US 2010/0137360 A1Published application

Trpv1 antagonists

AssigneeAbbott Laboratories

InventorsArthur R. Gomtsyan, Eric A. Voight, Erol K. Bayburt, Jun Chen, Jerome F. Daanen, Stanley DiDomenico, Michael E. Kort, Philip R. Kym, Heath A. McDonald, Richard J. Perner, Robert G. Schmidt

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Abstract

Disclosed herein are compounds of formula (I) or pharmaceutically acceptable salts, solvates, prodrugs, salts of prodrugs, or combinations thereof, wherein R1, R2, R3, R4, and m are defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

Claims34

Dependent claims

A compound having formula (I)

or a pharmaceutically acceptable salt, solvate, prodrug, salt of a prodrug, or a combination thereof, wherein
R1 represents a group of formula (a), (b), (c), or (d)
Rx, at each occurrence, represents optional substituent(s) on any substitutable position of the bicyclic ring selected from the group consisting of alkyl, halogen, haloalkyl, OH, O(alkyl), O(haloalkyl), NH2, N(H)(alkyl), and N(alkyl)2;
Ra is hydrogen or methyl;
R2 and R3 are the same or different, and are each independently hydrogen, C1-C5 alkyl, or haloalkyl;
or
R2 and R3, together with the carbon atom to which they are attached, form a C3-C6 monocyclic cycloalkyl ring, optionally substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and halogen;
R4, at each occurrence, represents optional substituent(s) on any substitutable position of the bicyclic ring selected from the group consisting of alkyl, halogen, haloalkyl, O(alkyl), O(haloalkyl), and SCF3;
and
m and n are each independently 0, 1, 2, or 3;
with the proviso that the compound is other than
N-(7-tert-butyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-1H-indazol-4-yl-N′-[7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;
N-isoquinolin-5-yl-N′-[7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;
N-1H-indazol-4-yl-N′-(6-methyl-3,4-dihydro-2H-chromen-4-yl)urea;
N-isoquinolin-5-yl-N′-(6-methyl-3,4-dihydro-2H-chromen-4-yl)urea;
N-(6-fluoro-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(6-fluoro-3,4-dihydro-2H-chromen-4-yl)-N′-isoquinolin-5-ylurea;
N-(6-chloro-7-methyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(6-chloro-7-methyl-3,4-dihydro-2H-chromen-4-yl)-N′-isoquinolin-5-ylurea;
N-3,4-dihydro-2H-chromen-4-yl-N′-1H-indazol-4-ylurea;
N-(7-tert-butyl-3,4-dihydro-2H-chromen-4-yl)-N′-(3-methylisoquinolin-5-yl)urea;
N-(6-fluoro-3,4-dihydro-2H-chromen-4-yl)-N′-(3-methylisoquinolin-5-yl)urea;
N-(6-methyl-3,4-dihydro-2H-chromen-4-yl)-N′-(3-methylisoquinolin-5-yl)urea;
N-isoquinolin-5-yl-N′-(8-piperidin-1-yl-3,4-dihydro-2H-chromen-4-yl)urea;
N-3,4-dihydro-2H-chromen-4-yl-N′-isoquinolin-5-ylurea;
(+)-N-isoquinolin-5-yl-N′-[7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;
(−)-N-isoquinolin-5-yl-N′-[7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;
N-1H-indazol-4-yl-N′-[8-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;
(−)-N-1H-indazol-4-yl-N′-[7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;
(+)-N-1H-indazol-4-yl-N′-[7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;
N-1H-indazol-4-yl-N′-(8-piperidin-1-yl-3,4-dihydro-2H-chromen-4-yl)urea;
N-(8-tert-butyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-[8-chloro-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-N′-1H-indazol-4-ylurea;
(+)-N-(8-tert-butyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
(−)-N-(8-tert-butyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-1H-indazol-4-yl-N′-[8-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]urea;
N-[8-fluoro-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-N′-1H-indazol-4-ylurea;
N-1H-indazol-4-yl-N′-[7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]urea;
N-(6-fluoro-2-methyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-1H-indazol-4-yl-N′-(7-methoxy-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl)urea;
N-1H-indazol-4-yl-N′-(7-methoxy-2,2,8-trimethyl-3,4-dihydro-2H-chromen-4-yl)urea;
N-1H-indazol-4-yl-N′-(2,2,8-trimethyl-3,4-dihydro-2H-chromen-4-yl)urea;
N-1H-indazol-4-yl-N′-(7-methoxy-2,2-dimethyl-8-propyl-3,4-dihydro-2H-chromen-4-yl)urea;
N-(2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(7-fluoro-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(7,8-difluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(7-(3,3-dimethylbutyl)-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(7-tert-butyl-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(2,2-diethyl-7-fluoro-3,4-dihydro-2H-chromen-4-yl)-N′-(1-methyl-1H-indazol-4-yl)urea;
N-(7,8-difluoro-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(7-fluoro-2,2-dipropyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(2,2-dibutyl-7-fluoro-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(2-tert-butyl-7-fluoro-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(2-tert-butyl-7-fluoro-3,4-dihydro-2H-chromen-4-yl)-N′-(1-methyl-1H-indazol-4-yl)urea;
N-(8-tert-Butyl-3,4-dihydro-2H-chromen-4-yl)-N′-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)urea;
N-(7-Hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)-N′-(6-methyl-3,4-dihydro-2H-chromen-4-yl)urea;
N-[(4R)-3,4-Dihydro-2H-chromen-4-yl]-N′-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)urea;
N-[(4S)-3,4-Dihydro-2H-chromen-4-yl]-N′-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)urea;
1-(1H-indazol-4-yl)-3-(spiro[chroman-2,1′-cyclohexane]-4-yl)urea;
1-(7-fluorospiro[chroman-2,1′-cyclohexane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(7-fluorospiro[chroman-2,1′-cyclobutane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(7-fluorospiro[chroman-2,1′-cyclobutane]-4-yl)-3-(1-methyl-1H-indazol-4-yl)urea;
1-(6,7-dimethylspiro[chroman-2,1′-cyclohexane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(6,8-dichlorospiro[chroman-2,1′-cyclohexane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(6-chlorospiro[chroman-2,1′-cyclohexane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(7-tent-butylspiro[chroman-2,1′-cyclobutane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(6,8-difluorospiro[chroman-2,1′-cyclohexane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(6-ethoxyspiro[chroman-2,1′-cyclohexane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(1H-indazol-4-yl)-3-(6-methylspiro[chroman-2,1′-cyclopentane]-4-yl)urea;
1-(7-ethoxyspiro[chroman-2,1′-cyclopentane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(6,7-dimethylspiro[chroman-2,1′-cyclopentane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(7-fluorospiro[chroman-2,1′-cyclohexane]-4-yl)-3-(1-methyl-1H-indazol-4-yl)urea;
1-(1-methyl-1H-indazol-4-yl)-3-(spiro[chroman-2,1′-cyclohexane]4-yl)urea;
1-(1H-indazol-4-yl)-3-(7-methoxyspiro[chroman-2,1′-cyclohexane]-4-yl)urea;
(±)1-(3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(7-chloro-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6-bromo-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6-methoxy-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(7-methoxy-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6-methyl-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(7-methoxy-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(1-methylisoquinolin-5-yl)urea;
(±)1-(6-bromo-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(1-methylisoquinolin-5-yl)urea;
(±)1-(6-methyl-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(1-methylisoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(1-methylisoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(+)1-(3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(−)1-(3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(8-chloroisoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(3-methylisoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(1-methylisoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-6-methyl-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-7-methyl-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-6-fluoro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(+)1-(3,4-dihydro-6-fluoro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(−)1-(3,4-dihydro-6-fluoro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-7-methoxy-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
1-(6,8-difluoro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(8-chloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-6-methoxy-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(7-difluoromethoxy-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea hydrochloride;
(±)1-(7-difluoromethoxy-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(3-methylisoquinolin-5-yl)urea;
(±)1-(7-chloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(3-methylisoquinolin-5-yl)urea;
(+)1-(6,8-difluoro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(−)1-(6,8-difluoro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-8-difluoromethoxy-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6-chloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(−)1-(6-chloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6-bromo-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6,8-dichloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6-bromo-3,4-dihydro-7-methylspiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6,7-dichloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6-chloro-3,4-dihydro-7-methylspiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6-chloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(8-chloroisoquinolin-5-yl)urea;
(±)1-(6-fluoro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(8-chloroisoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-6-fluoro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(3-methylisoquinolin-5-yl)urea;
(±)1-(6-chloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(3-methylisoquinolin-5-yl)urea;
(±)1-(6-chloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(1-methylisoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-6-fluoro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(1-methylisoquinolin-5-yl)urea;
(±)1-(7-chloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(1H-indazol-4-yl)urea;
(−)-1-(3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(1H-indazol-4-yl)urea;
(+)-1-(3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(1H-indazol-4-yl)urea;
(±)1-(6-fluoro-3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(1H-indazol-4-yl)urea;
(±)1-(7-fluoro-3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(1H-indazol-4-yl)urea;
(±)1-(6,8-difluoro-3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(1H-indazol-4-yl)urea;
(+)-1-(6,8-difluoro-3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(1H-indazol-4-yl)urea;
(±)1-(1H-indazol-4-yl)-3-(7-methyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl)urea;
(±)1-(1H-indazol-4-yl)-3-(7-methoxy-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl)urea;
(±)1-(1H-indazol-4-yl)-3-(7-chloro-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl)urea;
(±)1-(3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(6-bromo-1H-indazol-4-yl)urea;
(±)1-(3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(6-fluoro-1H-indazol-4-yl)urea;
(+)-1-(3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(6-fluoro-1H-indazol-4-yl)urea;
(±)1-(3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(6-methoxy-1H-indazol-4-yl)urea;
or
(−)-1-(6,8-difluoro-3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(1H-indazol-4-yl)urea.

134 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/579,821Filed 15 Oct 2009
Priority: 17 Oct 2008
Published: 3 Jun 2010
Term ends: Not estimatedThe source records don’t support an estimate.

Classification25 codes

C07D 311/74
Ortho- or peri-condensed with carbocyclic rings or ring systems: benzo[b]pyrans, hydrogenated in the carbocyclic ring
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 1/08
Drugs for disorders of the alimentary tract or the digestive system: for nausea, cinetosis or vertigo; Antiemetics

Family

Application61/106,369Us provisional application · filed 17 Oct 2008
Application61/220,075Us provisional application · filed 24 Jun 2009
US 8,604,053 B2Related patent
US 2010/0137360 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound having formula (I)

or a pharmaceutically acceptable salt, solvate, prodrug, salt of a prodrug, or a combination thereof, wherein
R1 represents a group of formula (a), (b), (c), or (d)
Rx, at each occurrence, represents optional substituent(s) on any substitutable position of the bicyclic ring selected from the group consisting of alkyl, halogen, haloalkyl, OH, O(alkyl), O(haloalkyl), NH2, N(H)(alkyl), and N(alkyl)2;
Ra is hydrogen or methyl;
R2 and R3 are the same or different, and are each independently hydrogen, C1-C5 alkyl, or haloalkyl;
or
R2 and R3, together with the carbon atom to which they are attached, form a C3-C6 monocyclic cycloalkyl ring, optionally substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl and halogen;
R4, at each occurrence, represents optional substituent(s) on any substitutable position of the bicyclic ring selected from the group consisting of alkyl, halogen, haloalkyl, O(alkyl), O(haloalkyl), and SCF3;
and
m and n are each independently 0, 1, 2, or 3;
with the proviso that the compound is other than
N-(7-tert-butyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-1H-indazol-4-yl-N′-[7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;
N-isoquinolin-5-yl-N′-[7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;
N-1H-indazol-4-yl-N′-(6-methyl-3,4-dihydro-2H-chromen-4-yl)urea;
N-isoquinolin-5-yl-N′-(6-methyl-3,4-dihydro-2H-chromen-4-yl)urea;
N-(6-fluoro-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(6-fluoro-3,4-dihydro-2H-chromen-4-yl)-N′-isoquinolin-5-ylurea;
N-(6-chloro-7-methyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(6-chloro-7-methyl-3,4-dihydro-2H-chromen-4-yl)-N′-isoquinolin-5-ylurea;
N-3,4-dihydro-2H-chromen-4-yl-N′-1H-indazol-4-ylurea;
N-(7-tert-butyl-3,4-dihydro-2H-chromen-4-yl)-N′-(3-methylisoquinolin-5-yl)urea;
N-(6-fluoro-3,4-dihydro-2H-chromen-4-yl)-N′-(3-methylisoquinolin-5-yl)urea;
N-(6-methyl-3,4-dihydro-2H-chromen-4-yl)-N′-(3-methylisoquinolin-5-yl)urea;
N-isoquinolin-5-yl-N′-(8-piperidin-1-yl-3,4-dihydro-2H-chromen-4-yl)urea;
N-3,4-dihydro-2H-chromen-4-yl-N′-isoquinolin-5-ylurea;
(+)-N-isoquinolin-5-yl-N′-[7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;
(−)-N-isoquinolin-5-yl-N′-[7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;
N-1H-indazol-4-yl-N′-[8-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;
(−)-N-1H-indazol-4-yl-N′-[7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;
(+)-N-1H-indazol-4-yl-N′-[7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;
N-1H-indazol-4-yl-N′-(8-piperidin-1-yl-3,4-dihydro-2H-chromen-4-yl)urea;
N-(8-tert-butyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-[8-chloro-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-N′-1H-indazol-4-ylurea;
(+)-N-(8-tert-butyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
(−)-N-(8-tert-butyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-1H-indazol-4-yl-N′-[8-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]urea;
N-[8-fluoro-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-N′-1H-indazol-4-ylurea;
N-1H-indazol-4-yl-N′-[7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]urea;
N-(6-fluoro-2-methyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-1H-indazol-4-yl-N′-(7-methoxy-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl)urea;
N-1H-indazol-4-yl-N′-(7-methoxy-2,2,8-trimethyl-3,4-dihydro-2H-chromen-4-yl)urea;
N-1H-indazol-4-yl-N′-(2,2,8-trimethyl-3,4-dihydro-2H-chromen-4-yl)urea;
N-1H-indazol-4-yl-N′-(7-methoxy-2,2-dimethyl-8-propyl-3,4-dihydro-2H-chromen-4-yl)urea;
N-(2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(7-fluoro-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(7,8-difluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(7-(3,3-dimethylbutyl)-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(7-tert-butyl-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(2,2-diethyl-7-fluoro-3,4-dihydro-2H-chromen-4-yl)-N′-(1-methyl-1H-indazol-4-yl)urea;
N-(7,8-difluoro-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(7-fluoro-2,2-dipropyl-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(2,2-dibutyl-7-fluoro-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(2-tert-butyl-7-fluoro-3,4-dihydro-2H-chromen-4-yl)-N′-1H-indazol-4-ylurea;
N-(2-tert-butyl-7-fluoro-3,4-dihydro-2H-chromen-4-yl)-N′-(1-methyl-1H-indazol-4-yl)urea;
N-(8-tert-Butyl-3,4-dihydro-2H-chromen-4-yl)-N′-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)urea;
N-(7-Hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)-N′-(6-methyl-3,4-dihydro-2H-chromen-4-yl)urea;
N-[(4R)-3,4-Dihydro-2H-chromen-4-yl]-N′-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)urea;
N-[(4S)-3,4-Dihydro-2H-chromen-4-yl]-N′-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)urea;
1-(1H-indazol-4-yl)-3-(spiro[chroman-2,1′-cyclohexane]-4-yl)urea;
1-(7-fluorospiro[chroman-2,1′-cyclohexane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(7-fluorospiro[chroman-2,1′-cyclobutane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(7-fluorospiro[chroman-2,1′-cyclobutane]-4-yl)-3-(1-methyl-1H-indazol-4-yl)urea;
1-(6,7-dimethylspiro[chroman-2,1′-cyclohexane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(6,8-dichlorospiro[chroman-2,1′-cyclohexane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(6-chlorospiro[chroman-2,1′-cyclohexane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(7-tent-butylspiro[chroman-2,1′-cyclobutane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(6,8-difluorospiro[chroman-2,1′-cyclohexane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(6-ethoxyspiro[chroman-2,1′-cyclohexane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(1H-indazol-4-yl)-3-(6-methylspiro[chroman-2,1′-cyclopentane]-4-yl)urea;
1-(7-ethoxyspiro[chroman-2,1′-cyclopentane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(6,7-dimethylspiro[chroman-2,1′-cyclopentane]-4-yl)-3-(1H-indazol-4-yl)urea;
1-(7-fluorospiro[chroman-2,1′-cyclohexane]-4-yl)-3-(1-methyl-1H-indazol-4-yl)urea;
1-(1-methyl-1H-indazol-4-yl)-3-(spiro[chroman-2,1′-cyclohexane]4-yl)urea;
1-(1H-indazol-4-yl)-3-(7-methoxyspiro[chroman-2,1′-cyclohexane]-4-yl)urea;
(±)1-(3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(7-chloro-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6-bromo-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6-methoxy-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(7-methoxy-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6-methyl-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(7-methoxy-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(1-methylisoquinolin-5-yl)urea;
(±)1-(6-bromo-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(1-methylisoquinolin-5-yl)urea;
(±)1-(6-methyl-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(1-methylisoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-(1-methylisoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(+)1-(3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(−)1-(3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(8-chloroisoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(3-methylisoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(1-methylisoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-6-methyl-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-7-methyl-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-6-fluoro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(+)1-(3,4-dihydro-6-fluoro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(−)1-(3,4-dihydro-6-fluoro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-7-methoxy-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
1-(6,8-difluoro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(8-chloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-6-methoxy-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(7-difluoromethoxy-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea hydrochloride;
(±)1-(7-difluoromethoxy-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(3-methylisoquinolin-5-yl)urea;
(±)1-(7-chloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(3-methylisoquinolin-5-yl)urea;
(+)1-(6,8-difluoro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(−)1-(6,8-difluoro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-8-difluoromethoxy-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6-chloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(−)1-(6-chloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6-bromo-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6,8-dichloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6-bromo-3,4-dihydro-7-methylspiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6,7-dichloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6-chloro-3,4-dihydro-7-methylspiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(6-chloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(8-chloroisoquinolin-5-yl)urea;
(±)1-(6-fluoro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(8-chloroisoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-6-fluoro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(3-methylisoquinolin-5-yl)urea;
(±)1-(6-chloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(3-methylisoquinolin-5-yl)urea;
(±)1-(6-chloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(1-methylisoquinolin-5-yl)urea;
(±)1-(3,4-dihydro-6-fluoro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(1-methylisoquinolin-5-yl)urea;
(±)1-(7-chloro-3,4-dihydro-spiro-[2H-1-benzopyran-2,1′-cyclobutan]-4-yl)-3-(isoquinolin-5-yl)urea;
(±)1-(3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(1H-indazol-4-yl)urea;
(−)-1-(3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(1H-indazol-4-yl)urea;
(+)-1-(3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(1H-indazol-4-yl)urea;
(±)1-(6-fluoro-3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(1H-indazol-4-yl)urea;
(±)1-(7-fluoro-3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(1H-indazol-4-yl)urea;
(±)1-(6,8-difluoro-3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(1H-indazol-4-yl)urea;
(+)-1-(6,8-difluoro-3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(1H-indazol-4-yl)urea;
(±)1-(1H-indazol-4-yl)-3-(7-methyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl)urea;
(±)1-(1H-indazol-4-yl)-3-(7-methoxy-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl)urea;
(±)1-(1H-indazol-4-yl)-3-(7-chloro-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl)urea;
(±)1-(3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(6-bromo-1H-indazol-4-yl)urea;
(±)1-(3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(6-fluoro-1H-indazol-4-yl)urea;
(+)-1-(3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(6-fluoro-1H-indazol-4-yl)urea;
(±)1-(3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(6-methoxy-1H-indazol-4-yl)urea;
or
(−)-1-(6,8-difluoro-3,4-dihyrospiro[chromene-2,1′-cyclobutan]-4-yl)-3-(1H-indazol-4-yl)urea.

134 more elements

Facts

Application

12/579,821Filed 15 Oct 2009

Priority

17 Oct 2008

Published

3 Jun 2010

Term ends

Not estimatedThe source records don’t support an estimate.

Classification25 codes

C07D 311/74
Ortho- or peri-condensed with carbocyclic rings or ring systems: benzo[b]pyrans, hydrogenated in the carbocyclic ring
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 1/08
Drugs for disorders of the alimentary tract or the digestive system: for nausea, cinetosis or vertigo; Antiemetics