Non-steroidal progesterone receptor modulators

摘要: Amino compounds and their salts are new. of formula (C(R 1>)(R 2>)(A)-C(OH)(Y 1>-R 3>)-C(=X)-NH-R 4>) (I) A : 1-8C-alkyl, 2-8C-alkenyl, 2-8C-alkynyl (all optionally substituted by one or more Z), H, 3-10C-cycloalkyl 3-12-membered heterocycloalkyl residue (optionally replaced M); Z CN, halo, OH, nitro, C(O)R1b, CO 2R1b, O-R1b, S-R1b, SO 2NRR1cR1d, C(O)-NR1cR1d, OC(O)-NR1cR1d, C=NOR1b, NR1cR1d, PO 3(R1b) 2, NR1eCOR1b, NR1eCSR1b, NR1eS(O)R1b, NR1eS(O) NR1eCONR1cR1d, NR1eCOOR1b, NR1eC(NH)NR1cR1d, NR1eCSNR1cR1d, NR1eS(O)NR1cR1d, NR1eS(OH)NR1cR1d, S(O)NR1b, S(O)NR1cR1d, S(O) 2OR1b, CSNR1cR1d CR1b(OH)R1b; R1b 1-6C-alkyl, hydroxy-1-3C-alkyl, 1-3C-alkoxy-1-3C-alkyl, 2-8C-alkynyl, 3-10C-cycloalkyl, 6-12C-aryl a partially completely fluorinated 1-3C-fluoroalkyl; either R1c 1-6C-alkyl W 1>, 6-12C-aryl, 5-12-membered heteroaryl, C(O)R1b OH (preferred); R1d preferred), OH; R1cR1dN 3-7-membered ring containing O, S NR1f; R1f 1-3C-alkyl, 1-3C-alkanoyl, 1-3C-alkylsulfonyl 1-3C-alkoxycarbonyl; 1>NR 9>R1h; R 9>, R1h H 1-3C-alkyl; 9>R1h R1e 3-10C-cyclo-alkyl 6-12C-aryl; M COR1b, O-R1b NR1cR1d; 2>1-5C-alkyl Z; 1>R 2>C carbocyclic with 3-7 membered heterocyclic ring; 3>H 1-8C-alkyl K 1>), 3-12 (hetero)aryl L); 1>CN, 2NR1cR1d, M), L 1-6C-fluoroalkyl, 1-6C-fluoroalkoxy, 1-6C-alkoxy-1-6C-alkyl, 1-6C-alkoxy-1-6C-alkoxy, mono- bicyclic (CH 2) p-3-10C-cycloalkyl, p-heterocycloalkyl, pCN, pHal, pNO p-6-12C-aryl V 1>of , p-heteroaryl pPO pNR1cR1d, pNR1eCOR1b, pNR1eCSR1b, pNR1eS(O)R1b, pNR1eS(O) pNR1eCONR1cR1d, pNR1eCOOR1b, pNR1eC(NH)NR1cR1d-(CH pNR1eCSNR1cR1d, pNR1eS(O)NR1cR1d, pCOR1b, pCSR1b, pS(O)R1b, pS(O)(NH)R1b, pS(O) pSO pCO pCONR1cR1d, pCSNR1cR1d, pOR1b, pSR1b, pCR1b(OH)-R1b, p-C=NOR1b, O-(CH n-O, n-CH O-CH=CH n+2, where the terminal O C atom is directly bonded carbon atom; n 1 2; p 0-6; (O)-NR1cR1d, 1-6C-fluoroalkyl 1-6C-fluoroalkoxy; X 2H; Y 1>(CH m, -C=C- -CH=CH-; m 0 1; 4>3-12 mono (hetero)aromatic 1-3 substituents L), benzo[d][1,2]oxazin-1-one group (a), 3,4-dihydro-2H-naphthalen-1-one (b), 2H-naphthalen-1-one (c), isochroman-1-one (d), isochromen-1-one (e), 2H-isoquinolin-1-one (f), quinazoline (g), quinoline (h), 3H-isobenzofuran-1-one (a1), 3H-benzo[c]thiophen-1-one (b2), indan-1-one (c2), 2,3-dihydro-isoindol-1-one (d2), 1H-benzotriazole (e2), benzo[1,2,5]oxadiazole (f2), benzo[1,2,5]thiadiazole (g2), inden-1-one (h2), 2,3-dihydro-benzo[b]thiophene 1-oxide (i2), benzo[b]thiophene (j2) 1,1-dioxide (k2), (l2), groups (a)-(h) to base structure at 5th, 6th, 7th 8th position (a2)-(l2) basestructure 4th, 6th position; 5>H, 1-4C-alkyl 1-4C-fluoroalkyl; R6a, R6b R6aR6bC 3-6-membered ring. Provided that when is: then 1>is CH 3, 2>is not 3or 2H 5, 1>and 2>do combine form 3-4 2>are simultaneously cyclopropyl An independent claim included for pharmaceutical composition comprising least further active agent together auxiliary materials and/or carrier materials. [Image] ACTIVITY Gynecological; Analgesic; Cytostatic; Endocrine-Gen.; Contraceptive. MECHANISM OF ACTION Progesterone receptor modulator; binder. The progesterone antagonist activity was tested in uterus-cytosol estradiol-primed rabbit using transactivation assay (as described ). results showed (-)-N-(3-chloro-4-cyanophenyl)-2-hydroxy-2-cyclohexyl-2-phenylethynylacetamide exhibited an IC 50value 1.8 nM.