2-chloro-4-fluoro-5-(morpholinosulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      N-(1-adamantan-1-ylethyl)-5-(morpholinosulfonyl)-2-chloro-4-fluorobenzamide; and
      
      a pharmaceutically acceptable salt thereof.
  - 217. A compound according to claim 173, selected from the group consisting of:
    - N-adamantan-2-yl-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      N-(1-adamantan-1-ylethyl)-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N-((1S,4R)-1,7,7-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      N-(R)-bicyclo-[2.2.1]hept-2-yl-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      N-[1-(3-hydroxy-adamantan-1-yl)-ethyl]-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      4-methyl-3-(1,3-dihydroisoindole-2-sulfonyl)-N,S-(1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      N-(R)-bicyclo-[2.2.1]hept-2-yl-3-(1,3-dihydroisoindole-2-sulfonyl)-4-methylbenzamide;
      
      3-(1,3-dihydroisoindole-2-sulfonyl)-4-methyl-N-((1S,4R)-1,7,7-trimethylbicyclo-[2.2.1]hept-2-yl)-benzamide;
      
      3-(1,3-dihydroisoindole-2-sulfonyl)-N-[1-(3-hydroxyadamantan-1-yl)-ethyl]-4-methylbenzamide;
      
      N-adamantan-2-yl-3-(3,4-dihydro-2H-quinoline-1-sulfonyl)-4,5-dimethylbenzamide;
      
      N-(1-adamantan-1-ylethyl)-3-(3,4-dihydro-2H-quinoline-1-sulfonyl)-4,5-dimethylbenzamide;
      
      3-(3,4-dihydroquinolin-1 (2H)-ylsulfonyl)-4,5-dimethyl-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      N-adamantan-2-yl-3,4-dimethyl-5-(octahydroquinoline-1-sulfonyl)-benzamide;
      
      N-(1-adamantan-1-ylethyl)-3,4-dimethyl-5-(octahydroquinoline-1-sulfonyl)-benzamide;
      
      3,4-dimethyl-5-(octahydroquinolin-1 (2H)-ylsulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)benzamide;
      
      N-adamantan-2-yl-3-(2,6-dimethylmorpholine-4-sulfonyl)-4-methylbenzamide;
      
      N-(1-adamantan-1-ylethyl)-3-(2,6-dimethylmorpholine-4-sulfonyl)-4-methylbenzamide;
      
      3-(2,6-dimethylmorpholinosulfonyl)-4-methyl-N-((1S,4R)-1,3,3-trimethylbicylo-[2.2.1]heptan-2-yl)-benzamide;
      
      N-adamantan-2-yl-3-(2,6-dimethylmorpholine-4-sulfonyl)-4,5-dimethylbenzamide;
      
      N-(1-adamantan-1-ylethyl)-3-(2,6-dimethylmorpholine-4-sulfonyl)-4,5-dimethylbenzamide;
      
      3-(2,6-dimethylmorpholinosulfonyl)-4,5-dimethyl-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      N-adamantan-2-yl-5-(N-benzyl-N-methylsulfamoyl)-2-chloro-4-fluoro-benzamide;
      
      N-(1-adamantan-1-ylethyl)-5-(N-benzyl-N-methylsulfamoyl)-2-chloro-4-fluorobenzamide;
      
      5-(N-benzyl-N-methylsulfamoyl)-2-chloro-4-fluoro-N-((1S,4R)-1,3,3-trimethylbicyclo[2.2.1]-heptan-2-yl)benzamide;
      
      3,4-dimethyl-5-(morpholinosulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      N-(((1S,2R,5S)-6,6-dimethylbicyclo-[3.1.1]-heptan-2-yl)methyl)-3,4-dimethyl-5-(morpholinosulfonyl)-benzamide;
      
      N-(1-adamantan-1-ylethyl)-5-(morpholinosulfonyl)-4,5-dimethylbenzamide;
      
      3-(N-benzyl-N-methyl-sulfamoyl)-4,5-dimethyl-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)benzamide;
      
      3-(N-benzyl-N-methyl-sulfamoyl)-N-(((1S,2R,5S)-6,6-dimethylbicyclo-[3.1.1]-heptan-2-yl)methyl)-4,5-dimethylbenzamide;
      
      N-(1-adamantan-1-ylethyl)-5-(N-benzyl-N-methyl-sulfamoyl)-4,5-dimethylbenzamide;
      
      1-(2,3-dimethyl-5-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]heptan-2-ylcarbamoyl)-phenylsulfonyl)-N,N-diethylpiperidine-3-carboxamide;
      
      3-(azetidin-1-ylsulfonyl)-4-methyl-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      3-((S)-3-hydroxypyrrolidin-1-ylsulfonyl)-4-methyl-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      3-((R)-3-hydroxypyrrolidin-1-ylsulfonyl)-4-methyl-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)benzamide;
      
      3-(4-hydroxypiperidin-1-ylsulfonyl)-4-methyl-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      N,N-diethyl-1-(2-methyl-5-((1S,4R)-1,3,3-trimethylbicylo-[2.2.1]heptan-2-ylcarbamoyl)-phenylsulfonyl)-piperidine-3-carboxamide;
      
      3-(N-(2-methoxyethyl)-N-methylsulfamoyl)-4-methyl-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      N,N-diethyl-1-(2-methyl-5-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]heptan-2-ylcarbamoyl)-phenylsulfonyl)-pyrrolidine-3-carboxamide;
      
      N-(1-adamantan-1-ylmethyl)-5-(morpholinosulfonyl)-2-chloro-4-fluorobenzamide;
      
      4-methyl-3-(morpholinosulfonyl)-N-((1R,2R,3R,5S)-2,6,6-trimethylbicyclo-[3.1.1]-heptan-3-yl)-benzamide;
      
      4-methyl-3-(morpholinosulfonyl)-N-((1S,2S,3S,5R)-2,6,6-trimethylbicyclo-[3.1.1]heptan-3-yl)-benzamide;
      
      4-ethyl-3-(morpholine-4-sulfonyl)-N-((1S,4R)-1,3,3-trimethylbicylo[2.2.1]hept-2-yl)-benzamide;
      
      4-isopropyl-3-(morpholine-4-sulfonyl)-N-((1S,4R)-1,3,3-trimethylbicylo[2.2.1]hept-2-yl)-benzamide;
      
      4-propyl-3-(morpholine-4-sulfonyl)-N-((1S,4R)-1,3,3-trimethylbicylo[2.2.1]hept-2-yl)-benzamide;
      
      4-(3-methoxypropyl)-3-(morpholine-4-sulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]hept-2-yl)-benzamide;
      
      5-methyl-3-(morpholine-4-sulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      4,6-dimethyl-3-(morpholine-4-sulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]hept-2-yl)-benzamide;
      
      3-(N,N-dimethylsulfamoyl-4-bromo-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      4-bromo-3-(N-methylsulfamoyl)-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      4-bromo-3-(N-phenylsulfamoyl)-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      4-bromo-3-(morpholinosulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      4-bromo-3-(3-fluoropiperidin-1-ylsulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      4-bromo-3-(pyrrolidin-1-ylsulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      4-bromo-3-(3,5-dimethylpiperidin-1-ylsulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      4-bromo-3-(2,6-dimethylmorpholinosulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      ethyl 1-(2-bromo-5-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl-carbamoyl)-phenylsulfonyl)-piperidine-3-carboxylate;
      
      4-bromo-N-(((1S,2R,5S)-6,6-dimethylbicyclo-[3.1.1]-heptan-2-yl)methyl)-3-(N-(((1R,3S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-3-yl)methyl)sulfamoyl)-benzamide;
      
      2-chloro-4-fluoro-5-(morpholinosulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      N-(1-adamantan-1-ylethyl)-5-(morpholinosulfonyl)-2-chloro-4-fluorobenzamide; and
      
      a pharmaceutically acceptable salt thereof.
  - 218. A compound according to claim 215, selected from the group consisting of:
    - 3,4-dimethyl-5-(morpholinosulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      3-(azetidin-1-ylsulfonyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      3-(3-hydroxypyrrolidin-1-ylsulfonyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      4-(3-methoxypropyl)-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]hept-2-yl)-benzamide;
      
      5-methyl-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      N-(1-adamantan-1-yl-ethyl)-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N-(1,7,7-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      N-((6,6-dimethylbicyclo-[3.1.1]-heptan-2-yl)methyl)-3,4-dimethyl-5-(morpholino-sulfonyl)-benzamide;
      
      4-propyl-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      4-bromo-3-(3-fluoropiperidin-1-ylsulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide; and
      
      a pharmaceutically acceptable salt thereof.
  - 219. A compound according to claim 217, selected from the group consisting of:
    - 3,4-dimethyl-5-(morpholinosulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      3-(azetidin-1-ylsulfonyl)-4-methyl-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      3-((S)-3-hydroxypyrrolidin-1-ylsulfonyl)-4-methyl-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      4-(3-methoxypropyl)-3-(morpholine-4-sulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]hept-2-yl)-benzamide;
      
      5-methyl-3-(morpholine-4-sulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      N-(1-adamantan-1-yl-ethyl)-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N-((1S,4R)-1,7,7-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      N-(((1S,2R,5S)-6,6-dimethylbicyclo-[3.1.1]-heptan-2-yl)methyl)-3,4-dimethyl-5-(morpholino-sulfonyl)-benzamide;
      
      4-propyl-3-(morpholine-4-sulfonyl)-N,S-(1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      4-bromo-3-(3-fluoropiperidin-1-ylsulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide; and
      
      a pharmaceutically acceptable salt thereof.
  - 220. A compound according to claim 218, selected from the group consisting of:
    - 3,4-dimethyl-5-(morpholinosulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      3-(3-hydroxypyrrolidin-1-ylsulfonyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      N-(1-adamantan-1-yl-ethyl)-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N-(1,7,7-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      4-(3-methoxypropyl)-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]hept-2-yl)-benzamide; and
      
      a pharmaceutically acceptable salt thereof.
  - 221. A compound according to claim 219, selected from the group consisting of:
    - 3,4-dimethyl-5-(morpholinosulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      3-((S)-3-hydroxypyrrolidin-1-ylsulfonyl)-4-methyl-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      N-(1-adamantan-1-yl-ethyl)-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N-((1S,4R)-1,7,7-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      4-(3-methoxypropyl)-3-(morpholine-4-sulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo-[2.2.1]hept-2-yl)-benzamide; and
      
      a pharmaceutically acceptable salt thereof.

216. A compound selected from the groups consisting of:
- N-(2,2-dimethylpropyl)-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
  
  4-methyl-3-(morpholine-4-sulfonyl)-N-(1-morpholin-4-ylbutan-2-yl)-benzamide;
  
  3-(1,3-dihydroisoindole-2-sulfonyl)-N-(2,2-dimethylpropyl)-4-methylbenzamide;
  
  3-(1,3-dihydroisoindole-2-sulfonyl)-4-methyl-N-(1-morpholin-4-ylbutan-2-yl)-benzamide;
  
  4-methyl-3-(morpholinosulfonyl)-N(3,3,5-trimethylcyclohexyl)-benzamide;
  
  N-(3,3-dimethylbutan-2-yl)-4-methyl-3-(morpholinosulfonyl)-benzamide;
  
  N-(4-hydroxy-3,3-dimethylbutan-2-yl)-4-methyl-3-(morpholinosulfonyl)-benzamide;
  
  N,N-diisopropyl-4-methyl-3-(morpholinosulfonyl)-benzamide;
  
  4-bromo-3-(morpholine-4-sulfonyl)-N-(2,2-dimethylbutan-2-yl)-benzamide;
  
  4-bromo-3-(pyrrolidine-1-sulfonyl)-N-(2,2-dimethylbutan-2-yl)-benzamide;
  
  4-bromo-3-(N,N-dimethylsulfamoyl-N-(2,2-dimethylbutan-2-yl)-benzamide;
  
  4-(3-methoxyprop-1-ynyl)-3-(morpholinosulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl)benzamide 4-(3-methoxyprop-1-ynyl)-3-(morpholinosulfonyl)-N-((1S,4R)-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl)benzamide and a pharmaceutically acceptable salt thereof.

222. A pharmaceutical composition, comprising:
- a pharmaceutically acceptable carrier; and
  
  a compound of formula VI;
  
  wherein;
  
  R¹is H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroaralkyl, F, Cl, or Br;
  
  R²and R³are each independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroaralkyl, provided that at least one of R²and R³is other than H;
  
  or R²and R³when taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocycloalkyl ring, wherein 1 or 2 of the heterocycloalkyl ring carbon atoms independently may each be optionally replaced by —
  
  O—
  
  , —
  
  S—
  
  , —
  
  N(R⁹)—
  
  , —
  
  N(R¹⁰)—
  
  C(═
  
  O)—
  
  , or —
  
  C(═
  
  O)—
  
  N(R¹⁰)—
  
  ;
  
  R⁴is H or alkyl;
  
  R⁵is;
  
  each R^a, R^b, R^c, R^d, and R^eis independently H or alkyl;
  
  or R^dand R¹taken together with the carbon atom to which they are attached form a carbocyclic ring;
  
  or R^c, R^d, and R^e, taken together with the carbon atom to which they are attached, form a bicycloalkyl or tricycloalkyl ring;
  
  R⁶, R⁶, and R⁸are each independently H, F, Cl, Br, or alkyl;
  
  R⁹is H, alkyl, aryl, —
  
  C(═
  
  O)—
  
  R¹¹, —
  
  C(═
  
  O)—
  
  OR¹¹, —
  
  [C(R¹¹)(R¹¹)]_s—
  
  C(═
  
  O)—
  
  OR¹¹, —
  
  SO₂R¹¹, or —
  
  C(═
  
  O)N(R¹¹)R¹¹;
  
  R¹⁰is H, alkyl, or aryl;
  
  each R¹¹is independently H or alkyl;
  
  r is 0, 1, 2, or 3; and
  
  s is 1, 2, 3, or 4;
  
  provided that;
  
  (1) when R^dand R^etaken together with the carbon atom to which they are attached form a monocyclic carbocyclic ring, then R^cis alkyl or the monocyclic carbocyclic ring is an alkylcycloalkyl ring;
  
  (2) at least two of R^c, R^d, and R^eare other than H; and
  
  (3) when R¹is methyl or bromo, R², R⁴, R⁶, R⁷, and R⁸are each H, and R³is methyl, then R⁵is other than but-2-yl, pent-2-yl, hex-2-yl, hept-2-yl, 1,1,1-dimethyleth-1-yl, 1-dimethylprop-1-yl, 1,1-dimethylbut-1-yl, or 1,1-dimethylpent-1-yl;
  
  or a pharmaceutically acceptable salt thereof.
- View Dependent Claims (223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234)
- - 223. The pharmaceutical composition of claim 222, wherein when R^dand R^eare taken together with the carbon atom to which they are attached to form a monocyclic carbocyclic ring, then R^cis alkyl.
  - 224. A pharmaceutical composition of claim 222, wherein the compound of formula VI is selected from the group consisting of:
    - N-adamantan-2-yl-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      N-(1-adamantan-1-ylethyl)-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N-(1,7,7-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      N-bicyclo-[2.2.1]hept-2-yl-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      N-[1-(3-hydroxy-adamantan-1-yl)-ethyl]-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      N-(2,2-dimethylpropyl)-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N-(1-morpholin-4-ylbutan-2-yl)-benzamide;
      
      4-methyl-3-(1,3-dihydroisoindole-2-sulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      N-bicyclo-[2.2.1]hept-2-yl-3-(1,3-dihydroisoindole-2-sulfonyl)-4-methylbenzamide;
      
      3-(1,3-dihydroisoindole-2-sulfonyl)-4-methyl-N-(1,7,7-trimethylbicyclo-[2.2.1]hept-2-yl)-benzamide;
      
      3-(1,3-dihydroisoindole-2-sulfonyl)-N-(2,2-dimethylpropyl)-4-methylbenzamide;
      
      3-(1,3-dihydroisoindole-2-sulfonyl)-N-[1-(3-hydroxyadamantan-1-yl)-ethyl]-4-methylbenzamide;
      
      3-(1,3-dihydroisoindole-2-sulfonyl)-4-methyl-N-(1-morpholin-4-ylbutan-2-yl)-benzamide;
      
      N-adamantan-2-yl-3-(3,4-dihydro-2H-quinoline-1-sulfonyl)-4,5-dimethylbenzamide;
      
      N-(1-adamantan-1-ylethyl)-3-(3,4-dihydro-2H-quinoline-1-sulfonyl)-4,5-dimethylbenzamide;
      
      3-(3,4-dihydroquinolin-1 (2H)-ylsulfonyl)-4,5-dimethyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      N-adamantan-2-yl-3,4-dimethyl-5-(octahydroquinoline-1-sulfonyl)-benzamide;
      
      N-(1-adamantan-1-ylethyl)-3,4-dimethyl-5-(octahydroquinoline-1-sulfonyl)-benzamide;
      
      3,4-dimethyl-5-(octahydroquinolin-1 (2H)-ylsulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)benzamide;
      
      N-adamantan-2-yl-3-(2,6-dimethylmorpholine-4-sulfonyl)-4-methylbenzamide;
      
      N-(1-adamantan-1-ylethyl)-3-(2,6-dimethylmorpholine-4-sulfonyl)-4-methylbenzamide;
      
      3-(2,6-dimethylmorpholinosulfonyl)-4-methyl-N-(1,3,3-trimethylbicylo-[2.2.1]heptan-2-yl)-benzamide;
      
      N-adamantan-2-yl-3-(2,6-dimethylmorpholine-4-sulfonyl)-4,5-dimethylbenzamide;
      
      N-(1-adamantan-1-ylethyl)-3-(2,6-dimethylmorpholine-4-sulfonyl)-4,5-dimethylbenzamide;
      
      3-(2,6-dimethylmorpholinosulfonyl)-4,5-dimethyl-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      N-adamantan-2-yl-5-(N-benzyl-N-methylsulfamoyl)-2-chloro-4-fluoro-benzamide;
      
      N-(1-adamantan-1-ylethyl)-5-(N-benzyl-N-methylsulfamoyl)-2-chloro-4-fluorobenzamide;
      
      5-(N-benzyl-N-methylsulfamoyl)-2-chloro-4-fluoro-N-(1,3,3-trimethylbicyclo[2.2.1]-heptan-2-yl)benzamide;
      
      3,4-dimethyl-5-(morpholinosulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      N-((6,6-dimethylbicyclo-[3.1.1]-heptan-2-yl)methyl)-3,4-dimethyl-5-(morpholinosulfonyl)-benzamide;
      
      N-(1-adamantan-1-ylethyl)-5-(morpholinosulfonyl)-4,5-dimethylbenzamide;
      
      3-(N-benzyl-N-methyl-sulfamoyl)-4,5-dimethyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)benzamide;
      
      3-(N-benzyl-N-methyl-sulfamoyl)-N-((6,6-dimethylbicyclo-[3.1.1]-heptan-2-yl)methyl)-4,5-dimethylbenzamide;
      
      N-(1-adamantan-1-ylethyl)-5-(N-benzyl-N-methyl-sulfamoyl)-4,5-dimethylbenzamide;
      
      1-(2,3-dimethyl-5-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-ylcarbamoyl)-phenylsulfonyl)-N,N-diethylpiperidine-3-carboxamide;
      
      3-(azetidin-1-ylsulfonyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      3-(3-hydroxypyrrolidin-1-ylsulfonyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      3-(3-hydroxypyrrolidin-1-ylsulfonyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)benzamide;
      
      3-(4-hydroxypiperidin-1-ylsulfonyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      N,N-diethyl-1-(2-methyl-5-(1,3,3-trimethylbicylo-[2.2.1]heptan-2-ylcarbamoyl)-phenylsulfonyl)-piperidine-3-carboxamide;
      
      3-(N-(2-methoxyethyl)-N-methylsulfamoyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      N,N-diethyl-1-(2-methyl-5-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-ylcarbamoyl)-phenylsulfonyl)-pyrrolidine-3-carboxamide;
      
      N-(1-adamantan-1-ylmethyl)-5-(morpholinosulfonyl)-2-chloro-4-fluorobenzamide;
      
      4-methyl-3-(morpholinosulfonyl)-N(3,3,5-trimethylcyclohexyl)-benzamide;
      
      4-methyl-3-(morpholinosulfonyl)-N-(2,6,6-trimethylbicyclo-[3.1.1]-heptan-3-yl)-benzamide;
      
      4-methyl-3-(morpholinosulfonyl)-N-(2,6,6-trimethylbicyclo-[3.1.1]heptan-3-yl)-benzamide;
      
      N-(3,3-dimethylbutan-2-yl)-4-methyl-3-(morpholinosulfonyl)-benzamide;
      
      N-(4-hydroxy-3,3-dimethylbutan-2-yl)-4-methyl-3-(morpholinosulfonyl)-benzamide;
      
      N,N-diisopropyl-4-methyl-3-(morpholinosulfonyl)-benzamide;
      
      4-ethyl-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicylo[2.2.1]hept-2-yl)-benzamide;
      
      4-isopropyl-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicylo[2.2.1]hept-2-yl)-benzamide;
      
      4-propyl-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicylo[2.2.1]hept-2-yl)-benzamide;
      
      4-(3-methoxypropyl)-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]hept-2-yl)-benzamide;
      
      5-methyl-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      4,6-dimethyl-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]hept-2-yl)-benzamide;
      
      3-(N,N-dimethylsulfamoyl-4-bromo-N-(1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      4-bromo-3-(N-methylsulfamoyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      4-bromo-3-(N-phenylsulfamoyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      4-bromo-3-(morpholinosulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      4-bromo-3-(3-fluoropiperidin-1-ylsulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      4-bromo-3-(pyrrolidin-1-ylsulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      4-bromo-3-(3,5-dimethylpiperidin-1-ylsulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      4-bromo-3-(2,6-dimethylmorpholinosulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      ethyl 1-(2-bromo-5-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl-carbamoyl)-phenylsulfonyl)-piperidine-3-carboxylate;
      
      4-bromo-N-((6,6-dimethylbicyclo-[3.1.1]-heptan-2-yl)methyl)-3-(N-(((1R,3S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-3-yl)methyl)sulfamoyl)-benzamide;
      
      4-bromo-3-(morpholine-4-sulfonyl)-N-(2,2-dimethylbutan-2-yl)-benzamide;
      
      4-bromo-3-(pyrrolidine-1-sulfonyl)-N-(2,2-dimethylbutan-2-yl)-benzamide;
      
      4-bromo-3-(N,N-dimethylsulfamoyl-N-(2,2-dimethylbutan-2-yl)-benzamide;
      
      2-chloro-4-fluoro-5-(morpholinosulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      N-(1-adamantan-1-ylethyl)-5-(morpholinosulfonyl)-2-chloro-4-fluorobenzamide;
      
      N-benzyl-5-(N-benzyl-N-methylsulfamoyl)-2-chloro-4-fluoro-N-methylbenzamide; and
      
      a pharmaceutically acceptable salt thereof.
  - 225. A pharmaceutical composition according to claim 224, further comprising at least one cannabinoid.
  - 226. A pharmaceutical composition according to claim 225, wherein the cannabinoid is Δ
    - ⁹-tetrahydrocannabinol or cannabidiol.
  - 227. A pharmaceutical composition according to claim 224, further comprising at least one opioid.
  - 228. A pharmaceutical composition according to claim 227, wherein said opioid is selected from the group consisting of alfentanil, buprenorphine, butorphanol, codeine, dezocine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, levorphanol, loperamide, meperidine (pethidine), methadone, morphine, nalbuphine, oxycodone, oxymorphone, pentazocine, propiram, propoxyphene, sufentanil and tramadol, and mixtures thereof.
  - 229. A pharmaceutical composition according to claim 227, further comprising at least one analgesic.
  - 230. A pharmaceutical composition according to claim 229, wherein the analgesic is a COX2 inhibitor, aspirin, acetaminophen, ibuprophen, or naproxen, or a mixture thereof.
  - 231. A pharmaceutical composition according to claim 224, further comprising at least one agent selected from the group consisting of an anti-seizure agent, an anti-depressant, an NMDA receptor antagonist, an ion channel antagonist, a nicotinic receptor agonist, and an anti-Parkinson'"'"'s agent.
  - 232. A pharmaceutical composition according to claim 231 wherein said anti-seizure agent is carbamazepine, gabapentin, lamotrigine, or phenyloin, or a mixture thereof.
  - 233. A pharmaceutical composition according to claim 231 wherein said anti-depressant is amitryptiline.
  - 234. A pharmaceutical composition according to claim 231, wherein said anti-Parkinson'"'"'s agent is deprenyl, amantadine, levodopa, or carbidopa, or a mixture thereof.

235. A method of binding cannabinoid receptors in a patient in need thereof, comprising the step of:
- administering to said patient an effective amount of a compound of formula VI;
  
  wherein;
  
  R¹is H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroaralkyl, F, Cl, or Br;
  
  R²and R³are each independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroaralkyl, provided that at least one of R²and R³is other than H;
  
  or R²and R³when taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocycloalkyl ring, wherein 1 or 2 of the heterocycloalkyl ring carbon atoms independently may each be optionally replaced by —
  
  O—
  
  , —
  
  S—
  
  , —
  
  N(R⁹)—
  
  , —
  
  N(R¹⁰)—
  
  C(═
  
  O)—
  
  , or —
  
  C(═
  
  O)—
  
  N(R¹⁰)—
  
  ;
  
  R⁴is H or alkyl;
  
  R⁵is;
  
  each R^a, R^b, R^c, R^d, and R^eis independently H or alkyl;
  
  or R^dand R^etaken together with the carbon atom to which they are attached form a carbocyclic ring;
  
  or R^c, R^d, and R^e, taken together with the carbon atom to which they are attached, form a bicycloalkyl or tricycloalkyl ring;
  
  R⁶, R⁷, and R⁸are each independently H, F, Cl, Br, or alkyl;
  
  R⁹is H, alkyl, aryl, —
  
  C(═
  
  O)—
  
  R¹¹, —
  
  C(═
  
  O)—
  
  OR¹¹, —
  
  [C(R¹¹)(R¹¹)]_s—
  
  C(═
  
  O)—
  
  OR¹¹, —
  
  SO₂R¹¹, or —
  
  C(═
  
  O)N(R¹¹)R¹¹;
  
  R¹⁰is H, alkyl, or aryl;
  
  each R¹¹is independently H or alkyl;
  
  r is 0, 1, 2, or 3; and
  
  s is 1, 2, 3, or 4;
  
  provided that;
  
  (1) when R^dand R^etaken together with the carbon atom to which they are attached form a monocyclic carbocyclic ring, then R^cis alkyl or the monocyclic carbocyclic ring is an alkylcycloalkyl ring; and
  
  (2) at least two of R^c, R^d, and R^eare other than H;
  
  or a pharmaceutically acceptable salt thereof.
- View Dependent Claims (236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272)
- - 236. The method of claim 235, wherein when R^dand R^eare taken together with the carbon atom to which they are attached to form a monocyclic carbocyclic ring, then R^eis alkyl.
  - 237. A method of claim 235, wherein the compound of formula VI is selected from the group consisting of:
    - N-adamantan-2-yl-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      N-(1-adamantan-1-ylethyl)-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N-(1,7,7-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      N-bicyclo-[2.2.1]hept-2-yl-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      N-[1-(3-hydroxy-adamantan-1-yl)-ethyl]-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      N-(2,2-dimethylpropyl)-4-methyl-3-(morpholine-4-sulfonyl)-benzamide;
      
      4-methyl-3-(morpholine-4-sulfonyl)-N-(1-morpholin-4-ylbutan-2-yl)-benzamide;
      
      4-methyl-3-(1,3-dihydroisoindole-2-sulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      N-bicyclo-[2.2.1]hept-2-yl-3-(1,3-dihydroisoindole-2-sulfonyl)-4-methylbenzamide;
      
      3-(1,3-dihydroisoindole-2-sulfonyl)-4-methyl-N-(1,7,7-trimethylbicyclo-[2.2.1]hept-2-yl)-benzamide;
      
      3-(1,3-dihydroisoindole-2-sulfonyl)-N-(2,2-dimethylpropyl)-4-methylbenzamide;
      
      3-(1,3-dihydroisoindole-2-sulfonyl)-N-[1-(3-hydroxyadamantan-1-yl)-ethyl]-4-methylbenzamide;
      
      3-(1,3-dihydroisoindole-2-sulfonyl)-4-methyl-N-(1-morpholin-4-ylbutan-2-yl)-benzamide;
      
      N-adamantan-2-yl-3-(3,4-dihydro-2H-quinoline-1-sulfonyl)-4,5-dimethylbenzamide;
      
      N-(1-adamantan-1-ylethyl)-3-(3,4-dihydro-2H-quinoline-1-sulfonyl)-4,5-dimethylbenzamide;
      
      3-(3,4-dihydroquinolin-1 (2H)-ylsulfonyl)-4,5-dimethyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      N-adamantan-2-yl-3,4-dimethyl-5-(octahydroquinoline-1-sulfonyl)-benzamide;
      
      N-(1-adamantan-1-ylethyl)-3,4-dimethyl-5-(octahydroquinoline-1-sulfonyl)-benzamide;
      
      3,4-dimethyl-5-(octahydroquinolin-1 (2H)-ylsulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)benzamide;
      
      N-adamantan-2-yl-3-(2,6-dimethylmorpholine-4-sulfonyl)-4-methylbenzamide;
      
      N-(1-adamantan-1-ylethyl)-3-(2,6-dimethylmorpholine-4-sulfonyl)-4-methylbenzamide;
      
      3-(2,6-dimethylmorpholinosulfonyl)-4-methyl-N-(1,3,3-trimethylbicylo-[2.2.1]heptan-2-yl)-benzamide;
      
      N-adamantan-2-yl-3-(2,6-dimethylmorpholine-4-sulfonyl)-4,5-dimethylbenzamide;
      
      N-(1-adamantan-1-ylethyl)-3-(2,6-dimethylmorpholine-4-sulfonyl)-4,5-dimethylbenzamide;
      
      3-(2,6-dimethylmorpholinosulfonyl)-4,5-dimethyl-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      N-adamantan-2-yl-5-(N-benzyl-N-methylsulfamoyl)-2-chloro-4-fluoro-benzamide;
      
      N-(1-adamantan-1-ylethyl)-5-(N-benzyl-N-methylsulfamoyl)-2-chloro-4-fluorobenzamide;
      
      5-(N-benzyl-N-methylsulfamoyl)-2-chloro-4-fluoro-N-(1,3,3-trimethylbicyclo[2.2.1]-heptan-2-yl)benzamide;
      
      3,4-dimethyl-5-(morpholinosulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      N-((6,6-dimethylbicyclo-[3.1.1]-heptan-2-yl)methyl)-3,4-dimethyl-5-(morpholinosulfonyl)-benzamide;
      
      N-(1-adamantan-1-ylethyl)-5-(morpholinosulfonyl)-4,5-dimethylbenzamide;
      
      3-(N-benzyl-N-methyl-sulfamoyl)-4,5-dimethyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)benzamide;
      
      3-(N-benzyl-N-methyl-sulfamoyl)-N-((6,6-dimethylbicyclo-[3.1.1]-heptan-2-yl)methyl)-4,5-dimethylbenzamide;
      
      N-(1-adamantan-1-ylethyl)-5-(N-benzyl-N-methyl-sulfamoyl)-4,5-dimethylbenzamide;
      
      1-(2,3-dimethyl-5-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-ylcarbamoyl)-phenylsulfonyl)-N,N-diethylpiperidine-3-carboxamide;
      
      3-(azetidin-1-ylsulfonyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      3-(3-hydroxypyrrolidin-1-ylsulfonyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      3-(3-hydroxypyrrolidin-1-ylsulfonyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)benzamide;
      
      3-(4-hydroxypiperidin-1-ylsulfonyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      N,N-diethyl-1-(2-methyl-5-(1,3,3-trimethylbicylo-[2.2.1]heptan-2-ylcarbamoyl)-phenylsulfonyl)-piperidine-3-carboxamide;
      
      3-(N-(2-methoxyethyl)-N-methylsulfamoyl)-4-methyl-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      N,N-diethyl-1-(2-methyl-5-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-ylcarbamoyl)-phenylsulfonyl)-pyrrolidine-3-carboxamide;
      
      N-(1-adamantan-1-ylmethyl)-5-(morpholinosulfonyl)-2-chloro-4-fluorobenzamide;
      
      4-methyl-3-(morpholinosulfonyl)-N(3,3,5-trimethylcyclohexyl)-benzamide;
      
      4-methyl-3-(morpholinosulfonyl)-N-(2,6,6-trimethylbicyclo-[3.1.1]-heptan-3-yl)-benzamide;
      
      4-methyl-3-(morpholinosulfonyl)-N-(2,6,6-trimethylbicyclo-[3.1.1]heptan-3-yl)-benzamide;
      
      N-(3,3-dimethylbutan-2-yl)-4-methyl-3-(morpholinosulfonyl)-benzamide;
      
      N-(4-hydroxy-3,3-dimethylbutan-2-yl)-4-methyl-3-(morpholinosulfonyl)-benzamide;
      
      N,N-diisopropyl-4-methyl-3-(morpholinosulfonyl)-benzamide;
      
      4-ethyl-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicylo[2.2.1]hept-2-yl)-benzamide;
      
      4-isopropyl-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicylo[2.2.1]hept-2-yl)-benzamide;
      
      4-propyl-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicylo[2.2.1]hept-2-yl)-benzamide;
      
      4-(3-methoxypropyl)-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]hept-2-yl)-benzamide;
      
      5-methyl-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicyclo[2.2.1]-hept-2-yl)-benzamide;
      
      4,6-dimethyl-3-(morpholine-4-sulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]hept-2-yl)-benzamide;
      
      3-(N,N-dimethylsulfamoyl-4-bromo-N-(1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      4-bromo-3-(N-methylsulfamoyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      4-bromo-3-(N-phenylsulfamoyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-benzamide;
      
      4-bromo-3-(morpholinosulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      4-bromo-3-(3-fluoropiperidin-1-ylsulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      4-bromo-3-(pyrrolidin-1-ylsulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl)-benzamide;
      
      4-bromo-3-(3,5-dimethylpiperidin-1-ylsulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      4-bromo-3-(2,6-dimethylmorpholinosulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      ethyl 1-(2-bromo-5-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl-carbamoyl)-phenylsulfonyl)-piperidine-3-carboxylate;
      
      4-bromo-N-((6,6-dimethylbicyclo-[3.1.1]-heptan-2-yl)methyl)-3-(N-(((1R,3S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-3-yl)methyl)sulfamoyl)-benzamide;
      
      4-bromo-3-(morpholine-4-sulfonyl)-N-(2,2-dimethylbutan-2-yl)-benzamide;
      
      4-bromo-3-(pyrrolidine-1-sulfonyl)-N-(2,2-dimethylbutan-2-yl)-benzamide;
      
      4-bromo-3-(N,N-dimethylsulfamoyl-N-(2,2-dimethylbutan-2-yl)-benzamide;
      
      2-chloro-4-fluoro-5-(morpholinosulfonyl)-N-(1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl)-benzamide;
      
      N-(1-adamantan-1-ylethyl)-5-(morpholinosulfonyl)-2-chloro-4-fluorobenzamide; and
      
      a pharmaceutically acceptable salt thereof.
  - 238. A method according to claim 235, wherein the cannabinoid receptors are selected from the group consisting of CB1 and CB2 cannabinoid receptors.
  - 239. A method according to claim 238, wherein the cannabinoid receptors are located in the central nervous system.
  - 240. A method according to claim 235, wherein the cannabinoid receptors are located peripherally to the central nervous system.
  - 241. A method according to claim 238, wherein the compound selectively binds the CB2 cannabinoid receptors relative to the CB1 receptors.
  - 242. A method according to claim 235, wherein the binding agonizes the activity of the cannabinoid receptors.
  - 243. A method according to claim 235, wherein the binding antagonizes the activity of the cannabinoid receptors.
  - 244. A method according to claim 235, wherein the binding inversely agonizes the activity of the cannabinoid receptors.
  - 245. A method according to claim 235, further comprising administering to said patient an effective amount of at least one cannabinoid.
  - 246. A method according to claim 245, wherein said cannabinoid is Δ
    - ⁹-tetrahydrocannabinol or cannabidiol.
  - 247. A method according to claim 235, further comprising administering to said patient an effective amount of at least one opioid.
  - 248. A method according to claim 247, wherein said opioid is selected from alfentanil, buprenorphine, butorphanol, codeine, dezocine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, levorphanol, loperamide, meperidine (pethidine), methadone, morphine, nalbuphine, oxycodone, oxymorphone, pentazocine, propiram, propoxyphene, sufentanil and tramadol, and mixtures thereof.
  - 249. A method according to claim 235 which is for the treatment of a disease or disorder selected from the group consisting of a gastrointestinal disorder, inflammation, an auto-immune disease, an immune-related disorder, pain, hypertension, a neurodegenerative disease, a neurological disorder, and combinations thereof.
  - 250. A method according to claim 235 for providing cardioprotection against ischemic or reperfusion effects, inhibiting mechanical hyperalgesia associated with nerve injury, inducing apoptosis in malignant cells, modulating appetite, or combination thereof.
  - 251. A method according to claim 249, which is for the treatment of pain.
  - 252. A method according to claim 251, further comprising administering to said patient at least one cannabinoid.
  - 253. A method according to claim 251, wherein said pain is inflammatory pain, neuropathic pain, visceral pain, surgical pain, post-surgical pain, cancer related pain or a combination thereof.
  - 254. A method according to claim 253, for treating pain, further comprising administering to said patient codeine, carbamazepine, gabapentin, lamotrigine, phenyloin, amitryptiline, an NMDA receptor antagonist, an ion channel antagonist, a nicotinic receptor agonist, or a mixture thereof.
  - 255. A method according to claim 249, which is for the treatment of a gastrointestinal disorder.
  - 256. A method according to claim 255, wherein the gastrointestinal disorder is nausea, vomiting, loss of appetite, cachexia, diarrhea, inflammatory bowel disease, irritable bowel syndrome or combination thereof.
  - 257. A method according to claim 249, which is for the treatment of an auto-immune disease.
  - 258. A method according to claim 257, wherein the auto-immune disease is multiple sclerosis, rheumatoid arthritis, psoriasis, Crohn'"'"'s disease, systemic lupus erythematosus, myasthenia gravis, diabetes mellitus type I, osteoporosis, or a combination thereof.
  - 259. A method according to claim 249, which is for the treatment of an ischemic condition.
  - 260. A method according to claim 259, wherein said ischemic condition is renal ischemia, cerebral stroke, cerebral ischemia, or a combination thereof.
  - 261. A method according to claim 249, which is for the treatment of a neurological disorder.
  - 262. A method according to claim 261, wherein said neurological disorder is stroke, migraine, cluster headache, or combination thereof.
  - 263. A method according to claim 249, which is for the treatment of an immune-related disorder.
  - 264. A method according to claim 263, wherein said immune-related disorder is asthma, chronic pulmonary obstructive disorder, emphysema, bronchitis, allergy, tissue rejection in organ transplants, celiac disease, Sjö
    - gren'"'"'s syndrome, or a combination thereof.
  - 265. A method according to claim 249, which is for the treatment of neurodegenerative disease.
  - 266. A method according to claim 265, wherein said neurodegenerative disease is Parkinson'"'"'s disease, Alzheimer'"'"'s disease, Huntington'"'"'s disease, amyotrophic lateral sclerosis, or combination thereof.
  - 267. A method according to claim 265, further comprising administering to said patient deprenyl, amantadine, levodopa, or carbidopa.
  - 268. A method according to claim 250, which is for providing cardioprotection against ischemic or reperfusion effects.
  - 269. A method according to claim 268, wherein the ischemic or reperfusion effect is arrhythmia or hypertension.
  - 270. A method according to claim 250, which is for the inducing of apoptosis in malignant cells.
  - 271. A method according to claim 270, wherein the apoptosis occurs in vitro.
  - 272. A method according to claim 270, wherein the apoptosis occurs in vivo.

Specification

Resources

Litigation Campaign Assessment

Current Assignee
Adolor Corporation (Merck & Co., Inc.)
Original Assignee
Adolor Corporation (Merck & Co., Inc.)
Inventors
Dolle, Roland E., Zhou, Q. Jean, Worm, Karin

Granted Patent

US 7,297,796 B2
Time in Patent Office

Days
Field of Search
US Class Current

514/317
CPC Class Codes

C07C 2602/42   the bicyclo ring system con...

C07C 2603/74   Adamantanes

C07C 311/16   having the nitrogen atom of...

C07C 311/21   having the nitrogen atom of...

C07D 205/04   having no double bonds betw...

C07D 207/48   Sulfur atoms

C07D 209/44   Iso-indoles; Hydrogenated i...

C07D 211/46   having a hydrogen atom as t...

C07D 211/60   Carbon atoms having three b...

C07D 211/96   Sulfur atom

C07D 213/40   Acylated substituent nitrog...

C07D 215/58   with hetero atoms directly ...

C07D 295/26   Sulfur atoms

Sulfamoyl benzamide derivatives and methods of their use

First Claim

1 Assignment

0 Petitions

Accused Products

Abstract

Citations

272 Claims

Specification

Solutions

Use Cases

Quick Links

Sulfamoyl benzamide derivatives and methods of their use

First Claim

1 Assignment

Subscription Required

Subscription Required

0 Petitions

Subscription Required

Accused Products

Subscription Required

Abstract

Citations

272 Claims

Specification

Subscription Required

Solutions

Use Cases

Quick Links