Sharif, Naj, Hellberg, Mark, May, Jesse, McLaughlin , Marsha, Chen, Hwang-Hsing, Severns, Bryon, Kelly, Curtis, Holt, William, Young, Richard, Glennon, Richard and Dean , Thomas (2015) Ocular hypotensive response in non-human primates of (R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol (9) a selective 5-HT2 receptor agonist. Journal of Medicinal Chemistry, 58 (22). pp. 8818-8833. ISSN 0022-26231520-4804

Abstract

Recently it has been reported that 5-HT2 agonists effectively reduce intraocular pressure (IOP) in a non-human primate model of glaucoma. Although,1-((S)-aminopropyl)-1H-indazol-6-ol (A, AL-34662, Figure 1) was shown to have good efficacy in a non-human primate (NHP) model of ocular hypertension as well as a desirable physicochemical and permeability profile cardiovascular side effects preclude the development of this compound. Herein, we report selected structural modifications resulted in the identification of (R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol (9), which displayed an acceptable profile to support advancement for further preclinical evaluation as a candidate for proof-of-concept studies in man.

Item Type:	Article
Date Deposited:	12 Oct 2016 00:45
Last Modified:	12 Oct 2016 00:45
URI:	https://oak.novartis.com/id/eprint/25479