October 2022 | Page 4 of 21 | Heterocyclic Building Blocks-Naphthyridine

Kroth, Heiko et al. published their patent in 2011 |CAS: 445490-78-8

The Article related to pyridinediamine preparation amyloid beta protein abnormality ocular disease, glaucoma intraocular pressure amyloidosis naphthyridinylalkyl pyridinylalkyl pyridinediamine preparation and other aspects.SDS of cas: 445490-78-8

On April 21, 2011, Kroth, Heiko; Froestl, Wolfgang; Pfeifer, Andrea; Muhs, Andreas published a patent.SDS of cas: 445490-78-8 The title of the patent was Preparation of 2,6-diaminopyridine compounds for treating diseases associated with amyloid or amyloid-like proteins, especially ocular diseases. And the patent contained the following:

The invention is related to the preparation of diaminopyridines I [the pyridine rings A, B, and C are independently (un)substituted by ≥1 substituents selected from alkyl, NH2 and derivatives, CN, NO2, CO2H, etc.; R1, R2 = independently H, (un)substituted 5-10 membered heteroaryl, alkynyl, cycloalkyl, etc.; L1, L2 = independently NR3CR4R5(CR6R7)p, (CR8R9)qCR10R11NR12; R3, R12 = independently H, CH(:NOH) and derivatives, CONH2 and derivatives, (un)substituted 5-10 membered heterocycloalkylalkyl, etc.; R4-11 = independently SO2NH2 and derivatives, aminocarbonylalkyl, halo, OCONH2 and derivatives, etc.; p = 1-2; q = 0-2] and their pharmaceutical acceptable salts that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein and of diseases or conditions associated with amyloid-like proteins. The invention is also related to the use of I in the treatment of ocular diseases associated with pathol. abnormalities/changes in the tissues of the visual system. Thus, II was prepared by a multi-step synthesis from 2-bromo-6-methylpyridine and inhibited the aggregation of amyloid beta 1-42 peptide in a thioflavin T spectrofluorescence assay (IC50 = 12.9 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).SDS of cas: 445490-78-8

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

Ferrarini, P. L. et al. published their research in European Journal of Medicinal Chemistry in 1990 |CAS: 76629-10-2

The Article related to beta blocker naphthyridine imino ether preparation, adrenergic agonist naphthyridine imino ether preparation, naphthyridine imino ether adrenergic agonist antagonist, antihypertensive naphthyridine imino ether and other aspects.Related Products of 76629-10-2

On August 31, 1990, Ferrarini, P. L.; Mori, C.; Primofiore, G.; Da Settimo, A.; Breschi, M. C.; Martinotti, E.; Nieri, P.; Ciucci, M. A. published an article.Related Products of 76629-10-2 The title of the article was Synthesis and β-blocking activity of (E)- and (Z)-iminoethers of 1,8-naphthyridine. Potential antihypertensive agents. 4. And the article contained the following:

A series of (E)- (I, R = Br, Cl, Me, OMe or OEt, R1 = H or Br; R2 = iso-Pr, tert-Bu) and (Z)-imino ethers (II, R = Br, Cl, Me, OMe or OEt and R2 = iso-Pr or tert-Bu) of 1,8-naphthyridine were prepared from the corresponding ketones by a series of reactions involving oxime formation, reaction with epichlorohydrin followed by reaction with amines. The pharmacol. activities of these compounds were evaluated by using isolated guinea pig atria or trachea, or rat vas deferens. All compounds showed β2 adrenergic agonist and B1-blocking properties. Neither stimulation nor blocking activity was observed on α receptors. The activity was independent of the side-chain and no difference was observed in activity between (E)-I or (Z)-II. The experimental process involved the reaction of 7-Chloro-2,3-dihydro-1,8-naphthyridin-4(1H)-one(cas: 76629-10-2).Related Products of 76629-10-2

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

Raboisson, Pierre et al. published their research in European Journal of Medicinal Chemistry in 2006 |CAS: 445490-78-8

The Article related to pyridopyridineethoxy indolepropanoic acid preparation integrin receptor antagonist, pyridopyridinepropyl indolepropanoic acid preparation integrin receptor antagonist, oxopyrrolopyrimidinepropanoic acid pyridopyridineethoxy preparation integrin receptor antagonist and other aspects.Application of 445490-78-8

On July 31, 2006, Raboisson, Pierre; Manthey, Carl L.; Chaikin, Margery; Lattanze, Jennifer; Crysler, Carl; Leonard, Kristi; Pan, Wenxi; Tomczuk, Bruce E.; Marugan, Juan Jose published an article.Application of 445490-78-8 The title of the article was Novel potent and selective αvβ3/αvβ5 integrin dual antagonists with reduced binding affinity for human serum albumin. And the article contained the following:

Pyridopyridineethoxy- and pyridopyridinepropyl-substituted indolepropanoic acids, a pyridineaminopropoxydihydroindoleacetic acid, and a substituted oxopyrrolopyrimidinepropanoic acid are prepared as potential selective dual αvβ3 and αvβ5 integrin receptor antagonists with decreased binding to human serum albumin (HSA). Ammonium tetrahydronaphthyridinylethoxyindolepropanoate I•NH3 is the most effective of the compounds prepared, with subnanomolar affinity for both αvβ3 and αvβ5 (IC50 = 0.29 and 0.16 nM, resp.), low HSA protein binding (40% bound, Kd = 1.1 ± 0.4 × 103 μM), and improved in vitro stability toward human and mouse microsomes (99.9% and 98.7% remaining after 10 min) over previously prepared integrin receptor antagonists. The selectivities of I•NH3 toward α5β1 and IIbIIIa integrins is comparable to those of the initial lead integrin receptor antagonists. 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).Application of 445490-78-8

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

Asano, Yasutomi et al. published their patent in 2016 |CAS: 76629-10-2

The Article related to acylaminoacylpiperidine preparation serine palmitoyltransferase spt inhibitor, pyrazolopyridinylbenzamide preparation serine palmitoyltransferase spt inhibitor, congenital disease sphingolipid accumulation treatment prevention acylaminoacylpiperidine preparation, cancer niemann pick disease treatment prevention acylaminoacylpiperidine preparation and other aspects.Recommanded Product: 7-Chloro-2,3-dihydro-1,8-naphthyridin-4(1H)-one

On October 27, 2016, Asano, Yasutomi; Kojima, Takuto; Kurasawa, Osamu; Wong, Tzu-Tshin; Hirata, Yasuhiro; Iwamura, Naoki; Saito, Bunnai; Tanaka, Yuta; Arai, Ryosuke; Imamura, Shinichi; Yonemori, Kazuko; Miyamoto, Yasufumi; Kitamura, Shuji; Sano, Osamu published a patent.Recommanded Product: 7-Chloro-2,3-dihydro-1,8-naphthyridin-4(1H)-one The title of the patent was Preparation of 1-acyl-4-acylaminopiperidine derivatives as serine palmitoyltransferase (SPT) inhibitors. And the patent contained the following:

The present invention relates to the title compounds I [ring Ar = each (un)substituted aromatic heterocyclyl or C6-14 aromatic hydrocarbyl; ring A = each (un)substituted C6-14 aromatic hydrocarbyl or heterocyclyl; R1 = each (un)substituted C6-14 aryl, C3-10 cycloalkyl, or heterocyclyl; when R1 is (un)substituted heterocyclyl, R1 = Q or Q1; ring B = (un)substituted heterocyclyl; ring D = (un)substituted N-containing heterocyclyl; R2 = H or R1 and R2 are bonded together to form (un)substituted 5- or 6-membered aromatic heterocyclyl or (un)substituted benzene ring] or salts thereof. These compounds are serine palmitoyltransferase (SPT) inhibitors and potentially useful for treating or preventing SPT-related disease including congenital disease accompanied by sphingolipid accumulation, cancer, and Niemann-Pick disease in mammals. Thus, 188 mg 2-chlorobenzoyl chloride was gradually added to a solution of 283 mg (7-amino-2-methyl-2,5,6,7-tetrahydro-4H-pyrazolo[4,3-b]pyridin-4-yl)(3,4-dimethoxyphenyl)methanone and 270 mg Et3N in 5 mL CH2Cl2 under ice-cooling and the resulting mixture was stirred at room temperature for 1 h to give, after workup and silica gel chromatog., 2-chloro-N-(4-(3,4-dimethoxybenzoyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-b]pyridin-7-yl)benzamide (II). II at 1 μM inhibited 91% human serine palmitoyltransferase (SPT). A capsule and a tablet formulation containing II were described. The experimental process involved the reaction of 7-Chloro-2,3-dihydro-1,8-naphthyridin-4(1H)-one(cas: 76629-10-2).Recommanded Product: 7-Chloro-2,3-dihydro-1,8-naphthyridin-4(1H)-one

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

Wei, Guangfei’s team published research in Scientific Reports in 2021-12-31 | 6882-68-4

Scientific Reports published new progress about Alkaloids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Application of C15H24N2O.

Wei, Guangfei; Chen, Yongzhong; Guo, Xiaotong; Wei, Jianhe; Dong, Linlin; Chen, Shilin published the artcile< Biosyntheses characterization of alkaloids and flavonoids in Sophora flavescens by combining metabolome and transcriptome>, Application of C15H24N2O, the main research area is Sophora flavescens alkaloid flavonoid metabolome transcriptome biosynthesis.

Sophora flavescens are widely used for their pharmacol. effects. As its main pharmacol. components, alkaloids and flavonoids are distributed in the root tissues wherein mol. mechanisms remain elusive. In this study, metabolite profiles are analyzed using metabolomes to obtain biomarkers detected in different root tissues. These biomarkers include alkaloids, phenylpropanoids, and flavonoids. The high-performance liquid chromatog. anal. results indicate the differences in principal component contents. Oxymatrine, sophoridine, and matrine contents are the highest in the phloem, whereas trifolirhizin, maackiain, and kushenol I contents are the highest in the xylem. The transcript expression profiles also show tissue specificity in the roots. A total of 52 and 39 transcripts involved in alkaloid and flavonoid syntheses are found, resp. Among them, the expression levels of LYSA1, LYSA2, AO2, AO6, PMT1, PMT17, PMT34, and PMT35 transcripts are highly and pos. correlated with alkaloids contents. The expression levels of 4CL1, 4CL3, 4CL12, CHI5, CHI7, and CHI9 transcripts are markedly and pos. correlated with flavonoids contents. Moreover, the quant. profiles of alkaloids and flavonoids are provided, and the pivotal genes regulating their distribution in S. flavescens are determined These results contribute to the existing data for the genetic improvement and target breeding of S. flavescens.

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

Ishikawa, Makoto’s team published research in Autophagy in 2021 | 1223001-51-1

Autophagy published new progress about Apoptosis. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Quality Control of 1223001-51-1.

Ishikawa, Makoto; Takaseki, Sanae; Yoshitomi, Takeshi; Covey, Douglas F.; Zorumski, Charles F.; Izumi, Yukitoshi published the artcile< The neurosteroid allopregnanolone protects retinal neurons by effects on autophagy and GABRs/GABAA receptors in rat glaucoma models>, Quality Control of 1223001-51-1, the main research area is neurosteroid allopregnanolone GABR GABA receptor rat glaucoma model; Allopregnanolone; autophagy; glaucoma; intraocular pressure; neurosteroid.

In an ex vivo rat glaucoma model using dissected retinas, the neurosteroid allopregnanolone (AlloP) protects retinal ganglion cells (RGCs) via GABR/GABAA receptors. To determine the involvement of macroautophagy/autophagy in neuroprotection by AlloP, we examined the effects of autophagy activators, rapamycin and torin 2, and autophagy inhibitors, bafilomycin A1 and SAR405, on retinal retinal morphol. and expression of MAP1 LC3B/LC3B (microtubule-associated protein 1 light chain 3 beta) and SQSTM1 (sequestosome 1). Administration of rapamycin or torin 2 exerted partial histol. neuroprotection, while combined administration of AlloP with bafilomycin A1 or SAR405 induced severe degeneration in a hyperbaric condition. Electron microscopic analyses showed that the addition of AlloP significantly increased autophagosomes and degenerative autophagic vacuoles in the retinal nerve fiber layer. Immunoblotting showed that the addition of AlloP or autophagic activators increased the lipidated form of LC3B (LC3B-II) and suppressed SQSTM1. Moreover, bafilomycin A1 increased LC3B-II and SQSTM1 protein levels in the presence of AlloP without changes in corresponding mRNAs compared to AlloP-treated retinas in a hyperbaric condition. These data indicate that AlloP likely induces a protective form of autophagy in this model. In an in vivo rat model of glaucoma, we also observed neuroprotective effects of AlloP. Injection of polystyrene microbeads into the anterior chamber increased intraocular pressure about 3-fold and induced RGC apoptosis. A single intravitreal injection of AlloP or autophagy activators prevented apoptosis and protected RGCs with autophagy activation. We conclude that AlloP may serve as a potential therapeutic agent for the treatment of glaucoma via diverse mechanisms.

Autophagy published new progress about Apoptosis. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Quality Control of 1223001-51-1.

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

Shen, Chen’s team published research in Journal of Immunology in 2018-11-15 | 1223001-51-1

Journal of Immunology published new progress about Adhesion G protein-coupled receptor E1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Product Details of C24H15F3N4O.

Shen, Chen; Chen, Jin Hong; Lee, Youngyi; Hassan, Mehedi Md.; Kim, Su Jin; Choi, Eun Young; Hong, Seong-Tshool; Park, Byung-Hyun; Park, Ji Hyun published the artcile< mTOR- and SGK-mediated connexin 43 expression participates in lipopolysaccharide-stimulated macrophage>, Product Details of C24H15F3N4O, the main research area is mTOR SGK connexin43 peritoneal macrophage bacterial peritonitis.

Connexin 43 (Cx43) deficiency was found to increase mortality in a mouse model of bacterial peritonitis, and Cx43 is upregulated in macrophages by LPS treatment. In this study, we characterized a novel signaling pathway for LPS-induced Cx43 expression in RAW264.7 cells and thioglycolate-elicited peritoneal macrophages (TGEMs). LPS alone or LPS-containing conditioned medium (CM) upregulated Cx43. Overexpression or silencing of Cx43 led to the enhancement or inhibition, resp., of CM-induced TGEM migration. This response involved the inducible NO synthase (iNOS)/focal adhesion kinase (FAK)/Src pathways. Moreover, CM-induced migration was compromised in TGEMs from Cx43+/2 mice compared with TGEMs from Cx43+/+ littermates. Cx43 was upregulated by a serum/glucocorticoid-regulated kinase 1 (SGK) activator and downregulated, along with inhibition of CM-induced TGEM migration, by knockdown of the SGK gene or blockade of the SGK pathway. LPS-induced SGK activation was abrogated by Torin2, whereas LPS-induced Cx43 was downregulated by both Torin2 and rapamycin. Anal. of the effects of FK506 and methylprednisolone, common immunosuppressive agents following organ transplantation, suggested a link between these immunosuppressive drugs and impaired macrophage migration via the Cx43/iNOS/Src/FAK pathway. In a model of Escherichia coli infectious peritonitis, GSK650349-, an SGK inhibitor, or Torin2-treated mice showed less accumulation of F4/80+CD11b+ macrophages in the peritoneal cavity, with a delay in the elimination of bacteria. Furthermore, following pretreatment with Gap19, a selective Cx43 hemichannel blocker, the survival of model mice was significantly reduced. Taken together, our study suggested that Cx43 in macrophages was associated with macrophage migration, an important immune process in host defense to infection.

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

Lei, Lijing’s team published research in Toxins in 2021 | 6882-68-4

Toxins published new progress about Alfalfa. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Safety of (41S,7aR,13aR,13bR)-Dodecahydro-1H-dipyrido[2,1-f:3′,2′,1′-ij][1,6]naphthyridin-10(41H)-one.

Lei, Lijing; Zhao, Yu; Shi, Kai; Liu, Ying; Hu, Yunxia; Shao, Hua published the artcile< Phytotoxic activity of alkaloids in desert plant Sophora alopecuroides>, Safety of (41S,7aR,13aR,13bR)-Dodecahydro-1H-dipyrido[2,1-f:3′,2′,1′-ij][1,6]naphthyridin-10(41H)-one, the main research area is phytotoxic activity oxymatrine Sophora desert plant; Sophora alopecuroides L.; abscisic acid (ABA); alkaloids; allelopathy; antioxidant defense system; cytokinin (CTK); indole-3-acetic acid (IAA); malondialdehyde (MDA).

Sophora alopecuroides is known to produce relatively large amounts of alkaloids; however, their ecol. consequences remain unclear. In this study, we evaluated the allelopathic potential of the main alkaloids, including aloperine, matrine, oxymatrine, oxysophocarpine, sophocarpine, sophoridine, as well as their mixture both in distilled H2O and in the soil matrix. Our results revealed that all the alkaloids possessed inhibitory activity on four receiver species, i.e., Amaranthus retroflexus, Medicago sativa, Lolium perenne and Setaria viridis. The strength of the phytotoxicity of the alkaloids was in the following order: sophocarpine > aloperine > mixture > sophoridine > matrine > oxysophocarpine > oxymatrine (in Petri dish assays), and matrine > mixture > sophocarpine > oxymatrine > oxysophocarpine > sophoridine > aloperine (in pot experiments). In addition, the mixture of the alkaloids was found to significantly increase the IAA content, MDA content and POD activity of M. sativa seedlings, whereas CTK content, ABA content, SOD activity and CAT activity of M. sativa seedlings decreased markedly. Our results suggest S. alopecuroides might produce allelopathic alkaloids to improve its competitiveness and thus facilitate the establishment of its dominance; the potential value of these alkaloids as environmentally friendly herbicides is also discussed.

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

Li, Jian-Chun’s team published research in Bioorganic Chemistry in 2021-05-31 | 6882-68-4

Bioorganic Chemistry published new progress about Anti-HIV agents. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Recommanded Product: (41S,7aR,13aR,13bR)-Dodecahydro-1H-dipyrido[2,1-f:3′,2′,1′-ij][1,6]naphthyridin-10(41H)-one.

Li, Jian-Chun; Dai, Wei-Feng; Liu, Dan; Zhang, Zhi-Jun; Jiang, Ming-Yan; Rao, Kai-Rui; Li, Rong-Tao; Li, Hong-Mei published the artcile< Quinolizidine alkaloids from Sophora alopecuroides with anti-inflammatory and anti-tumor properties>, Recommanded Product: (41S,7aR,13aR,13bR)-Dodecahydro-1H-dipyrido[2,1-f:3′,2′,1′-ij][1,6]naphthyridin-10(41H)-one, the main research area is Sophora Quinolizidine alkaloid anti inflammatory antitumor; Anti-inflammatory; Anti-tumor; Leguminosae; Quinolizidine alkaloids; Sophora alopecuroides.

Forty-three quinolizidine alkaloids (1-43), including twelve new matrine-type ones, sophalodes A-L (1-7, 17, 19 and 28-30), were isolated from the seeds of Sophora alopecuroides. Structurally, compounds 1-4 were the first examples of C-11 oxidized matrine-type alkaloids from Sophora plants. The structures and absolute configurations of new compounds were elucidated by extensive spectroscopic techniques, X-ray diffraction anal., and quantum chem. calculation In addition, the NMR data and absolute configuration of compound 18 was reported for the first time. All the isolates were evaluated for their inhibition on nitric oxide production induced by lipopolysaccharide in RAW 264.7 macrophages, among them, compounds 29, 38 and 42 exhibited the most significant activity with IC50 values of 29.19, 25.86 and 33.30μM, resp. Further research about new compound 29 showed that it also suppressed the protein levels of iNOS and COX-2, which revealed its anti-inflammatory potential. Moreover, addnl. research showed that compound 16 exhibited marginal cytotoxicity against HeLa cell lines, with an IC50 value of 24.27μM.

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

Watanabe, Tatsuro’s team published research in Anticancer Research in 2016-01-31 | 1223001-51-1

Anticancer Research published new progress about Adult T-cell leukemia. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Safety of 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one.

Watanabe, Tatsuro; Sato, Akemi; Kobayashi-Watanabe, Naomi; Sueoka-Aragane, Naoko; Kimura, Shinya; Sueoka, Eisaburo published the artcile< Torin2 potentiates anticancer effects on adult T-cell leukemia/lymphoma by inhibiting mammalian target of rapamycin>, Safety of 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is T cell leukemia lymphoma Torin2 anticancer mTOR signaling; AKT; Adult T-cell leukemia/lymphoma; growth inhibition; mammalian target of rapamycin.

Background: Torin2 is a second-generation ATP-competitive inhibitor of the mammalian target of rapamycin (mTOR). Dysregulation of mTOR signaling pathway, consisting of mTOR complexes mTORC1 and mTORC2, is a promising therapeutic target in some human malignancies. We examined antitumor effects of Torin2 in adult T-cell leukemia/lymphoma (ATL)-related cell lines compared to those of rapamycin, a classical mTOR inhibitor. Materials and Methods: Cell growth was monitored by detecting viable cells with Cell Counting Kit-8 or trypan blue. Cell cycle was studied by flow cytometric anal. The phosphorylation status of proteins in the mTOR signaling pathway was examined by western blot anal. Results: Torin2 exhibited greater efficacy in cell growth inhibition than rapamycin, associated with a strong reduction of phosphorylated v-akt murine thymoma viral oncogene homolog (AKT) (Ser 473), that is downstream of mTORC2. Conclusion: Since mTORC2 activates AKT, Torin2 might inhibit both mTORC1 and mTORC2, resulting in stronger growth inhibition of ATL cells.

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