title: Design and optimization of quinazoline derivatives as melanin concentrating hormone receptor 1 (MCHR1) antagonists: part 2.
abstract: Melanin concentrating hormone receptor 1 (MCHR1) antagonists have potential for the treatment of obesity and several CNS disorders. In the preceding article, we have described a novel series of quinazolines as MCHR1 antagonists and demonstrated in vivo proof of principle with an early lead. Herein we describe the detailed SAR and SPR studies to identify an optimized lead candidate having good efficacy in a sub-chronic DIO model with a good cardiovascular safety window.
authors.affiliation: Discovery Research, Dr. Reddy's Laboratories Ltd, Bollaram Road, Miyapur, Hyderabad 500049, India. pradipks@drreddys.com
authors.forename: Sanjita
authors.initials: S
authors.lastname: Sasmal
authors.forename: D
authors.initials: D
authors.lastname: Balasubrahmanyam
authors.forename: Hariprasada R
authors.initials: HR
authors.lastname: Kanna Reddy
authors.forename: Gade
authors.initials: G
authors.lastname: Balaji
authors.forename: Gujjary
authors.initials: G
authors.lastname: Srinivas
authors.forename: Srisailam
authors.initials: S
authors.lastname: Cheera
authors.forename: Chandrasekhar
authors.initials: C
authors.lastname: Abbineni
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Sasmal
authors.forename: Ish
authors.initials: I
authors.lastname: Khanna
authors.forename: V J
authors.initials: VJ
authors.lastname: Sebastian
authors.forename: Vikram P
authors.initials: VP
authors.lastname: Jadhav
authors.forename: Manvendra P
authors.initials: MP
authors.lastname: Singh
authors.forename: Rashmi
authors.initials: R
authors.lastname: Talwar
authors.forename: J
authors.initials: J
authors.lastname: Suresh
authors.forename: Dhanya
authors.initials: D
authors.lastname: Shashikumar
authors.forename: K
authors.initials: K
authors.lastname: Harinder Reddy
authors.forename: V
authors.initials: V
authors.lastname: Sihorkar
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Frimurer
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Rist
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Elster
authors.forename: Thomas
authors.initials: T
authors.lastname: Högberg
mesh_terms: D002318:Cardiovascular Diseases / Q000517:prevention & control; D015195:Drug Design; D006801:Humans; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
chemical_list: C103263:MCHR1 protein, human; D011799:Quinazolines; D011979:Receptors, Pituitary Hormone; D017481:Receptors, Somatostatin; C092274:melanin-concentrating hormone receptor