4743-57-1Relevant articles and documents
Discovery and Optimization of Orally Bioavailable Phthalazone and Cinnolone Carboxylic Acid Derivatives as S1P2 Antagonists against Fibrotic Diseases
Allart, Brigitte,Auberval, Marielle,Blanc, Javier,Borgonovi, Monica,Brys, Reginald,Bucher, Denis,Christophe, Thierry,Coornaert, Beatrice,De Wachter, Maxim,Duys, Inge,El Bkassiny, Sandy,Heckmann, Bertrand,Houvenaghel, Nicolas,Jagerschmidt, Catherine,Jans, Mia,Jansen, Koen,Jaunet, Alex,Lecru, Lola,Letfus, Vatroslav,Mammoliti, Oscar,Marsais, Florence,Menet, Christel,Oste, Line,Palisse, Adeline,Poljak, Tanja,Pujuguet, Philippe,Rupcic, Renata,Saniere, Laurent,Smehil, Mario,Sonck, Kathleen,Triballeau, Nicolas,Tricarico, Giovanni,Waeckel, Ludovic,Wakselman, Emanuelle
, p. 14557 - 14586 (2021/10/20)
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease. Current treatments only slow down disease progression, making new therapeutic strategies compelling. Increasing evidence suggests that S1P2 antagonists could be effective agents against fibrotic diseases. Our compound collection was mined for molecules possessing substructure features associated with S1P2 activity. The weakly potent indole hit 6 evolved into a potent phthalazone series, bearing a carboxylic acid, with the aid of a homology model. Suboptimal pharmacokinetics of a benzimidazole subseries were improved by modifications targeting potential interactions with transporters, based on concepts deriving from the extended clearance classification system (ECCS). Scaffold hopping, as a part of a chemical enablement strategy, permitted the rapid exploration of the position adjacent to the carboxylic acid. Compound 38, with good pharmacokinetics and in vitro potency, was efficacious at 10 mg/kg BID in three different in vivo mouse models of fibrotic diseases in a therapeutic setting.
Synthesis, antimicrobial and cytotoxicity studies of some novel modified strobilurin derivatives
Sridhara, Ajjanna M.,Reddy, Kallam R. Venugopala,Keshavayya, Jathi,Ambika, Dasannana Malige S.,Gopinath, Vadiraj S.,Bose, Prosenjit,Goud, Sanath Kumar,Peethambar, Sanenahalli K.
scheme or table, p. 849 - 856 (2012/01/05)
A series of some new 3-isoxazoline substituted methyl-3-methoxy-2-(4-oxo-3, 4-dihydrophthalazin-1-yl)prop-2-enoate derivatives were designed and synthesized from methyl-(4-oxo-3,4-dihydrophthalazin-1-yl)acetate, which in turn was prepared from phthalic anhydride. The structures of synthesized new compounds were characterized by spectral data and studied for their antimicrobial activities and cytotoxicity. Several of these compounds showed good antimicrobial activity.
Piperazine- and piperidine-derivatives as melanocortin receptor agonists
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Page/Page column 97, (2010/02/06)
The present invention relates to melanocortin receptor agonists of formula I, which is useful in the treatment of obesity, diabetes and male and/or female sexual dysfunction.
