- Pyrazolopyrimidinones which inhibit type 5 cyclic guanosine 3',5'-monophosphate phosphodiesterase (cGMP PDE5) for the treatment of sexual dysfunction
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Compounds of formulae (IA) and (IB) or pharmaceutically or veterinarily acceptable salts thereof, or pharmaceutically or veterinarily acceptable solvates of either entity, wherein R1 is C1 to C3 alkyl substituted with C3 to C6 cycloalkyl, CONR5R6 or a N-linked heterocyclic group; (CH2)nHet or (CH2)nAr; R2 is C1 to C6 alkyl; R3 is C1 to C6 alkyl optionally substituted with C1 to C4 alkoxy; R4 is SO2NR7R8; R5 and R6 are each independently selected from H and C1 to C4 alkyl optionally substituted with C1 to C4 alkoxy, or, together with the nitrogen atom to which they are attached, form a 5- or 6-membered heterocyclic group; R7 and R8, together with the nitrogen atom to which they are attached, form a 4-R10-piperazinyl group; R10 is H or C1 to C4 alkyl optionally substituted with OH, C1 to C4 alkoxy or CONH2; H is an optionally substituted C-linked 5- or 6-membered heterocyclic group; Ar is optionally substituted phenyl; and n is 0 or 1; are potent and selective cGMP PDE5 inhibitors useful in the treatment of, inter alia, male erectile dysfunction and female sexual dysfunction.
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Page column 54
(2010/02/06)
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- 2--1H-thienoimidazoles. A Novel Class of Gastric H+/K+-ATPase Inhibitors
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2-thienoimidazoles were synthesized and investigated as potential inhibitors of gastric H+/K+-ATPase.The isomers of the two possible thienoimidazole series were found to be potent inhibitors of gastric acid secretion in vitro and in vivo.Structure-activity relationships indicate that especially lipophilic alkoxy, benzyloxy, and phenoxy substituents with additional electron-demanding properties in the 4-position of the pyridine moiety combined with an unsubstituted thienoimidazole lead to highly active compounds with a favorable chemical stability.Various substitution patterns in the thienoimidazole moiety result in lower biological activity.The heptafluorobutyloxy derivative saviprazole (HOE 731, 5d) was selected for further development and is currently undergoing clinical evaluation.Comprehensive pharmacological studies indicate a pharmacodynamic profile different to omeprazole, the first H+/K+-ATPase blocker introduced on the market.
- Weidmann, Klaus,Herling, Andreas W.,Lang, Hans-Jochen,Scheunemann, Karl-Heinz,Rippel, Robert,et al.
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p. 438 - 450
(2007/10/02)
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- SYNTHESES OF A NATURALLY OCCURRING HYDROXAMIC ACID AND ITS ANALOGUES
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A naturally occurring cyclic hydroxamic acid, isolated from Pseudomonas species, and its analogues were synthesized via six steps starting from 2-hydroxy-3-methoxypyridine.The antimicrobial activity of the synthesized compounds is described.
- Ohta, Akihiro,Takahashi, Nobuhiro,Shirokoma, Yasuko
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p. 875 - 884
(2007/10/02)
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- IMIDAZOLYLMETHYLTHIOETHYL DITHIOCARBAMATE COMPOUNDS
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The compounds are dithiocarbamates and isothioureas which are histamine H 2-antagonists. Two compounds of the invention are 2-(5-methyl-4-imidazolylmethylthio)ethyl N-methyldithiocarbamate and S-[2-(5-methyl-4-imidazolyl-methylthio)ethyl]-N-cyano-N'-methylisothiourea.
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