940890-82-4

Upstream product

• 209287-19-4 ferulic acid 
• 24973-22-6 3-methoxy-4-methylbenzaldehyde 
• 940890-71-1 3-(3-methoxy-4-methyl-phenyl)acrylic acid methyl ester 
• 1427527-68-1 C₁₁H₁₁NO₂ 
• 209286-01-1 6-Methoxy-7-methyl-2H-isoquinolin-1-one 

Relevant academic research and scientific papers

Optimisation of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors

Rho kinase is an important target implicated in a variety of cardiovascular diseases. Herein, we report the optimisation of the fragment derived ATP-competitive ROCK inhibitors 1 and 2 into lead compound 14A. The initial goal of improving ROCK-I potency relative to 1, whilst maintaining a good PK profile, was achieved through removal of the aminoisoquinoline basic centre. Lead 14A was equipotent against both ROCK-I and ROCK-II, showed good in vivo efficacy in the spontaneous hypertensive rat model, and was further optimised to demonstrate the scope for improving selectivity over PKA versus hydroxy Fasudil 3.

Isoquinoline derivatives

The invention relates to isoquinoline derivatives having the general Formula I wherein X is O, S or NH; Y is OH or NH2; m is 0, 1 or 2; n is 1 or 2; R1 is H, when Y is NH2; or R. is H, (C1-4)alkyl or halogen, when Y is OH; R2 and R3 are independently H, (C1-4)alkyl or halogen; R is H or (C1-6)alkyl, optionally substituted with OH, (C1-4)-alkyloxy, (C1-4)alkyloxycarbonyl, (C3-7)cycloalkyl, which may optionally comprise a heteroatom selected from O and S, (C6-10)aryl, (C6-10)aryloxy or a 5- or 6-membered heteroaryl group comprising 1-3 heteroatoms independently selected from O, N and S, each aryl or heteroaryl group being optionally substituted with 1-3 substituents independently selected from (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkylsulfonyl and halogen; or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising the same as well as to the use of the isoquinoline derivatives in the treatment of ROCK-I related disorders such as hypertension, atherosclerosis and glaucoma.

ISOQUINOLINE DERIVATIVES

The invention relates to isoquinoline derivatives having the general Formula (I) wherein X is O, S or NH; Y is OH or NH2; m is 0, 1 or 2; n is 1 or 2; R1 is H, when Y is NH2; or R1 is H, (C1-4)alkyl or halogen, when Y is OH; R2 and R3 are independently H, (C1-4)alkyl or halogen; R is H or (C1-6)alkyl, optionally substituted with OH, (C1-4)- alkyloxy, (C1-4)alkyloxycarbonyl, (C3-7)cycloalkyl, which may optionally comprise a heteroatom selected from O and S, (C6-10)aryl, (C6-10)aryloxy or a 5- or 6-membered heteroaryl group comprising 1-3 heteroatoms independently selected from O, N and S, each aryl or heteroaryl group being optionally substituted with 1-3 substituents independently selected from (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkylsulfonyl and halogen; or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising the same as well as to the use of the isoquinoline derivatives in the treatment of ROCK-I related disorders such as hypertension, atherosclerosis and glaucoma.