Month: October 2022

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

On December 13, 2007, Arnould, Jean-Claude; Delouvrie, Benedicte; Ducray, Richard; Lambert-Van Der Brempt, Christine Marie Paul published a patent.COA of Formula: C15H22N2O3 The title of the patent was Preparation of tyrosine derivatives, especially N-(benzoyl)-O-[2-[(pyridin-2-yl)amino]ethyl]-L-tyrosines and related compounds, as α5β1 integrin antagonists for treating solid tumors. And the patent contained the following:

The invention is related to tyrosine derivatives I [Xa = O, S; R1 = Br, Cl, cyclopentylmethyl, C1-3 alkyl, etc.; R2, each R3 = independently H, halo, CN, OH, NH2, (un)substituted alk(en/yn)yl, alkanoylamino, N-alkylsulfamoyl, etc.; or R2R3 = C1-3 alkylenedioxy; m = 0-3; R4 = H, (un)substituted heterocyclyl, heteroaryl, etc.; A = Ph, pyridinyl, thiophenyl; n = 0-4; each R5 = independently halo, OH, SH, carbamoyl, sulfamoyl, alkylsulfonyl, alkynoylamino, etc.; or 2 R5’s optionally form a C1-3 alkylenedioxy; X = a bond, O, S, SO, SO2, CO, (un)substituted CH:CH, etc.; Y = (un)substituted alkylene, cycloalk(en)ylene, heterocyclyl; Z = a bond, O, S, (un)substituted alkylene, CC, etc.;] and their pharmaceutically acceptable salts and prodrugs, to processes for preparing them, and to pharmaceutical compositions containing them for use as α5β1 integrin antagonists in the treatment in warm-blooded animals such as humans of diseases that have a significant angiogenesis or vascular component such as for treatment of solid tumors. The invention is also related to α5β1 antagonists that also exhibit appropriate selectivity profile(s) against other integrins. Thus, etherification of tert-Bu 7-(2-hydroxyethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate with Me N-(2,6-dichlorobenzoyl)-L-tyrosinate (preparation given), cleavage of the tert-butoxycarbonyl group and saponification of the Me ester gave tyrosine derivative II. The effects of compounds I as α5β1 integrin inhibitors were tested (e.g., the invention compound II had IC50 values of 0.0004 μM in a binding assay and 0.002 μM in an adhesion 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).COA of Formula: C15H22N2O3

The Article related to tyrosine preparation alpha5beta1 integrin antagonist solid tumor, antitumor benzoyl pyridinylaminoethyl tyrosine derivative preparation alpha5beta1 integrin antagonist, Amino Acids, Peptides, and Proteins: Amino Acids and other aspects.COA of Formula: C15H22N2O3

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

On May 20, 2010, Shipps, Gerald W., Jr.; Cheng, Cliff C.; Achab, Abdelghani Abe; Yao, Zhiping; Whitehurst, Charles E.; Zhang, Mingxuan; Yang, Xianshu; Herr, Robert Jason; Zych, Andrew John; Roy, Sudipta; Yang, Jinhai published a patent.Electric Literature of 445490-78-8 The title of the patent was Preparation of benzyltetrahydronaphthyridinylethylurea derivatives and analogs for use as HIV blockers. And the patent contained the following:

Title compounds I [L = (un)substituted urea, isothiourea, sulfamide, etc.; R1 = (un)substituted tetrahydronaphthalene, tetrahydronaphthyridine, dihydrobenzothio pyran; each R2 independently = H, (un)substituted alkyl, or cycloalkyl; each R3 independently = H, (un)substituted alkyl, cycloalkyl, or aryl; R4 = (un)substituted aryl, cycloalkyl, or heteroaryl ring containing 1 to 3 heteroatoms selected from O, S, or N; m = 1 to 3; n = 0 to 2], and their pharmaceutically acceptable salts, are prepared and disclosed as HIV blockers. Thus, e.g., II was prepared by coupling of 3,4-dichlorobenzyl isocyanate with 2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethanamine hydrochloride. Select I were evaluated in HIV CXCR4 affinity assays, e.g., II demonstrated an IC50 value of 2.4 μM. 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).Electric Literature of 445490-78-8

The Article related to naphthyridinylethylurea benzyltetrahydro derivative preparation hiv blocker, benzyltetrahydronaphthyridinylethylurea analog preparation hiv blocker, Heterocyclic Compounds (One Hetero Atom): Pyridines and other aspects.Electric Literature of 445490-78-8

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

On October 6, 2008, Harris, Craig S.; Germain, Herve; Pasquet, Georges published an article.Quality Control of tert-Butyl 7-(2-hydroxyethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate The title of the article was Facile preparation of thiophene C2-ethers using the Mitsunobu reaction. And the article contained the following:

The preparation of thiophene ethers generally requires forcing conditions thus limiting the choice of alkyl substituent. Herein, we report the first successful generally applicable conditions for the selective O-alkylation of 2(5H)-thiophenone. 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).Quality Control of tert-Butyl 7-(2-hydroxyethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

The Article related to thiophenone alc mitsunobu alkylation, thiophene ether preparation, Heterocyclic Compounds (One Hetero Atom): Thiophenes and other aspects.Quality Control of tert-Butyl 7-(2-hydroxyethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

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

On October 20, 2016, Fukunaga, Hirofumi; Dozono, Hiroyuki; Hino, Akihiro; Oshikiri, Shinobu; Nagano, Akio published a patent.Computed Properties of 445490-78-8 The title of the patent was Therapeutic or diagnostic agents for integrin-related disease comprising nitrogen-containing compounds metal complexes. And the patent contained the following:

Disclosed is a therapeutic or diagnostic agents for integrin-related disease comprising metal complexes with nitrogen-containing compounds The nitrogen-containing compounds are, represented by formula I [A1 = chelate group; R1, R2 = H, (un)substituted C1-6 alkyl, amino protective group; Z1-Z5 = N, CR3; R3 = H, halo, (un)substituted C1-6 alkyl, (un)substituted pyridinyl-containing sulfonyl group; L1 = [NR13(CR14CR15O)qCR16CO]r; L2, L3 = (un)substituted C1-6 alkylene; R13 = H, (un)substituted C1-6 alkyl, amino protective group; R14, R15 = H, (un)substituted C1-6 alkyl; R16 = H, (un)substituted C1-6 alkyl, aromatic or heterocycle amide-containing group]. Thus, reacting tetrahydronaphthyridine terminal-containing cysteic acid (preparation given) with tri-tert-Bu 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate, and deprotecting tert-Bu groups with aqueous LiOH, gave tetraazacyclododecane ring-containing tricarboxylic acid. The tetraazacyclododecane ring-containing tricarboxylic acid can give complexes with radioactive metals showing high concentration and retention in the cancer cells. 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).Computed Properties of 445490-78-8

The Article related to heterocycle metal complex preparation integrin disorder cancer radiopharmaceutical diagnostic, Radiation Biochemistry: Disease Diagnosis and Therapy and other aspects.Computed Properties of 445490-78-8

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

On May 17, 2018, Ye, Xiang-Yang; Morales, Christian L.; Higgins, Mendi A.; Mull, Eric published a patent.Name: tert-Butyl 7-(2-hydroxyethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate The title of the patent was Indazole derivatives as αV integrin antagonists and their preparation. And the patent contained the following:

The invention provides compounds of formula I or II, or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αV- containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αV-containing integrins, such as pathol. fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions Compounds of formula I and II wherein A, E, G and J are independently N,C and NH, with the proviso that at least one of A, E, G and J is C and attached to Y; X is (un)substituted C1-4 alkylene; Y is a bond, O, S, NH, C1-3 alkoxy, etc.; R1 is guanidino, (un)substituted imidazolylamino, (un)substituted pyridinylamino, (un)substituted benzimidazolylamino, etc.; R2 is H, halo and c1-6 alkyl; R3 is H, C1-6 alkyl, C3-10 carbocyclyl, etc.; R3a is H; R3R2a can be taken together to form (un)substituted C3-6 carbocyclyl and (un)substituted 3- to 6-membered heterocyclyl; R4 is H, C1-6 alkyl, C3-10 carbocyclyl, etc.; R5 is H, (un)substituted C1-6 alkyl, (un)substituted Ph, (un)substituted benzyl, etc.; dashed bonds are single and double bonds; and pharmaceutically acceptable salts thereof, are claimed. Example compound III was prepared by a multistep procedure (procedure given). The invention compounds were evaluated for their αVβ6 integrin antagonistic activity. From the assay, it was determined that compound III exhibited IC50 value of 1600 nM. 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).Name: tert-Butyl 7-(2-hydroxyethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

The Article related to indazole preparation integrin alpha v antagonist, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazoles and other aspects.Name: tert-Butyl 7-(2-hydroxyethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

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

On May 17, 2018, Zhao, Guohua; Devasthale, Pratik; Ye, Xiang-Yang; Selvakumar, Kumaravel; Dhanusu, Suresh; Balasubramanian, Palanikumar; Guernon, Leatte R.; Civiello, Rita; Han, Xiaojun; Parker, Michael F.; Jacutin-Porte, Swanee E. published a patent.Synthetic Route of 445490-78-8 The title of the patent was 3-Substituted propanoic acids as alpha V integrin inhibitors and their preparation. And the patent contained the following:

The invention provides compounds of formula I or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αV-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αV-containing integrins, such as pathol. fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions Compounds of formula I wherein A, E and G are independently N, O, S, NH and derivatives, CHR6b and CR6b; M and L are N and C, with the proviso that M and L are not both N; Z is (un)substituted C1-6 alkylene; Z is a bond, O, S, NH, (un)substituted O-C1-3 alkylene, etc.; R1 is guanidino, (un)substituted imidazolylamino, (un)substituted pyridinylamino, (un)substituted benzimidazolyl, etc.; R2 is H and C1-6 alkyl; R3 is H, C1-6 alkyl, C3-10 carbocyclyl, C6-10 aryl, etc.; R2R3 an be taken together to form and (un)substituted carbocyclyl and heterocyclyl; R4 is H, C1-10 alkyl, C3-10 carbocyclyl, 3- to 10-membered heterocyclyl, R5 is H, (un)substituted C1-6 alkyl, (un)substituted Ph, (un)substituted benzyl, etc.; R6b is H, halo, CN, NO2, OH, etc.; and pharmaceutically acceptable salts thereof, are claimed. Example compound II was prepared by a multistep procedure (procedure given). The invention compounds were evaluated for their αV integrin inhibitory activity. From the assay, it was determined that compound II exhibited IC50 value of 50 nM, 2.4 nM, 1.5 nM and 262 nM towards αVβ6, αVβ3, αVβ5 and αVβ8, resp. 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).Synthetic Route of 445490-78-8

The Article related to substituted propanoic acid preparation alpha v integrin inhibitor, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazoles and other aspects.Synthetic Route of 445490-78-8

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