Substituted heterocycle fused gamma-carbolines

• US 7,081,455 B2
• Filed: 02/25/2004
• Issued: 07/25/2006
• Est. Priority Date: 06/15/1999
• Status: Expired due to Term

• Current Assignee: Bristol-Myers Squibb Pharma Company (Bristol-Myers Squibb Company)
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Mitchell, Ian S., Deng, Wei, Lee, Taekyu, Robichaud, Albert J., Chen, Wenting, McClung, Christopher D., Zawrotny, David M., Calvello, Emilie J.
• Primary Examiner(s): Kifle, Bruck
• Application Number:
  US10/786,935
• Publication Number:
  US 20040209864A1
• Time in Patent Office: 881 Days
• Field of Search: 514/212.05, 514/212.06, 514/214.02, 514/214.03, 514/286, 514/288
• US Class Current: 514/212.05
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 221/18 Ring systems of four or more rings
• CPC Class Codes: C07D 223/32 containing carbocyclic rings other than six-membered
• CPC Class Codes: C07D 471/06 Peri-condensed systems
• CPC Class Codes: C07D 491/06 Peri-condensed systems
• CPC Class Codes: C07D 495/06 Peri-condensed systems

Abstract

The present invention is directed to methods of treating addictive behavior and sleep disorders by administering compounds represented by structural Formula (I)

or pharmaceutically acceptable salt forms thereof, wherein R¹, R⁵, R^6a, R^6b, R⁷, R⁸, R⁹, X, b, k, m, and n, and the dashed lines are described herein. The compounds used in the method of treatment of this invention are serotonin agonists and antagonists and are useful in the control or prevention of central nervous system disorders including addictive behavior and sleep disorders.

Claims

1. A method for treating a human suffering from sleep disorders associated with 5HT2A receptor modulation, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula (I):

2. The method as defined in claim 1 where in the compound administered:

X is —

CHR¹⁰—

or —

C(═

O)—

;

R¹ is selected from

H,

C(—

O)R²,

C(═

O)OR²,

C_1-8 alkyl,

C_2-8 alkenyl,

C_2-8 alkynyl,

C_3-7 cycloalkyl,

C_1-6 alkyl substituted with 0–

2 R²,

C_2-6 alkenyl substituted with 0–

2 R²,

C_2-6 alkynyl substituted with 0–

2 R²,

aryl substituted with 0–

2 R², and

5–

6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with 0–

2 R²;

R², at each occurrence, is independently selected from

F, Cl, CH₂F, CHF₂, CF₃,

C_1-4 alkyl,

C_2-4 alkenyl,

C_2-4 alkynyl,

C_3-6 cycloalkyl,

phenyl substituted with 0–

5 R⁴²;

C_3-10 carbocyclic group substituted with 0–

3 R⁴¹, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R⁴¹;

R⁵ is H, methyl, ethyl, propyl, or butyl;

R^6a is selected from

H, —

OH, —

NR⁴⁶R⁴⁷, —

CF₃,

C_1-4 alkyl, C_1-4 alkoxy, C_1-4 haloalkyl, and

aryl substituted with 0–

3 R⁴⁴;

R^6b is H;

R⁷ and R⁹, at each occurrence, are independently selected from

H, halo, —

CF₃, —

OCF₃, —

OH, —

CN, —

NO₂, —

NR⁴⁶R⁴⁷,

C_1-8 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, C_1-4 haloalkyl, C_1-8 alkoxy, (C_1-4 haloalkyl)oxy,

C_3-10 cycloalkyl substituted with 0–

2 R³³,

C_1-4 alkyl substituted with 0–

2 R¹¹,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

aryl substituted with 0–

5 R³³,

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

OR¹², SR¹², NR¹²R¹³, C(O)H, C(O)R¹², C(O)NR¹²R¹³, NR¹⁴C(O)R¹², C(O)OR¹², OC(O)R¹², OC(O)OR¹², CH(═

NR¹⁴)NR¹²R¹³, NHC(═

NR¹⁴)NR¹²R¹³, S(O)R¹², S(O)₂R¹², S(O)NR¹²R¹³, S(O)₂NR¹²R¹³, NR¹⁴S(O)R¹², NR¹⁴S(O)₂R¹², NR¹²C(O)R¹⁵, NR¹²C(O)OR¹⁵, NR¹²S(O)₂R¹⁵, and NR¹²C(O)NHR¹⁵;

R⁸ is selected from

H, halo, —

CF₃, —

OCF₃, —

OH, —

CN, —

NO₂,

C_1-8 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, C_1-4 haloalkyl, C_1-8 alkoxy, (C_1-4 haloalkyl)oxy,

C_3-10 cycloalkyl substituted with 0–

2 R³³,

C_1-4 alkyl substituted with 0–

2 R¹¹,

C_2-4 alkenyl substituted with 0–

2 R¹¹,

C_2-4 alkynyl substituted with 0–

1 R¹¹,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

aryl substituted with 0–

5 R³³,

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

OR¹², SR¹², NR¹²R¹³, C(O)H, C(O)R¹², C(O)NR¹²R¹³, NR¹⁴C(O)R¹², C(O)OR¹², OC(O)R¹², OC(O)OR¹², CH(═

NR¹⁴)NR¹²R¹³, NHC(═

NR¹⁴)NR¹²R¹³, S(O)R¹², S(O)₂R¹², S(O)NR¹²R¹³, S(O)₂NR¹²R¹³, NR¹⁴S(O)R¹², NR¹⁴S(O)₂R¹², NR¹²C(O)R¹⁵, NR¹²C(O)OR¹⁵, NR¹²S(O)₂R¹⁵, and NR¹²C(O)NHR¹⁵;

R¹⁰ is selected from H, —

OH,

C_1-6 alkyl substituted with 0–

1 R^10B,

C_2-6 alkenyl substituted with 0–

1 R^10B,

C_2-6 alkynyl substituted with 0–

1 R^10B, and

C_1-6 alkoxy;

R^10B is selected from

C_1-4 alkoxy,

C_3-6 cycloalkyl,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

phenyl substituted with 0–

3 R³³, and

5–

6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

2 R⁴⁴;

R¹¹ is selected from

H, halo, —

CF₃, —

CN, —

NO₂,

C_1-8 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, C_1-4 haloalkyl, C_1-8 alkoxy, C_3-10 cycloalkyl,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

aryl substituted with 0–

5 R³³,

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

OR¹², SR¹², NR¹²R¹³, C(O)H, C(O)R¹², C(O)NR¹²R¹³, NR¹⁴C(O)R¹², C(O)OR¹², OC(O)R¹², OC(O)OR¹², CH(═

NR¹⁴)NR¹²R¹³, NHC(═

NR¹⁴)NR¹²R¹³, S(O)R¹², S(O)₂R¹², S(O)NR¹²R¹³, S(O)₂NR¹²R¹³, NR¹⁴S(O)R¹², NR¹⁴S(O)₂R¹², NR¹²C(O)R¹⁵, NR¹²C(O)OR¹⁵, NR¹²S(O)₂R¹⁵, and NR¹²C(O)NHR¹⁵;

R¹², at each occurrence, is independently selected from

C_1-4 alkyl substituted with 0–

1 R^12a,

C_2-4 alkenyl substituted with 0–

1 R^12a,

C_2-4 alkynyl substituted with 0–

1 R^12a,

C_3-6 cycloalkyl substituted with 0–

3 R³³,

phenyl substituted with 0–

5 R³³;

C_3-10 carbocyclic group substituted with 0–

3 R³³, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

R^12a, at each occurrence, is independently selected from

phenyl substituted with 0–

5 R³³;

C_3-10 carbocyclic group substituted with 0–

3 R³³, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

R¹³, at each occurrence, is independently selected from

H, C_1-4 alkyl, C_2-4 alkenyl, and C_2-4 alkynyl;

alternatively, R¹² and R¹³ join to form a 5- or 6-membered ring optionally substituted with —

O—

or —

N(R¹⁴)—

;

alternatively, R¹² and R¹³ when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1–

3 heteroatoms selected from the group consisting of N, O, and S, wherein said bicyclic heterocyclic ring system is unsaturated or partially saturated, wherein said bicyclic heterocyclic ring system is substituted with 0–

3 R¹⁶;

R¹⁴, at each occurrence, is independently selected from H and C_1-4 alkyl;

R¹⁵, at each occurrence, is independently selected from

H, C_1-4 alkyl, C_2-4 alkenyl, and C_2-4 alkynyl;

R¹⁶, at each occurrence, is independently selected from

H, OH, halo, CN, NO₂, CF₃, SO₂R⁴⁵, NR⁴⁶R⁴⁷, —

C(═

O)H,

C_1-4 alkyl, C_2-4 alkenyl, C_2-4 alkynyl, C_1-4 haloalkyl,

C_1-3 haloalkyl-oxy-, and C_1-3 alkyloxy-;

R³¹, at each occurrence, is independently selected from

H, OH, halo, CF₃, SO₂R⁴⁵, NR⁴⁶R⁴⁷, and C_1-4 alkyl;

R³³, at each occurrence, is independently selected from

H, OH, halo, CN, NO₂, CF₃, SO₂R⁴⁵, NR⁴⁶R⁴⁷, —

C(═

O)H,

C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl,

C_3-6 cycloalkyl, C_1-14 haloalkyl, C_1-14 haloalkyl-oxy-, C_1-4 alkyloxy-,

C_1-4 alkylthio-, C_1-4 alkyl-C(═

O)—

, C_1-4 alkyl-C(═

O)NH—

, C_1-4 alkyl-OC(═

O)—

,

C_1-4 alkyl-C(═

O)O—

, C_3-6 cycloalkyl-oxy-, C_3-6 cycloalkylmethyl-oxy-;

C_1-6 alkyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy; and

C_2-6 alkenyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy;

R⁴¹, at each occurrence, is independently selected from

H, CF₃, halo, OH, CO₂H, SO₂R⁴⁵, NR⁴⁶R⁴⁷, NO₂, CN;

C_2-8 alkenyl, C_2-8 alkynyl, C_1-4 alkoxy, C_1-4 haloalkyl

C_1-4 alkyl substituted with 0–

1 R⁴³,

aryl substituted with 0–

3 R⁴², and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R⁴⁴;

R⁴², at each occurrence, is independently selected from

H, CF₃, halo, OH, CO₂H, SO₂R⁴⁵, NR⁴⁶R⁴⁷, NO₂, CN, CH(═

NH)NH₂, NHC(═

NH)NH₂,

C_2-6 alkenyl, C_2-6 alkynyl, C_1-4 alkoxy, C_1-4 haloalkyl, C_3-6 cycloalkyl,

C_1-4 alkyl substituted with 0–

1 R⁴³,

aryl substituted with 0–

3 R⁴⁴, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R⁴⁴;

R⁴³ is C_3-6 cycloalkyl or aryl substituted with 0–

3 R⁴⁴;

R⁴⁴, at each occurrence, is independently selected from H, halo, —

OH, NR⁴⁶R⁴⁷, CO₂H, SO₂R⁴⁵, —

CF₃, —

OCF₃, —

CN, —

NO₂, C_1-4 alkyl, and C_1-4 alkoxy;

R⁴⁵ is C_1-4 alkyl;

R⁴⁶, at each occurrence, is independently selected from H and C_1-4 alkyl;

R⁴⁷, at each occurrence, is independently selected from H and C_1-4 alkyl;

k is 1 or 2;

m is 0, 1, or 2; and

n is 0, 1, 2, or 3.

3. The method as defined in claim 2 where in the compound administered:

X is —

CHR¹⁰—

;

R¹ is selected from

H,

C(═

O)R²,

C(═

O)OR²,

C_1-6 alkyl,

C_2-6 alkenyl,

C_2-6 alkynyl,

C_3-6 cycloalkyl,

C_1-4 alkyl substituted with 0–

2 R²,

C_2-4 alkenyl substituted with 0–

2 R², and

C_2-4 alkynyl substituted with 0–

2 R²;

R², at each occurrence, is independently selected from

C_1-4 alkyl,

C_2-4 alkenyl,

C_2-4 alkynyl,

C_3-6 cycloalkyl,

phenyl substituted with 0–

5 R⁴²;

C_3-10 carbocyclic group substituted with 0–

3 R⁴¹, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R⁴¹;

R⁵ is H, methyl, ethyl, propyl, or butyl;

R^6a is selected independently from

H, —

OH, —

NR⁴⁶R⁴⁷, —

CF₃, C_1-3 alkyl, and C_1-3 alkoxy;

R^6b is H;

R⁷ and R⁹, at each occurrence, are independently selected from

H, halo, —

CF₃, —

OCF₃, —

OH, —

CN, —

NO₂, —

NR⁴⁶R⁴⁷,

C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 haloalkyl, C_1-6 alkoxy, (C_1-4 haloalkyl)oxy,

C_3-10 cycloalkyl substituted with 0–

2 R³³,

C_1-4 alkyl substituted with 0–

2 R¹¹,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

aryl substituted with 0–

5 R³³,

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

OR¹², SR¹², NR¹²R¹³, C(O)H, C(O)R¹², C(O)NR¹²R¹³, NR¹⁴C(O)R¹², C(O)OR¹², OC(O)R¹², OC(O)OR¹², CH(═

NR¹⁴)NR¹²R¹³, NHC(═

NR¹⁴)NR¹²R¹³, S(O)R¹², S(O)₂R¹², S(O)NR¹²R¹³, S(O)₂NR¹²R¹³, NR¹⁴S(O)R¹², and NR¹⁴S(O)₂R¹²;

R⁸ is selected from

H, halo, —

CF₃, —

OCF₃, —

OH, —

CN, —

NO₂,

C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 haloalkyl, C_1-6 alkoxy, (C_1-4 haloalkyl)oxy,

C_3-10 cycloalkyl substituted with 0–

2 R³³,

C_1-4 alkyl substituted with 0–

2 R¹,

C_2-4 alkenyl substituted with 0–

2 R¹¹,

C_2-4 alkynyl substituted with 0–

1 R¹¹,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

aryl substituted with 0–

5 R³³,

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

OR¹², SR¹², NR¹²R¹³, C(O)H, C(O)R¹², C(O)NR¹²R¹³, NR¹⁴C(O)R¹², C(O)OR¹², OC(O)R¹², OC(O)OR¹², CH(═

NR¹⁴)NR¹²R¹³, NHC(═

NR¹⁴)NR¹²R¹³, S(O)R¹², S(O)₂R¹², S(O)NR¹²R¹³, S(O)₂NR¹²R¹³, NR¹⁴S(O)R¹², NR¹⁴S(O)₂R¹², NR¹²C(O)R¹⁵, NR¹²C(O)OR¹⁵, NR¹²S(O)₂R¹⁵, and NR¹²C(O)NHR¹⁵;

R¹⁰ is selected from H, —

OH,

C_1-6 alkyl substituted with 0–

1 R^10B,

C_2-6 alkenyl substituted with 0–

1 R^10B,

C_2-6 alkynyl substituted with 0–

1 R^10B, and

C_1-6 alkoxy;

R^10B is selected from

C_1-4 alkoxy,

C_3-6 cycloalkyl,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

phenyl substituted with 0–

3 R³³, and

5–

6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

2 R⁴⁴;

R¹¹ is selected from

H, halo, —

CF₃, —

CN, —

NO₂, C_1-6 alkyl,

C_2-6 alkenyl, C_2-6 alkynyl, C_1-4 haloalkyl, C_1-6 alkoxy, C_3-10 cycloalkyl,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

aryl substituted with 0–

5 R³³,

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

OR¹², SR¹², NR¹²R¹³, C(O)H, C(O)R¹², C(O)NR¹²R¹³, NR¹⁴C(O)R¹², C(O)OR¹², OC(O)R¹², OC(O)OR¹², CH(═

NR¹⁴)NR¹²R¹³, NHC(═

NR¹⁴)NR¹²R¹³, S(O)R¹², S(O)₂R¹², S(O)NR¹²R¹³, S(O)₂NR¹²R¹³, NR¹⁴S(O)R¹², and NR¹⁴S(O)₂R¹²;

R¹², at each occurrence, is independently selected from

C_1-4 alkyl substituted with 0–

1 R^12a,

C_2-4 alkenyl substituted with 0–

1 R^12a,

C_2-4 alkynyl substituted with 0–

1 R^12a,

C_3-6 cycloalkyl substituted with 0–

3 R³³,

phenyl substituted with 0–

5 R³³;

C_3-10 carbocyclic group substituted with 0–

3 R³³, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

R^12a, at each occurrence, is independently selected from

phenyl substituted with 0–

5 R³³;

C_3-10 carbocyclic group substituted with 0–

3 R³³, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

R¹³, at each occurrence, is independently selected from

H, C_1-4 alkyl, C_2-4 alkenyl, and C_2-4 alkynyl;

alternatively, R¹² and R¹³ join to form a 5- or 6-membered ring optionally substituted with —

O—

or —

N(R¹⁴)—

;

alternatively, R¹² and R¹³ when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1–

3 heteroatoms selected from the group consisting of N, O, and S, wherein said bicyclic heterocyclic ring system is unsaturated or partially saturated, wherein said bicyclic heterocyclic ring system is substituted with 0–

3 R¹⁶;

R¹⁴, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;

R¹⁵, at each occurrence, is independently selected from

H, C_1-4 alkyl, C_2-4 alkenyl, and C_2-4 alkynyl;

R¹⁶, at each occurrence, is independently selected from

H, OH, F, Cl, CN, NO₂, CF₃, SO₂R⁴⁵, NR⁴⁶R⁴⁷, —

C(═

O)H,

methyl, ethyl, methoxy, ethoxy, trifluoromethyl, and trifluoromethoxy;

R³¹, at each occurrence, is independently selected from

H, OH, halo, CF₃, SO₂R⁴⁵, NR⁴⁶R⁴⁷, and C_1-4 alkyl;

R³³, at each occurrence, is independently selected from

H, OH, halo, CN, NO₂, CF₃, SO₂R⁴⁵, NR⁴⁶R⁴⁷, —

C(═

O)H,

C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl,

C_3-6 cycloalkyl, C_1-4 haloalkyl, C_1-14 haloalkyl-oxy-, C_1-4 alkyloxy-,

C_1-4 alkylthio-, C_1-4 alkyl-C(═

O)—

, C_1-4 alkyl-C(═

O)NH—

, C_1-4 alkyl-OC(═

O)—

,

C_1-4 alkyl-C(═

O)O—

, C_3-6 cycloalkyl-oxy-, C_3-6 cycloalkylmethyl-oxy-;

C_1-6 alkyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy; and

C_2-6 alkenyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy;

R⁴¹, at each occurrence, is independently selected from

H, CF₃, halo, OH, CO₂H, SO₂R⁴⁵, NR⁴⁶R⁴⁷, NO₂, CN,

C_2-8 alkenyl, C_2-8 alkynyl, C_1-4 alkoxy, C_1-4 haloalkyl

C_1-4 alkyl substituted with 0–

1 R⁴³,

aryl substituted with 0–

3 R⁴², and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R⁴⁴;

R⁴², at each occurrence, is independently selected from

H, CF₃, halo, OH, CO₂H, SO₂R⁴⁵, NR⁴⁶R⁴⁷, NO₂, CN, CH(═

NH)NH₂, NHC(═

NH)NH₂,

C_2-6 alkenyl, C_2-6 alkynyl, C_1-4 alkoxy, C_1-4 haloalkyl, C_3-6 cycloalkyl,

C_1-4 alkyl substituted with 0–

1 R⁴³,

aryl substituted with 0–

3 R⁴⁴, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R⁴⁴;

R⁴³ is C_3-6 cycloalkyl or aryl substituted with 0–

3 R⁴⁴;

R⁴⁴, at each occurrence, is independently selected from H, halo, —

OH, NR⁴⁶R⁴⁷, CO₂H, SO₂R⁴⁵, —

CF₃, —

OCF₃, —

CN, —

NO₂, C_1-4 alkyl, and C_1-4 alkoxy;

R⁴⁵ is C_1-4 alkyl;

R⁴⁶, at each occurrence, is independently selected from H and C_1-4 alkyl;

R⁴⁷, at each occurrence, is independently selected from H and C_1-4 alkyl;

k is 1 or 2;

m is 0 or 1; and

n is 0, 1 or 2.

4. The method as defined in claim 2 where in the compound administered:

X is —

CH₂—

;

R¹ is selected from

H,

C_1-4 alkyl,

C_2-4 alkenyl,

C_2-4 alkynyl,

C_3-4 cycloalkyl,

C_1-3 alkyl substituted with 0–

1 R²,

C_2-3 alkenyl substituted with 0–

1 R², and

C_2-3 alkynyl substituted with 0–

1 R²;

R², at each occurrence, is independently selected from

C_1-4 alkyl,

C_2-4 alkenyl,

C_2-4 alkynyl,

C_3-6 cycloalkyl,

phenyl substituted with 0–

5 R⁴²;

C_3-6 carbocyclic group substituted with 0–

3 R⁴¹, and

5–

6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R⁴¹;

R⁵ is H, methyl, ethyl, propyl, or butyl;

R^6a is H, methyl, ethyl, methoxy, —

OH, or —

CF₃;

R^6b is H;

R⁷ and R⁹, at each occurrence, are independently selected from

H, halo, —

CF₃, —

OCF₃, —

OH, —

CN, —

NO₂, —

NR⁴⁶R⁴⁷,

C_1-4 alkyl, C_2-4 alkenyl, C_2-4 alkynyl, C_1-4 haloalkyl, C_1-4 alkoxy, (C_1-4 haloalkyl)oxy,

C_3-10 cycloalkyl substituted with 0–

2 R³³,

C_1-4 alkyl substituted with 0–

2 R¹¹,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

aryl substituted with 0–

5 R³³, and

5–

6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

R⁸ is selected from

H, halo, —

CF₃, —

OCF₃, —

OH, —

CN, —

NO₂,

C_1-4 alkyl, C_2-4 alkenyl, C_2-4 alkynyl, C_1-4 haloalkyl, C_1-4 alkoxy, (C_1-4 haloalkyl)oxy,

C_3-10 cycloalkyl substituted with 0–

2 R³³,

C_1-4 alkyl substituted with 0–

2 R¹¹,

C_2-4 alkenyl substituted with 0–

2 R¹¹,

C_2-4 alkynyl substituted with 0–

1 R¹¹,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

aryl substituted with 0–

5 R³³,

5–

6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

OR¹², SR¹², NR¹²R¹³, NR¹²C(O)R¹⁵, NR¹²C(O)OR¹⁵, NR¹²S(O)₂R¹⁵, and NR¹²C(O)NHR¹⁵;

R¹¹ is selected from

H, halo, —

CF₃, —

CN, —

NO₂,

C_1-4 alkyl, C_2-4 alkenyl, C_2-4 alkynyl, C_1-4 haloalkyl, C_1-4 alkoxy, (C_1-4 haloalkyl)oxy,

C_3-10 cycloalkyl substituted with 0–

2 R³³,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

aryl substituted with 0–

5 R³³, and

5–

6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

R¹², at each occurrence, is independently selected from

C_1-4 alkyl substituted with 0–

1 R^12a,

C_2-4 alkenyl substituted with 0–

1 R^12a,

C_2-4 alkynyl substituted with 0–

1 R^12a,

C_3-6 cycloalkyl substituted with 0–

3 R³³,

phenyl substituted with 0–

5 R³³;

C_3-10 carbocyclic group substituted with 0–

3 R³³, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

R^12a, at each occurrence, is independently selected from

phenyl substituted with 0–

5 R³³;

C_3-10 carbocyclic group substituted with 0–

3 R³³, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

R¹³, at each occurrence, is independently selected from

H, C_1-4 alkyl, C_2-4 alkenyl, and C_2-4 alkynyl;

alternatively, R¹² and R¹³ join to form a 5- or 6-membered ring optionally substituted with —

O—

or —

N(R¹⁴)—

;

alternatively, R¹² and R¹³ when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1–

3 heteroatoms selected from the group consisting of one N, two N, three N, one N one O, and one N one S;

wherein said bicyclic heterocyclic ring system is unsaturated or partially saturated, wherein said bicyclic heterocyclic ring system is substituted with 0–

2 R¹⁶;

R¹⁴, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;

R¹⁵, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;

R¹⁶, at each occurrence, is independently selected from

H, OH, F, Cl, CN, NO₂, methyl, ethyl, methoxy, ethoxy, trifluoromethyl, and trifluoromethoxy;

R³¹, at each occurrence, is independently selected from

H, OH, halo, CF₃, methyl, ethyl, and propyl;

R³³, at each occurrence, is independently selected from

H, OH, halo, CN, NO₂, CF₃, SO₂R⁴⁵, NR⁴⁶R⁴⁷, —

C(═

O)H,

C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl,

C_3-6 cycloalkyl, C_1-4 haloalkyl, C_1-4 haloalkyl-oxy-, C_1-4 alkyloxy-,

C_1-4 alkylthio-, C_1-4 alkyl-C(═

O)—

, C_1-4 alkyl-C(═

O)NH—

, C_1-4 alkyl-OC(═

O)—

,

C_1-4 alkyl-C(═

O)O—

, C_3-6 cycloalkyl-oxy-, C_3-6 cycloalkylmethyl-oxy-;

C_1-6 alkyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy; and

C_2-6 alkenyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy;

R⁴¹, at each occurrence, is independently selected from

H, CF₃, halo, OH, CO₂H, SO₂R⁴⁵, NR⁴⁶R⁴⁷, NO₂, CN,

C_2-4 alkenyl, C_2-4 alkynyl, C_1-3 alkoxy, C_1-3 haloalkyl, and C_1-3 alkyl;

R⁴², at each occurrence, is independently selected from

H, CF₃, halo, OH, CO₂H, SO₂R⁴⁵, NR⁴⁶R⁴⁷, NO₂, CN, CH(═

NH)NH₂, NHC(═

NH)NH₂,

C_2-4 alkenyl, C_2-4 alkynyl, C_1-3 alkoxy, C_1-3 haloalkyl, C_3-6 cycloalkyl, and C_1-3 alkyl;

R⁴³ is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, or pyridyl, each substituted with 0–

3 R⁴⁴;

R⁴⁴, at each occurrence, is independently selected from H, halo, —

OH, NR⁴⁶R⁴⁷, CO₂H, SO₂R⁴⁵, —

CF₃, —

OCF₃, —

CN, —

NO₂, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, and butoxy;

R⁴⁵ is methyl, ethyl, propyl, or butyl;

R⁴⁶, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;

R⁴⁷, at each occurrence, is independently selected from from H, methyl, ethyl, propyl, and butyl;

k is 1;

m is 1; and

n is 0, 1 or 2.

5. The method as defined in claim 2 where in the compound administered:

X is —

CH₂—

;

R¹ is selected from

H,

C_1-4 alkyl,

C_2-4 alkenyl,

C_2-4 alkynyl,

C_3-4 cycloalkyl,

C_1-3 alkyl substituted with 0–

1 R²,

C_2-3 alkenyl substituted with 0–

1 R², and

C_2-3 alkynyl substituted with 0–

1 R²;

R², at each occurrence, is independently selected from

C_1-4 alkyl,

C_2-4 alkenyl,

C_2-4 alkynyl,

C_3-6 cycloalkyl,

phenyl substituted with 0–

5 R⁴²;

C_3-6 carbocyclic group substituted with 0–

3 R⁴¹, and

5–

6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R⁴¹;

R⁵ is H, methyl, ethyl, propyl, or butyl;

R^6a is H, methyl, ethyl, methoxy, —

OH, or —

CF₃;

R^6b is H;

R⁷ and R⁹, at each occurrence, are independently selected from

H, F, Cl, —

CH₃, —

OCH₃, —

CF₃, —

OCF₃, —

CN, and —

NO₂,

R⁸ is selected from

H, F, Cl, Br, —

CF₃, —

OCF₃, —

OH, —

CN, —

NO₂,

C_1-4 alkyl, C_2-4 alkenyl, C_2-4 alkynyl, C_1-4 haloalkyl, C_1-4 alkoxy, (C_1-4 haloalkyl)oxy,

C_3-10 cycloalkyl substituted with 0–

2 R³³,

C_1-4 alkyl substituted with 0–

2 R¹¹,

C_2-4 alkenyl substituted with 0–

2 R¹¹,

C_2-4 alkynyl substituted with 0–

1 R¹¹,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

aryl substituted with 0–

5 R³³,

5–

6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

OR¹², SR¹², NR¹²R¹³, NR¹²C(O)R¹⁵, NR¹²C(O)OR¹⁵, NR¹²S(O)₂R¹⁵, and NR¹²C(O)NHR¹⁵;

R¹¹ is selected from

H, halo, —

CF₃, —

CN, —

NO₂,

C_1-4 alkyl, C_2-4 alkenyl, C_2-4 alkynyl, C_1-4 haloalkyl, C_1-4 alkoxy, (C_1-4 haloalkyl)oxy,

C_3-10 cycloalkyl substituted with 0–

2 R³³,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

aryl substituted with 0–

5 R³³, and

5–

6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

R¹², at each occurrence, is independently selected from

C_1-4 alkyl substituted with 0–

1 R^12a,

C_2-4 alkenyl substituted with 0–

1 R^12a,

C_2-4 alkynyl substituted with 0–

1 R^12a,

C_3-6 cycloalkyl substituted with 0–

3 R³³,

phenyl substituted with 0–

5 R³³;

C_3-10 carbocyclic group substituted with 0–

3 R³³, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

R^12a, at each occurrence, is independently selected from

phenyl substituted with 0–

5 R³³;

C_3-10 carbocyclic group substituted with 0–

3 R³³, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

R¹³, at each occurrence, is independently selected from

H, C_1-4 alkyl, C_2-4 alkenyl, and C_2-4 alkynyl;

alternatively, R¹² and R¹³ join to form a 5- or 6-membered ring optionally substituted with —

O—

or —

N(R¹⁴)—

;

alternatively, R¹² and R¹³ when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1–

3 heteroatoms selected from the group consisting of N, O, and S;

wherein said bicyclic heterocyclic ring system is selected from indolyl, indolinyl, indazolyl, benzimidazolyl, benzimidazolinyl, benztriazolyl, benzoxazolyl, benzoxazolinyl, benzthiazolyl, and dioxobenzthiazolyl;

wherein said bicyclic heterocyclic ring system is substituted with 0–

1 R¹⁶;

R¹⁴, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;

R¹⁵, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;

R¹⁶, at each occurrence, is independently selected from

H, OH, F, Cl, CN, NO₂, methyl, ethyl, methoxy, ethoxy, trifluoromethyl, and trifluoromethoxy;

R³¹, at each occurrence, is independently selected from

H, OH, halo, CF₃, methyl, ethyl, and propyl;

R³³, at each occurrence, is independently selected from

H, OH, halo, CN, NO₂, CF₃, SO₂R⁴⁵, NR⁴⁶R⁴⁷, —

C(═

O)H,

C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl,

C_3-6 cycloalkyl, C_1-4 haloalkyl, C_1-4 haloalkyl-oxy-, C_1-14 alkyloxy-,

C_1-4 alkylthio-, C_1-4 alkyl-C(═

O)—

, C_1-4 alkyl-C(═

O)NH—

, C_1-4 alkyl-OC(═

O)—

,

C_1-4 alkyl-C(═

O)O—

, C_3-6 cycloalkyl-oxy-, C_3-6 cycloalkylmethyl-oxy-;

C_1-6 alkyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy; and

C_2-6 alkenyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy;

R⁴¹, at each occurrence, is independently selected from

H, CF₃, halo, OH, CO₂H, SO₂R⁴⁵, NR⁴⁶R⁴⁷, NO₂, CN,

C_2-4 alkenyl, C_2-4 alkynyl, C_1-3 alkoxy, C_1-3 haloalkyl, and C_1-3 alkyl;

R⁴², at each occurrence, is independently selected from

H, CF₃, halo, OH, CO₂H, SO₂R⁴⁵, NR⁴⁶R⁴⁷, NO₂, CN, CH(═

NH)NH₂, NHC(═

NH)NH₂,

C_2-4 alkenyl, C_2-4 alkynyl, C_1-3 alkoxy, C_1-3 haloalkyl, C_3-6 cycloalkyl, and C_1-3 alkyl;

R⁴³ is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, or pyridyl, each substituted with 0–

3 R⁴⁴;

R⁴⁴, at each occurrence, is independently selected from H, halo, —

OH, NR⁴⁶R⁴⁷, CO₂H, SO₂R⁴⁵, —

CF₃, —

OCF₃, —

CN, —

NO₂, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, and butoxy;

R⁴⁵ is methyl, ethyl, propyl, or butyl;

R⁴⁶, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;

R⁴⁷, at each occurrence, is independently selected from from H, methyl, ethyl, propyl, and butyl;

k is 1;

m is 1; and

n is 0, 1 or 2.

6. The method as defined in claim 2 where in the compound administered:

X is —

CH₂—

;

R¹ is selected from H,

C_1-5 alkyl substituted with 0–

1 R²,

C_2-5 alkenyl substituted with 0–

1 R², and

C_2-3 alkynyl substituted with 0–

1 R²;

R² is C_3-6 cycloalkyl;

R⁵ is H, methyl, ethyl, or propyl;

R^6a is H, methyl, or ethyl;

R^6b is H;

R⁷ and R⁹, at each occurrence, are independently selected from

H, F, Cl, —

CH₃, —

OCH₃, —

CF₃, —

OCF₃, —

CN, and —

NO₂,

R⁸ is selected from

methyl substituted with R¹¹;

ethenyl substituted with R¹¹;

OR¹², SR¹², NR¹²R¹³, NR¹²C(O)R¹⁵, NR¹²C(O)OR¹⁵, NR¹²S(O)₂R¹⁵, and NR¹²C(O)NHR¹⁵;

R¹¹ is selected from

phenyl-substituted with 0–

5 fluoro;

2-(H₃CCH₂C(═

O))-phenyl-substituted with R³³;

2-(H₃CC(═

O))-phenyl-substituted with R³³;

2-(HC(═

O))-phenyl-substituted with R³³;

2-(H₃CCH(OH))-phenyl-substituted with R³³;

2-(H₃CCH₂CH(OH))-phenyl-substituted with R³³;

2-(HOCH₂)-phenyl-substituted with R³³;

2-(HOCH₂CH₂)-phenyl-substituted with R³³;

2-(H₃COCH₂)-phenyl-substituted with R³³;

2-(H₃COCH₂CH₂)-phenyl-substituted with R³³;

2-(H₃CCH(OMe))-phenyl-substituted with R³³;

2-(H₃COC(═

O))-phenyl-substituted with R³³;

2-(HOCH₂CH═

CH)-phenyl-substituted with R³³;

2-((MeOC═

O)CH═

CH)-phenyl-substituted with R³³;

2-(methyl)-phenyl-substituted with R³³;

2-(ethyl)-phenyl-substituted with R³³;

2-(i-propyl)-phenyl-substituted with R³³;

2-(F₃C)-phenyl-substituted with R³³;

2-(NC)-phenyl-substituted with R³³;

2-(H₃CO)-phenyl-substituted with R³³;

2-(fluoro)-phenyl-substituted with R³³;

2-(chloro)-phenyl-substituted with R³³;

3-(NC)-phenyl-substituted with R³³;

3-(H₃CO)-phenyl-substituted with R³³;

3-(fluoro)-phenyl-substituted with R³³;

3-(chloro)-phenyl-substituted with R³³;

4-(NC)-phenyl-substituted with R³³;

4-(fluoro)-phenyl-substituted with R³³;

4-(chloro)-phenyl-substituted with R³³;

4-(H₃CS)-phenyl-substituted with R³³;

4-(H₃CO)-phenyl-substituted with R³³;

4-(ethoxy)-phenyl-substituted with R³³;

4-(i-propoxy)-phenyl-substituted with R³³;

4-(i-butoxy)-phenyl-substituted with R³³;

4-(H₃CCH₂CH₂C(═

O))-phenyl-substituted with R³³;

4-((H₃C)₂CHC(═

O))-phenyl-substituted with R³³;

4-(H₃CCH₂C(═

O))-phenyl-substituted with R³³;

4-(H₃CC(═

O))-phenyl-substituted with R³³;

4-(H₃CCH₂CH₂CH(OH))-phenyl-substituted with R³³;

4-((H₃C)₂CHCH(OH))-phenyl-substituted with R³³;

4-(H₃CCH₂CH(OH))-phenyl-substituted with R³³;

4-(H₃CCH(OH))-phenyl-substituted with R³³;

4-(cyclopropyloxy)-phenyl-substituted with R³³;

4-(cyclobutyloxy)-phenyl-substituted with R³³; and

4-(cyclopentyloxy)-phenyl-substituted with R³³;

R¹² is selected from

phenyl-substituted with 0–

5 fluoro;

2-(H₃CCH₂C(═

O))-phenyl-substituted with R³³;

2-(H₃CC(═

O))-phenyl-substituted with R³³;

2-(HC(═

O))-phenyl-substituted with R³³;

2-(H₃CCH(OH))-phenyl-substituted with R³³;

2-(H₃CCH₂CH(OH))-phenyl-substituted with R³³;

2-(HOCH₂)-phenyl-substituted with R³³;

2-(HOCH₂CH₂)-phenyl-substituted with R³³;

2-(H₃COCH₂)-phenyl-substituted with R³³;

2-(H₃COCH₂CH₂)-phenyl-substituted with R³³;

2-(H₃CCH(OMe))-phenyl-substituted with R³³;

2-(H₃COC(═

O))-phenyl-substituted with R³³;

2-(HOCH₂CH═

CH)-phenyl-substituted with R³³;

2-((MeOC═

O)CH═

CH)-phenyl-substituted with R³³;

2-(methyl)-phenyl-substituted with R³³;

2-(ethyl)-phenyl-substituted with R³³;

2-(i-propyl)-phenyl-substituted with R³³;

2-(F₃C)-phenyl-substituted with R³³;

2-(NC)-phenyl-substituted with R³³;

2-(H₃CO)-phenyl-substituted with R³³;

2-(fluoro)-phenyl-substituted with R³³;

2-(chloro)-phenyl-substituted with R³³;

3-(NC)-phenyl-substituted with R³³;

3-(H₃CO)-phenyl-substituted with R³³;

3-(fluoro)-phenyl-substituted with R³³;

3-(chloro)-phenyl-substituted with R³³;

4-(NC)-phenyl-substituted with R³³;

4-(fluoro)-phenyl-substituted with R³³;

4-(chloro)-phenyl-substituted with R³³;

4-(H₃CS)-phenyl-substituted with R³³;

4-(H₃CO)-phenyl-substituted with R³³;

4-(ethoxy)-phenyl-substituted with R³³;

4-(i-propoxy)-phenyl-substituted with R³³;

4-(i-butoxy)-phenyl-substituted with R³³;

4-(H₃CCH₂CH₂C(═

O))-phenyl-substituted with R³³;

4-((H₃C)₂CHC(═

O))-phenyl-substituted with R³³;

4-(H₃CCH₂C(═

O))-phenyl-substituted with R³³;

4-(H₃CC(═

O))-phenyl-substituted with R³³;

4-(H₃CCH₂CH₂CH(OH))-phenyl-substituted with R³³;

4-((H₃C)₂CHCH(OH))-phenyl-substituted with R³³;

4-(H₃CCH₂CH(OH))-phenyl-substituted with R³³;

4-(H₃CCH(OH))-phenyl-substituted with R³³;

4-(cyclopropyloxy)-phenyl-substituted with R³³;

4-(cyclobutyloxy)-phenyl-substituted with R³³; and

4-(cyclopentyloxy)-phenyl-substituted with R³³;

R¹³ is H, methyl, or ethyl;

alternatively, R¹² and R¹³ join to form a 5- or 6-membered ring selected from pyrrolyl, pyrrolidinyl, imidazolyl, piperidinyl, piperizinyl, methylpiperizinyl, and morpholinyl;

alternatively, R¹² and R¹³ when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1–

3 heteroatoms selected from the group consisting of N, O, and S;

wherein said bicyclic heterocyclic ring system is selected from indolyl, indolinyl, indazolyl, benzimidazolyl, benzimidazolinyl, benztriazolyl, benzoxazolyl, benzoxazolinyl, benzthiazolyl, and dioxobenzthiazolyl;

wherein said bicyclic heterocyclic ring system is substituted with 0–

1 R¹⁶;

R¹⁵ is H, methyl, ethyl, propyl, or butyl;

R¹⁶, at each occurrence, is independently selected from

H, OH, F, Cl, CN, NO₂, methyl, ethyl, methoxy, ethoxy, trifluoromethyl, and trifluoromethoxy;

R³³, at each occurrence, is independently selected from

H, F, Cl, —

CH₃, —

OCH₃, —

CF₃, —

OCF₃, —

CN, and —

NO₂;

k is 1;

m is 1; and

n is 1 or 2.

7. The method as defined in claim 2 where the compound administered is a compound of Formula (I-a):

8. The method as defined in claim 7 where the compound administered is a compound of Formula (V):

9. The method as defined in claim 1 where in the compound administered:

X is —

CHR¹⁰—

or —

C(═

O)—

;

R¹ is selected from

C_1-6 alkyl substituted with Z,

C_2-6 alkenyl substituted with Z,

C_2-6 alkynyl substituted with Z,

C_3-6 cycloalkyl substituted with Z,

aryl substituted with Z,

5–

6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with Z;

C_1-6 alkyl substituted with 0–

2 R²,

C_2-6 alkenyl substituted with 0–

2 R²,

C_2-6 alkynyl substituted with 0–

2 R²,

aryl substituted with 0–

2 R², and

5–

6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with 0–

2 R²;

Z is selected from H,

—

CH(OH)R²,

—

C(ethylenedioxy)R²,

—

SR²,

—

NR²R³,

—

C(O)R²,

—

C(O)NR²R³,

—

NR³C(O)R²,

—

C(O)OR²,

—

OC(O)R²,

—

CH(═

NR⁴)NR²R³,

—

NHC(═

NR⁴)NR²R³,

—

S(O)R²,

—

S(O)₂R²,

—

S(O)₂NR²R³, and —

NR³S(O)₂R²;

R², at each occurrence, is independently selected from

C_1-4 alkyl,

C_2-4 alkenyl,

C_2-4 alkynyl,

C_3-6 cycloalkyl,

aryl substituted with 0–

5 R⁴²;

C_3-10 carbocyclic group substituted with 0–

3 R⁴¹, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R⁴¹;

R³, at each occurrence, is independently selected from

H, C_1-4 alkyl, C_2-4 alkenyl, C_2-4 alkynyl, and

C_1-4 alkoxy;

alternatively, R² and R³ join to form a 5- or 6-membered ring optionally substituted with —

O—

or —

N(R⁴)—

;

R⁴, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;

R⁵ is H, methyl, ethyl, propyl, or butyl;

R^6a is selected from

H, —

OH, —

NR⁴⁶R⁴⁷, —

CF₃,

C_1-4 alkyl, C_2-4 alkenyl, C_2-4 alkynyl, C_1-4 alkoxy, C_1-4 haloalkyl, C_3-6 cycloalkyl, and

aryl substituted with 0–

3 R⁴⁴;

R^6b is H;

R⁷, R⁸, and R⁹, at each occurrence, are independently selected from

H, halo, —

CF₃, —

OCF₃, —

OH, —

CN, —

NO₂, —

NR⁴⁶R⁴⁷,

C_1-8 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, C_1-4 haloalkyl, C_1-8 alkoxy, (C_1-4 haloalkyl)oxy,

C_1-4 alkyl substituted with 0–

2 R¹¹,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

aryl substituted with 0–

5 R³³,

5–

10 membered heterocyclic ring system containing from 14 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

OR¹², SR¹², NR¹²R¹³, C(O)H, C(O)R¹², C(O)NR¹²R¹³, NR¹⁴C(O)R¹², C(O)OR¹², OC(O)R¹², OC(O)OR¹², CH(═

NR¹⁴)NR¹²R¹³, NHC(═

NR¹⁴)NR¹²R¹³, S(O)R¹², S(O)₂R¹², S(O)NR¹²R¹³, S(O)₂NR¹²R¹³, NR¹⁴S(O)R¹², NR¹⁴S(O)₂R¹², NR¹²C(O)R¹⁵, NR¹²C(O)OR¹⁵, NR¹²S(O)₂R¹⁵, and NR¹²C(O)NHR¹⁵;

R¹⁰ is selected from H, —

OH,

C_1-6 alkyl substituted with 0–

1 R^10B,

C_2-6 alkenyl substituted with 0–

1 R^10B,

C_2-6 alkynyl substituted with 0–

1 R^10B, and

C_1-6 alkoxy;

R^10B is selected from

C_1-4 alkoxy,

C_3-6 cycloalkyl,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

phenyl substituted with 0–

3 R³³, and

5–

6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

2 R⁴⁴;

R¹¹ is selected from

H, halo, —

CF₃, —

CN, —

NO₂,

C_1-8 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, C_1-4 haloalkyl, C_1-8 alkoxy, C_3-10 cycloalkyl,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

aryl substituted with 0–

5 R³³,

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

OR¹², SR¹², NR¹²R¹³, C(O)H, C(O)R¹², C(O)NR¹²R¹³, NR¹⁴C(O)R¹², C(O)OR¹², OC(O)R¹², OC(O)OR¹², CH(═

NR¹⁴)NR¹²R¹³, NHC(═

NR¹⁴)NR¹²R¹³, S(O)R¹², S(O)₂R¹², S(O)NR¹²R¹³, S(O)₂NR¹²R¹³, NR¹⁴S(O)R¹², and NR¹⁴S(O)₂R¹²;

R¹², at each occurrence, is independently selected from

C_1-4 alkyl,

C_2-4 alkenyl,

C_2-4 alkynyl,

C_3-6 cycloalkyl,

phenyl substituted with 0–

5 R³³;

C_3-10 carbocyclic group substituted with 0–

3 R³³, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

R¹³, at each occurrence, is independently selected from

H, C_1-4 alkyl, C_2-4 alkenyl, and C24 alknyl;

alternatively, R¹² and R¹³ join to form a 5- or 6-membered ring optionally substituted with —

O—

or —

N(R¹⁴)—

;

R¹⁴, at each occurrence, is independently selected from H and C_1-4 alkyl;

R³¹, at each occurrence, is independently selected from

H, OH, halo, CF₃, SO₂R⁴⁵, NR⁴⁶R⁴⁷, methyl, ethyl, and propyl;

R³³, at each occurrence, is independently selected from

H, OH, halo, CN, NO₂, CF₃, SO₂R⁴⁵, NR⁴⁶R⁴⁷,

C_1-3 alkyl, C_2-3 alkenyl, C_2-3 alkynyl, C_3-5 cycloalkyl, C_1-3 haloalkyl, C_1-3 haloalkyl-oxy-, C_1-3 alkyloxy-, C_1-3 alkylthio-, C_1-3 alkyl-C(═

O)—

, and C_1-3 alkyl-C(═

O)NH—

;

R⁴¹, at each occurrence, is independently selected from

H, CF₃, halo, OH, CO₂H, SO₂R⁴⁵, NR⁴⁶R⁴⁷, NO₂, CN, ═

O,

C_2-8 alkenyl, C_2-8 alkynyl, C_1-4 alkoxy, C_1-4 haloalkyl

C_1-4 alkyl substituted with 0–

1 R⁴³,

aryl substituted with 0–

3 R⁴², and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R⁴⁴;

R⁴², at each occurrence, is independently selected from

H, CF₃, halo, OH, CO₂H, SO₂R⁴⁵, SR⁴⁵, NR⁴⁶R⁴⁷, OR⁴⁸, NO₂, CN, CH(═

NH)NH₂, NHC(═

NH)NH₂,

C_2-6 alkenyl, C_2-6 alknyl, C_1-4 alkoxy, C_1-4 haloalkyl, C_3-6 cycloalkyl,

C_1-4 alkyl substituted with 0–

1 R⁴³,

aryl substituted with 0–

3 R⁴⁴, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R⁴⁴;

R⁴³ is C_3-6 cycloalkyl or aryl substituted with 0–

3 R⁴⁴;

R⁴⁴, at each occurrence, is independently selected from H, halo, —

OH, NR⁴⁶R⁴⁷, CO₂H, SO₂R⁴⁵, —

CF₃, —

OCF₃, —

CN, —

NO₂, C_1-4 alkyl, and C_1-4 alkoxy;

R⁴⁵ is C_1-4 alkyl;

R⁴⁶, at each occurrence, is independently selected from H and C_1-4 alkyl;

R⁴⁷, at each occurrence, is independently selected from H, C_1-4 alkyl,

—

C(—

O)NH(C_1-4 alkyl), —

SO₂(C_1-4 alkyl),

—

SO₂(phenyl), —

C(═

O)O(C_1-4 alkyl), —

C(═

O)(C_1-4 alkyl), and —

C(═

O)H;

R⁴⁸, at each occurrence, is independently selected from H, C_1-4 alkyl,

—

C(═

O)NH(C_1-4 alkyl), —

C(═

O)O(C_1-4 alkyl),

—

C(═

O)(C_1-4 alkyl), and —

C(═

O)H;

k is 1 or 2;

m is 0, 1, or 2; and

n is 0, 1 or 2.

10. The method as defined in claim 9 where in the compound administered:

X is —

CHR¹⁰—

or —

C(═

O)—

;

R¹ is selected from

C_2-5 alkyl substituted with Z,

C_2-5 alkenyl substituted with Z,

C_2-5 alkynyl substituted with Z,

C_3-6 cycloalkyl substituted with Z,

aryl substituted with Z,

5–

6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with Z;

C_1-5 alkyl substituted with 0–

2 R²,

C_2-5 alkenyl substituted with 0–

2 R², and

C_2-5 alkynyl substituted with 0–

2 R²;

Z is selected from H,

—

CH(OH)R²,

—

C(ethylenedioxy)R²,

—

SR²,

—

NR²R³,

—

C(O)R²,

—

C(O)NR²R³,

—

NR³C(O)R²,

—

C(O)OR²,

—

OC(O)R²,

—

CH(═

NR⁴)NR²R³,

—

NHC(═

NR⁴)NR²R³,

—

S(O)R²,

—

S(O)₂R²,

—

S(O)₂NR²R³, and —

NR³S(O)₂R²;

R², at each occurrence, is independently selected from

C_1-4 alkyl,

C_2-4 alkenyl,

C_2-4 alkynyl,

C_3-6 cycloalkyl,

aryl substituted with 0–

5 R⁴²;

C_3-10 carbocyclic group substituted with 0–

3 R⁴¹, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R⁴¹;

R³, at each occurrence, is independently selected from

H, C_1-4 alkyl, C_2-4 alkenyl, C_2-4 alkynyl, and

C_1-4 alkoxy;

alternatively, R² and R³ join to form a 5- or 6-membered ring optionally substituted with —

O—

or —

N(R⁴)—

;

R⁴, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;

R⁵ is H, methyl, or ethyl;

R^6a is selected from

H, —

OH, —

NR⁴⁶R⁴⁷, —

CF₃,

C_1-4 alkyl, C_2-4 alkenyl, C_2-4 alkynyl, C_1-4 alkoxy, C_1-4 haloalkyl, and C_3-6 cycloalkyl;

R^6b is H;

R⁷, R⁸, and R⁹, at each occurrence, are independently selected from

H, halo, —

CF₃, —

OCF₃, —

OH, —

OCH₃, —

CN, —

NO₂, —

NR⁴⁶R⁴⁷,

C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-4 haloalkyl, C_1-6 alkoxy, (C_1-4 haloalkyl)oxy,

C_1-4 alkyl substituted with 0–

2 R¹¹,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

aryl substituted with 0–

5 R³³,

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

OR¹², SR¹², NR¹²R¹³, C(O)H, C(O)R¹², C(O)NR¹²R¹³, NR¹⁴C(O)R¹², C(O)OR¹², OC(O)R¹², CH(═

NR¹⁴)NR¹²R¹³, NHC(═

NR¹⁴)NR¹²R¹³, S(O)R¹², S(O)₂R¹², S(O)₂NR¹²R¹³, NR¹⁴S(O)₂R¹², NR¹⁴S(O)R¹², NR¹⁴S(O)₂R¹², NR¹²C(O)R¹⁵, NR¹²C(O)OR¹⁵, NR¹²S(O)₂R¹⁵, and NR¹²C(O)NHR¹⁵;

R¹⁰ is selected from H, —

OH, C_1-6 alkyl, C_1-4 alkoxy, and

C_1-2 alkyl substituted with 0–

1 R^10B;

R^10B is C_3-6 cycloalkyl or

phenyl substituted with 0–

3 R³³;

R¹¹ is selected from

H, halo, —

CF₃, —

OCF₃, —

OH, —

OCH₃, —

CN, —

NO₂, —

NR⁴⁶R⁴⁷,

C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-4 haloalkyl, C_1-6 alkoxy, (C_1-4 haloalkyl)oxy,

C_3-10 carbocyclic group substituted with 0–

3 R³³,

aryl substituted with 0–

5 R³³,

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

OR¹², SR¹², NR¹²R¹³, C(O)H, C(O)R¹², C(O)NR¹²R¹³, NR¹⁴C(O)R¹², C(O)OR¹², OC(O)R¹², CH(═

NR¹⁴)NR¹²R¹³, NHC(═

NR¹⁴)NR¹²R¹³, S(O)R¹², S(O)₂R¹², S(O)₂NR¹²R¹³, and NR¹⁴S(O)₂R¹²;

R¹², at each occurrence, is independently selected from

C_1-4 alkyl,

C_2-4 alkenyl,

C_2-4 alkynyl,

C_3-6 cycloalkyl,

phenyl substituted with 0–

5 R³³;

C_3-10 carbocyclic group substituted with 0–

3 R³³, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R³¹;

R¹³, at each occurrence, is independently selected from

H, C_1-4 alkyl, C_2-4 alkenyl, and C_2-4 alkynyl;

alternatively, R¹² and R¹³ join to form a 5- or 6-membered ring optionally substituted with —

O—

or —

N(R¹⁴)—

;

R¹⁴, at each occurrence, is independently selected from H and C_1-4 alkyl;

R³¹, at each occurrence, is independently selected from

H, OH, halo, CF₃, methyl, and ethyl;

R³³, at each occurrence, is independently selected from

H, OH, halo, CN, NO₂, CF₃, methyl, and ethyl;

R⁴¹, at each occurrence, is independently selected from

H, CF₃, halo, OH, CO₂H, SO₂R⁴⁵, NR⁴⁶R⁴⁷, NO₂, CN, ═

O,

C_2-8 alkenyl, C_2-8 alkynyl, C_1-4 alkoxy, C_1-4 haloalkyl,

C_1-4 alkyl substituted with 0–

1 R⁴³,

aryl substituted with 0–

3 R⁴², and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R⁴⁴;

R⁴², at each occurrence, is independently selected from

H, CF₃, halo, OH, CO₂H, SO₂R⁴⁵, SR⁴⁵, NR⁴⁶R⁴⁷, OR⁴⁸, NO₂, CN, CH(═

NH)NH₂, NHC(═

NH)NH₂,

C_2-6 alkenyl, C_2-6 alkynyl, C_1-4 alkoxy, C_1-4 haloalkyl, C_3-6 cycloalkyl,

C_1-4 alkyl substituted with 0–

1 R⁴³,

aryl substituted with 0–

3 R⁴⁴, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R⁴⁴;

R⁴³ is C_3-6 cycloalkyl or aryl substituted with 0–

3 R⁴⁴;

R⁴⁴, at each occurrence, is independently selected from H, halo, —

OH, NR⁴⁶R⁴⁷, CO₂H, SO₂R⁴⁵, —

CF₃, —

OCF₃, —

CN, —

NO₂, C_1-4 alkyl, and C_1-4 alkoxy;

R⁴⁵ is C_1-4 alkyl;

R⁴⁶, at each occurrence, is independently selected from H and C_1-3 alkyl;

R⁴⁷, at each occurrence, is independently selected from H, C_1-4 alkyl,

—

C(═

O)NH(C_1-4 alkyl), —

SO₂(C_1-4 alkyl),

—

SO₂(phenyl), —

C(═

O)O(C_1-4 alkyl), —

C(═

O)(C_1-4 alkyl), and —

C(═

O)H;

R⁴⁸, at each occurrence, is independently selected from H, C_1-4 alkyl,

—

C(═

O)NH(C_1-4 alkyl), —

C(═

O)O(C_1-4 alkyl),

—

C(═

O)(C1A alkyl), and —

C(═

O)H;

k is 1 or 2;

m is 0, 1, 2; and

n is 0, 1 or 2.

11. The method as defined in claim 9 where in the compound administered:

X is —

CH₂—

;

R¹ is selected from

C_2-4 alkyl substituted with Z,

C_2-4 alkenyl substituted with Z,

C_2-4 alkynyl substituted with Z,

C_3-6 cycloalkyl substituted with Z,

aryl substituted with Z,

5–

6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with Z;

C_2-4 alkyl substituted with 0–

2 R², and

C_2-4 alkenyl substituted with 0–

2 R²;

Z is selected from H,

—

CH(OH)R²,

—

C(ethylenedioxy)R²,

—

SR²,

—

NR²R³,

—

C(O)R²,

—

C(O)NR²R³,

—

NR³C(O)R²,

—

C(O)OR²,

—

S(O)R²,

—

S(O)₂R²,

—

S(O)₂NR²R³, and —

NR³S(O)₂R²;

R², at each occurrence, is independently selected from

phenyl substituted with 0–

5 R⁴²;

C_3-10 carbocyclic group substituted with 0–

3 R⁴¹, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R⁴¹;

R³, at each occurrence, is independently selected from

H, C_1-4 alkyl, C_2-4 alkenyl, C_2-4 alkynyl, and

C_1-4 alkoxy;

alternatively, R² and R³ join to form a 5- or 6-membered ring optionally substituted with —

O—

or —

N(R⁴)—

;

R⁴, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;

R⁵ is H;

R^6a is selected from H, —

OH, —

CF₃, methyl, ethyl, propyl, butyl, methoxy, and, ethoxy;

R^6b is H;

R⁷, R⁸, and R⁹, at each occurrence, are independently selected from

H, halo, —

CF₃, —

OCF₃, —

OH, —

OCH₃, —

CN, —

NO₂,

C_1-4 alkyl, C_1-4 haloalkyl, C_1-4 alkoxy, (C_1-3 haloalkyl)oxy, and

C_1-4 alkyl substituted with 0–

2 R¹¹;

R¹¹ is selected from

H, halo, —

CF₃, —

OCF₃, —

OH, —

OCH₃, —

CN, —

NO₂,

C_1-4 alkyl, C_1-4 haloalkyl, C_1-4 alkoxy, and (C_1-3 haloalkyl)oxy;

R³³, at each occurrence, is independently selected from

H, OH, halo, CF₃, and methyl;

R⁴¹, at each occurrence, is independently selected from

H, CF₃, halo, OH, CO₂H, SO₂R⁴⁵, NR⁴⁶R⁴⁷, NO₂, CN, ═

O,

C_2-8 alkenyl, C_2-8 alkynyl, C_1-4 alkoxy, C_1-4 haloalkyl,

C_1-4 alkyl substituted with 0–

1 R⁴³,

aryl substituted with 0–

3 R⁴², and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R⁴⁴;

R⁴², at each occurrence, is independently selected from

H, CF₃, halo, OH, CO₂H, SO₂R⁴⁵, SR⁴⁵, NR⁴⁶R⁴⁷, OR⁴⁸, NO₂, CN, CH(═

NH)NH₂, NHC(═

NH)NH₂,

C_2-6 alkenyl, C_2-6 alkynyl, C_1-4 alkoxy, C_1-4 haloalkyl, C_3-6 cycloalkyl,

C_1-4 alkyl substituted with 0–

1 R⁴³,

aryl substituted with 0–

3 R⁴⁴, and

5–

10 membered heterocyclic ring system containing from 1–

4 heteroatoms selected from the group consisting of N, O, and S substituted with 0–

3 R⁴⁴;

R⁴³ is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, or pyridyl, each substituted with 0–

3 R⁴⁴;

R⁴⁴, at each occurrence, is independently selected from H, halo, —

OH, NR⁴⁶R⁴⁷, CO₂H, SO₂R⁴⁵, —

CF₃, —

OCF₃, —

CN, —

NO₂, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, and butoxy;

R⁴⁵ is methyl, ethyl, propyl, or butyl;

R⁴⁶, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;

R⁴⁷, at each occurrence, is independently selected from

H, methyl, ethyl, n-propyl, i-propyl, n-butyl,

i-butyl, —

C(═

O)NH(methyl), —

C(═

O)NH(ethyl),

—

SO₂(methyl), —

SO₂(ethyl), —

SO₂(phenyl),

—

C(═

O)O(methyl), —

C(═

O)O(ethyl), —

C(═

O)(methyl),

—

C(═

O)(ethyl), and —

C(═

O)H;

R⁴⁸, at each occurrence, is independently selected from

H, methyl, ethyl, n-propyl, i-propyl, —

C(═

O)NH(methyl), —

C(═

O)NH(ethyl), —

C(═

O)O(methyl), —

C(═

O)O(ethyl), —

C(═

O)(methyl), —

C(═

O)(ethyl), and —

C(═

O)H;

k is 1;

m is 0, 1, or 2; and

n is 0, 1 or 2.

12. The method as defined in claim 9 where in the compound administered:

X is —

CH₂—

;

R¹ is selected from

ethyl substituted with Z,

propyl substituted with Z,

butyl substituted with Z,

propenyl substituted with Z,

butenyl substituted with Z,

ethyl substituted with R²,

propyl substituted with R²,

butyl substituted with R²,

propenyl substituted with R², and

butenyl substituted with R²;

Z is selected from H,

—

CH(OH)R²,

—

OR²,

—

SR²,

—

NR²R³,

—

C(O)R²,

—

C(O)NR²R³,

—

NR³C(O)R²,

—

C(O)OR²,

—

S(O)R²,

—

S(O)₂R²,

—

S(O)₂NR²R³, and —

NR³S(O)₂R²;

R², at each occurrence, is independently selected from

phenyl substituted with 0–

3 R⁴²;

naphthyl substituted with 0–

3 R⁴²;

cyclopropyl substituted with 0–

3 R⁴¹;

cyclobutyl substituted with 0–

3 R⁴¹;

cyclopentyl substituted with 0–

3 R⁴¹;

cyclohexyl substituted with 0–

3 R⁴¹;

pyridyl substituted with 0–

3 R⁴¹;

indolyl substituted with 0–

3 R⁴¹;

indolinyl substituted with 0–

3 R⁴¹;

benzimidazolyl substituted with 0–

3 R⁴¹;

benzotriazolyl substituted with 0–

3 R⁴¹;

benzothienyl substituted with 0–

3 R⁴¹;

benzofuranyl substituted with 0–

3 R⁴¹;

phthalimid-1-yl substituted with 0–

3 R⁴¹;

inden-2-yl substituted with 0–

3 R⁴¹;

2,3-dihydro-1H-inden-2-yl substituted with 0–

3 R⁴¹;

indazolyl substituted with 0–

3 R⁴¹;

tetrahydroquinolinyl substituted with 0–

3 R⁴¹; and

tetrahydro-isoquinolinyl substituted with 0–

3 R⁴¹;

R³, at each occurrence, is independently selected from

H, methyl, and ethyl;

R⁵ is H;

R^6a is selected from H, —

OH, methyl, and methoxy;

R^6b is H;

R⁷, R⁸, and R⁹, at each occurrence, are independently selected from H, F, Cl, methyl, ethyl, methoxy, —

CF₃,

and —

OCF₃;

R⁴¹, at each occurrence, is independently selected from

H, F, Cl, Br, OH, CF₃, NO₂, CN, ═

O, methyl, ethyl, propyl, butyl, methoxy, and ethoxy;

R⁴², at each occurrence, is independently selected from

H, F, Cl, Br, OH, CF₃, SO₂R⁴⁵, SR⁴⁵, NR⁴⁶R⁴⁷, OR⁴⁸, NO₂, CN, ═

O, methyl, ethyl, propyl, butyl, methoxy, and ethoxy;

R⁴⁵ is methyl, ethyl, propyl, or butyl;

R⁴⁶, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;

R⁴⁷, at each occurrence, is independently selected from

H, methyl, ethyl, n-propyl, i-propyl, n-butyl,

i-butyl, —

C(═

O)NH(methyl), —

C(═

O)NH(ethyl),

—

SO₂(methyl), —

SO₂(ethyl), —

SO₂(phenyl),

—

C(═

O)O(methyl), —

C(═

O)O(ethyl), —

C(═

O)(methyl),

—

C(═

O)(ethyl), and —

C(═

O)H;

R⁴⁸, at each occurrence, is independently selected from

H, methyl, ethyl, n-propyl, i-propyl, —

C(═

O)NH(methyl), —

C(═

O)NH(ethyl), —

C(═

O)O(methyl), —

C(═

O)O(ethyl), —

C(═

O)(methyl), —

C(—

O)(ethyl), and —

C(═

O)H;

k is 1;

m is 0, 1, or 2; and

n is 0, 1 or 2.

13. The method as defined in claim 9 where the compound administered is a compound of Formula (I-a):

14. The method as defined in claim 13 where the compound administered is a compound of Formula (V-a):

15. The method as defined in claim 1 where the compound administered is selected from the group:

(±

)-cis-9-(cyclopropylcarbonyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

(±

)-cis-9-isobutyryl-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

tert-butyl(±

)-cis-2-(2-chlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

tert-butyl(±

)-cis-2-(2,4-dichlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

tert-butyl(±

)-cis-2-(3,4-dichlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

tert-butyl(±

)-cis-2-(2,3-dichlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

tert-butyl(±

)-cis-2-[2-chloro-4-(trifluoromethyl)phenyl]-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

tert-butyl(±

)-cis-2-(2-chloro-4-methoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

tert-butyl(±

)-cis-2-(5-isopropyl-2-methoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

tert-butyl(±

)-cis-2-(3-fluorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

tert-butyl(±

)-cis-2-(2,4-dimethoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH7)-carboxylate;

(±

)-cis-2-(2-chlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

(±

)-cis-2-(2,4-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

(±

)-cis-2-(3,4-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

(±

)-cis-2-(2,3-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

(±

)-cis-2-[2-chloro-4-(trifluoromethyl)phenyl]-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

(±

)-cis-2-(2-chloro-4-methoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido [4,3-b]pyrrolo[3,2,1-hi]indole;

(±

)-cis-2-(4-isopropyl-2-methoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

(±

)-cis-2-(3-fluorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

(±

)-cis-2-(2,4-dimethoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

tert-butyl(±

)-cis-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;

tert-butyl(±

)-cis-2-bromo-5,6,8,9,11,11a-hexahydro-4H-pyrido [3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;

tert-butyl(±

)-cis-2-(2,3-dichlorophenyl)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;

tert-butyl(±

)-cis-2-(3,4-dichlorophenyl)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;

tert-butyl(±

)-cis-2-[2-chloro-4-(trifluoromethyl)phenyl]-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;

(±

)-cis-2-(2,3-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(±

)-cis-2-(3,4-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(±

)-cis-2-[2-chloro-4-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

4-((±

)-cis-2-(2-chlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-9(6aH)-yl)-1-(4-fluorophenyl)-1-butanone;

4-((±

)-cis-2-(2,4-dichlorophenyl)-4,5,7,8,10,11a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-9(6aH)-yl)-1-(4-fluorophenyl)-1-butanone;

4-((±

)-cis-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]qionolin-10(7aH)-yl)-1-(4-fluorophenyl)-1-butanone;

4-((±

)-cis-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-9(6aH)-yl)-1-(4-fluorophenyl)-1-butanone;

(6aS,10aR)-2-(2-fluoro-4-methoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

tert-butyl(6aS,10aR)-2-[4-ethoxy-2-(trifluoromethyl)phenyl]-4,5,7,8,10,10a-hexahydropyrido [4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

(6aS,10aR)-2-[4-ethoxy-2-(trifluoromethyl)phenyl]-4,5,6a,7,8,9,10,10a-octahydropyrido [4,3-b]pyrrolo[3,2,1-hi]indole;

tert-butyl(6aS,10aR)-2-(4-chloro-2-fluorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

(6aS,10aR)-2-(4-chloro-2-fluorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

tert-butyl(6aS,10aR)-2-[4-isopropoxy-2-(trifluoromethyl)phenyl]-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

(6aS,10aR)-2-[4-isopropoxy-2-(trifluoromethyl)phenyl]-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

tert-butyl(6aS,10aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

(6aS,10aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

tert-butyl(6aS,10aR)-2-phenyl-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

(6aS,10aR)-2-phenyl-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

tert-butyl(6aS,10aR)-2-(2-methylphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

(6aS,10aR)-2-(2-methylphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

tert-butyl(6aS,10aR)-2-[2-(trifluoromethyl)phenyl]-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

(6aS,10aR)-2-[2-(trifluoromethyl)phenyl]-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

tert-butyl(6aS,10aR)-2-(3,4-dimethoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

(6aS,10aR)-2-(3,4-dimethoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

tert-butyl(6aS,10aR)-2-(2,5-dichlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

(6aS,10aR)-2-(2,5-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

tert-butyl(6aS,10aR)-2-(3,5-dichlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

(6aS,10aR)-2-(3,5-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

tert-butyl(6aS,10aR)-2-(2-isopropyl-4-methoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

(6aS,10aR)-2-(2-isopropyl-4-methoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

tert-butyl(6aS,10aR)-2-(5-fluoro-4-methoxy-2-methylphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

(6aS,10aR)-2-(5-fluoro-4-methoxy-2-methylphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

tert-butyl(6aS,10aR)-2-(4-methoxy-2-methylphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

(6aS,10aR)-2-(4-methoxy-2-methylphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

tert-butyl(6aS,10aR)-2-(2-chloro-4-methoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

(6aS,10aR)-2-(2-chloro-4-methoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

tert-butyl(6aS,10aR)-2-(3-chloro-2-methylphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;

(6aS,10aR)-2-(3-chloro-2-methylphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

2-[(6aS,10aR)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]-2-yl]-5-methoxybenzaldehyde;

(6aS,10aR)-2-(2,6-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;

N-[4-[(6aS,10aR)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-2-yl]-3-(trifluoromethyl)phenyl]-N-methylamine;

4-[(6aS,10aR)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-2-yl]-3-(trifluoromethyl)phenylamine;

1-(2-[(6aS,10aR)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-2-yl]-5-methoxyphenyl)ethanol;

tert-butyl(±

)-cis-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole-11(8aH)-carboxylate;

tert-butyl(8aS,12aR)-2-bromo-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole-11(8aH)-carboxylate;

(8aS,12aR)-2-(2,4-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-(2,3-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-(3,4-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-(3,5-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-(2,5-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-(2,6-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-(2-chlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-(3-chlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-(4-chlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(±

)-cis-2-(2,6-difluorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-(2,6-difluorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-(2,3-difluorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-(3,4-difluorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-(3-fluorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-[2-chloro-4-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-(2-chloro-4-methoxyphenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-(2-fluoro-4-methoxyphenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-(4-methoxy-2-methylphenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-[2-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-[4-isopropoxy-2-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-[2,4-bis(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

(8aS,12aR)-2-[4-fluoro-2-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;

4-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-3-(trifluoromethyl)aniline;

4-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-N-methyl-3-(trifluoromethyl)aniline;

2-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]benzaldehyde;

{2-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]phenyl}methanol;

2-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-5-methoxybenzaldehyde;

{2-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-5-methoxyphenyl}methanol;

4-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-3-methylbenzonitrile;

1-{2-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-5-methoxyphenyl}ethanol;

tert-butyl(7aS,11aR)-2-bromo-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;

(7aS,11aR)-2-(2,4-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(3,4-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(3,5-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(2,5-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(2,6-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(2-chlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(3-chlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(4-chlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(2,6-difluorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(2,6-difluorophenyl)-10-methyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(2,3-difluorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(3,4-difluorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(3-fluorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-[2-chloro-4-methoxyphenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-[2-fluoro-4-methoxyphenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,111aR)-2-(4-methoxy-2-methylphenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

4-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-3-(trifluoromethyl)phenol;

(7aS,11aR)-2-[2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-[4-isopropoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-[2,4-bis(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-[4-fluoro-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

4-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-3-(trifluoromethyl)aniline;

4-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-N-methyl-3-(trifluoromethyl)aniline;

4-[(7aS,1 aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-3-methylbenzonitrile;

2-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]benzaldehyde;

{2-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]phenyl}methanol;

2-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-5-methoxybenzaldehyde;

{2-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-5-methoxyphenyl}methanol;

(8aS,12aR)-2-[4-ethoxy-2-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3b]indole;

(7aS,11aR)-2-[4-ethoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(8aS,12aR)-2-[3-chloro-2-methylphenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3b]indole;

(7aS,11aR)-2-[3-chloro-2-methylphenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-[5-fluoro-2-methylphenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(±

)-cis-2-(2,3-dichlorophenyl)-10-propyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(2,3-dichlorophenyl)-10-propyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(±

)-cis-10-butyl-2-(2,3-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-10-butyl-2-(2,3-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(2,3-dichlorophenyl)-10-(4-pentenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(2,3-dichlorophenyl)-10-(3-methyl-2-butenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(2,4-dichlorophenyl)-10-propyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-10-butyl-2-(2,4-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(2,4-dichlorophenyl)-10-(4-pentenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-(2,4-dichlorophenyl)-10-(3-methyl-2-butenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-10-(cyclobutylmethyl)-2-(2,3-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-10-methyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-10-ethyl-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-10-propyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-10-butyl-2-[4-methoxy-2-(trifluoromethyl)phenyl]-10-methyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-10-(4-pentenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-10-(3-methyl-2-butenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-10-(2-fluoroethyl)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-10-(2,2-difluoroethyl)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-10-(cyclobutylmethyl)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

4-((7aS,11aR)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(4-fluorophenyl)-1-butanone;

4-((7aR,11aS)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(4-fluorophenyl)-1-butanone;

4-((7aS,11aR)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinolin-10(7ah)-yl)-1-(2-aminophenyl)-1-butanone;

4-((7aR,11aS)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(2-aminophenyl)-1-butanone;

(±

)-cis-3-(5,6,8,9,11,11a-hexahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)propyl 4-fluorophenyl ether;

4-((±

)-cis-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(4-pyridinyl)-1-butanone;

(±

)-cis-10-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(7aS,11aR)-10-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline;

(±

)-cis-4-(4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-11(8aH)-yl)-1-(4-fluorophenyl)-1-butanone;

4-((8aS,12aR)-4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-11(8aH)-yl)-1-(4-fluorophenyl)-1-butanone;

4-((8aR,12aS)-4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-11(8aH)-yl)-1-(4-fluorophenyl)-1-butanone;

4-((±

)4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-11(8aH)-yl)-1-(2-amino-4-fluorophenyl)-1-butanone;

4-((±

)-cis-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(2-amino-4-fluorophenyl)-1-butanone;

4-((7aS,11aR)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(2-amino-4-fluorophenyl)-1-butanone; and

4-((7aR,11aS)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(2-amino-4-fluorophenyl)-1-butanone.

16. The method as defined in claim 1 where the compound administered is selected from the group:

4-[(±

)-5,6,8,9,10,11,12,12a-octahydro-4H,7aH-azepino[4′

,5′

;

4,5]pyrrolo[3,2,1-ij]quinolin-10-yl]-1-(4-fluorophenyl)-1-butanone;

4-[(±

)-5,6,8,9,10,11,12,12a-octahydro-4H,7aH-azepino[4′

,5′

;

4,5]pyrrolo[3,2,1-ij]quinolin-10-yl]-1-(2-amino-4-fluorophenyl)-1-butanone;

4-[(±

)-4,5,6,7,9,10,11,12,13,13a-decahydro-11H-diazepino[4,5-b;

3,2,1-hi]indol-11-yl]-1-(4-fluorophenyl)-1-butanone;

4-[(±

)-4,5,6,7,9,10,11,12,13,13a-decahydro-11H-diazepino[4,5-b;

3,2,1-hi]indol-11-yl]-1-(2-amino-4-fluorophenyl)-1-butanone;

tert-butyl(±

)-cis-5,6,8,9,10,11,12,12a-octahydro-4H,7aH-azepino[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline-11-carboxylate;

tert-butyl(±

)-cis-2-bromo-5,6,8,9,10,11,12,12a-octahydro-4H,7aH-azepino[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline-11-carboxylate; and

(±

)-cis-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,8,9,10,11,12,12a-octahydro-4H,7aH-azepino[3′

,4′

;

4,5]pyrrolo[3,2,1-ij]quinoline.

17. The method as defined in claim 1 where the compound administered is selected from the group:

tert-butyl(±

)-cis-2-bromo-4-oxo-4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indole-11(8aH)-carboxylate;

tert-butyl(±

)-cis-2-(2,4-dichlorophenyl)-4-oxo-4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indole-11(8aH)-carboxylate;

(±

)-cis-2-(2,4-dichlorophenyl)-6,7,8a,9,10,11,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-4(5H)-one;

(8aS,12aR)-2-(2,4-dichlorophenyl)-6,7,8a,9,10,11,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-4(5H)-one;

(8aR,12aS)-2-(2,4-dichlorophenyl)-6,7,8a,9,10,11,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-4(5H)-one;

(8aS,12aR)-2-(2,4-dichlorophenyl)-6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-4-ol; and

(8aR,12aS)-2-(2,4-dichlorophenyl)-6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-4-ol.