Patent FR-2775288-A1 (FR)
Title: New streptogramin B derivatives useful as antibacterial agents and synergists for streptogramin A antibacterial agents - e.g. pyrido- or pyrimidino-pristinamyin IE derivatives
Inventor: DESMAZEAU PASCAL
IPC: A61P31/04
Filed: 1998-02-26
Abstract: Streptogramin B derivatives (I) are new. Streptogramin B derivatives of formula (I) and their salts are new: Y  = N or CR3; R1 = (a) H, 1-8C alkyl, 2-8C alkenyl, 3-8C cycloalkyl, 3- to 8-membered (un)saturated heterocyclyl, Ar or NR'R, or also (b) halomethyl, hydroxymethyl, (1-4C alkoxy)methyl, (1-4C alkylthio)methyl, (1-4C alkylsulfinyl)methyl, (1-4C alkylsulfonyl)methyl, (1-4C acyloxy)methyl, benzoyloxymethyl or (CH2)nNR'R when Y is CR3, or also (c) CHO, COOH, 2-5C alkoxycarbonyl or CONR'R when Y is CH, or also (d) XR or NH2 when Y is N;  Ar = phenyl optionally substituted by halogen, OH, 1-4C alkyl, 1-4C alkoxy, 1-4C alkylthio, 1-4C alkylsulfinyl, 1-4C alkylsulfonyl, NH2, 1-4C alkylamino or di(1-4C alkyl)amino; R', R = H or 1-3C alkyl, or NR'R is a 3- to 8-membered ring that optionally contains another heteroatom selected from O, S or N optionally substituted by 1-4C alkyl, 2-8C alkenyl, 3-6C cycloalkyl, 4- to 6-membered (un)saturated heterocyclyl, benzyl or Ar; n = 1-4; X = O, S, SO, SO2 or NH; R = 1-8C alkyl, 3-6C cycloalkyl, Ar or (CH2)mNR'R; m = 2-4; R2 = H or 1-3C alkyl; R3 = H, 1-4C alkyl, COOH, 2-5C alkoxycarbonyl or CONR'R; Ra = Me or Et; either (1): Rb, Rc = H; and Rd = H, NHMe or NMe2; or (2): Rb = H; Rc = H, Cl, Br or 3-5C alkenyl; and Rd = N(Me)R'; or (3): Rb = H; Rd = NHMe or NMe2; and Rc =  Cl or Br; or (4): Rb = H; Rd = NMe2; and Rc = 3-5C alkenyl; or (5): Rb, Rd = H; and  Rc = halogen, 1-4C alkylamino, di(1-4C alkyl)amino, 1-4C alkoxy, OCF3, 1-4C alkylthio, 1-6C alkyl or trihalomethyl; or (6): Rb, Rc = H; and Rd = halogen, NHEt, NEt2, NMeEt, 1-4C alkoxy, OCF3, 1-4C alkylthio, 1-4C alkylsulfinyl, 1-4C alkylsulfonyl, 1-6C alkyl, phenyl or trihalomethyl; or (7): Rb = H; Rc = halogen, 1-4C alkylamino, di(1-4C alkyl)amino, 1-4C alkoxy, OCF3, 1-4C alkylthio or 1-3C alkyl; and Rd = halogen, NH2, 1-4C alkylamino, di(1-4C alkyl)amino, 1-4C alkoxy, OCF3, 1-4C alkylthio, 1-6C alkyl or trihalomethyl; or (8): Rc = H; Rb, Rd =  Me; R' = 1-4C alkyl, 2-4C hydroxyalkyl, 2-8C alkenyl, phenyl(2-8C)alkenyl, (3-6C cycloalkyl)methyl, CH2Ar, CH2Het, CH2CN or CH2CORe; Het = 5- or 6-membered (un)saturated heterocyclyl containing 1-2 heteroatoms selected from S, O or N optionally substituted by 1-4C alkyl, 2-8C alkenyl, 3-6C cycloalkyl, 4- to 6-membered (un)saturated heterocyclyl, Ar or benzyl; Re = OH, 1-6C alkoxy, 2-6C alkenyloxy, benzyloxy, OCH2Het', 1-4C alkylamino, N-(1-4C alkyl)methylamino, NHHet or N(Me)Het; Het' = 5- or 6-membered heterocyclyl containing 1-2 heteroatoms selected from S, O or N; Het = 5- or 6-membered heterocyclyl containing 1-2 heteroatoms selected from S, O and N optionally substituted by 1-4C alkyl, benzyl or 2-5C alkoxycarbonyl. Independent claims are also included for the following:  (A) intermediates of formula (IX): R5 = H or =CR2R4, provided that Ra = Me and Rb-Rd = (1)-(8) or Ra = Et and Rb-Rd = (2)-(8) when R5 = CR2R4, and that Rb-Rd = (2), except that R' cannot be Et if Rb and Rc = H, when R5 = H; (B) pharmaceutical compositions containing (I) and optionally a streptogramin A derivative;  (C) associations of (I) with at least one streptogramin A derivative selected from pristinamycins IIA-IIG or known semisynthetic derivatives or compounds of formula ( alpha ): R1 = NR'R; R' = H or Me; R = H, alkyl, cycloalkyl, allyl, propargyl, benzyl, OH, alkoxy, cycloalkoxy, allyloxy, propargyloxy, benzyloxy or NR3R4; R3, R4 = Me, or NR3R4 is 4- or 5-membered (un)saturated heterocyclyl optionally containing another heteroatom selected from N, O or S; R2 = H, Me or Et.