On March 31, 2007, Raboisson, Pierre; DesJarlais, Renee L.; Reed, Rolanda; Lattanze, Jennifer; Chaikin, Margery; Manthey, Carl L.; Tomczuk, Bruce E.; Marugan, Juan Jose published an article.Related Products of 445490-78-8 The title of the article was Identification of novel short chain 4-substituted indoles as potent αvβ3 antagonist using structure-based drug design. And the article contained the following:
The vitronectin receptor αvβ3 has been identified as a promising potential target for the treatment of osteoporosis, diabetic retinopathy and cancer. The authors have recently reported 5-substituted indoles 3-[5-[2-(5,6,7,8-tetrahydro[1,8]naphthyridin-2-yl)ethoxy]indol-1-yl]-3-(3-pyridyl)propionic acid 3 and 3-[5-[2-(5,6,7,8-tetrahydro[1,8]naphthyridin-2-yl)ethoxy]indol-1-yl]-3-(3,4-methylenedioxyphenyl)propionic acid 4, as an original series of potent αvβ3 antagonists with subnanomolar activity. Ligand-protein docking analyses have been performed to generate binding models of three different chem. classes of known αvβ3 antagonists with αvβ3. Results of this docking study suggested that indoles bearing the basic tetrahydronaphthyridine group at position 4 can easily adopt the correct binding conformation and should be as potent as our current 5-substituted indole leads 3 and 4. This hypothesis was nicely demonstrated by the synthesis of a series of 1,4-disubstituted indoles through a tandem of reactions involving: (i) the N-alkylation of indoles 15 and 22 with propargyl esters and cesium fluoride, and (ii) a Heck coupling reaction between 4-bromoindole and 7-vinyl-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-Bu ester 12, or (iii) a reductive amination involving the N-substituted-4-aminoindole 23 and the BOC-protected tetrahydro[1,8]naphthyridine aldehyde 13. Among the compounds assayed, compound (I) showed the most promising activity on αvβ3 (IC50 = 0.5 nM), and was found to have the same potency as our current leads 3 and 4, while maintaining selectivity over αIIbβIIIa. Moreover, based on the reasonable apparent permeability coefficient in an in vitro CACO-2 cell monolayer assay (Papp apical/basolateral = 2.2 × 10-6 cm/s, Papp basolateral/apical = 2.5 × 10-6 cm/s), I is expected to be absorbed through the intestine in human. Thus, 1,4-disubstituted indole I represents a new lead for this novel class of conformationally restricted αvβ3 antagonists. Addnl., this study validates the pharmacophore model previously postulated and provides an improved basis for further structure-based drug design in the field of αvβ3. The experimental process involved the reaction of tert-Butyl 7-(2-hydroxyethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate(cas: 445490-78-8).Related Products of 445490-78-8
The Article related to pyridylterahydronaphthyridinylethylindol propionate preparation structure integrin antagonist, Pharmacology: Structure-Activity and other aspects.Related Products of 445490-78-8
Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem