title: Design and synthesis of novel, potent and selective hypoxanthine analogs as adenosine A1receptor antagonists and their biological evaluation.
abstract: Multipronged approach was used to synthesize a library of diverse C-8 cyclopentyl hypoxanthine analogs from a common intermediate III. Several potent and selective compounds were identified and evaluated for pharmacokinetic (PK) properties in Wistar rats. One of the compounds 14 with acceptable PK parameters was selected for testing in in vivo primary acute diuresis model. The compound demonstrated significant diuretic activity in this model.
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India. Electronic address: summon.koul@advinus.com.
authors.forename: Summon
authors.initials: S
authors.lastname: Koul
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Vidya
authors.initials: V
authors.lastname: Ramdas
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Dinesh A
authors.initials: DA
authors.lastname: Barawkar
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Yogesh B
authors.initials: YB
authors.lastname: Waman
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Neela
authors.initials: N
authors.lastname: Prasad
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Madadi
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Yogesh D
authors.initials: YD
authors.lastname: Shejul
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Bonagiri
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Sujay
authors.initials: S
authors.lastname: Basu
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Suraj
authors.initials: S
authors.lastname: Menon
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Srinivasa B
authors.initials: SB
authors.lastname: Reddy
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Chaturvedi
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Srinivas Rao
authors.initials: SR
authors.lastname: Chennamaneni
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Bedse
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Rhishikesh
authors.initials: R
authors.lastname: Thakare
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Jayasagar
authors.initials: J
authors.lastname: Gundu
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Sumit
authors.initials: S
authors.lastname: Chaudhary
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Siddhartha
authors.initials: S
authors.lastname: De
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Ashwinkumar V
authors.initials: AV
authors.lastname: Meru
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Venkata
authors.initials: V
authors.lastname: Palle
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Anita
authors.initials: A
authors.lastname: Chugh
authors.affiliation: Drug Discovery Unit, Advinus Therapeutics Ltd., Hinjewadi, Pune 411 057, India.
authors.forename: Kasim A
authors.initials: KA
authors.lastname: Mookhtiar
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002853:Chromatography, Liquid; D015195:Drug Design; D057809:HEK293 Cells; D006801:Humans; D007042:Hypoxanthines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D013058:Mass Spectrometry; D066244:Proton Magnetic Resonance Spectroscopy; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D007042:Hypoxanthines
keywords: Adenosine; BG-9928; Diuresis; Glomerular; Hypoxanthine; Rolofylline