Heterocyclic Building Blocks-Naphthyridine

On February 29, 2000, Nishijima, Kazumi; Nishida, Hidemitsu; Yamashita, Yoshiaki; Ito, Manabu; Onuki, Yoshiaki; Mizota, Masahiro; Miyano, Sotaro published an article.Electric Literature of 76629-10-2 The title of the article was Synthesis and diuretic activity of bicyclic fused heterocycles containing oxime-O-sulfonic acid moiety. And the article contained the following:

In order to investigate the origin of the loop-type diuretic activity of M17055, several variants were designed and synthesized by modifying the quinolinone skeleton, and their diuretic activities were compared with the lead M17055 and furosemide in dogs. It was found that the neg. charge distribution pattern afforded by the dispositional arrangement of the 4-oxime-O-sulfonic acid and 1-N-acyl carbonyl moiety attached to the tetrahydropyridine ring system is inevitable for the development of the activity, which strongly supports the previously proposed model for the active site of the Na+-K+-2Cl- cotransporter. The experimental process involved the reaction of 7-Chloro-2,3-dihydro-1,8-naphthyridin-4(1H)-one(cas: 76629-10-2).Electric Literature of 76629-10-2

The Article related to oxime sulfonate heterocycle preparation diuretic structure, Pharmacology: Structure-Activity and other aspects.Electric Literature of 76629-10-2

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

On October 10, 2019, Anderson, Niall A.; Campos, Sebastien; Butler, Sharon; Copley, Royston C. B.; Duncan, Ian; Harrison, Stephen; Le, Joelle; Maghames, Rosemary; Pastor-Garcia, Aleix; Pritchard, John M.; Rowedder, James E.; Smith, Claire E.; Thomas, Jack; Vitulli, Giovanni; Macdonald, Simon J. F. published an article.Formula: C15H22N2O3 The title of the article was Discovery of an Orally Bioavailable Pan αv Integrin Inhibitor for Idiopathic Pulmonary Fibrosis. And the article contained the following:

The heterodimeric transmembrane αv integrin receptors have recently emerged as potential targets for the treatment of idiopathic pulmonary fibrosis. Herein, we describe how subtle modifications of the central aromatic ring of a series of phenylbutyrate-based antagonists of the vitronectin receptors αvβ3 and αvβ5 significantly change the biol. activities against αvβ6 and αvβ8. This resulted in the discovery of a pan αv antagonist (compound 39, 4-40 nM for the integrin receptors named above) possessing excellent oral pharmacokinetic properties in rats (with a clearance of 7.6 mL/(min kg) and a bioavailability of 97%). 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).Formula: C15H22N2O3

The Article related to phenylbutyrate derivative preparation oral integrin inhibitor idiopathic pulmonary fibrosis, Pharmacology: Structure-Activity and other aspects.Formula: C15H22N2O3

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

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

On March 15, 2018, Jiang, Lan; Morgans, David John; Bergne, Gustave; Chen, Chun; Li, Hui; Andre, Patrick; Halcomb, Randall Lynn; Cha, Jacob; Hom, Timothy published a patent.Category: naphthyridine The title of the patent was Preparation of N-acyl amino acid compounds as αvβ1 integrin inhibitors for treating tissue specific fibrosis. And the patent contained the following:

The invention is related to the preparation of compounds R1CONHCH(CO2H)CH2ALR2 [R1 = (un)substituted C6-14 aryl or C5-10-membered heteroaryl; R2 = (un)substituted 5- to 10-membered heteroaryl containing at least 2 ring N’s, 3- to 12-membered heterocyclyl containing at least 2 ring N’s, NHR3, etc.; R3 =(un)substituted 5- to 10-membered heteroaryl containing at least 1 ring N, or 3- to 12-membered heterocyclyl containing at least 1 ring N, wherein the 5- to 10- membered heteroaryl and 3- to 12-membered heterocyclyl; -A-L- = -A1-L1-,-A2-L2-, A3; A1 = (un)substituted C3-8 cycloalkyiene, C3-8 cycloalkenylene, C6-14 arylene, 5- to 10-membered heteroarylene or 3- to 12-membered heterocyclylene; A2 = = (un)substituted C3-8 cycloalkyiene, C3-8 cycloalkenylene; A3 = = (un)substituted C5-10 cycloalkyiene, C5-10 cycloalkenylene; L1 = OZ, (un)substituted saturated 3- to 4-membered heterocyclylene, OZX1, etc.; Z = CR5aR5b; R5a, R5b = independently H, C1-6 alkyl; X1 = (un)substituted C1-6 alkylene or C2-6 alkenylene; with the exception of specified compounds], e.g., I, that are αvβ1 integrin inhibitors, pharmaceutical compositions containing them and for treating tissue specific fibrosis. Thus, I was prepared by a multi-step synthesis starting from 2-aminonicotinaldehyde and Et 4-oxopentanoate using Me (2S)-2-[(benzyloxycarbonyl)amino]-3-(4-hydroxyphenyl)propanoate and benzoic acid. The compounds of the invention were tested for αvβ1 integrin inhibition in a cell adhesion assay and in a solid phase integrin αvβ1 binding assay. 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).Category: naphthyridine

The Article related to acyl amino acid alpha v beta 1 integrin inhibitor, preparation acyl amino acid tissue specific fibrosis, Amino Acids, Peptides, and Proteins: Amino Acids and other aspects.Category: naphthyridine

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem