Contraceptive compositions containing antiprogesting and progestinic

• Main Authors: ZHANG PUWEN, G.S. GRUBB, E.A. TEREFENKO
• Format: Patent
• Language: Chinese; English
• Published: 15.12.2004
• Edition: 7
• Subjects: HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

本发明涉及用呈通式(I)的孕激素受体拮抗剂的取代吲哚衍生物或其药学上可接受的盐的周期性联用治疗和疗法：其中R#+[1]和R#+[2]是单取代基或稠合形成螺环或杂螺环；R#+[3]是H、OH、NH#-[2]、C#-[1]-C#-[6]烷基、取代的C#-[1]-C#-[6]烷基、C#-[3]-C#-[6]链烯基、取代的C#-[1]-C#-[6]链烯基、炔基、或取代的炔基、COR#+[C]；R#+[C]是H、C#-[1]-C#-[3]烷基、取代的C#-[1]-C#-[3]烷基、芳基、取代的芳基、C#-[1]-C#-[3]烷氧基、取代的C#-[1]-C#-[3]烷氧基、C#-[1]-C#-[3]氨烷基、或取代的C#-[1]-C#-[3]氨烷基；R#+[4]是H、卤素、CN、NO#-[2]、C#-[1]-C#-[6]烷基、取代的C#-[1]-C#-[6]烷基、炔基、或取代的炔基、C#-[1]-C#-[6]烷氧基、取代的C#-[1]-C#-[6]烷氧基、氨基、C#-[1]-C#-[6]氨烷基、或取代的C#-[1]-C#-[6]氨烷基；和R#+[5]选自5或6元三取代的苯环，其中有1、2或3个杂原子选自O、S、SO、SO#-[2]或NR#+[6]，并含有1或2个各选自以下的取代基：H、卤素、CN、NO#-[2]、氨基、和C#-[1]-C#-[3]烷基、C#-[1]-C#-[3]烷氧基、C#-[1]-C#-[3]氨烷基、COR#+[F]、或NR#+[G]COR#+[F]。这些治疗方法可用于避孕或用于治疗和/或预防继发性闭经、功能失调性出血、子宫平滑肌瘤、子宫内膜异位；多囊性卵巢综合征，子宫粘膜、卵巢、乳腺、结肠、前列腺的癌和腺癌，或将周期性月经出血的副作用最小化。本发明的其他用途还包括刺激摄食。∴ This invention relates to cyclic combination therapies and regimens utilizing substituted indoline derivative compounds which are antagonists of the progesterone receptor having general structure (I): wherein R and R may be single substituents or fused to form spirocyclic or hetero-spirocyclic rings; R 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, COR; R 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; R 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 R 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 NR and containing one or two independent substituents from the group including H, halogen, CN, NO2 , amino, and C1 to C3 alkyl, C1 to C3 alkoxy, C1 to C3 aminoalkyl, COR, or NRCOR; or pharmaceutically acceptable salt thereof. These methods of treatment may be used for contraception or for the treatment and/or prevention of secondary amenorrhea, dysfunctional bleeding, uterine leiomyomata, endometriosis; polycystic ovary syndrome, carcinomas and adenocarcinomas of the endormetrium, ovary, breast, colon, prostate, or minimization of side effects or cyclic menstrual bleeding. Additional uses of the invention inlcude stimulation of food intake.