title: Indolin-2-one p38α inhibitors III: bioisosteric amide replacement.
abstract: Crystallographic structural information was used in the design and synthesis of a number of bioisosteric derivatives to replace the amide moiety in a lead series of p38α inhibitors which showed general hydrolytic instability in human liver preparations. Triazole derivative 13 was found to have moderate bioavailability in the rat and demonstrated potent in-vivo activity in an acute model of inflammation.
authors.affiliation: Almirall Research Center, Almirall Laboratories, Ctra. Laureà Miró 408, E-08980 St. Feliu de Llobregat, Barcelona, Spain. paul.eastwood@almirall.com
authors.forename: Paul
authors.initials: P
authors.lastname: Eastwood
authors.forename: Jacob
authors.initials: J
authors.lastname: González
authors.forename: Elena
authors.initials: E
authors.lastname: Gómez
authors.forename: Francisco
authors.initials: F
authors.lastname: Caturla
authors.forename: Nuria
authors.initials: N
authors.lastname: Aguilar
authors.forename: Marta
authors.initials: M
authors.lastname: Mir
authors.forename: Josep
authors.initials: J
authors.lastname: Aiguadé
authors.forename: Victor
authors.initials: V
authors.lastname: Matassa
authors.forename: Cristina
authors.initials: C
authors.lastname: Balagué
authors.forename: Adelina
authors.initials: A
authors.lastname: Orellana
authors.forename: María
authors.initials: M
authors.lastname: Domínguez
mesh_terms: D000577:Amides / Q000737:chemistry*; D000818:Animals; D006860:Hydrogen Bonding; D007211:Indoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D007211:Indoles; D047428:Protein Kinase Inhibitors; C456900:indolin-2-one; D048051:p38 Mitogen-Activated Protein Kinases