US 7,531,542 B2
Benzooxazole and benzothiazole antagonists of gonadotropin releasing hormone receptor
Daniel M. Green, Ambler, Pa. (US); Diane B. Hauze, Radnor, Pa. (US); Charles W. Mann, Philadelphia, Pa. (US); Jeffrey C. Pelletier, Lafayette Hill, Pa. (US); and Matthew D. Vera, Royersford, Pa. (US)
Assigned to Wyeth, Madison, N.J. (US)
Filed on May 09, 2006, as Appl. No. 11/431,266.
Claims priority of provisional application 60/682689, filed on May 18, 2005.
Prior Publication US 2006/0264631 A1, Nov. 23, 2006
Int. Cl. A61K 31/497 (2006.01); C07D 413/00 (2006.01); C07D 417/00 (2006.01); C07D 419/00 (2006.01)
U.S. Cl. 514—254.02  [544/368] 30 Claims
 
1. A compound of the formula (I):

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt thereof,
wherein
W is O or S;
Y is Q and Z is R18; or Y is R18 and Z is Q, wherein Q is

OG Complex Work Unit Drawing
Ar is phenyl, 2-thiophenyl or 3-thiophenyl;
R1 and R2 are each independently hydrogen; or linear or branched (C1-C6)-alkyl, (C2-C6)-alkenyl, or (C2-C6)-alkynyl, each optionally substituted with halogen, —N3, —NO2, —CN, —OR23, —SR23, —SO2R23, —SO2N(R23)2, —N(R23)2, —COR23, —CO2R23, —NR23CO2R23, —NR23COR23, —NR23CON(R23)2, or —CON(R23)2; or R1 and R2 may together form a three- to seven-membered cycloalkyl group, wherein the cycloalkyl group formed by R1 and R2 is optionally substituted with halogen, —N3, —NO2, —CN, —OR23, —SR23, —SO2R23, —SO2N(R23)2, —N(R23)2, —COR23, —CO2R23, —NR23CO2R23, —NR23COR23, —NR23CON(R23)2, —CON(R23)2, or —(CH2)nOR23;
R3 is one of the following:

OG Complex Work Unit Drawing

OG Complex Work Unit Drawing
each R3 also having up to three R10 substituents attached to the ring of R3 containing at least one N;
R4, R5, R10, R21, R22, R23, R24, R25, R26, and R27 are each independently hydrogen; or linear or branched (C1-C6)-alkyl, (C2-C6)-alkenyl, or (C2-C6)-alkynyl;
each R6 is independently hydrogen; linear or branched (C1-C6)-alkyl, (C2-C6)-alkenyl, or (C2-C6)-alkynyl, each optionally substituted with halogen, —N3, —NO2, —CN, —OR23, —SR23, —SO2R23, —SO2N(R23)2, —N(R23)2, —COR23, —CO2R23, —NR23CO2R23, —NR23COR23, —NR23CON(R23)2, or —CON(R23)2; —NR13R14; —C(OH)(CF3)2; —CH(CF3)2; —C(CF3)3—XR13; or —COR13; and when the two R6 are ortho to each other, they may together form a five- to seven-membered cyclic group containing up to 3 heteroatoms selected from N, O, or S, and wherein the cyclic group formed by the ortho R6 groups is optionally substituted with halogen, —N3, —NO2, —CN, —OR23, —SR23, —SO2R23, —SO2N(R23)2, —N(R23)2, —COR23, —CO2R23, —NR23CO2R23,
—NR23COR23, —NR23CON(R23)2, —CON(R23)2, or —(CH2)nOR23;
R7 and R9 are each independently hydrogen; linear or branched (C1-C6)-alkyl, (C2-C6)-alkenyl, or (C2-C6)-alkynyl; —(CH2)nXR12; —(CH2)nR17; —COXR11; —XR11; —CO2R11; or —CONR11R12;
R8 is hydrogen; linear or branched (C1-C6)-alkyl, (C2-C6)-alkenyl, or (C2-C6)-alkynyl; —(CH2)mCO2R11; or —(CH2)mCONR11R12;
R11 and R12 are each independently hydrogen; linear or branched (C1-C6)-alkyl, (C2-C6)-alkenyl, or (C2-C6)-alkynyl; or R11 and R12 may together form a three- to seven-membered heterocyclic group containing up to 3 heteroatoms selected from N, O, or S;
R13 and R14 are each independently hydrogen; linear or branched (C1-C6)-alkyl, (C2-C6)-alkenyl, or (C2-C6)-alkynyl, each optionally substituted with halogen, —N3, —NO2, —CN, —OR23, —SR23, —SO2R23, —SO2N(R23)2, —N(R23)2, —COR23, —CO2R23, —R23CO2R23, —NR23COR23, —NR23CON(R23)2, or —CON(R23)2; aryl; or aryl optionally substituted with one to three substituents selected from halogen, R15, —OR15, or —NR15R16; or R13 and R14 may together form a three- to seven-membered heterocyclic group containing up to 3 heteroatoms selected from N, O, or S, and wherein the heterocyclic group formed by R13 and R14 is optionally substituted with halogen, —N3, —NO2, —CN, —OR23, —SR23, —SO2R23, —SO2N(R23)2, —N(R23)2, —COR23, —CO2R23, —NR23CO2R23, —NR23COR23, —NR23CON(R23)2, —CON(R23)2, or —(CH2)nOR23;
R15 and R16 are each independently hydrogen; or linear or branched (C1-C6)-alkyl, (C2-C6)-alkenyl, or (C2-C6)-alkynyl; or both R15 and R16 may together form a three- to seven-membered heterocyclic group containing up to 3 heteroatoms selected from N, O, or S;
R17 is phenyl, 2-pyridyl, 3-pyridyl, or 4-pyridyl;
R18, R19, and R20 are each independently hydrogen; linear or branched (C1-C6)-alkyl, (C2-C6)-alkenyl, or (C2-C6)-alkynyl, each optionally substituted with halogen, —N3, —NO2, —CN, —OR23, —SR23, —SO2R23, —SO2N(R23)2, —N(R23)2, —COR23, —CO2R23, —NR23CO2R23, —NR23COR23, —NR23CON(R23)2, or —CON(R23)2; halogen; —NR13R14; —C(OH)(CF3)2; —CH(CF3)2; —C(CF3)3; —XR13; —COR13; —CO2R13; or —CON(R13)(R14);
X is —O—, —NR12—, or —SOm—;
each m is independently 0, 1, or 2; and
each n is independently 0, 1, 2, 3, or 4.