title: A review on ROCK-II inhibitors: From molecular modelling to synthesis.
abstract: Rho kinase enzyme expressed in different disease conditions and involved in mediating vasoconstriction and vascular remodeling in the pathogenesis. There are two isoforms of Rho kinases, namely ROCK I and ROCK II, responsible for different physiological function due to difference in distribution, but almost similar in structure. The Rho kinase 2 belongs to AGC family and is widely distributed in brain, heart and muscles. It is responsible for contraction of vascular smooth muscles by calcium sensitization. Its defective and unwanted expression can lead to many medical conditions like multiple sclerosis, myocardial ischemia, inflammatory responses, etc. Many Rho kinase 1 and 2 inhibitors have been designed for Rho/Rho kinase pathway by use of molecular modeling studies. Most of the designed compounds have been modeled based on ROCK 1 enzyme. This article is focused on Rho kinase 2 inhibitors as there are many ways to improvise by use of Computer aided drug designing as very less quantum of research work carried out. Herein, the article highlights different stages of designing like docking, SAR and synthesis of ROCK inhibitors and recent advances. It also highlights future prospective to improve the activity.
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, S.G. Highway, Ahmedabad 382481, Gujarat, India.
authors.forename: Surmil
authors.initials: S
authors.lastname: Shah
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, S.G. Highway, Ahmedabad 382481, Gujarat, India. Electronic address: jignasasavjani@gmail.com.
authors.forename: Jignasa
authors.initials: J
authors.lastname: Savjani
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology; D052160:Benzothiazoles / Q000737:chemistry; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011720:Pyrazoles / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000577:Amides; D052160:Benzothiazoles; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; C108830:Y 27632; D054460:rho-Associated Kinases; C039109:isoquinoline
keywords: Docking; Regulation; Rho kinase-2 (ROCK-2) inhibitors; SAR; Synthesis