| 摘要 |
A new composition comprises: (1) a 2-phenyl-imidazo (5,1-f) (1,2,4)-triazin-4(3H)-one derivative of formula (I) inhibiting cyclic guanosine monophosphate phosphodiesterase (cGMP PDE); and (2) a local anesthetic (II) (other than benzyl alcohol). A new composition comprises: (1) a 2-phenyl-imidazo (5,1-f) (1,2,4)-triazin-4(3H)-one derivative of formula (I) inhibiting cyclic guanosine monophosphate phosphodiesterase (cGMP PDE); and (2) at least one local anesthetic (II) (other than benzyl alcohol). R1 = H or 1-4C alkyl; R2 = 1-4C alkyl; R3, R4 = 1-5C alkyl (optionally substituted by 1 or 2 of OH or OMe); or NR3R4 = piperidino, morpholino, thiomorpholino or 4-(R7)-piperazino, all optionally substituted (possibly geminally) by 1 or 2 of OH, CHO, COOH, up to 6C acyl or up to 6C alkoxycarbonyl, by 1-6C alkyl (optionally substituted by 1 or 2 of OH or COOH) and/or by pyrrolidino or piperidino; R7 = H, CHO, up to 6C acyl, up to 6C alkoxycarbonyl, 1-6C alkyl (optionally substituted by 1 or 2 of OH, COOH, 1-6C alkoxy or up to 6C alkoxycarbonyl) or 3-8C cycloalkyl); R5, R6 = H, 1-6C alkyl, OH or 1-6C alkoxy. (II) is selected from: (1) compounds of formula (II'); (2) compounds of formula (II''); (3) 2-methoxycarbonyl-4-methyl-3-(2-(propylamino)-propionamido)-thiophene; (4) 2-butoxy-4-(N-(2-diethylaminoethyl)-carbamoyl)-quinoline; (5) 3-butyl-1-(2-dimethylaminoethyl)-isoquinoline; (6) N-(N-(1,1-dimethylpropyl)-N-methylcarbamoylmethyl)-N-(2-hydroxyethyl)-glycine-N-(1,1-dimethyl-2-phenylethyl)-N-methylamide; (7) polydodecanol; and (8) benoxinate. or their salts or hydrates. A1 = H, NH2, NHT, OT or OCH2Ph; T = 1-6C alkyl; A2 = OT (optionally substituted by NHT, NT2 or Het) or -(CH2)p-Het; Het = saturated 5- or 6-membered heterocycle, which contains and is bonded via N, optionally contains 1 or 2 other N, O or S heteroatoms and is optionally substituted by 1-3 T; A3 = H, halo or OT; B1 = H or OH; B2 = -T'-N(T)2 or Het'; T' = 1-6C alkylene (optionally substituted by one or more T); Het' = Het not bonded via N; B3 = T, halo or COOT; p = 1-6; and n = 1 or 2. Independent claims are included for nasal spray applicators or powder inhalers (both preferably of unit dose type) containing the composition. |
