title: Discovery of novel and potent heterocyclic carboxylic acid derivatives as protein tyrosine phosphatase 1B inhibitors.
abstract: A series of novel heterocyclic carboxylic acid based protein tyrosine phosphatase 1B (PTP1B) inhibitors with hydrophobic tail have been synthesized and characterized. Structure-activity relationship (SAR) optimization resulted in identification of several potent, selective (over the highly homologous T-cell protein tyrosine phosphatase, TCPTP) and metabolically stable PTP1B inhibitors. Compounds 7a, 19a and 19c showed favorable cell permeability and pharmacokinetic properties in mouse with moderate to very good oral (% F=13-70) bio-availability.
authors.affiliation: Drug Discovery Facility, Advinus Therapeutics Ltd, Hinjewadi, Pune, India. sujay.basu@advinus.com
authors.forename: Sujay
authors.initials: S
authors.lastname: Basu
authors.forename: Uppuleti Viplava
authors.initials: UV
authors.lastname: Prasad
authors.forename: Dinesh A
authors.initials: DA
authors.lastname: Barawkar
authors.forename: Siddhartha
authors.initials: S
authors.lastname: De
authors.forename: Venkata P
authors.initials: VP
authors.lastname: Palle
authors.forename: Suraj
authors.initials: S
authors.lastname: Menon
authors.forename: Meena
authors.initials: M
authors.lastname: Patel
authors.forename: Sachin
authors.initials: S
authors.lastname: Thorat
authors.forename: Umesh P
authors.initials: UP
authors.lastname: Singh
authors.forename: Koushik
authors.initials: K
authors.lastname: Das Sarma
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Waman
authors.forename: Sanjay
authors.initials: S
authors.lastname: Niranjan
authors.forename: Vishal
authors.initials: V
authors.lastname: Pathade
authors.forename: Ashwani
authors.initials: A
authors.lastname: Gaur
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Reddy
authors.forename: Shariq
authors.initials: S
authors.lastname: Ansari
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1