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