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    • 5. 发明授权
    • Cyclothiocarbamate derivatives as progesterone receptor modulators
    • 环硫代氨基甲酸酯衍生物作为孕酮受体调节剂
    • US06436929B1
    • 2002-08-20
    • US09552354
    • 2000-04-19
    • Puwen ZhangAndrew FensomeEugene A. TerefenkoLin ZhiTodd K. JonesJames P. EdwardsChristopher M. TegleyJay E. WrobelMark A. Collins
    • Puwen ZhangAndrew FensomeEugene A. TerefenkoLin ZhiTodd K. JonesJames P. EdwardsChristopher M. TegleyJay E. WrobelMark A. Collins
    • A61K31535
    • A61K31/536A61K31/538C07D265/18C07D413/04
    • 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 trisubstituted benzene ring or an optionally substituted five or six membered heterocyclic ring with 1, 2, or 3 ring heteroatoms selected from the group of O, S, SO, SO2 or NR6; or a pharmaceutically acceptable salt thereof, as well as methods of using these compounds for contraception and the treatment of progesterone-related maladies.
    • 本发明提供作为孕酮受体的激动剂并具有以下结构的化合物:其中R 1和R 2是选自H,任选取代的C 1至C 6烷基,烯基,炔基或炔基的独立取代基C 3至C 8环烷基, 芳基,取代的芳基或杂环基,或CORA或NRBCORA; 或R 1和R 2稠合形成任选取代的3至8元螺环烷基或烯基环或含有一至三个选自O,S和N的杂原子的螺环; RA选自H,氨基或任选取代的C 1至C 3烷基,芳基,C 1至C 3烷氧基或C 1至C 3氨基烷基; RB是H,C 1至C 3烷基或取代的C 1至C 3烷基; R 3是H,OH,NH 2,CORC或任选取代的C 1至C 6烷基,C 3至C 6烯基或炔基; RC选自H或任选取代的C 1至C 3烷基,芳基,C 1至C 3烷氧基或C 1至C 3氨基烷基; Q1是S,NR7或CR8R9; R5是任选的三取代的苯环或具有1,2或3个选自O,S,SO,SO 2或NR 6的环杂原子的任选取代的五元或六元杂环; 或其药学上可接受的盐,以及使用这些化合物用于避孕和治疗孕酮相关性疾病的方法。
    • 6. 发明授权
    • 1,2,3,4-tetrahydro-2-thioxo-quinolinyl and 1,2,3,4-tetrahydro-2-oxo-quinolinyl derivatives as progesterone receptor modulators
    • 1,2,3,4-四氢-2-硫代 - 喹啉基和1,2,3,4-四氢-2-氧代喹啉基衍生物作为孕酮受体调节剂
    • US06693103B2
    • 2004-02-17
    • US10023063
    • 2001-12-17
    • Puwen ZhangAndrew FensomeEugene A. TerefenkoJay E. WrobelJames P. EdwardsTodd K. JonesChristopher M. TegleyLin Zhi
    • Puwen ZhangAndrew FensomeEugene A. TerefenkoJay E. WrobelJames P. EdwardsTodd K. JonesChristopher M. TegleyLin Zhi
    • C07D215227
    • C07D215/227A61K31/4704A61K31/517A61K31/536C07D215/38C07D239/80C07D265/16C07D413/04
    • This invention provides compounds which are agonists and antagonists of the progesterone receptor having the general structure: wherein: R1 and R2 are independently selected from H, CORA, or NRBCORA, or optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or heterocyclic moieties; or R1 and R2 are fused 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, C1 to C3 alkyl, or substituted C1 to C3 alkyl; R3 is H, OH, NH2, CORC or optionally substituted alkyl, alkenyl, or alkynyl; RC is H or optionally substituted alkyl, aryl, alkoxy, or aminoalkyl; R4 is H, halogen, CN, NO2, or optionally substituted alkyl alkynyl, alkoxy, amino or aminoalkyl; R5 is an optionally substituted benzene or five or six membered ring with 1, 2, or 3 heteroatoms selected from O, S, SO, SO2 or NR6; R6 is H or C1 to C3 alkyl; G1 is O, NR7, or CR7R8; G2 is CO, CS, 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, and methods using these compounds in mammals as agonists or antagonists of the progesterone receptor.
    • 本发明提供作为孕酮受体的激动剂和拮抗剂的化合物,其具有以下通式结构:其中:R 1和R 2独立地选自H,COR A或NR C COR 3, 或任选取代的烷基,烯基,炔基,环烷基,芳基或杂环部分;或R 1和R 2稠合形成:3至8元螺环烷基,烯基或杂环; R A是H或任选取代的烷基,芳基,烷氧基或氨基烷基; R B是H,C 1至C 3烷基或取代的C 1至C 3烷基; R 3是H,OH,NH 2,COR C或任选取代的烷基,烯基或炔基; R C是H或任选取代的烷基,芳基,烷氧基或氨基烷基; R 4是H,卤素,CN,NO 2或任选取代的烷基炔基,烷氧基,氨基或氨基烷基; R 5是任选取代的苯或具有1,2或3个选自O,S,SO,SO 2或NR 6的杂原子的五或六元环; R 6是H或C 1至C 3烷基; G1是O,NR7或CR7R8; G2是CO,CS或CR7R8; 条件是当G1为O时,G2为CR7R8,G1和G2不能为CR7R8; R 7和R 8是H或任选取代的烷基,芳基或杂环部分; 或其药学上可接受的盐,以及在哺乳动物中使用这些化合物作为孕酮受体的激动剂或拮抗剂的方法。
    • 7. 发明授权
    • Cyclic regimens using quinazolinone and benzoxazine derivatives
    • 使用喹唑啉酮和苯并恶嗪衍生物的循环方案
    • US06498154B1
    • 2002-12-24
    • US09552357
    • 2000-04-19
    • Gary S. GrubbLin ZhiTodd K. JonesPuwen ZhangJames P. EdwardsAndrew FensomeEugene A. TerefenkoJay E. WrobelChristopher M. Tegley
    • Gary S. GrubbLin ZhiTodd K. JonesPuwen ZhangJames P. EdwardsAndrew FensomeEugene A. TerefenkoJay E. WrobelChristopher M. Tegley
    • A61K3156
    • A61K31/565A61K31/57A61K45/06A61K2300/00
    • 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. These methods may be used for contraception or treatment and/or prevention of secondary amenorrhea, dysfunctional bleeding, uterine leiomyomata, endometriosis; polycystic ovary syndrome, carcinomas and adenocarcinomas of the endometrium, ovary, breast, colon, prostate, or minimization of side effects or cyclic menstrual bleeding. Additional uses of the invention include stimulation of food intake.
    • 本发明涉及利用与孕激素,雌激素或两者作为一般结构的孕酮受体拮抗剂的化合物的环状组合疗法:其中:R1和R2是H,CORA或NRBCORA,烷基,烯基,炔基,环烷基 ,芳基或杂环基; 或R1和R2融合形成3至8元螺环烷基,烯基或杂环; RA为H或任选取代的烷基,芳基,烷氧基或氨基烷基; RB是H或烷基; R3是H,OH,NH2,CORC或烷基,烯基或炔基; RC是H,烷基,芳基,烷氧基或氨基烷基; R4是H,卤素,CN,NO2,烷基,炔基,烷氧基,氨基或氨基烷基; R5是苯或5-或6-元杂环; R6是H或烷基; G1是O,NR7或CR7R8; G2为CO或CR7R8; 条件是当G1为O时,G2为CR7R8,G1和G2不能为CR7R8; R 7和R 8是H或任选取代的烷基,芳基或杂环部分; 或其药学上可接受的盐。 这些方法可用于避孕或治疗和/或预防继发性闭经,功能障碍性出血,子宫平滑肌瘤,子宫内膜异位症; 多囊卵巢综合征,子宫内膜,卵巢,乳腺,结肠,前列腺的癌和腺癌,或副作用最小化或周期性月经出血。 本发明的额外用途包括刺激食物摄取。
    • 9. 发明授权
    • Cyclic urea and cyclic amide derivatives
    • 环状脲和环状酰胺衍生物
    • US06369056B1
    • 2002-04-09
    • US09552356
    • 2000-04-19
    • Puwen ZhangArthur A. SantilliAndrew FensomeEugene A. TerefenkoAndrew Q. VietJay E. WrobelJames P. EdwardsTodd K. JonesChristopher M. TegleyLin Zhi
    • Puwen ZhangArthur A. SantilliAndrew FensomeEugene A. TerefenkoAndrew Q. VietJay E. WrobelJames P. EdwardsTodd K. JonesChristopher M. TegleyLin Zhi
    • A61K31535
    • C07D498/04
    • This invention provides compounds of the formula: wherein: A, B and D are N or CH, with the proviso that A, B and D can not all be CH; R1 and R2 are independent substituents selected from H, CORA, NRBCORA, or optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or groups; or R1 and R2 are fused to form an optionally substituted 3 to 8 membered spirocyclic or heterocyclic ring; RA is H or optionally substituted alkyl, aryl, alkoxy, or aminoalkyl; RB is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl; R3 is H, OH, NH2, or optionally substituted alkyl, or alkenyl, or CORC; RC is H or optionally substituted alkyl, aryl, alkoxy, or aminoalkyl; R4 is a substituted benzene ring or a five or six membered ring with 1, 2, or 3 heteroatoms from the group including O, S, SO, SO2 or NR5; RF is H or optionally substituted alkyl, aryl, alkoxy, or aminoalkyl; RG is H, alkyl, or substituted alkyl; R5 is H or alkyl; Q is O, S, NR6, or CR7R8; R6 is CN, SO2CF3, or optionally substituted alkyl, cycloalkyl, aryl, or heterocyclic ring; R7 and R8 are H, NO2, CN CO2R9, or optionally substituted alkyl, cycloalkyl, aryl, or heterocyclic; R9 is C1 to C3 alkyl; or CR7R8 form a six membered ring of the structure below: W is O or a chemical bond; or a pharmaceutically acceptable salt thereof, as well as their use and pharmaceutical compositions as agonists and antagonists of the progesterone receptor.
    • 本发明提供下式的化合物:其中:A,B和D为N或CH,条件是A,B和D不能全部为CH; R1和R2是选自H,CORA,NRBCORA或任选取代的烷基,烯基,炔基,环烷基,芳基或基团的独立取代基; 或R 1和R 2稠合形成任选取代的3至8元螺环或杂环; RA为H或任选取代的烷基,芳基,烷氧基或氨基烷基; RB是H,C 1至C 3烷基或取代的C 1至C 3烷基; R3是H,OH,NH2或任选取代的烷基或烯基或CORC; RC为H或任选取代的烷基,芳基,烷氧基或氨基烷基; R4是取代的苯环或具有1,2或3个杂原子的五或六元环,所述杂原子包括O,S,SO,SO 2或NR 5; RF是H或任选取代的烷基,芳基,烷氧基或氨基烷基; RG是H,烷基或取代的烷基; R5是H或烷基; Q是O,S,NR6或CR7R8; R6是CN,SO2CF3或任选取代的烷基,环烷基,芳基或杂环; R 7和R 8是H,NO 2,CN CO 2 R 9或任选取代的烷基,环烷基,芳基或杂环; R9为C1至C3烷基; 或CR7R8形成以下结构的六元环:W为O或化学键; 或其药学上可接受的盐,以及它们的用途和药物组合物作为孕激素受体的激动剂和拮抗剂。