Patent number: 6509334
Abstract: This invention provides compounds of Formula (I):
wherein R1 and R2 may be single substituents or fused to form spirocyclic or hetero-spirocyclic rings; R3 is H, OH, NH2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C6 alkenyl, substituted C1 to C6 alkenyl, alkynyl, or substituted alkynyl, CORC; RC is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl; R4 is H, halogen, CN, NO2, C1 to C6 alkyl, substituted C1 to C6 alkyl, alkynyl, or substituted alkynyl, C1 to C6 alkoxy, substituted C1 to C6 alkoxy, amino, C1 to C6 aminoalkyl, or substituted C1 to C6 aminoalkyl; and R5 is selected from a trisubstituted benzene ring of a five or six membered ring with 1, 2, or 3 heteroatoms from the group including O, S, SO, SO2 or NR6 and containing one or two independent substituents from the group including H, halogen, CN, N02, amino, and C1 to C3 alkyl, C1 to C3 alkoxy, C1 to C3 a
Type:
Grant
Filed:
April 19, 2000
Date of Patent:
January 21, 2003
Assignees:
American Home Products Corporation, Ligand Pharmaceuticals, Inc.
Inventors:
Puwen Zhang, Eugene A. Terefenko, Andrew Fensome, Jay E. Wrobel, Horace Fletcher, III, Lin Zhi, Todd K. Jones, James P. Edwards, Christopher M. Tegley
Patent number: 6503939
Abstract: This invention relates to cyclic combination therapies and regimens utilizing substituted indoline derivative compounds that are antagonists of the progesterone receptor having the structure:
wherein: R1 and R2 are (i) H, OH, OAc, alkylaryl, alkylheteroaryl, 1-propynyl, 3-propynyl, and optionally substituted alkyl, O(alkyl), aryl, or heteroaryl; (ii) a ring or (iii) a double bond; R3 is H, OH, NH2, CORA; or optionally substituted alkenyl or alkynyl; RA=H or optionally substituted alkyl, alkoxy, or aminoalkyl groups; R4=H, halo, CN, NH2, or optionally substituted alkyl, alkoxy, or aminoalkyl; R5 is a benzene ring; heterocyclic ring; an indole or benzothiophene; or pharmaceutically acceptable salt. R6 and R7 are H, methyl, ethyl, propyl, butyl, iso-propyl, isobutyl, cyclohexyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl.
Type:
Grant
Filed:
October 15, 2001
Date of Patent:
January 7, 2003
Assignees:
Wyeth, Ligand Pharmaceuticals, Inc.
Inventors:
Gary S. Grubb, John W. Ullrich, Andrew Fensome, Jay E. Wrobel, James P. Edwards, Todd K. Jones, Christopher M. Tegley, Lin Zhi
Patent number: 6498154
Abstract: This invention relates to cyclic combination therapies utilizing, in combination with progestins, estrogens, or both, compounds which are progesterone receptor antagonists of the general structure:
wherein: R1 and R2 are H, CORA, or NRBCORA, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or heterocyclic; or R1 and R2 fuse to form 3 to 8 membered spirocyclic alkyl, alkenyl or heterocyclic rings; RA is H or optionally substituted alkyl, aryl, alkoxy, or aminoalkyl groups; RB is H or alkyl; R3 is H, OH, NH2, CORC or alkyl, alkenyl, or alkynyl; RC is H, alkyl, aryl, alkoxy, or aminoalkyl; R4 is H, halogen, CN, NO2, alkyl, alkynyl, alkoxy, amino or aminoalkyl; R5 is benzene or 5- or 6-membered heterocyclic ring; R6 is H or alkyl; G1 is O, NR7, or CR7R8; G2 is CO or CR7R8; provided that when G1 is O, G2 is CR7R8, and G1 and G2 cannot both be CR7R8; R7 and R8 are H or an optionally substituted alkyl, aryl, or heterocyclic moiety; or pharmaceutically acceptable salt thereof.
Type:
Grant
Filed:
April 19, 2000
Date of Patent:
December 24, 2002
Assignees:
Wyeth, Ligand Pharmaceuticals, Inc.
Inventors:
Gary S. Grubb, Lin Zhi, Todd K. Jones, Puwen Zhang, James P. Edwards, Andrew Fensome, Eugene A. Terefenko, Jay E. Wrobel, Christopher M. Tegley
Patent number: 6444668
Abstract: This invention relates to cyclic combination therapies and regimens utilizing substituted indoline derivative compounds which are antagonists of the progesterone receptor having the general structure:
wherein R1 and R2 may be single substituents or fused to form spirocyclic or hetero-spirocyclic rings; R3 is H, OH, NH2, C1 to C6 alkyl, substituted C1 to C6 allyl C3 to C6 alkenyl, substituted C1 to C6 alkenyl, alkynyl, or substituted alknyl, CORC; RC is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl; R4 is H, halogen, CN, NO2, C1 to C6 alkyl, substituted C1 to C6 alkyl alkynyl, or substituted alkynyl, C1 to C6 alkoxy, substituted C1 to C6 alkoxy, amino, C1 to C6 aminoalkyl, or substituted C1 to C6 aminoalkyl; and R5 is selected from a trisubstituted benzene ring of a five or six membered ring with 1, 2, or 3 heteroatoms from the group including O, S, SO, SO2 or NR6 and
Type:
Grant
Filed:
April 19, 2000
Date of Patent:
September 3, 2002
Assignees:
Wyeth, Ligand Pharmaceuticals, Inc.
Inventors:
Gary S. Grubb, Puwen Zhang, Eugene A. Terefenko, Andrew Fensome, Jay E. Wrobel, Horace Fletcher, III, James P. Edwards, Todd K. Jones, Christopher M. Tegley, Lin Zhi
Patent number: 6441019
Abstract: This invention provides compounds of the formula:
wherein A and B are independent substituents selected from S, CH or N; provided that when A is S, B is CH or N; and when B is S, A is CH or N; and A and B cannot both be CH; and when A and B both equal N, one N may be optionally substituted with an C1 to C6 alkyl group; R1 and R2 are independent substituents selected from the group of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, C2 to C6 alkenyl, substituted C2 to C6 alkenyl, C2 to C6 alkynyl, substituted C2 to C6 alkynyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, CORA, or NRBCORA; or R1 and R2 are fused to form optionally substituted 3 to 8 membered spirocyclic alkyl, alkenyl or heterocyclic ring, the heterocyclic ring containing one to three heteroatoms selected from the group of O, S and N; or pharmaceutically useful salts thereof.
Type:
Grant
Filed:
July 17, 2001
Date of Patent:
August 27, 2002
Assignees:
Wyeth, Ligand Pharmaceuticals, Inc.
Inventors:
Arthur A. Santilli, Andrew Q. Viet, Puwen Zhang, Andrew Fensome, Jay E. Wrobel, James P. Edwards, Todd K. Jones, Christopher M. Tegley, Lin Zhi
Patent number: 6436929
Abstract: The present invention provides compounds which are agonists of the progesterone receptor and have the structures:
wherein R1 and R2 are independent substituents selected from the group of H, optionally substituted C1 to C6 alkyl, alkenyl, alkynyl, or alkynyl groups C3 to C8 cycloalkyl, aryl, substituted aryl, or heterocyclic groups, or CORA or NRBCORA; or R1 and R2 are fused to form an optionally substituted 3 to 8 membered Spiro cyclic alkyl or alkenyl ring or a Spiro cyclic ring containing one to three heteroatoms selected from O, S and N; RA is selected from H, amino, or optionally substituted C1 to C3 alkyl, aryl, C1 to C3 alkoxy, or C1 to C3 aminoalkyl groups; RB is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl; R3 is H, OH, NH2, CORC, or optionally substituted C1 to C6 alkyl, C3 to C6 alkenyl, or alkynyl groups; RC is selected from H or optionally substituted C1 to C3 alkyl, aryl, C1 to C3 alkoxy, or C1 to C3 aminoalkyl groups; Q1 is S, NR7, or CR8R9; R5 is an optionally trisubstitu
Type:
Grant
Filed:
April 19, 2000
Date of Patent:
August 20, 2002
Assignees:
Wyeth, Ligand Pharmaceuticals, Inc.
Inventors:
Puwen Zhang, Andrew Fensome, Eugene A. Terefenko, Lin Zhi, Todd K. Jones, James P. Edwards, Christopher M. Tegley, Jay E. Wrobel, Mark A. Collins
Patent number: 6423699
Abstract: This invention relates to cyclic combination therapies and regimens utilizing substituted indoline derivative compounds which are antagonists of the progesterone receptor having the general structure:
wherein:
A is O, S, or NR4;
B is a bond between A and C═Q, or the moiety CR5R6; R4, R5, R6 are independently selected from H or optionally substituted C1 to C6 alkyl, C2 to C6 alkenyl, C2 to C6 alkynyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, or heterocyclic groups, or cyclic alkyl constructed by fusing R4 and R5 to from a 5 to 7 membered ring; R1 is selected from H, OH, NH2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C6 alkenyl, substituted C1 to C6 alkenyl, alkynyl, substituted alkynyl, —COH, or optionally substituted —CO(C1 to C3 alkyl), —CO(aryl), —CO(C1 to C3 alkoxy), or —CO(C1 to C3 aminoalkyl) groups; R2 is selected from H, halogen, CN, NO2, or optionally substituted C1 to C6 alkyl C1 to C6 alkoxy, or C1 to C6 aminoalkyl gro
Type:
Grant
Filed:
April 19, 2000
Date of Patent:
July 23, 2002
Assignees:
American Home Products Corporation, Ligand Pharmaceutical, Inc.
Inventors:
Gary S. Grubb, Puwen Zhang, Reinhold R. W. Bender, Jay E. Wrobel, James P. Edwards, Todd K. Jones, Christopher M. Tegley, Lin Zhi