New oxindole derivatives useful for treating vasopressin- or oxytocin-dependent diseases

摘要

Oxindole derivatives (I) are new. Oxindole derivatives of formula (I) are new. A : optionally substituted 6-10C aryl; B' : an optionally substituted 6-10C monocyclic or fused bicyclic aromatic or partially aromatic group; R 1>, R 2>H, halo, ACN, CN, 1-6C haloalkyl, 1-6C haloalkoxy, NO 2, AORx1, ORx1, OAAr, OAr, AAr, R, R', OR', 1-4C alkylthio, ANRx2Rx3, NRx2Rx3, ACORx1, CORx1, SO 2Rx1, ACOORx1, COORx1, OACOORx1, ASRx1, SRx1, AAr', Ar', AOCORx1, OCORx1, ASO 2NRx2Rx3, ACONRx2Rx3, CONRx2Rx2, AOCONRx2Rx3, ASORx1, ASO 2Rx1, NHCOOAr, NHCOOAAr or NHCOOAr; or R 1>, R 2>= H or heteroaryl optionally substituted with Rx1; A : 1-4C alkylene; R : 1-6C alkyl; R' : 2-6C alkenyl or alkynyl; Ar : 6-10C aryl or heteroaryl; Ar' : 3-7C cycloalkyl, 3-7C heterocycloalkyl or 3-7C heterocycloalkenyl; Rx1 : H, R, R', (1-4C)alkoxy(1-5C)alkyl, ANHR, ANRR, ACOR,, Ar, AAr, Ar', AAr'; Rx2, Rx3 : Rx1, SO 2Rx1, COORx1, CONRx1Rx1 or CORx1, or Rx2+Rx3 forms a ring; Y : -Ry-Z-; Ry : -NRy1-(CRy2Ry3) n-N((CRy4Ry5) mRy6)-; Ry1-Ry6 : H, 1-6C alkyl or 3-7C cycloalkyl, or pairs of Ry1-Ry6 can form rings; n : 1-3; m : 0-3; Z : optionally substituted 5- or 6-membered heterocyclyl or heteroaryl. [Image] ACTIVITY : Urotropic; Hemostatic; Anticoagulant; Hypotensive; Cardiant; Vasotropic; Nephrotropic; Antiinflammatory; Hepatotropic; Antiulcer; Antiemetic; Antidepressant; Tranquilizer; Nootropic; Neuroprotective; Neuroleptic. MECHANISM OF ACTION : Vasopressin V1b receptor antagonist. 5-Chloro-1-(2,4-dimethoxyphenylsulfonyl)-3-(2-methoxyphenyl)-3-(4-(4-pyridyl)-1-piperazinyl)-1,3-dihydro-2-indolinone had an affinity constant of less than 50 nM for human V1b receptor.