US 9,006,228 B2Granted

Substituted cyclopropyl compounds, compositions containing such compounds, and methods of treatment

AssigneeMerck Sharp & Dohme Corp.

InventorsMichael Miller, Andrew Stamford, Kallol Basu, Harold B. Wood, Duane DeMong, Wanying Sun, Joie Garfunkle, Christopher Moyes, Zhiyong Hu, Ping Liu, Scott D. Edmondson, Xing Dai, Byron Gabriel DuBois

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Abstract

Substituted cyclopropyl compounds of the formula I: and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR-119. Pharmaceutical compositions and methods of treatment are also included.

Claims19

Dependent claims

A compound represented by the formula:

or a pharmaceutically acceptable salt thereof, wherein:
ring A represents a 5- or 6-membered aryl or heteroaryl ring, the heteroaryl ring containing 1-4 heteroatoms, 1-4 of which are nitrogen atoms, and 0-1 of which are oxygen or sulfur atoms;
m is an integer selected from 1-3;
Ra is selected from:
H;
C1-4alkyl;
hydroxyC1-4alkyl;
or C1-4alkoxyC1-4alkyl;
R1 is selected from:
C1-6alkyl;
OC1-6alkyl;
C(O)C1-6alkyl;
C(O)C3-6cycloalkyl;
C(O)NHC1-6alkyl;
S(O)0-2C1-6alkyl;
SO2C3-6cycloalkyl;
SO2NRbRc, wherein Rb and Rc are independently selected from H or C1-6alkyl;
—CH2CONRdRe wherein Rd and Re are independently selected from the group consisting of H, C1-6alkyl, C3-6cycloalkyl, haloC1-6alkyl, haloC3-6cycloalkyl, C1-6alkoxy, and C3-6cycloalkylC1-6alkoxy;
wherein Rd and Re, if individually alkyl or alkoxy, can together form a 4-6-membered saturated heterocyclic ring having 1 nitrogen atom which 4-6-membered ring may be optionally substituted with 1-3 substituents independently selected from halogen, hydroxy, oxo, C1-6alkoxy;
or CO2C1-6alkyl;
—CH2-heteroaryl, wherein the heteroaryl is a 5-6 membered heteroaryl ring containing 1-4 heteroatoms independently selected from nitrogen or oxygen;
—CH2CH3CONRdRe, with Rd and Re defined above;
or a 5-6 membered heteroaryl ring containing 1-4 heteroatoms, 1-4 of which are nitrogen atoms, and 0-1 of which are oxygen or sulfur atoms,
wherein the R1 alkyl, cycloalkyl and heteroaryl moiety is optionally substituted with 1-3 of halogen;
hydroxy;
C1-6alkyl;
NH2;
and O—C1-6alkyl;
each R2 is independently selected from halogen, CN, C1-6alkyl or haloC1-6alkyl;
B represents (a) a 6 membered aryl ring or a 5-6 membered heteroaryl ring containing 1-4 heteroatoms, 1-4 of which are nitrogen atoms, and 0-1 of which are oxygen or sulfur atoms, said ring being optionally substituted with 1-3 groups selected from R3, wherein
each R3 is independently selected from
halogen;
hydroxyl;
C1-6alkyl;
C(O)OC1-6alkyl;
C═O;
CN;
C1-6alkoxy;
C3-6cycloalkyl;
C(═O)—(O)n—R′, wherein n is an integer from 0-3 and R′ is C1-6alkyl or H;
5-6 membered heteroaryl ring containing 1-4 heteroatoms independently selected from nitrogen or oxygen;
C(═O)—Rf, wherein Rf is 5-6 membered heteroaryl ring containing 1-4 heteroatoms independently selected from nitrogen or oxygen;
or haloC1-6alkoxy;
wherein the R3 alkyl moiety is optionally substituted with 1-3 substituents independently selected from:
halogen,
hydroxy,
C1-6alkyl, or
C1-6alkoxy;
or b) CO2R4, wherein
R4 is selected from:
C1-6alkyl;
or
C3-6cycloalkyl,
wherein the alkyl and cycloalkyl are optionally substituted with 1-3 substituents independently selected from:
halogen,
C1-6alkyl, or
C3-6 cycloalkyl.

54 more elements

A compound which is:

5-chloro-2-{4-[(1R,2R)-2-({[5-(methylsulfonyl)pyridin-2-yl]methoxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-methyl-2-{4-[(1R,2R)-2-({[5-(methylsulfonyl)pyridin-2-yl]methoxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-ethyl-2-{4-[(1R,2R)-2-({[5-(methylsulfonyl)pyridin-2-yl]methoxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-bromo-2-{4-[(1R,2R)-2-({[5-(methylsulfonyl)pyridin-2-yl]methoxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-fluoro-2-{4-[(1R,2R)-2-({[5-(methylsulfonyl)pyridin-2-yl]methoxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-methoxy-2-{4-[(1R,2R)-2-({[5-(methylsulfonyl)pyridin-2-yl]methoxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
2-{4-[(1R,25)-24 {[5-(methylsulfonyl)pyridin-2-yl]methoxy}methyl)cyclopropyl]piperidin-1-yl}-5-(1H)-pyrazol-4-yl)pyrimidine;
propyl 4-[(1R,2R)-2-({[4(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine-1-carboxylate;
isopropyl 4-[(1R,2R)-2-({[4(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine-1-carboxylate;
isobutyl 4-[(1R,2R)-2-({[4(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine-1-carboxylate;
1-methylcyclopropyl 4-[(1R,2R)-2-({[4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine-1-carboxylate;
cyclobutyl 4-[(1R,2R)-2-({[4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine-1-carboxylate;
cyclopropylmethyl 4-[(1R,2R)-2-({[4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine-1-carboxylate;
5-chloro-2-{4-[(1R,2R)-2-({[4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-methoxy-2-{4-[(1R,2R)-2-({[4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-fluoro-2-{4-[(1R,2R)-2-({[4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
methyl 2-{4-[(1R,2R)-2-({[4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine-1-yl}pyrimidine-5-carboxylate;
5-cyclopropyl-2-{4-[(1R,2R)-2-({[4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-isobutyl-2-{4-[(1R,2R)-2-({[4-(methylsulfonyl)benzyl]oxy}methyl)cyclo-propyl]piperidin-1-yl}pyrimidine;
5-ethyl-2-{4-[(1R,2R)-2-({[4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-methyl-2-{4-[(1R,2R)-2-({[4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
2-{4-[(1R,2R)-2-({[4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}-5-propylpyrimidine;
5-isopropyl-2-{4-[(1R,2R)-2-({[4-(methylsulfonyl)benzyl]oxy}methyl)cyclo propyl]piperidin-1-yl}pyrimidine;
1-(3-isopropyl-1,2,4-oxadiazol-5-yl)-4-[(1R,2R)-2-({[4-(methylsulfonyl)benzyl]oxy}methyl)cyclo propyl]piperidine;
4-[(1R,2R))-2-({[4-(cyclopropylsulfonyl)benzyl]oxy}methyl)cyclopropyl]-1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidine;
4-[(1R,2R)-2-({[4-(ethylsulfonyl)benzyl]oxy}methyl)cyclopropyl]-1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidine;
1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-4-[(1R,2R)-2-({[4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine;
1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-4-[(1R,2R)-2-({[4-(cyclopropylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine;
1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-4-[(1R,2R)-2-({[4-(ethylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine;
1-(3-ethyl-1,2,4-oxadiazol-5-yl)-4-[(1R,2R)-2-({[4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine;
1-(3-cyclobutyl-1,2,4-oxadiazol-5-yl)-4-[(1R,2R)-2-({[4-(cyclopropylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine;
1-(3-cyclobutyl-1,2,4-oxadiazol-5-yl)-4-[(1R,2R)-2-({[4-(ethylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine;
tert-butyl 4-[(1R,2R)-2-({[3-fluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine-1-carboxylate;
tert-butyl 4-[(1R,2R)-2-({[4-(ethylsulfonyl)-3-fluorobenzyl]oxy}methyl)cyclopropyl]piperidine-1-carboxylate;
4-[(1R,2R)-2-({[3-fluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]-1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidine;
1-(3-ethyl-1,2,4-oxadiazol-5-yl)-4-[(1R,2R)-2-({[3-fluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine;
1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-4-[(1R,2R)-2-({[3-fluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine;
4-[(1R,2R)-2-({[3-fluoro-4-(ethylsulfonyl)benzyl]oxy}methyl)cyclopropyl]-1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidine;
1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-4-[(1R,2R)-2-({[3-fluoro-4-(ethylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine;
5-ethyl-2-{4-[(1R,2R)-2-({[3-fluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-chloro-2-{4-[(1R,2R)-2-({[3-fluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
isopropyl 4-[(1R,2R)-2-({[3-fluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine-1-carboxylate;
1-methylcyclopropyl 4-[(1R,2R)-2-({[3-fluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine-1-carboxylate;
tert-butyl 4-[(1R,2R)-2-({[3,5-difluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine-1-carboxylate;
5-chloro-2-{4-[(1R,2R)-2-({[3,5-difluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-chloro-2-{4-[(1R,2R)-2-({[3,5-difluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
2-{4-[(1R,2R)-2-({[3,5-difluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}-5-fluoropyrimidine;
5-cyclopropyl-2-{4-[(1R,2R)-2-({[3,5-difluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
1-methylcyclopropyl 4-[(1R,2R)-2-({[3,5-difluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine-1-carboxylate;
isopropyl 4-[(1R,2R)-2-({[3,5-difluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidine-1-carboxylate;
4-[(1R,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-2-fluoro phenyl}(cyclopropyl)methanone;
tert-butyl 4-[(1R,2R)-2-({[4-(cyclopropylcarbonyl)-3,5-difluorobenzyl]oxy}methyl)cyclopropyl]piperidine-1-carboxylate;
4-[(1R,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-2,6-difluoro phenyl}(cyclopropyl)methanone;
5-ethyl-2-{4-[(1R,2R)-2-({[4-(1,3-oxazol-2-yl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-ethyl-2-{4-[(1R,2R)-2-({[4-(1,3-thiazol-5-yl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
2-{4-[(1R,2R)-2-({[4-(cyclopropylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}-5-ethyl pyrimidine;
5-ethyl-2-{4-[(1R,2R)-2-({[4-(ethylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
(2R)-1-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]phenyl}propan-2-ol;
(2S)-1-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]phenyl}propan-2-ol;
2-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]phenyl}ethanol;
5-ethyl-2-{4-[(1R,2R)-2-({[4-(1H-tetrazol-1-yl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-ethyl-2-{4-[(1R,2R)-2-({[4-(1H-1,2,3-triazol-1-yl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-ethyl-2-{4-[(1R,2R)-2-({[4-(1,2,4-oxadiazol-5-yl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
(2S)-)-4-({4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]phenyl}sulfonyl)butan-2-ol;
5-ethyl-2-{4-[(1R,2R)-2-((1R)-2-methoxy-1-{[4-(methylsulfonyl)benzyl]oxy ethyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-ethyl-2-{4-[(1R,2R)-2-((1S)-2-methoxy-1-{[4-(methylsulfonyl)benzyl]oxy ethyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-ethyl-2-{4-[(1R,2R)-2-((1S)-2-methoxy-1-{[4-(ethylsulfonyl)benzyl]oxy ethyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-chloro-2-{4-[(1R,2R)-2-({[3,5-difluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-fluoro-2-{4-[(1R,2R)-2-({[3,5-difluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-bromo-2-{4-[(1R,2R)-2-({[3,5-difluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
2-{4-[(1R,2R)-2-({[2-fluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine-5-carbaldehyde;
5-cyano-2-{4-[(1R,2R)-2-({[3,5-difluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-methoxy-2-{4-[(1R,2R)-2-({[3,5-difluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
5-methyl-2-{4-[(1R,2R)-2-({[3,5-difluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
2-(2-{4-[(1R,2R)-2-({[2-fluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidin-5-yl)propan-2-ol;
2-(5-{4-[(1R,2R))-2-({[2-fluoro(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrazin-2-yl)propan-2-ol;
2-{4-[(1R,2R)-2-({[2-fluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}-5-(methoxymethyl)pyrimidine;
4-[(1R,2R)-2-({[2-fluoro-4-(methylsulfonyl)benzyl]oxy}methyl)cyclopropyl]-1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidine;
tert-butyl 4-{(1R,2R)-2-[({2-fluoro-4-[(2-hydroxyethyl)sulfonyl]benzyl}oxy)methyl]cyclopropyl}piperidine-1-carboxylate;
2-({4-[({(1R,2R))-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl-1}methoxy)methyl]-3-fluorophenyl}sulfonyl)ethanol;
2-({4-[({(1R,2R))-2-[1-(5-bromopyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluorophenyl}sulfonyl)ethanol;
2-({4-[({(1R,2R))-2-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluorophenyl}sulfonyl)ethanol;
2-({4-[({(1R,2R))-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluorophenyl}sulfonyl)ethanol;
2-({4-[({(1R,2R))-2-[1-(5-propylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluorophenyl}sulfonyl)ethanol;
2-[(3-fluoro-4-{[((1R,2R)-2-{1-[5-(3-furyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl)methoxy]methyl}phenyl)sulfonyl]ethanol;
2-({6-[({(1R,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]pyridin-3-yl}sulfonyl)ethanol;
2-({6-[({(1R,2R)-2-[1-(5-bromopyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]pyridin-3-yl}sulfonyl)ethanol;
2-({6-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]pyridin-3-yl}sulfonyl)ethanol;
2-({6-[({(1R,2R)-2-[1-(5-propylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]pyridin-3-yl}sulfonyl)ethanol;
2-({6-[({(1R,2R)-2-[1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]pyridin-3-yl}sulfonyl)ethanol;
tert-butyl 4-(1R,2R)-2-[({4-[(2-oxopropyl)thio]benzyl}oxy)methyl]cyclopropyl}piperidine-1-carboxylate;
tert-butyl 4-(1R,2R)-2-[({4-[(2-hydroxy-2-methylpropyl)thio]benzyl}oxy)methyl]cyclopropyl}piperidine-1-carboxylate;
tert-butyl 4-(1R,2R)-2-[({4-[(2R/S-hydroxypropyl)thio]benzyl}oxy)methyl]cyclo propyl}piperidine-1-carboxylate;
tert-butyl 4-(1R,2R)-2-[({4-[(2R/S-hydroxypropyl)sulfonyl]benzyl}oxy)methyl]cyclopropyl}piperidine-1-carboxylate;
1-({4-[({(1R,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluoro phenyl}sulfonyl)propan-2-ol;
1-({4-[({(1R,2R)-2-[1-(5-fluoropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluoro phenyl}sulfonyl)propan-2-ol;
1-({4-[({(1R,2R)-2-[1-(5-bromopyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluoro phenyl}sulfonyl)propan-2-ol;
1-({4-[({(1R,2R)-2-[1-(5-chloropyrazin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluoro phenyl}sulfonyl)propan-2-ol;
3-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluorophenyl}pyridazine;
3-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluorophenyl}-6-methylpyridazine;
3-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluorophenyl}-6-methoxypyridazine;
4-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluorophenyl}pyridazine;
5-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluorophenyl}pyrimidin-2-amine;
5-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluorophenyl}-2-methoxypyrimidine;
4-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluorophenyl}pyrimidin-2-amine;
4-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluorophenyl}-2-methoxypyrimidine;
2-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluorophenyl}pyrazin-2-amine;
5-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluorophenyl}pyrimidine;
2-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluorophenyl}pyrazine;
4-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluorophenyl}pyrimidine;
5-ethyl-2-{4-[(1R,2R)-2-({[2-fluoro-4-(2-methyl-1,3-thiazol-5-yl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine;
4-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-2-fluorophenyl}pyrimidine;
5-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-2-fluorophenyl}pyrimidine;
3-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-2-fluorophenyl}pyridazine;
4-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-2-fluorophenyl}pyridazine;
4-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-2-fluorophenyl}-6-methoxypyridazine;
4-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-2-fluorophenyl}-6-methylpyridazine;
5-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-2-fluorophenyl}pyrimidin-2-amine;
4-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]-3-fluorophenyl}-2-methoxypyrimidine;
5-ethyl-2-[4-((1R,2R))-2-{[(4-pyrimidin-5-ylbenzyl)oxy]methyl}cyclopropyl)piperidin-1-yl]pyrimidine;
5-ethyl-2-[4-((1R,2R))-2-{[(4-pyridazin-4-ylbenzyl)oxy]methyl}cyclopropyl)piperidin-1-yl]pyrimidine;
5-ethyl-2-[4-((1R,2R))-2-{[(4-pyridazin-4-ylbenzyl)oxy]methyl}cyclopropyl)piperidin-1-yl]pyrimidine;
and
5-ethyl-2-[4-((1R,2R))-2-{[(4-pyrazin-2-ylbenzyl)oxy]methyl}cyclopropyl)piperidin-1-yl]pyrimidine;
2-(4-((1R,2R)-2-(((2-fluoro-4-(methylsulfonyl)benzyl)oxy)methyl)cyclopropyl)piperidin-1-yl)-5-(methoxymethyl)pyrimidine;
2-(4-((1R,2R)-2-(((2-fluoro-4-(methylsulfonyl)benzyl)oxy)methyl)cyclopropyl)piperidin-1-yl)-5-(1-methoxyethyl)pyrimidine;
2-(4-((1R,2R)-2-(((4-(ethylsulfonyl)-2-fluorobenzyl)oxy)methyl)cyclopropyl)piperidin-1-yl)-5-(methoxymethyl)pyrimidine;
2-(4-((1R,2R)-2-(((3,5-difluoro-4-(methylsulfonyl)benzyl)oxy)methyl)cyclopropyl)piperidin-1-yl)-5-(methoxymethyl)pyrimidine;
5-ethoxy-2-(4-((1R,2R)-2-(((3-fluoro-4-(methylsulfonyl)benzyl)oxy)methyl)cyclopropyl)piperidin-1-yl)pyrimidine;
2-(4-((1R,2R)-2-(((3-fluoro-4-(methylsulfonyl)benzyl)oxy)methyl)cyclopropyl)piperidin-1-yl)-5-(-methoxyethyl)pyrimidine;
2-(4-((1R,2R)-2-((3-fluoro-4-(1H-tetrazol-1-yl)benzyloxy)methyl)cyclopropyl)piperidin-1-yl)-5-(methoxymethyl)pyrimidine;
2-(4-((1R,2R)-2-(((5-(1H-tetrazol-1-yl)pyridin-2-yl)methoxy)methyl)cyclopropyl)piperidin-1-yl)-5-ethylpyrimidine;
5-(4-((1R,2R)-2-((2-fluoro-4-(1H-tetrazol-1-yl)benzyloxy)methyl)cyclopropyl)piperidin-1-yl)-3-isopropyl-1,2,4-oxadiazole;
5-(4-((1R,2R)-2-(((2-fluoro-4-(1H-tetrazol-1-yl)benzyl)oxy)methyl)cyclopropyl)piperidin-1-yl)-3-(methoxymethyl)-1,2,4-oxadiazole;
1-methylcyclopropyl 4-((1R,2R)-2-((2-fluoro-4-(1H-tetrazol-1-yl)benzyloxy)methyl)cyclopropyl)piperidine-1-carboxylate;
2-(3-fluoro-4-((((1R,2R)-2-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)cyclopropyl)methoxy)methyl)phenyl)-N,N-dimethylacetamide;
2-(3-fluoro-4-((((1R,2R)-2-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)cyclopropyl)methoxy)methyl)phenyl)-1-(3-methoxyazetidin-1-yl)ethanone;
2-(3-fluoro-4-((((1R,2R)-2-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)cyclopropyl)methoxy)methyl)phenyl)-1-(3-fluoroazetidin-1-yl) ethanone;
2-(2-fluoro-4-((((1R,2R)-2-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)cyclopropyl)methoxy)methyl)phenyl)-N—N-dimethylacetamide;
2-(2-fluoro-4-((((1R,2R)-2-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)cyclopropyl)methoxy)methyl)phenyl)-1-morpholinoethanone;
2-(2-fluoro-4-((((1R,2R)-2-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)cyclopropyl)methoxy)methyl)phenyl)-1-(3-methoxyazetidin-1-yl)ethanone;
2-(2-fluoro-4-((((1R,2R)-2-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)cyclopropyl)methoxy)methyl)phenyl)-1-(3-hydroxyazetidin-1-yl)ethanone;
2-(2-fluoro-4-((((1R,2R)-2-(1-(3-(methoxymethyl)-1,2,4-oxadiazol-5-yl)piperidin-4-yl)cyclopropyl)methoxy)methyl)phenyl)-1-(3-hydroxyazetidin-1-yl)ethanone;
1-(azetidin-1-yl)-2-(3-fluoro-4-((((1R,2R)-2-(1-(5-(methoxymethyl) pyrimidin-2-yl)piperidin-4-yl)cyclopropyl)methoxy)methyl)phenyl)ethanone;
2-(3-fluoro-4-((((1R,2R)-2-(1-(5-(methoxymethyl)pyrimidin-2-yl)piperidin-4-yl)cyclopropyl)methoxy)methyl)phenyl)-1-morpholinoethanone;
2-(3-fluoro-4-((((1R,2R)-2-(1-(5-(methoxymethyl)pyrimidin-2-yl)piperidin-4-yl)cyclopropyl)methoxy)methyl)phenyl)-N,N-dimethylacetamide;
2-(3-fluoro-4-((((1R,2R)-2-(1-(5-(methoxymethyl)pyrimidin-2-yl)piperidin-4-yl)cyclopropyl)methoxy)methyl)phenyl)-1-(3-fluoroazetidin-1-yl)ethanone;
or a pharmaceutically acceptable salt thereof.

145 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/126,685Filed 11 Jun 2012 · us provisional application
Priority: 16 Jun 2011
Published: US 2014/0128368 A18 May 2014
Granted: 14 Apr 2015
Term ends: Not estimatedThe source records don’t support an estimate.

Classification12 codes

C07D 211/24
With hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms: by sulfur atoms to which a second hetero atom is attached
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
C07D 211/22
With hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms: by oxygen atoms

Family

Application61/497,703Us provisional application · filed 16 Jun 2011
Application61/655,010Us provisional application · filed 4 Jun 2012
US 2014/0128368 A1Pre-grant publication · published 8 May 2014
US 9,006,228 B2This patent

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

Timeline

Citations

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