Orally administrable acid stable antiulcer benzimidazole derivatives
AssigneeKopran Research Laboratories Limited
InventorsSubhash Mali, Rajan Gupte, Jayant Deshpande, Kamlesh Ranbhan
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Abstract
Orally administrable acid stable anti-ulcer benzimidazole derivatives which are polymer based. The process of preparation comprises condensing a benzimidazole with a biocompatible partially orally biodegradable synthetic cross linked polymer in aqueous medium at 5-80° C. and pH 4-11 under inert atmosphere. The weight percentage of benzimidazole with respect to the polymeric benzimidazole is 1-50. The reaction mixture is cooled and the product is isolated and dried at 25-45° C. There is also provided a formulation of the polymeric benzimidazoles in combination with pharmaceutically acceptable excipients.
Claims17
Orally administrable administrable acid stable anti-ulcer benzimidazole compound of the formula I:
- wherein R6=H or CH3, X=—OCOCH2COO—,
- or —CONHCH2NHCO—, R7=H, CH3, C2H5 or CONH2, Y=OH or NH,, E=—COO—, R is benzimidazole moiety of the formula IIA:
- wherein each of R1, R2, R3, R4, R5=H, C1-12 alkyl, C1-8 (un)substituted aryl, C1-8 alkoxy, C6-12 aryloxy, C1-5 alkoxy carbonyl, C6-12 aryloxy carbonyl, C1-5 alkoxy alkyl, C6-12 alkoxyaryl, C1-5, haloalkyl, C1-5 alkyl, C1-5 haloalkoxy alkyl or C6-12 aryl thioethers, (un)substituted amines or diamines, (un)substituted amides, halo, cyano, nitro, carboxylic acid or carbocyclic or enantiomers thereof;
- or a pharmaceutically acceptable acid addition salt thereof.
A process for the preparation of orally administrable acid stable anti-ulcer benzimidazole compound of the formula I:
- wherein R6=H or CH3, X='OCOCH2COO—,
- or —CONHCH2NHCO—, R7=H, CH3, C2H5 or CONH2, Y=OH or NH2, E=—COO—, B is benzimidazole moiety of the formula IIA:
- wherein each of R1, R2, R3, R4, R5, R5=H, C1-12 alkyl, C6-12 (un)substituted aryl, C1-8 alkoxy, C6-12, aryloxy, C1-5 alkoxy carbonyl, C1-5, alkoxy carbonyl, C1-5 alkoxy alkyl, C6-12 alkoxyaryl, C1-5 haloalkyl C1-5, alkyl, C1-5 haloalkoxy alkyl or C6-12 aryl thioethers, (un)substituted amines or diamines, (un)substituted, amides, halo, cyano, nitro, carboxylic acid or carbocyclic or enantiomers thereof;
- or a pharmaceutically acceptable acid addition salt thereof, the process comprising:
- a) condensing a benzimidazole of the formula II:
- wherein each of R1, R2, R3, R4, R5 is as defined above, with a biocompatible partially orally biodegradable synthetic cross linked polymer of the formula III:
- wherein R6, R7, X and E each is as defined above and Y′=O or N, in aqueous medium at 5-80° C. and pH 4-11 under inert atmosphere and stirring;
- the weight percentage of the benzimidazole with respect to the benzimidazole compound being 1-50;
- b) cooling, isolating and drying the resulting polymeric benzimidazole at 25=45° C.;
- and
- c) if desired, converting the polymeric benzimidazole into a pharmaceutically acceptable acid addition salt.
A composition of an orally administrable acid stable anti-ulcer benzimidazole compound of the formula I:
- wherein R6=H or CH3, X=—OCOCH2COO—,
- or —CONHCH2NHCO—, R7=H, CH3, C2H5 or CONH2, Y=OH or NH2, E=—COO—, B is benzimidazole moiety of the formula IIA:
- wherein each of R1, R2, R3, R4, R5=H, C1-12 alkyl, C6-12 (un)substituted aryl, C1-5, alkoxy, C6-12, aryloxy, C1-3 alkoxy carbonyl, C6-12 aryloxy carbonyl, C1-5 alkoxy alkyl, C6-12 alkoxyaryl, C1-5 haloalkyl, C1-5 alkyl, C1-5 haloalkoxy alkyl or C6-12 aryl thioethers, (un)substituted amities or diamines, (un)substituted amides, halo, cyano, nitro, carboxylic acid or carbocyclic or enantiomers thereof or a pharmaceutically acceptable acid addition salt thereof, in combination with at least one pharmaceutically acceptable excipient.
Dependencies are inferred from the claim text.