Heterocyclic analgesic compounds and methods of use thereof

• US 6,635,661 B2
• Filed: 03/02/2001
• Issued: 10/21/2003
• Est. Priority Date: 05/25/2000
• Status: Expired due to Term

• Current Assignee: Sepracor Incorporated
• Original Assignee: Sepracor Incorporated
• Inventors: Heffernan, Michele L. R., Cuny, Gregory D., Hauske, James R., Aquila, Brian M., Bannister, Thomas D., Shao, Liming, Wu, Xinhe, Wang, Fengjiang
• Primary Examiner(s): Coleman, Brenda
• Application Number:
  US09/798,803
• Publication Number:
  US 20020016337A1
• Time in Patent Office: 963 Days
• Field of Search: 514/331, 546/234
• US Class Current: 514/331
• CPC Class Codes: A61K 31/397 having four-membered rings, e.g. azetidine
• CPC Class Codes: A61K 31/438 The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
• CPC Class Codes: A61K 31/4523 containing further heterocyclic ring systems
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/5375 1,4-Oxazines, e.g. morpholine
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/553 having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: C07D 205/04 having no double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: C07D 205/06 having one double bond between ring members or between a ring member and a non-ring member
• CPC Class Codes: C07D 211/26 with hydrocarbon radicals, substituted by nitrogen atoms
• CPC Class Codes: C07D 211/42 attached in position 3 or 5
• CPC Class Codes: C07D 211/56 Nitrogen atoms nitro radicals C07D211/38
• CPC Class Codes: C07D 211/60 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 211/70 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 221/04 Ortho- or peri-condensed ring systems
• CPC Class Codes: C07D 223/04 with only hydrogen atoms, halogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 223/10 attached in position 2
• CPC Class Codes: C07D 241/04 : having no double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: C07D 243/08 : not condensed with other rings
• CPC Class Codes: C07D 265/30 : not condensed with other rings
• CPC Class Codes: C07D 267/10 : not condensed with other rings
• CPC Class Codes: C07D 333/38 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 401/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 : containing three or more hetero rings
• CPC Class Codes: C07D 409/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 409/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 491/10 : Spiro-condensed systems

Abstract

One aspect of the present invention relates to novel heterocyclic compounds. A second aspect of the present invention relates to the use of the novel heterocyclic compounds as ligands for various cellular receptors, including opiate receptors, other G-protein-coupled receptors, and ion channels. An additional aspect of the present invention relates to the use of the novel heterocyclic compounds as analgesics.

Claims

1. A compound represented by G:

wherein

R represents phenyl, 2-fluorophenyl, 3-fluorophenyl, or 4-fluorophenyl;

R′

represents H or OH; and

the stereochemical configuration at any stereocenter of a compound represented by G is R, S, or a mixture of these configurations.

2. The compound of claim 1, wherein R represents 2-fluorophenyl, 3-fluorophenyl, or 4-fluorophenyl;

and R′

represents H.

3. The compound of claim 1, wherein R represents 3-fluorophenyl;

and R′

represents H.

4. The compound of claim 1, wherein R represents phenyl;

and R′

represents OH.

5. The compound of claim 1, wherein said compound is represented by 1:

6. The compound of claim 1, wherein said compound is represented by 2:

7. The compound of claim 1, wherein said compound is represented by 3:

8. The compound of claim 1, wherein said compound is represented by 4:

9. The compound of claim 1, wherein said compound is represented by 5:

10. The compound of claim 1, wherein said compound is represented by 6:

11. The compound of claim 1, wherein said compound is represented by 7:

12. The compound of claim 1, wherein said compound is represented by 8:

13. The compound of claim 1, wherein said compound is represented by 9:

14. The compound of claim 1, wherein said compound is represented by 10:

15. The compound of claim 1, wherein said compound is represented by 11:

16. The compound of claim 1, wherein said compound is represented by 12:

17. A composition, comprising a compound of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16;

and a pharmaceutically acceptable excipient.

18. The composition of claim 17, wherein said pharmaceutically acceptable excipient is selected from the group consisting of cyclodextrins, liposomes, micelle forming agents, and polymeric carriers.

19. A method of treating pain, drug addiction, or tinnitus in a mammal, comprising the step of administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16.

20. The method of claim 19, wherein said mammal is a primate, equine, canine or feline.

21. The method of claim 19, wherein said mammal is a human.

22. The method of claim 19, wherein said compound is administered orally.

23. The method of claim 19, wherein said compound is administered intravenously.

24. The method of claim 19, wherein said compound is administered sublingually.

25. The method of claim 19, wherein said compound is administered ocularly.

26. The method of claim 19, wherein said compound is administered transdermally.