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Design and synthesis of novel annulated thienopyrimidines as phosphodiesterase 5 (PDE5) inhibitors
Author(s) -
ElSharkawy Lina Y.,
ElSakhawy Rowaida A.,
AbdelHalim Mohammad,
Lee Kevin,
Piazza Gary A.,
Ducho Christian,
Hartmann Rolf W.,
Abadi Ashraf H.
Publication year - 2018
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201800018
Subject(s) - cycloalkene , benzylamine , chemistry , cycloheptene , substituent , stereochemistry , selectivity , aryl , ring size , phosphodiesterase , ring (chemistry) , aniline , medicinal chemistry , organic chemistry , enzyme , catalysis , alkyl
Novel cycloalkene‐fused thienopyrimidine analogues with enhanced phosphodiesterase 5 (PDE5) inhibitory properties are presented. The structure of the reported scaffold was modulated through variation of the terminal cycloalkene ring size, as well as by varying the substituents at position 4 through the attachment of different groups including aniline, benzylamine, cyclohexylethylamine, methyl/acetyl/aryl piperazines, and aryl hydrazones. Compound 15Y with a benzylamine substituent and cycloheptene as terminal ring showed the highest PDE5 inhibitory activity with an IC 50 value as low as 190 nM and with good selectivity versus PDE7 and PDE9.