Back to results
US 9,168,248 B2Granted
Spiro compounds useful as inhibitors of stearoyl-coenzyme A delta-9 desaturase
AssigneeMerck Canada Inc.
InventorsNicolas Lachance, Jean-Philippe Leclerc, Chun Sing Li, Oscar Miguel Moradei
Life of this patent
Estimating the term…
Abstract
Heteroaromatic compounds of structural formula (I) are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, such as atherosclerosis; obesity; diabetes; neurological disease; metabolic syndrome; insulin resistance; and liver steatosis.
Claims13
A compound of structural formula I:
- or a pharmaceutically acceptable salt thereof;
- wherein
- A is selected from the group consisting of:
- wherein r is 0 or 1;
- and s is 0 or 1;
- B is selected from the group consisting of:
- each R1 is independently selected from the group consisting of:
- hydrogen, halogen, and C1-3 alkyl, wherein alkyl is unsubstituted or substituted with one to three substituents independently selected from halogen and hydroxy;
- each R2 is independently selected from the group consisting of:
- (1) hydrogen,
- (2) halogen,
- (3) C1-6 alkyl,
- (4) (CH2)nORe,
- (5) (CH2)nN(Re)2,
- (6) (CH2)nCN,
- (7) (CH2)nCORe, and
- (8) (CH2)nS(O)qRe,
- wherein alkyl is unsubstituted or substituted with hydroxy or one to three halogens, and
- wherein any CH2 in R2 is unsubstituted or substituted with one to two groups independently selected from halogen, hydroxy, and C1-4 alkyl unsubstituted or substituted with one to five fluorines;
- each R3 is independently selected from the group consisting of:
- (1) hydrogen,
- (2) halogen,
- (3) —C1-6 alkyl,
- (4) —C1-6 alkenyl,
- (5) —OC1-6 alkyl,
- (6) (CH2)nORe,
- (7) (CH2)nN(Re)2,
- (8) (CH2)nC≡N,
- (9) (CH2)nCORe, and
- (10) (CH2)nS(O)qRe,
- wherein alkyl is unsubstituted or substituted with one to three substituents selected from:
- hydroxy, halogen, and C1-4 alkyl wherein alkyl are unsubstituted or substituted with one to three substituents selected from:
- halogen, hydroxy, and C1-4 alkyl unsubstituted or substituted with one to five fluorines, and wherein any CH2 in R3 is unsubstituted or substituted with one to two groups independently selected from halogen, hydroxy, and C1-4 alkyl unsubstituted or substituted with one to five fluorines;
- R4 is
- each Ra is independently selected from the group consisting of:
- (1) hydrogen,
- (2) halogen,
- (3) cyano,
- (4) C1-4 alkyl, unsubstituted or substituted with one to five fluorines,
- (5) C1-4 alkoxy, unsubstituted or substituted with one to five fluorines,
- (6) C1-4 alkylthio, unsubstituted or substituted with one to five fluorines,
- (7) C1-4 alkylsulfonyl,
- (8) —CO2H,
- (9) C1-4 alkyloxycarbonyl, and
- (10) C1-4 alkylcarbonyl;
- each Re is independently selected from the group consisting of:
- (1) hydrogen, and
- (2) C1-6 alkyl,
- wherein alkyl is unsubstituted or substituted with one to three substituents independently selected from the group consisting of:
- halogen, cyano, —C1-4 alkoxy, —C1-4 alkylthio, —C1-4 alkylsulfonyl, —C2H, and —CO2C1-4 alkyl;
- n is an integer from 0 to 3;
- q is an integer from 1 to 2;
- t is an integer from 0 to 8;
- d is an integer from 0 to 2;
- and
- e is an integer from 0 to 2,
- provided that d+e is 2.
54 more elements
A compound that is
- or a pharmaceutically acceptable salt thereof.
A compound that is
Dependencies are inferred from the claim text.