Back to results
US 9,006,268 B2Granted
Prolylcarboxypeptidase inhibitors
AssigneeMerck Sharp & Dohme Corp.
InventorsJohn S. Debenham, Jinlong Jiang, Christina B. Madsen-Duggan, Dong-Ming Shen
Life of this patent
Estimating the term…
Abstract
Compounds of structural formula I are inhibitors of prolylcarboxypeptidase (PrCP). The compounds of the present invention are useful for the prevention and treatment of conditions related to the enzymatic activity of PrCP such as abnormal metabolism, including obesity; diabetes; metabolic syndrome; obesity related disorders; and diabetes related disorders.
Claims9
A compound of structural formula I:
- or a pharmaceutically acceptable salt thereof;
- wherein
- X is selected from the group consisting of:
- (1) —O—,
- (2) —S—, and
- (3) —NRa—;
- Y is selected from the group consisting of:
- (1) —N—, and
- (2) —CH—;
- Z is selected from the group consisting of:
- (1) —CH2—, and
- (2) —NR5—,
- provided that if Y is N, then Z is not —NR5—;
- each R1 is independently selected from the group consisting of:
- (1) phenyl, and
- (2) —(CH2)2-phenyl,
- wherein each CH2, and phenyl is unsubstituted or substituted with one to two groups independently selected from Rb;
- each R2 is independently selected from the group consisting of:
- (1) hydrogen,
- (2) —OH,
- (3) halogen,
- (4) —CF3,
- (5) —OCF3,
- (6) —C1-6 alkyl,
- (7) —OC1-6 alkyl,
- (8) —CO2H, and
- (9) —C(O)N(Rg)2,
- wherein each alkyl is unsubstituted or substituted with one to four substituents selected from Rc;
- each R3 is independently selected from the group consisting of:
- (1) —(CH2)paryl, and
- (2) —(CH2)pheteroaryl,
- wherein CH2, aryl and heteroaryl are unsubstituted or substituted with one to three substituents selected from Rd;
- R4 is phenyl, wherein phenyl is unsubstituted or substituted with one to three substituents selected from Re;
- each R5 is independently selected from the group consisting of:
- (1) hydrogen,
- (2) —CO2C1-6 alkyl,
- (3) —C(O)N(Rg)C1-6alkyl,
- (4) —C(O)C1-6 alkyl, and
- (5) —(CH2)qaryl,
- wherein each alkyl and aryl is unsubstituted or substituted with one to four substituents selected from Rh;
- each Ra is independently selected from the group consisting of:
- (1) hydrogen, and
- (2) —C1-6 alkyl;
- each Rb is independently selected from the group consisting of:
- (1) oxo,
- (2) —OH,
- (3) —CF3,
- (4) —OCF3,
- (5) halogen,
- (6) C1-6 alkyl,
- (7) —OC1-6 alkyl,
- (8) —CO2H, and
- (9) —CO2C1-6 alkyl;
- each Rc is independently selected from the group consisting of:
- (1) —OH,
- (2) —CN,
- (3) —CF3,
- (4) —OCF3,
- (5) halogen,
- (6) —C1-6 alkyl,
- (7) —OC1-6 alkyl,
- (8) —CO2H, and
- (9) —CO2C1-6 alkyl;
- each Rd is independently selected from the group consisting of:
- (1) —OH,
- (2) —CN,
- (3) —CF3,
- (4) —OCF3,
- (5) halogen,
- (6) —C1-6 alkyl,
- (7) —OC1-6 alkyl,
- (8) —CO2H, and
- (9) —CO2C1-6 alkyl;
- each Re is independently selected from the group consisting of:
- (1) —OH,
- (2) —CN,
- (3) —CF3,
- (4) —OCF3,
- (5) halogen,
- (6) —C1-6 alkyl,
- (7) —OC1-6 alkyl,
- (8) —CO2H, and
- (9) —CO2C1-6 alkyl;
- each Rf is independently selected from the group consisting of:
- (1) hydrogen, and
- (2) —C1-6 alkyl;
- each Rg is independently selected from the group consisting of:
- (1) hydrogen, and
- (2) —C1-6 alkyl;
- each Rh is independently selected from the group consisting of:
- (1) —OH,
- (2) oxo,
- (3) —CN,
- (4) —CF3,
- (5) —OCF3,
- (6) halogen,
- (7) —C1-6 alkyl,
- (8) —OC1-6 alkyl,
- (9) —CO2H, and
- (10) —CO2C1-6 alkyl;
- m is selected from 0, 1, 2 and 3;
- n is selected from 0, 1, 2, and 3;
- p is selected from 0, 1, 2 and 3;
- and
- q is selected from 0, 1, 2 and 3.
102 more elements
Dependencies are inferred from the claim text.