Design, synthesis and evaluation of biological activity of novel fasudil analogues was written by Li, Hang;Wang, Donghua;Liu, Shuai;Sun, Changhai;Chen, Meizhu;Wang, Xinran;Chen, Ligong. And the article was included in Pharmazie in 2014.Synthetic Route of C14H18ClN3O2S This article mentions the following:
Nine isoquinoline Rho kinase inhibitors were designed and synthesized on the basis of a ligand-binding pocket model. With fasudil, the only Rho kinase inhibitor marketed to date, as a reference compound, their biol. activities were determined, including assays of Rho kinase inhibitory activity, synapse formation, cell viability. Bio-assays were performed by means of MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays and lactate dehydrogenase (LDH) assays. The obtained results indicated that (R)-6H-1-(5-isoquinolinesulfonyl)-2-hydroxy methyl-1-pyrrolidine and (R)-6H-1-(5-isoquinolinesulfonyl)-2-chloromethyl-1-pyrrolidine exhibited excellent Rho kinase inhibitory activity, deactivation of Rho kinase led to accelerated synapse formation and enhanced cell viability. Therefore they might be potential candidates for preventing various neurol. disorders. The brief study on the structure-activity relationship of these isoquinoline analogs demonstrated that modification of inhibitors targeting region D of the Rho kinase binding pocket is quite efficacious, the existence of free amino, chloro- or hydroxyl group as binding sites with region D of Rho kinase is necessary for increasing the inhibitory activity. In the experiment, the researchers used many compounds, for example, 5-((1,4-Diazepan-1-yl)sulfonyl)isoquinoline hydrochloride (cas: 105628-07-7Synthetic Route of C14H18ClN3O2S).
5-((1,4-Diazepan-1-yl)sulfonyl)isoquinoline hydrochloride (cas: 105628-07-7) belongs to isoquinoline derivatives. Isoquinoline is a structural isomer of quinoline, which have antiseptic, antipyretic and anti-cyclic properties, and can be used as antimalarial drugs and for the preparation of other antimalarial medicine. It protonates to form salts upon treatment with strong acids, such as HCl. It forms adducts with Lewis acids, such as BF3.Synthetic Route of C14H18ClN3O2S
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem