2-Aminoquinoline compounds

• US 7,084,156 B2
• Filed: 11/22/2002
• Issued: 08/01/2006
• Est. Priority Date: 11/27/2001
• Status: Expired due to Fees

• Current Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.)
• Original Assignee: Merck & Co., Inc.
• Inventors: Hoang, MyLe, Chaung, Danny, Sailer, Andreas W., Jiang, JinLong, Chang, Lehua, DeVita, Robert J., Young, Jonathan R., Lin, Peter
• Primary Examiner(s): SEAMAN, D MARGARET M
• Application Number:
  US10/496,615
• Publication Number:
  US 20050026915A1
• Time in Patent Office: 1,348 Days
• Field of Search: 546/159, 546/162, 546/178, 514/312, 514/314, 514/313
• US Class Current: 514/312
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/10 : Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07D 215/227 : only one oxygen atom which is attached in position 2
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 : containing three or more hetero rings
• CPC Class Codes: C07D 405/14 : containing three or more hetero rings
• CPC Class Codes: C07D 413/14 : containing three or more hetero rings
• CPC Class Codes: C07D 417/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings
• CPC Class Codes: C07D 491/04 : Ortho-condensed systems
• CPC Class Codes: C07D 495/10 : Spiro-condensed systems

Abstract

The present invention is concerned with compounds of the general Formula I:

and pharmaceutically acceptable salts thereof, which are useful as melanin concentrating hormone receptor antagonists, particularly MCH-1R antagonists. As such, compounds of the present invention are useful for the treatment or prevention of obesity or eating disorders associated with excessive food intake and complications thereof, osteoarthritis, certain cancers, AIDS wasting, cachexia, frailty (particularly in elderly), mental disorders stress, cognitive disorders, sexual function, reproductive function, kidney function, locomotor disorders, attention deficit disorder (ADD), substance abuse disorders and dyskinesias, Huntington'"'"'s disease, epilepsy, memory function, and spinal muscular atrophy. Compounds of formula I may therefore be used in the treatment of these conditions, and in the manufacture of a medicament useful in treating these conditions. Pharmaceutical formulations comprising one of the compounds of formula (I) as an active ingredient are disclosed, as are processes for preparing these compounds.

Claims

1. A compound of structural formula (I):

2. The compound according to claim 1, wherein:

R¹ and R² are independently selected from the group consisting of;

(1) hydrogen,

(2) C_1-6 alkyl,

(3) C_2-6 alkenyl,

(4) cycloalkyl-C_0-6 alkyl,

(5) heterocycloalkyl-C_0-6 alkyl,

(6) aryl-C_0-6 alkyl, and

(7) heteroaryl-C_0-10 alkyl;

wherein alkyl and alkenyl moieties above are optionally substituted with one to three substituents independently selected from R^a;

wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl moieties above are optionally substituted with one to three substituents independently selected from R^b;

or, R¹ and R² together with the nitrogen atom to which they are attached, form a 4- to 11-membered bridged or unbridged or spirocyclic heterocyclic ring, optionally containing one additional heteroatom selected from N, S, and O, optionally having one or more degrees of unsaturation, optionally fused to a 6-membered heteroaromatic or aromatic ring, either unsubstituted or substituted with an R^b substituent;

R³ and R⁴ are independently selected from the group consisting of;

(1) hydrogen,

(2) halogen,

(3) C_1-8 alkyl,

(4) trifluoromethyl,

(5) C_2-6 alkenyl,

(6) cycloalkyl,

(7) cycloalkyl-C_1-6 alkyl,

(8) cycloheteroalkyl,

(9) cycloheteroalkyl-C_1-6 alkyl,

(10) aryl,

(11) aryl-C_1-6 alkyl,

(12) heteroaryl,

(13) heteroaryl-C_1-6 alkyl,

(14) —

OR⁷,

(15) —

NR⁷R⁷,

(16) —

CO₂R⁷, and

(17) —

C(O)NR⁷R⁷;

wherein alkyl and alkenyl moieties above are optionally substituted with one to four substituents independently selected from R^a; and

wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl moieties above are optionally substituted with an R^b substituent;

R⁵ is

hydrogen

(10);

R⁶ is selected from the group consisting of;

(1) —

(CH₂)_n-heteroaryl-R⁷,

(2) —

(CH₂)_nNR⁷C(O)R⁷, and

(3) —

(CH₂)_nN(R⁷)₂,

wherein one or two of the hydrogen atoms in (CH₂)_n may be substituted with R^a;

R⁷ is independently selected at each occurrence from the group consisting of;

(1) hydrogen,

(2) C_1-6 alkyl,

(3) aryl,

(4) heteroaryl,

(5) cycloalkyl,

(6) heterocycloalkyl,

(7) aryl C_1-3 alkyl,

(8) heteroaryl C_1-3 alkyl,

(9) cycloalkyl C_1-3 alkyl,

(10) heterocycloalkyl C_1-3 alkyl,

(11) aryl C_2-3 alkenyl,

(12) heteroaryl C_2-3 alkenyl,

(13) cycloalkyl C_2-3 alkenyl, and

(14) heterocycloalkyl C_2-3 alkenyl,

wherein the alkyl and alkenyl moieties are optionally substituted with one to four substituents selected from R^a; and

wherein the aryl, heteroaryl, cycloalkyl and heterocycloalkyl moieties are independently substituted with one to four substituents selected from R^b; and

wherein sulfur-containing heterocyclic rings may be mono- or di-oxidized on the sulfur atom;

each R^a is independently selected from;

(1) —

OR^d,

(2) —

NR^dS(O)_mR^d,

(3) —

NO₂,

(4) halogen,

(5) —

S(O)_mR^d,

(6) —

SR^d,

(7) —

S(O)₂OR^d,

(8) —

S(O)_pN(R^d)₂,

(9) —

N(R^d)₂,

(10) —

O(CR^dR^d)_nN(R^d)₂,

(11) —

C(O)R^d,

(12) —

CO₂R^d,

(13) —

CO₂(CR^dR^d)_nCON(R^d)₂,

(14) —

OC(O)R^d,

(15) —

CN,

(16) —

C(O)N(R^d)₂,

(17) —

NR^dC(O)R^d,

(18) —

OC(O)N(R^d)₂,

(19) —

NR^dC(O)OR^d,

(20) —

NR^dC(O)N(R^d)₂,

(21) —

CR^d(N—

OR^d),

(22) —

CF₃,

(23) cycloalkyl,

(24) cycloheteroalkyl, and

(25) oxo;

each R^b is independently selected from;

(1) R^a,

(2) —

Sn(CH₃)₃,

(3) C_1-10 alkyl,

(4) C_2-10 alkenyl,

(5) heteroaryl,

(6) aryl, and

(7) aryl-C_1-10 alkyl;

wherein alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, heteroaryl, and aryl are optionally substituted with one to four R^c substituents;

each R^c is independently selected from;

(1) halogen,

(2) amino,

(3) carboxy,

(4) C_1-4 alkyl,

(5) C_1-4 alkoxy,

(6) aryl,

(7) aryl C_1-4 alkyl,

(8) hydroxy,

(9) —

CF₃,

(10) —

OC(O)C_1-4 alkyl,

(11) —

OC(O)N(R^d)₂, and

(12) aryloxy;

each R^d is independently selected from hydrogen, C_1-6 alkyl, C_2-6 alkenyl;

C_2-6 alkynyl;

cycloalkyl;

cycloalkyl-C_1-6 alkyl;

cycloheteroalkyl;

cycloheteroalkyl-C_1-6 alkyl;

aryl;

heteroaryl;

aryl-C_1-6 alkyl; and

heteroaryl-C_1-6 alkyl;

wherein the alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, heteroaryl, and aryl in R^d are optionally substituted with one to two substituents independently selected from a R^e;

each R^e is selected from halo, methyl, methoxy, trifluoromethyl, trifluoromethoxy, and hydroxy;

m is selected from 1 and 2;

n is selected from;

0, 1, 2, 3, 4, and 5;

p is selected from 0, 1, and 2;

and pharmaceutically acceptable salts thereof.

3. The compound according to claim 2, wherein:

R¹ is selected from the group consisting of;

(1) hydrogen, and

(2) C_1-6 alkyl, optionally substituted with one to three substituents independently selected from R^a;

R² is selected from the group consisting of;

(1) hydrogen,

(2) C_1-6 alkyl,

(3) cycloalkyl-C_0-6 alkyl,

(4) heterocycloalkyl-C_0-6 alkyl,

(5) aryl-C_0-6 alkyl, and

(6) heteroaryl-C_0-10 alkyl;

wherein alkyl moieties above are optionally substituted with one to three substituents independently selected from R^a; and

wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl moieties above are optionally substituted with one to three substituents independently selected from R^b;

or, R¹ and R² together with the nitrogen atom to which they are attached, form a 4- to 11-membered bridged or unbridged or spirocyclic heterocyclic ring, optionally containing one additional heteroatom selected from N, S, and O, either unsubstituted or substituted with an R^b substituent;

R³ is selected from the group consisting of;

(1) hydrogen,

(2) halogen,

(3) C_1-8 alkyl,

(4) trifluoromethyl,

(5) —

OH,

(6) —

OCH₃,

(7) —

NH₂,

(8) —

CO₂R⁷, and

(9) —

C(O)NH₂;

wherein alkyl moieties above are optionally substituted with one to two substituents independently selected from R^a;

R⁴ is selected from the group consisting of;

(1) hydrogen,

(2) halogen,

(3) C_1-8 alkyl,

(4) trifluoromethyl,

(5) cycloalkyl,

(6) cycloheteroalkyl,

(7) aryl,

(8) aryl-C_1-6 alkyl,

(9) heteroaryl,

(10) —

OH,

(11) —

OCH,

(12) —

NH₂,

(13) —

CO₂R⁷, and

(14) —

C(O)NH₂;

wherein alkyl moieties above are optionally substituted with one to four substituents independently selected from R^a; and

wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl moieties above are optionally substituted with an R^b substituent;

R⁵ is

hydrogen

(10);

R⁶ is selected from the group consisting of;

(1) —

(CH₂)_n-heteroaryl-R⁷,

(2) —

(CH₂)_nNR⁷C(O)R⁷, and

(3) —

(CH₂)_nN(R⁷)₂,

wherein one or two of the hydrogen atoms in (CH₂)_n may be substituted with R^a;

R⁷ is independently selected at each occurrence from the group consisting of;

(1) hydrogen,

(2) C_1-6 alkyl,

(3) aryl,

(4) heteroaryl,

(5) cycloalkyl,

(6) heterocycloalkyl,

(7) aryl C_1-3 alkyl,

(8) heteroaryl C_1-3 alkyl,

(9) cycloalkyl C_1-3 alkyl,

(10) heterocycloalkyl C_1-3 alkyl,

(11) aryl C_2-3 alkenyl,

(12) heteroaryl C_2-3 alkenyl,

(13) cycloalkyl C_2-3 alkenyl, and

(14) heterocycloalkyl C_2-3 alkenyl,

wherein the alkyl and alkenyl moieties are optionally substituted with one to three substituents selected from R^a; and

wherein the aryl, heteroaryl, cycloalkyl and heterocycloalkyl moieties are independently substituted with one to three substituents selected from R^b; and

wherein sulfur-containing heterocyclic rings may be mono- or di-oxidized on the sulfur atom;

each R^a is independently selected from;

(1) —

OR^d,

(2) —

NR^dS(O)_mR^d,

(3) —

NO₂,

(4) halogen,

(5) —

S(O)_mR^d,

(6) —

SR^d,

(7) —

S(O)₂OR^d,

(8) —

S(O)_pN(R^d)₂,

(9) —

N(R^d)₂,

(10) —

O(CR^dR^d)_nN(R^d)₂,

(11) —

C(O)R^d,

(12) —

CO₂R^d,

(13) —

CO₂(CR^dR^d)_nCON(R^d)₂,

(14) —

OC(O)R^d,

(15) —

CN,

(16) —

C(O)N(R^d)₂,

(17) —

NR^dC(O)R^d,

(18) —

OC(O)N(R^d)₂,

(19) —

NR^dC(O)OR^d,

(20) —

NR^dC(O)N(R^d)₂,

(21) —

CR^d(N—

OR^d),

(22) —

CF₃,

(23) cycloalkyl,

(24) cycloheteroalkyl, and

(25) oxo;

each R^b is independently selected from;

(1) R^a,

(2) —

Sn(CH₃)₃,

(3) C_1-10 alkyl,

(4) C_2-10 alkenyl,

(5) heteroaryl,

(6) aryl, and

(7) aryl-C_1-10 alkyl;

wherein alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, heteroaryl, and aryl moieties in R^a and R^b are optionally substituted with one to four R^c substituents;

each R^c is independently selected from;

(1) halogen,

(2) amino,

(3) carboxy,

(4) C_1-4 alkyl,

(5) C_1-4 alkoxy,

(6) aryl,

(7) aryl C_1-4 alkyl,

(8) hydroxy,

(9) —

CF₃,

(10) —

OC(O)C_1-4 alkyl,

(11) —

OC(O)N(R^d)₂, and

(12) aryloxy;

R^d is independently selected from hydrogen, C_1-6 alkyl, C_2-6 alkenyl;

C_2-6 alkynyl;

cycloalkyl;

cycloalkyl-C_1-6 alkyl;

cycloheteroalkyl;

cycloheteroalkyl-C_1-6 alkyl;

aryl;

heteroaryl;

aryl-C_1-6 alkyl; and

heteroaryl-C_1-6 alkyl;

wherein the alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, heteroaryl, and aryl in R^d are optionally substituted with one to two substituents independently selected from a R^e;

each R^e is selected from halo, methyl, methoxy, trifluoromethyl, trifluoromethoxy, and hydroxy;

m is selected from 1 and 2;

n is selected from;

0, 1, 2, 3, and 4;

p is selected from 0, 1, and 2;

and pharmaceutically acceptable salts thereof.

4. The compound according to claim 3, wherein:

R¹ is selected from the group consisting of;

(1) hydrogen,

(2) methyl,

(3) ethyl, and

(4) propyl,

optionally substituted with one to three substituents independently selected from R^a;

R² is selected from the group consisting of;

(1) hydrogen,

(2) C_1-6 alkyl,

(3) cycloalkyl-C_0-6 alkyl,

(4) heterocycloalkyl-C_0-6 alkyl, and

(5) aryl-C_0-6 alkyl,

wherein alkyl moieties above are optionally substituted with one to three substituents independently selected from R^a; and

wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl moieties above are optionally substituted with one to three substituents independently selected from R^b;

or, R¹ and R² together with the nitrogen atom to which they are attached, form a 4- to 11-membered bridged or unbridged or spirocyclic heterocyclic ring, optionally containing one additional heteroatom selected from N, S, and O, either unsubstituted or substituted with an R^b substituent;

R³ is selected from the group consisting of;

(1) hydrogen,

(2) halogen,

(3) C_1-8 alkyl, and

(4) trifluoromethyl,

wherein alkyl moieties above are optionally substituted with one to two substituents independently selected from R^a;

R⁴ is selected from the group consisting of;

(1) hydrogen,

(2) C_1-8 alkyl,

(3) trifluoromethyl,

(4) cycloalkyl,

(5) cycloheteroalkyl,

(6) aryl,

(7) heteroaryl,

(8) —

NH₂,

(9) —

CO₂H,

(10) —

CO₂CH₃, and

(11) —

CO₂CH₂CH₃;

wherein alkyl moieties above are optionally substituted with one to two substituents independently selected from R^a; and

wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl moieties above are optionally substituted with an R^b substituent;

R⁵ is

hydrogen

(6);

R⁶ is selected from the group consisting of;

(1) —

(CH₂)_n-heteroaryl-R⁷,

(2) —

(CH₂)_nNR⁷C(O)R⁷, and

(3) —

(CH₂)_nN(R⁷)₂,

wherein one or two of the hydrogen atoms in (CH₂)_n may be substituted with R^a;

R⁷ is independently selected at each occurrence from the group consisting of;

(1) hydrogen,

(2) C_1-6 alkyl,

(3) aryl,

(4) heteroaryl,

(5) cycloalkyl,

(6) heterocycloalkyl,

(7) aryl C_1-3 alkyl,

(8) heteroaryl C_1-3 alkyl,

(9) cycloalkyl C_1-3 alkyl,

(10) heterocycloalkyl C_1-3 alkyl,

(11) aryl C_2-3 alkenyl,

(12) heteroaryl C_2-3 alkenyl,

(13) cycloalkyl C_2-3 alkenyl, and

(14) heterocycloalkyl C_2-3 alkenyl,

wherein the alkyl and alkenyl moieties are optionally substituted with one to three substituents selected from R^a; and

wherein the aryl, heteroaryl, cycloalkyl and heterocycloalkyl moieties are independently substituted with one to three substituents selected from R^b; and

wherein sulfur-containing heterocyclic rings may be mono- or di-oxidized on the sulfur atom;

each R^a is independently selected from;

(1) —

OR^d,

(2) —

NHSO₂CH₃,

(3) —

NO₂,

(4) halogen,

(5) —

S(O)_mCH₃,

(6) —

SR^d,

(7) —

S(O)₂OR^d,

(8) —

S(O)_pN(R^d)₂,

(9) —

N(R^d)₂,

(10) —

O(CR^dR^d)_nN(R^d)₂,

(11) —

C(O)R^d,

(12) —

CO₂R^d,

(13) —

CO₂(CR^dR^d)_nCON(R^d)₂,

(14) —

OC(O)R^d,

(15) —

CN,

(16) —

C(O)N(R^d)₂,

(17) —

NR^dC(O)R^d,

(18) —

OC(O)N(R^d)₂,

(19) —

NR^dC(O)OR^d,

(20) —

NR^dC(O)N(R^d)₂,

(21) —

CR^d(N—

OR^d),

(22) —

CF₃,

(23) cycloalkyl,

(24) cycloheteroalkyl, and

(25) oxo;

each R^b is independently selected from;

(1) R^a,

(2) —

Sn(CH₃)₃,

(3) C_1-6 alkyl,

(4) C_2-6 alkenyl,

(5) heteroaryl,

(6) aryl, and

(7) aryl-C_1-10 alkyl;

wherein alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, heteroaryl, and aryl moieties in R^a and R^b are optionally substituted with one to four R^c substituents;

each R^c is independently selected from;

(1) halogen,

(2) amino,

(3) carboxy,

(4) C_1-4 alkyl,

(5) C_1-4 alkoxy,

(6) aryl,

(7) aryl C_1-4 alkyl,

(8) hydroxy,

(9) —

CF₃,

(10) —

OC(O)C_1-4 alkyl,

(11) —

OC(O)N(R^d)₂, and

(12) aryloxy;

R^d is independently selected from hydrogen, C_1-6 alkyl, C_2-6 alkenyl;

C_2-6 alkynyl;

cycloalkyl;

cycloalkyl-C_1-6 alkyl;

cycloheteroalkyl;

cycloheteroalkyl-C_1-6 alkyl;

aryl;

heteroaryl;

aryl-C_1-6 alkyl; and

heteroaryl-C_1-6 alkyl;

wherein the alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, heteroaryl, and aryl in R^d are optionally substituted with one to two substituents independently selected from a R^e;

each R^e is selected from halogen, methyl, methoxy, trifluoromethyl, trifluoromethoxy, and hydroxy;

m is selected from 1 and 2;

n is selected from;

0, 1, 2, 3, and 4;

p is selected from 0, 1, and 2;

and pharmaceutically acceptable salts thereof.

5. The compound according to claim 4, wherein:

R¹ is selected from the group consisting of;

(1) hydrogen, and

(2) methyl;

optionally substituted with one to three substituents independently selected from R^a;

R² is selected from the group consisting of;

(1) methyl,

(2) ethyl,

(3) n-propyl,

(4) isopropyl,

(5) t-butyl,

(6) n-butyl,

(7) cyclopropyl,

(8) cyclobutyl,

(9) cyclopentyl,

(10) cyclohexyl,

(11) heterocycloalkyl-C_0-6 alkyl, wherein the heterocycloalkyl moiety is selected from azetidinyl, pyrrolidinyl, and pyridyl and

(12) phenyl-C_0-6 alkyl,

wherein alkyl moieties above are optionally substituted with one to three substituents independently selected from R^a; and

wherein cycloalkyl, heterocycloalkyl, and aryl moieties above are optionally substituted with one to three substituents independently selected from R^b;

or, R¹ and R² together with the nitrogen atom to which they are attached, form a 4- to 11-membered heterocyclic ring, selected from;

azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, 1-thia-4-azacyclohexyl, 2,5-diazabicyclo[2.2.2]octanyl, azacycloheptyl, 2-oxa-5-azabicyclo[2.2.1]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, 2-azabicyclo[2.2.1]heptyl, 7-azabicyclo[2.2.1]heptyl, 2,5-diazabicyclo[2.2.2]octyl, 2-azabicyclo[2.2.2]octyl, and 3-azabicyclo[3.2.2]nonyl, 2,7-diazaspiro[4.4]nonyl, 2,7-diazaspiro[4.5]decyl, 2,7-diazaspiro[4.6]undecyl, 1,7-diazaspiro[4.4]nonyl, 2,6-dizaospiro[4.5]decyl, 2,6-diazaspiro[4.6]-undecyl, either unsubstituted or substituted with an R^b substituent;

R³ is selected from the group consisting of;

(1) hydrogen,

(2) halogen,

(3) methyl,

(4) ethyl,

(5) propyl, and

(6) trifluoromethyl,

wherein alkyl moieties above are optionally substituted with one to two substituents independently selected from R^a;

R⁴ is selected from the group consisting of;

(1) hydrogen,

(2) methyl,

(3) ethyl,

(4) propyl,

(5) trifluoromethyl,

(6) —

CO₂H,

(7) —

CO₂CH₃ and

(8) —

CO₂CH₂CH₃;

wherein alkyl moieties above are optionally substituted with one to three substituents independently selected from R^a;

R⁵ is hydrogen;

R⁶ is selected from the group consisting of;

(1)-heteroaryl-R⁷,

(2) —

NHC(O)R⁷,

(3) —

NH(R⁷), and

(4) —

(CH₂)_nNH(R⁷),

wherein one or two of the hydrogen atoms in (CH₂)_n may be substituted with R^a;

R⁷ is independently selected at each occurrence from the group consisting of;

(1) hydrogen,

(2) C_1-6 alkyl,

(3) aryl, selected from;

phenyl, naphthyl, indanyl, indenyl, indolyl, quinazolinyl, quinolinyl, benzthiazolyl, benzoxazolyl, dihydroindanyl, benzisodiazolyl, spirocyclohexylindolinyl, spiro-(dihydrobenzothiophenyl)piperidinyl, spiro-indolinylpiperidinyl, indolinyl, tetrahydroisoquinolinyl, isoindolinyl, benzothiadiazolyl, benzotriazolyl, 1,3-dihydro-2-benzofuranyl, benzothiophenyl, benzodioxolyl, tetrahydronaphthyl, 2,3-dihydrobenzofuranyl, dihydrobenzopyranyl, and 1,4-benzodioxanyl,

(4) heteroaryl, selected from;

pyrrolyl, isoxazolyl, isothiazolyl, pyrazolyl, pyridyl, oxazolyl, oxadiazolyl, thiadiazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, furanyl, triazinyl, thienyl, pyrimidyl, pyridazinyl, pyrazinyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, benzothiophenyl, furo[2,3-b]pyridyl, quinolyl, indolyl, isoquinolyl, quinazolinyl, benzisodiazolyl, triazolopyrimidinyl, 5,6,7,8-tetrahydroquinolinyl, 2,1,3-benzothiadiazolyl, and thienopyridinyl,

(5) cycloalkyl, selected from;

cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, tetrahydronaphthyl, decahydronaphthyl, indanyl, bicyclo[2.2.2]octanyl, tetrahydronaphthyl, and dihydroindanyl,

(6) heterocycloalkyl, selected from;

azetidinyl, pyridyl, pyrrolidinyl, piperidinyl, piperazinyl, imidazolidinyl, morpholinyl, 1-thia-4-aza-cyclohexane, 2,5-diazabicyclo[2.2.2]octanyl, 2,3-dihydrofuro[2,3-b]pyridyl, benzoxazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, dihydroindolyl, indolyl, indolinyl, isoindolinyl, 1,3-dihydro-2-benzofuranyl, benzodioxolyl, hexahydrothienopyridinyl, thienopyridinyl, azacycloheptyl, 4,4-spiro[2,3-dihydrobenzothiophen-3,3-yl]piperidinyl, and 4,4-spiro[indoli-3,3-yl]piperidinyl,

(7) aryl C_1-3 alkyl, wherein the aryl moiety is selected from;

phenyl, naphthyl, indanyl, indenyl, indolyl, quinazolinyl, quinolinyl, benzthiazolyl, benzoxazolyl, dihydroindanyl, benzisodiazolyl, spirocyclohexylindolinyl, spiro-(dihydrobenzothiophenyl)piperidinyl, spiro-indolinylpiperidinyl, indolinyl, tetrahydroisoquinolinyl, isoindolinyl, benzothiadiazolyl, benzotriazolyl, 1,3-dihydro-2-benzofuranyl, benzothiophenyl, benzodioxolyl, tetrahydronaphthyl, 2,3-dihydrobenzofuranyl, dihydrobenzopyranyl, and 1,4-benzodioxanyl,

(8) heteroaryl C_1-3 alkyl, wherein the heteroaryl moiety is selected;

pyrrolyl, isoxazolyl, isothiazolyl, pyrazolyl, pyridyl, oxazolyl, oxadiazolyl, thiadiazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, furanyl, triazinyl, thienyl, pyrimidyl, pyridazinyl, pyrazinyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, benzothiophenyl, furo[2,3-b]pyridyl, quinolyl, indolyl, isoquinolyl, quinazolinyl, benzisodiazolyl, triazolopyrimidinyl, 5,6,7,8-tetrahydroquinolinyl, 2,1,3-benzothiadiazolyl, and thienopyridinyl,

(9) cycloalkyl C_1-3 alkyl, wherein the cycloalkyl moiety is selected from;

cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, tetrahydronaphthyl, decahydronaphthyl, indanyl, bicyclo[2.2.2]octanyl, tetrahydronaphthyl, and dihydroindanyl,

(10) heterocycloalkyl C_1-3 alkyl, wherein the heterocycloalkyl moiety is selected from;

azetidinyl, pyridyl, pyrrolidinyl, piperidinyl, piperazinyl, imidazolidinyl, morpholinyl, 1-thia-4-aza-cyclohexane, 2,5-diazabicyclo[2.2.2]octanyl, 2,3-dihydrofuro[2,3-b]pyridyl, benzoxazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, dihydroindolyl, indolyl, indolinyl, isoindolinyl, 1,3-dihydro-2-benzofuranyl, benzodioxolyl, hexahydrothienopyridinyl, thienopyridinyl, azacycloheptyl, 4,4-spiro[2,3-dihydrobenzothiophen-3,3-yl]piperidinyl, and 4,4-spiro[indoli-3,3-yl]piperidinyl,

(11) aryl C_2-3 alkenyl, wherein the aryl moiety is selected from;

phenyl, naphthyl, indanyl, indenyl, indolyl, quinazolinyl, quinolinyl, benzthiazolyl, benzoxazolyl, dihydroindanyl, benzisodiazolyl, spirocyclohexylindolinyl, spiro-(dihydrobenzothiophenyl)piperidinyl, spiro-indolinylpiperidinyl, indolinyl, tetrahydroisoquinolinyl, isoindolinyl, benzothiadiazolyl, benzotriazolyl, 1,3-dihydro-2-benzofuranyl, benzothiophenyl, benzodioxolyl, tetrahydronaphthyl, 2,3-dihydrobenzofuranyl, dihydrobenzopyranyl, and 1,4-benzodioxanyl,

(12) heteroaryl C_2-3 alkenyl, wherein the heteroaryl moiety is selected from;

pyrrolyl, isoxazolyl, isothiazolyl, pyrazolyl, pyridyl, oxazolyl, oxadiazolyl, thiadiazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, furanyl, triazinyl, thienyl, pyrimidyl, pyridazinyl, pyrazinyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, benzothiophenyl, furo[2,3-b]pyridyl, quinolyl, indolyl, isoquinolyl, quinazolinyl, benzisodiazolyl, triazolopyrimidinyl, 5,6,7,8-tetrahydroquinolinyl, 2,1,3-benzothiadiazolyl, and thienopyridinyl,

(13) cycloalkyl C_2-3 alkenyl, wherein the cycloalkyl moiety is selected from;

cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, tetrahydronaphthyl, decahydronaphthyl, indanyl, bicyclo[2.2.2]octanyl, tetrahydronaphthyl, and dihydroindanyl, and

(14) heterocycloalkyl C_2-3 alkenyl, wherein the heterocycloalkyl moiety is selected from;

azetidinyl, pyridyl, pyrrolidinyl, piperidinyl, piperazinyl, imidazolidinyl, morpholinyl, 1-thia-4-aza-cyclohexane, 2,5-diazabicyclo[2.2.2]octanyl, 2,3-dihydrofuro[2,3-b]pyridyl, benzoxazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, dihydroindolyl, indolyl, indolinyl, isoindolinyl, 1,3-dihydro-2-benzofuranyl, benzodioxolyl, hexahydrothienopyridinyl, thienopyridinyl, azacycloheptyl, 4,4-spiro[2,3-dihydrobenzothiophen-3,3-yl]piperidinyl, and 4,4-spiro[indoli-3,3-yl]piperidinyl;

wherein the alkyl moieties are optionally substituted with one to three substituents selected from R^a; and

wherein the aryl, heteroaryl, cycloalkyl and heterocycloalkyl moieties are independently substituted with one to three substituents selected from R^b; and

wherein sulfur-containing heterocyclic rings may be mono- or di-oxidized on the sulfur atom;

each R^a is independently selected from;

(1) —

OR^d,

(2) —

NHSO₂CH₃,

(3) —

NO₂,

(4) halogen,

(5) —

S(O)_mCH₃,

(6) —

SCH₃,

(7) —

SCF₃,

(8) —

S(O)₂OR^d,

(9) —

S(O)_pN(R^d)₂,

(10) —

N(CH₃)₂,

(11) —

NH₂,

(12) —

O(CR^dR^d)_nN(R^d)₂,

(13) —

C(O)R^d,

(14) —

CO₂H,

(15) —

CO₂CH₃,

(16) t-butyloxycarbonyl,

(17) —

CO₂(CR^dR^d)_nCON(R^d)₂,

(18) —

OC(O)R^d,

(19) —

CN,

(20) —

C(O)N(R^d)₂,

(21) —

NR^dC(O)R^d,

(22) —

OC(O)N(R^d)₂,

(23) —

NR^dC(O)OR^d,

(24) —

NR^dC(O)N(R^d)₂,

(25) —

CR^d(N—

OR^d),

(26) —

CF₃,

(27) cycloalkyl,

(28) cycloheteroalkyl, and

(29) oxo;

each R^b is independently selected from;

(1) —

R^a,

(2) —

Sn(CH₃)₃,

(3) C_1-6 alkyl,

(4) C_2-6 alkenyl,

(5) heteroaryl,

(6) aryl, and

(7) aryl-C_1-10 alkyl;

wherein alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, heteroaryl, and aryl moieties in R^a and R^b are optionally substituted with one to four R^c substituents;

each R^c is independently selected from;

(1) halogen,

(2) amino,

(3) carboxy,

(4) C_1-4 alkyl,

(5) C_1-4 alkoxy,

(6) aryl,

(7) aryl C_1-4 alkyl,

(8) hydroxy,

(9) —

CF₃,

(10) —

OC(O)C_1-4 alkyl,

(11) —

OC(O)N(R^d)₂, and

(12) aryloxy;

R^d is independently selected from hydrogen, C_1-6 alkyl, C_2-6 alkenyl;

C_2-6 alkynyl;

cycloalkyl;

cycloalkyl-C_1-6 alkyl;

cycloheteroalkyl;

cycloheteroalkyl-C_1-6 alkyl;

aryl;

heteroaryl;

aryl-C_1-6 alkyl; and

heteroaryl-C_1-6 alkyl;

wherein the alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, heteroaryl, and aryl in R^d are optionally substituted with one to two substituents independently selected from a R^e;

each R^e is selected from halogen, methyl, methoxy, trifluoromethyl, trifluoromethoxy, and hydroxy;

m is selected from 1 and 2;

n is selected from;

0, 1, 2, 3, and 4;

p is selected from 0, 1, and 2;

and pharmaceutically acceptable salts thereof.

6. The compound according to claim 1 of structural formula:

7. The compound according to claim 1 of structural formula:

8. The compound according to claim 1 of structural formula:

9. The compound according to claim 1, selected from:

(1) (2E)-3-(4-chlorophenyl)-N-[2-(dimethylamino)quinolin-6-yl]prop-2-enamide,

(2) (2E)-N-[2-(dimethylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(3) (2E)-3-(4-chlorophenyl)-N-[2-(ethylamino)quinolin-6-yl]prop-2-enamide,

(4) (2E)-N-[2-(ethylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(5) (2E)-3-(4-chlorophenyl)-N-[2-(propylamino)quinolin-6-yl]prop-2-enamide,

(6) (2E)-N-[2-(propylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(7) (2E)-3-(4-chlorophenyl)-N-[2-(isopropylamino)quinolin-6-yl]prop-2-enamide,

(8) (2E)-N-[2-(isopropylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(9) (2E)-N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-(4-chlorophenyl)prop-2-enamide,

(10) (2E)-N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(11) (2E)-N-[2-(2-azabicyclo[2.2.2]oct-2-yl)-3-methylquinolin-6-yl]-3-(4-chlorophenyl)prop-2-enamide,

(12) (2E)-N-[2-(dimethylamino)-4-methylquinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(13) N-[2-(dimethylamino)-4-methylquinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(14) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]—

N′

-[4-(methylthio)phenyl]urea,

(15) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-[6-(trifluoromethyl)pyridin-3-yl]propanamide,

(16) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-[4-(trifluoromethoxy)phenyl]urea,

(17) (2E)-N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-(4-ethylphenyl)prop-2-enamide,

(18) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-(4-isopropylphenyl)urea,

(19) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-(4-ethylphenyl)propanamide,

(20) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-[4-(trifluoromethyl)phenyl]urea,

(21) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-(4-methoxyphenyl)urea,

(22) (2E)-N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-(4-methoxyphenyl)prop-2-enamide,

(23) N-[2-(dimethylamino)quinolin-6-yl]-N′

-[4-(methylthio)phenyl]urea,

(24) (2E)-N-[2-(2-azabicyclo[2.2.2]oct-2-yl)-4-methylquinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(25) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)-4-methylquinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(26) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-(4-ethylphenyl)urea,

(27) N-(2-pyrrolidin-1-ylquinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]propanamide,

(28) (2E)-N-(2-pyrrolidin-1-ylquinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(29) (2E)-N-(2-azetidin-1-ylquinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(30) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(31) N-(2-azetidin-1-ylquinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]propanamide,

(32) (2E)-N-[2-(butylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(33) (2E)-N-[2-(isobutylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(34) N-[2-(isobutylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(35) (2E)-N-[2-(2-azabicyclo[2.2.1]hept-2-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(36) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-(2,3-dihydro-1H-inden-5-yl)urea,

(37) (2E)-N-[2-(sec-butylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(38) N-[2-(sec-butylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(39) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-(4-propylphenyl)urea,

(40) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)-3-methylquinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(41) N-[2-(cyclopentylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(42) N-(2-{[(1R)-1-methylpropyl]amino}quinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]propanamide,

(43) (2E)-N-[2-(2-azabicyclo[2.2.1]hept-2-yl)-3-methylquinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(44) N-{2-[isopropyl(methyl)amino]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide

(45) N-(2-{[(1S)-1-methylpropyl]amino}quinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]propanamide,

(46) N-(3-methyl-2-pyrrolidin-1-ylquinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]propanamide,

(47) (2E)-N-(4-ethyl-2-pyrrolidin-1-ylquinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]propanamide,

(48) N-[2-(3-methylpyrrolidin-1-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(49) N-[2-(2-methylpyrrolidin-1-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(50) N-{2-[(1,2-dimethylpropyl)amino]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(51) N-{2-[ethyl(methyl)amino]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(52) N-{2-[methyl(propyl)amino]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(53) N-(2-azetidin-1-yl-3-methylquinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]propanamide,

(54) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-(2,2-difluoro-1,3-benzodioxol-5-yl)urea,

(55) N-[2-(isopropylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(56) N-{2-[isopropyl(methyl)amino]quinolin-6-yl}-3-[6-(trifluoromethyl)pyridin-3-yl]propanamide,

(57) N-(2-azetidin-1-yl-3-methylquinolin-6-yl)-N′

-[4-(trifluoromethyl)phenyl]urea,

(58) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)-3-methylquinolin-6-yl]-N′

-[4-(trifluoromethyl)phenyl]urea,

(59) N-(3-methyl-2-pyrrolidin-1-ylquinolin-6-yl)-N′

-[4-(trifluoromethyl)phenyl]urea,

(60) N-{2-[(1-methylbutyl)amino]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(61) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)quinolin-6-yl]-N′

-(2,2-difluoro-1,3-benzodioxol-5-yl)urea,

(62) N-[2-(2-azabicyclo[2.2.2]hept-2-yl)quinolin-6-yl]-N′

-(2-methyl-1,3-benzothiazol-6-yl)urea,

(63) N-{2-[cyclopentyl(methyl)amino]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(64) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)-3-methylquinolin-6-yl]-N′

-[4-(trifluoromethyl)phenyl]propanamide,

(65) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-{4-[(trifluoromethyl)thio]phenyl}urea,

(66) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)-3-methylquinolin-6-yl]-3-[6-(trifluoromethyl)pyridin-3-yl]propanamide,

(67) N-{2-[cyclobutyl(methyl)amino]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(68) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-(1,3-benzothiazol-2-yl)propanamide,

(69) N-{2-[(1R,4S)-2-azabicyclo[2.2.1]hept-2-yl]quinolin-6-yl}-3-[6-(trifluoromethyl)pyridin-3-yl]propanamide,

(70) N-{2-[(1S,4R)-2-azabicyclo[2.2.1]hept-2-yl]quinolin-6-yl}-3-[6yl]propanamide,

(71) (2E)-N-{2-[isopropyl(methyl)amino]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(72) (2E)-3-(4-chlorophenyl)-N-{2-[isopropyl(methyl)amino]quinolin-yl}prop-2-enamide,

(73) N-[2-(pyrrolidin-3-ylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(74) N-{2-[3-(acetylamino)pyrrolidin-1-yl]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(75) N-[2-(3-{[(methylamino)carbonyl]amino}pyrrolidin-1-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(76) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)quinolin-6-yl]-N′

-(4-ethylphenyl)urea,

(77) (2E)-N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-[4-(methylthio)phenyl]prop-2-enamide,

(78) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)quinolin-6-yl]-N′

-{4-[(trifluoromethyl)thio]phenyl}urea,

(79) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)quinolin-6-yl]-N′

-[4-(methylthio)phenyl]urea,

(80) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)quinolin-6-yl]-N′

-[4-(trifluoromethoxy)phenyl]urea,

(81) N-{2-[methyl(tetrahydrofuran-3-yl)amino]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(82) N-(2-{3-[(methylsulfonyl)amino]pyrrolidin-1-yl}quinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]propanamide,

(83) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)quinolin-6-yl]-3-(1,3-benzothiazol-2-yl)propanamide,

(84) N-{2-[sec-butyl(methyl)amino]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(85) N-{2-[3-(propionylamino)pyrrolidin-1-yl]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(86) 2-{methyl[6-({3-[4-(trifluoromethyl)phenyl]propanoyl}amino)quinolin-2-yl]amino}propylacetate,

(87) N-{2-[methyl(1-tetrahydrofuran-2-ylethyl)amino]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(88) N-[2-(3-{[(dimethylamino)carbonyl]amino}pyrrolidin-1-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(89) 2-methyl-N-{1-[6-({3-[4-(trifluoromethyl)phenyl]propanoyl}amino)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

(90) N-{2-[3-(dimethylamino)pyrrolidin-1-yl]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(91) N-{1-[6-({3-[4-(trifluoromethyl)phenyl]propanoyl}amino)quinolin-2-yl]pyrrolidin-3-yl}cyclohexanecarboxamide,

(92) N-(4-ethylphenyl)-N′

-{2-[isopropyl(methyl)amino]quinolin-6-yl}urea,

(93) 2,2-dimethyl-N-{1-[6-({3-[4-(trifluoromethyl)phenyl]propanoyl}amino)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

(94) (2E)-N-[2-(3-aminopyrrolidin-1-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide

(95) N-{2-[isopropyl(methyl)amino]quinolin-6-yl}-N′

-[4-(methylthio)phenyl]urea,

(96) N-{2-[isopropyl(methyl)amino]quinolin-6-yl}-N′

-[4-(trifluoromethyl)phenyl]urea,

(97) N-{1-[6-({[(4-ethylphenyl)amino]carbonyl}amino)quinolin-2-yl]pyrrolidin-3-yl}-2,2-dimethylpropanamide,

(98) N-{2-[3-(dimethylamino)pyrrolidin-1-yl]quinolin-6-yl}-N′

-(4-ethylphenyl)urea,

(99) tert-butyl methyl{1-[6-({3-[4-(trifluoromethyl)phenyl]propanoyl}amino)quinolin-2-yl]pyrrolidin-3-yl}carbamate,

(100) N-(2,2-difluoro-1,3-benzodioxol-5-yl)-N′

-{2-[3-(dimethylamino)pyrrolidin-1-yl]quinolin-6-yl}urea,

(101) N-{2-[(3S)-3-aminopyrrolidin-1-yl]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(102) N-{2-[3-(methylamino)pyrrolidin-1-yl]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(103) 2,2-dimethyl-N-{(3S)-1-[6-({3-[4-(trifluoromethyl)phenyl]propanoyl}amino)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

(104) 2,2-dimethyl-N-{(3R)-1-[6-({3-[4-(trifluoromethyl)phenyl]propanoyl}amino)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

(105) N,2,2-trimethyl-N-{1-[6-({3-[4-(trifluoromethyl)phenyl]propanoyl}amino)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

(106) N-{2-[(3S)-3-(propionylamino)pyrrolidin-1-yl]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(107) (2E)-N-(2-{3-[(methylsulfonyl)amino]pyrrolidin-1-yl}quinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(108) (2E)-N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-[4-(ethylthio)phenyl]prop-2-enamide,

(109) tert-butyl 1-(6-{[(2E)-3-(4-chlorophenyl)prop-2-enoyl]amino}quinolin-2-yl)pyrrolidin-3-ylcarbamate,

(110) (2E)-N-[2-(3-aminopyrrolidin-1-yl)quinolin-6-yl]-3-(4-chlorophenyl)prop-2-enamide,

(111) N-{1-[6-({[(4-ethylphenyl)amino]carbonyl}amino)quinolin-2-yl]pyrrolidin-3-yl}methanesulfonamide,

(112) N-{2-[3-(dimethylamino)pyrrolidin-1-yl]quinolin-6-yl}-N′

-[4-(trifluoromethyl)phenyl]urea,

(113) N-{2-[3-(dimethylamino)pyrrolidin-1-yl]quinolin-6-yl}-N′

-[4-(trifluoromethoxy)phenyl]urea,

(114) N-{2-[(3R)-3-(propionylamino)pyrrolidin-1-yl]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(115) N-[2-(7-methyl-2,7-diazaspiro[4.4]non-2-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide, (116) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N²-(4-ethylphenyl)ethane-1,2-diamine,

(117) N-[2-(7-benzyl-2,7-diazaspiro[4.4]non-2-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(118) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)-4-(dimethylamino)quinolin-6-yl]-4′

-(trifluoromethyl)-1,1′

-biphenyl-4-carboxamide,

(119) N-[2-(2,7-diazaspiro[4.4]non-2-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(120) N-{2-[isopropyl(methyl)amino]quinolin-6-yl}-N′

-[4-(trifluoromethoxy)phenyl]urea,

(121) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-[6-(trifluoromethyl)pyridin-3-yl]urea,

(122) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-(6-ethylpyridin-3-yl)urea,

(123) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-[4-(methylsulfonyl)phenyl]propanamide,

(124) 2,2-dimethyl-N-{1-[6-(5-{2-[4-(trifluoromethyl)phenyl]ethyl}-1,2,4-oxadiazol-3-yl)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

(125) 1-[6-(5-{2-[4-(trifluoromethyl)phenyl]ethyl}-1,2,4-oxadiazol-3-yl)quinolin-2-yl]pyrrolidin-3-amine,

(126) N-{1-[6-(5-{2-[4-(trifluoromethyl)phenyl]ethyl}-1,2,4-oxadiazol-3-yl)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

(127) 2-methyl-N-{1-[6-(5-{2-[4-(trifluoromethyl)phenyl]ethyl}-1,2,4-oxadiazol-3-yl)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

(128) N-{1-[6-(3-{2-[4-(trifluoromethyl)phenyl]ethyl}-1,2,4-oxadiazol-5-yl)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

and pharmaceutically accepted salts thereof.

10. The compound according to claim 9, selected from:

(1) (2E)-3-(4-chlorophenyl)-N-[2-(dimethylamino)quinolin-6-yl]prop-2-enamide,

(2) (2E)-N-[2-(dimethylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(3) (2E)-N-[2-(ethylamino)quinolin-6-yl]-3-[4-(trifluoromethlyl)phenyl]prop-2-enamide,

(4) (2E)-N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-(4-chlorophenyl)prop-2-enamide,

(5) (2E)-N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(6) (2E)-N-[2-(dimethylamino)-4-methylquinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(7) N-[2-(dimethylamino)4-methylquinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(8) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-[4-(methylthio)phenyl]urea,

(9) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-[6-(trifluoromethyl)pyridin-3-yl]propanamide,

(10) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-[4-(trifluoromethoxy)phenyl]urea,

(11) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-(4-isopropylphenyl)urea,

(12) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-(4-ethylphenyl)propanamide,

(13) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-[4-(trifluoromethyl)phenyl]urea,

(14) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-(4-methoxyphenyl)urea,

(15) (2E)-N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-(4-methoxyphenyl)prop-2-enamide,

(16) N-[2-(dimethylamino)quinolin-6-yl]-N′

-[4-(methylthio)phenyl]urea,

(17) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-(4-ethylphenyl)urea,

(18) N-(2-pyrrolidin-1-ylquinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]propanamide,

(19) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(20) N-(2-azetidin-1-ylquinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]propanamide,

(21) N-[2-(isobutylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(22) (2E)-N-[2-(2-azabicyclo[2.2.1]hept-2-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(23) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-(2,3-dihydro-1H-inden-5-yl)urea,

(24) N-[2-(sec-butylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(25) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-(4-propylphenyl)urea,

(26) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)-3-methylquinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(27) N-[2-(cyclopentylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(28) N-(2-{[(1R)-1-methylpropyl]amino}quinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]propanamide,

(29) (2E)-N-[2-(2-azabicyclo[2.2.1]hept-2-yl)-3-methylquinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(30) N-{2-[isopropyl(methyl)amino]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(31) N-[2-(3-methylpyrrolidin-1-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(32) N-[2-(2-methylpyrrolidin-1-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(33) N-(2-azetidin-1-yl-3-methylquinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]propanamide,

(34) N-[2-(isopropylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(35) N-{2-[isopropyl(methyl)amino]quinolin-6-yl }-3-[6-(trifluoromethyl)pyridin-3-yl]propanamide,

(36) N-(2-azetidin-1-yl-3-methylquinolin-6-yl)-N′

-[4-(trifluoromethyl)phenyl]urea,

(37) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)-3-methylquinolin-6-yl]-N′

-[4-(trifluoromethmethyl)phenyl]urea,

(38) N-(3-methyl-2-pyrrolidin-1-ylquinolin-6-yl)-N′

-[4-(trifluoromethyl)phenyl]urea,

(39) N-{2-[cyclopentyl(methyl)amino]quinolin-6-yl )-3-[4-(trifluoromethyl)phenyl]propanamide,

(40) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)-3-methylquinolin-6-yl]-N′

-[4-(trifluoromethoxy)phenyl]urea,

(41) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-{4-[(trifluoromethyl)thio]phenyl}urea,

(42) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)-3-methylquinolin-6-yl]-3-[6-(trifluoromethylpyridin-3-yl]propanamide,

(43) N-{2-[(1R,4S)-2-azabicyclo[2.2.1]hept-2-yl]quinolin-6-yl}-3-[6-(trifluoromethyl)pyridin-3-yl]propanamide,

(44) N-{2-[(1S,4R)-2-azabicyclo[2.2.1]hept-2-yl]quinolin-6-yl}-3-[6-trifluoromethyl)pyridin-3-yl]propanamide,

(45) (2E)-N-{2-[isopropyl(methyl)amino]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(46) (2E)-3-(4-chlorophenyl)-N-{2-[isopropyl(methyl)amino]quinolin-6-yl}prop-2-enamide

(47) N-[2-(pyrrolidin-3-ylamino)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(48) N-{2-[3-(acetylamino)pyrrolidin-1-yl]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(49) N-[2-(3-{[(methylamino)carbonyl]amino}pyrrolidin-1-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(50) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)quinolin-6-yl]-N′

-(4-ethylphenyl)urea,

(51) (2E)-N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-[4-(methylthio)phenyl]prop-2-enamide,

(52) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)quinolin-6-yl]-N′

-{4-[(trifluoromethyl)thio]phenyl}urea,

(53) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)quinolin-6-yl]-N′

-[4-(methylthio)phenyl]urea,

(54) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)quinolin-6-yl]-N′

-[4-(trifluoromethoxy)phenyl]urea,

(55) N-{2-[methyl(tetrahydrofuran-3-yl)amino]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(56) N-(2-{3-[(methylsulfonyl)amino]pyrrolidin-1-yl}quinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]propanamide,

(57) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)quinolin-6-yl]-3-(1,3-benzothiazol-2-yl)propanamide,

(58) N-{2-[3-(propionylamino)pyrrolidin-1-yl]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(59) N-[2-(3-{[(dimethylamino)carbonyl]amino}pyrrolidin-1-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(60) 2-methyl-N-{1-[6-({3-[4-(trifluoromethyl)phenyl]propanoyl}amino)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

(61) N-{2-[3-(dimethylamino)pyrrolidin-1-yl]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(62) N-{1-[6-({3-[4-(trifluoromethyl)phenyl]propanoyl}amino)quinolin-2-yl]pyrrolidin-3-yl}cyclohexanecarboxamide,

(63) 2,2-dimethyl-N-{1-[6-({3-[4-(trifluoromethyl)phenyl]propanoyl}amino)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

(64) (2E)-N-[2-(3-aminopyrrolidin-1-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(65) N-{2-[isopropyl(methyl)amino]quinolin-6-yl}-N′

-[4-(methylthio)phenyl]urea,

(66) N-{2-[isopropyl(methyl)amino]quinolin-6-yl}-N′

-[4-(trifluoromethyl)phenyl]urea,

(67) N-{1-[6-({[(4-ethylphenyl)amino]carbonyl}amino)quinolin-2-yl]pyrrolidin-3-}-2,2-dimethylpropanamide,

(68) N-{2-[3-(dimethylamino)pyrrolidin-1-yl]quinolin-6-yl}-N′

-(4-ethylphenyl)urea,

(69) N-{2-[(3S)-3-aminopyrrolidin-1-yl]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(70) N-{2-[3-(methylamino)pyrrolidin-1-yl]quinolin-6-yl}-3-[4-(trifluoromethylphenyl]propanamide,

(71) 2,2-dimethyl-N-{(3S)-1-[6-({3-[4-(trifluoromethyl)phenyl]propanoyl}amino)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

(72) 2,2-dimethyl-N-{(3R)-1-[6-(3-[4-(trifluoromethyl)phenyl]propanoyl}amino)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

(73) N,2,2-trimethyl-N-{1-[6-({3-[4-(trifluoromethyl)phenyl]propanoyl}amino)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

(74) N-{2-[(3S)-3-(propionylamino)pyrrolidin-1-yl]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(75) (2E)-N-(2-{3-[(methylsulfonyl)amino]pyrrolidin-1-yl}quinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(76) (2E)-N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-[4-(ethylthio)phenyl]prop-2-enamide,

(77) tert-butyl 1-(6-{[(2E)-3-(4-chlorophenyl)prop-2-enoyl]amino}quinolin-2-yl)pyrrolidin-3-ylcarbamate,

(78) (2E)-N-[2-(3-aminopyrrolidin-1-yl)quinolin-6-yl]-3-(4-chlorophenyl)prop-2-enamide,

(79) N-{1-[6-({[(4-ethylphenyl)amino]carbonyl}amino)quinolin-2-yl]pyrrolidin-3-yl}methanesulfonamide,

(80) N-{2-[3-(dimethylamino)pyrrolidin-1-yl]quinolin-6-yl}-N′

-[4-(trifluoromethyl)phenyl]urea,

(81) N-{2-[3-(dimethylamino)pyrrolidin-1-yl]quinolin-6-yl}-N′

-[4-(trifluoromethoxy)phenyl]urea,

(82) N-{2-[(3R)-3-(propionylamino)pyrrolidin-1-yl]quinolin-6-yl}-3-[4-(trifluoromethyl)phenyl]propanamide,

(83) N-[2-(7-methyl-2,7-diazaspiro[4.4]non-2-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(84) N′

-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N²-(4-ethylphenyl)ethane-1,2-diamine,

(85) N-[2-(7-benzyl-2,7-diazaspiro[4.4]non-2-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(86) N-[2-(2-azabicyclo[2.2.1]hept-2-yl)4-(dimethylamino)quinolin-6-yl]-4′

-trifluoromethyl)-1,1′

-biphenyl-4-carboxamide,

(87) N-[2-(2,7-diazaspiro[4.4]non-2-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide,

(88) N-{2-[isopropyl(methyl)amino]quinolin-6-yl}-N′

-[4-(trifluoromethoxy)phenyl]urea,

(89) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-[6-(trifluoromethyl)pyridin-3-yl]urea,

(90) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-N′

-(6-ethylpyridin-3-yl)urea,

(91) N-[2-(2-azabicyclo[2.2.2]oct-2-yl)quinolin-6-yl]-3-[4-(methylsulfonyl)phenyl]propanamide,

(92) 2,2-dimethyl-N-{1-[6-(5-{2-[4-(trifluoromethyl)phenyl]ethyl}-1,2,4-oxadiazol-3-yl)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

(93) 1-[6-(5-{2-[4-(trifluoromethyl)phenyl]ethyl}-1,2,4-oxadiazol-3-yl)quinolin-2-yl]pyrrolidin-3-amine,

(94) N-{1-[6-(5-{2-[4-(trifluoromethyl)phenyl]ethyl}-1,2,4-oxadiazol-3-yl)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

(95) 2-methyl-N-{1-[6-(5-{2-[4-(trifluoromethyl)phenyl]ethyl}-1,2,4-oxadiazol-3-yl)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

(96) N-{1-[6-(3-{2-[4-(trifluoromethyl)phenyl]ethyl}-1,2,4-oxadiazol-5-yl)quinolin-2-yl]pyrrolidin-3-yl}propanamide,

and pharmaceutically acceptable salts thereof.

11. A method of treating or suppressing a disease mediated by the MCH receptor by reducing food intake in a subject in need thereof comprising administration of a therapeutically effective amount of a compound according to claim 1.

12. The method according to claim 11 wherein the disease is mediated by the MCH₁R receptor.

13. A method of treating obesity in a subject in need thereof comprising administration of a therapeutically effective amount of a compound according to claim 1.

14. The method according to claim 13, additionally comprising administration of a therapeutically effective amount of an anorectic agent or a selective serotonin reuptake inhibitor.

15. The method according to claim 14 wherein the anorectic agent is selected from:

aminorex, amphechloral, amphetamine, benzphetamine, chlorphentermine, clobenzorex, cloforex, clominorex, clortermine, cyclexedrine, dexfenfluramine, dextroamphetamine, diethylpropion, diphemethoxidine, N-ethylamphetamine, fenbutrazate, fenfluramine, fenisorex, fenproporex, fludorex, fluminorex, furfurylmethylamphetamine, levamfetamine, levophacetoperane, mazindol, mefenorex, metamfepramone, methamphetamine, norpseudoephedrine, pentorex, phendimetrazine, phenmetrazine, phentermine, phenylpropanolamine, picilorex and sibutramine; and

the selective serotonin reuptake inhibitor is selected from;

fluoxetine, fluvoxamine, paroxetine and sertraline.

16. A method of preventing obesity in a person at risk for obesity comprising administration to said person of about 0.01 mg to about 100 mg per kg of a compound according to claim 1.

17. A composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.

18. A method of treating depression in a subject in need thereof comprising administering an effective amount of an MCH-1R receptor antagonist compound according to claim 1 to the subject.