1253954-99-2

Upstream product

• 5332-26-3 N-(bromomethyl)phtalimide 
• 243641-04-5 methyl 2-(4-(triisopropylsilyloxy)phenyl)acetate 
• 80522-42-5 triisopropylsilyl trifluoromethanesulfonate 
• 14199-15-6 Methyl 4-hydroxyphenylacetate 

Downstream Products

• 1253955-00-8 2-(2-carboxy-2-(4-(triisopropylsilyloxy)phenyl)ethylcarbamoyl)benzoic acid 
• 1253955-01-9 3-(1,3-dioxoisoindolin-2-yl)-N-(isoquinolin-6-yl)-2-(4-(triisopropylsilyloxy)phenyl)propanamide 
• 1253955-03-1 tert-butyl 3-(isoquinolin-6-ylamino)-3-oxo-2-(4-(triisopropylsilyloxy)phenyl)propylcarbamate 
• 1253955-04-2 tert-butyl 2-(4-hydroxyphenyl)-3-(isoquinolin-6-ylamino)-3-oxopropylcarbamate 

Relevant academic research and scientific papers

BETA-AMINO-ISOQUINOLINYL AMIDE COMPOUNDS

Disclosed are alpha-axyl-beta-axmno isoquinoline amide compounds and substituted benzamide compounds. In particular, the invention provides compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds of the invention are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovascular diseases, and diseases characterized by abnormal growth, such as cancers. The invention further provides compositions containing isoquinoline amide compounds.

Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma

Inhibition of Rho kinase (ROCK) to improve fluid outflow through the trabecular meshwork and lower intraocular pressure is a strategy for the development of new anti-glaucoma agents. Alpha-aryl-beta-amino isoquinoline analogs were identified as potent ROCK inhibitors. Compounds that provided a longer duration of intraocular pressure reduction in Dutch Belted rabbits also inhibited norepinephrine transporter. Ester 60 improved bioavailability of its parent ROCK inhibitor, 29 (Ki = 0.2 nM) and demonstrated an effective and sustained IOP reduction for 24 h after dosing. From these studies, netarsudil (a.k.a. AR-13324) was discovered and is currently in clinical trials for the treatment of glaucoma and ocular hypertension.

DUAL-ACTION INHIBITORS AND METHODS OF USING SAME

Provided are compounds, compositions, and methods for treating diseases and conditions wherein an inhibitor of a kinase, such as rho kinase (ROCK), and an inhibitor of one or more of the monoamine transporters, such as NET or SERT, act in concert to improve the condition.