On May 14, 2020, Lee, Matthew Randolph; Varano, Anthony Joseph published a patent.Reference of 4-Bromo-5-nitroisoquinoline The title of the patent was Sulfonylisoquinoline derivatives as Rock kinase inhibitors and their preparation. And the patent contained the following:
The invention relates to compounds of formula I as Rho-associated protein kinases (ROCK) inhibitors useful for treatment of cerebral cavernous malformation syndrome and cardiovascular diseases. Compounds of formulas I and II wherein ring X is partially saturated aza-containing heteroaryl; Y is CH or N; m is 0, 1, 2 and 3; each R1 is independently CN, OH, hydroxyalkyl, halo, etc.; R2 is H and halo; R3 is H, halo and C1-3 alkyl; with provisions; and pharmaceutically acceptable salts thereof, are claimed. Example compound III was prepared by sulfonylation of 1-chloroisoquinoline with chlorosulfonic acid; the resulting 1-chloroisoquinoline-5-sulfonyl chloride underwent hydrolysis to give 1-hydroxyisoquinoline-5-sulfonic acid, which underwent chlorination to give the corresponding sulfonyl chloride, which underwent amidation with 4-methylisoindoline to give compound III. Exemplified I were evaluated for selective ROCK kinase inhibitory activity from which III demonstrated IC50 values in the range of >1000 nM and ≤10,000 nM for both ROCK1 and ROCK2 compared to IC50 values of >10,000 for PKACA, AKT1, and PKG, resp. The experimental process involved the reaction of 4-Bromo-5-nitroisoquinoline(cas: 58142-46-4).Reference of 4-Bromo-5-nitroisoquinoline
The Article related to sulfonylisoquinoline derivative preparation rock kinase inhibitor cavernous malformation syndrome, selective rock1 rock2 inhibitor cardiovascular disease, Heterocyclic Compounds (One Hetero Atom): Quinolines and Isoquinolines and other aspects.Reference of 4-Bromo-5-nitroisoquinoline
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem