Prodrugs of the pyridyl methyl sulfinyl benzimidazoles

C - Chemistry – Metallurgy – 07 – D

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Details

C07D 417/14 (2006.01) A61K 31/4184 (2006.01) A61K 31/4439 (2006.01) C07D 235/28 (2006.01) C07D 401/12 (2006.01) C07D 401/14 (2006.01) C07D 409/14 (2006.01) C07D 471/04 (2006.01) C07D 491/048 (2006.01) C07D 495/04 (2006.01) C07F 9/6558 (2006.01)

Patent

CA 2338311

Prodrugs of the pyridyl methyl sulfinyl benzimidazole type proton pump inhibitor drugs have a hydrolysable sulfinyl or arylsulfonyl group attached to the benzimidazole nitrogen, or include a group that forms a Mannich base with the benzimidazole nitrogen. The prodrugs of the invention hydrolyse under physiological conditions to provide the proton pump inhibitors with a half life measurable in hours, and are capable of providing sustained plasma concentrations of the proton pump inhibitor drugs for longer time than presently used drugs. The generation of the proton pump inhibitor drugs from the prodrugs of the invention under physiological conditions allows for more effective treatment of several diseases and conditions caused by gastric acid secretion. A prodrug of the invention has the general formula Het1-X-S(O)-Het2.

Cette invention se rapporte à des promédicaments des médicaments inhibiteurs de la pompe à protons du type pyridyle méthyle sulfinyle benzimidazole, qui comportent un groupe sulfinyle ou arylsulfonyle hydrolysable, fixé à l'azote du benzimidazole, ou contiennent un groupe qui forme une base Mannich avec l'azote du benzimidazole. Ces promédicaments s'hydrolysent dans des conditions physiologiques, pour former des inhibiteurs de la pompe à protons ayant une demi-vie mesurable en heures, et ils sont capables de fournir des concentrations de plasma soutenues des médicaments inhibiteurs de la pompe à protons pendant une durée plus longue que les médicaments utilisés actuellement. La production de ces médicaments inhibiteurs de la pompe à protons à partir des promédicaments faisant l'objet de cette invention dans des conditions physiologiques permet un traitement plus efficace de plusieurs maladies et états pathologiques causés par la sécrétion d'acide gastrique.

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