Month: October 2022

Jayne, Charles L.; Andreani, Teresa; Chan, Tin-Yau; Chelliah, Mariappan V.; Clasby, Martin C.; Dwyer, Michael; Eagen, Keith A.; Fried, Steve; Greenlee, William J.; Guo, Zhuyan; Hawes, Brian; Hruza, Alan; Ingram, Richard; Keertikar, Kartik M.; Neelamkavil, Santhosh; Reichert, Paul; Xia, Yan; Chackalamannil, Samuel published the artcile< Discovery of hydroxy pyrimidine Factor IXa inhibitors>, Recommanded Product: 4,6-Dichloro-5-methoxypyrimidine, the main research area is hydroxypyrimidine preparation Factor IXa inhibitor structure activity; Factor IXa; Factor IXa inhibition; Pyrimidine; Thrombosis.

The synthesis and structure activity relationship development of a pyrimidine series of heterocyclic Factor IXa inhibitors, I and II [R = Q, Q1, Q2, etc.], is described. Increased selectivity over Factor Xa inhibition was achieved through SAR expansion of the P1 element. Select compounds were evaluated in vivo to assess their plasma levels in rat.

Bioorganic & Medicinal Chemistry Letters published new progress about Blood coagulation factor inhibitors (factor IXa). 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Recommanded Product: 4,6-Dichloro-5-methoxypyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Takahashi, Bitoku; Ohta, Kiminori; Kawachi, Emiko; Fukasawa, Hiroshi; Hashimoto, Yuichi; Kagechika, Hiroyuki published the artcile< Novel Retinoid X Receptor Antagonists: Specific Inhibition of Retinoid Synergism in RXR-RAR Heterodimer Actions>, Related Products of 89793-12-4, the main research area is retinoid X receptor antagonist preparation cell differentiation obesity diabetes; pyrimidinecarboxylate RXR antagonist cell differentiation obesity diabetes.

Several 2-(arylamino)pyrimidine-5-carboxylic acids were designed as novel retinoid X receptor (RXR) antagonists. Two of the tested compounds alone did not exhibit differentiation-inducing activity toward HL-60 cells and did not affect the activity of a retinoic acid receptor (RAR) agonist, Am80, but did inhibit the synergistic activity of an RXR agonist, PA024, in the presence of Am80. The activity of these compounds was ascribed to selective antagonism at the RXR site of RXR-RAR heterodimers.

Journal of Medicinal Chemistry published new progress about Acute promyelocytic leukemia. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Related Products of 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Papavassiliou, G. C.; Yiannopoulos, S. Y.; Zambounis, J. S. published the artcile< Bis(diazino)tetrathiafulvalenes and similar π-donors>, Safety of 4,5-Dichloropyrimidine, the main research area is tetrathiafulvalene bisdiazino; bispyrazinotetrathiafulvalene preparation charge transfer conductivity.

Bis(pyrazino)tetrathiafulvalene (I), bis(quinoxalino)tetrathiafulvalene, bis(pyrimidino)tetrathiafulvalenes, bis(pyridazino)tetrathiafulvalenes, bis(pyrazino)tetraselenafulvalene, and bis(quinoxalino) tetraselenafulvalene were prepared These compounds were found to be π-donors and gave charge transfer salts. The perchlorate salt of I was found to be a 3-D conductor. Thus, 2,3-dimercaptopyrazine was treated with SOCl2 to give the dithiocarbonate II, which was treated with (EtO)3P to give I.

Molecular Crystals and Liquid Crystals published new progress about Electric conductivity. 6554-61-6 belongs to class pyrimidines, and the molecular formula is C4H2Cl2N2, Safety of 4,5-Dichloropyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Timar, M.; Sauvard, S.; Botez, A.; Simionovici, M.; Winter, D.; Georgescu, C. M.; Cristescu, C.; Panaitescu, Th. published the artcile< Pharmacological effects of some 6-azauracil derivatives>, Reference of 4956-05-2, the main research area is .

With respect to the L.D.50 of 6-azauracil derivatives in mice, rats, and dogs, 5-bromo-6-azauracil (180 reg./kg. given intraperitoneally (I.P.) or subcutaneously (s.c.)), 5-dimethylamino-6-azauracil (I) (90 mg./kg. given I.P.), 5-benzylthio-6-azauracil (II) (140 mg./kg. given I.P.), and 5-hexylthio-6-azauracil (III) (80 mg./kg. given I.P.) had a toxicity near to or less than that of azauracil (200 mg./kg. given s.c. or I.P.) with an L.D.50 of 1612 mg./kg. with I.P. and 2076 mg./kg. with s.c. 6-Azauracil-5-isothiuronium-HBr (27 mg./kg. given s.c.) and 5-(2-amino-1,3,4-thiadiazol-5-yl)thio-6-azauracil (IV) (25 mg./kg. given s.c.) were the most toxic with an L.D.50 of 267 and of 21 mg./kg., resp. Azauracil had a slight sedative effect, but 5-phenylthio-6-azauracil (V) (70 mg./kg. given I.P. and s.c.), II (140 mg./kg. given I.P.), III (170 mg./kg. given I.P.), and 6-butylthio-6-azauracil (80 mg./kg. given I.P.), had a more marked neurodepressant activity. Apparently, neurodepressant activity depends on the length of the chain since the presence of an aromatic ring in the terminal position of the lateral chain at C-6 in these compounds did not prevent the neurodepressant effect, while the presence of other rings, as in 5-morpholinyl-6-azauracil, I, and IV, eliminates it. In the absence of any lateral chain, as in V, neurotropic activity was abolished. None of the substances, using doses of 10% of the L.D.50, caused modifications of the arterial pressure. With respect to the reactivity to chem. mediators, II and III had a slight cholinergic and antihistaminic effect of very short duration. The carotid sinus pressor reflex was not abolished at any time following the administration of the derivatives of triazine tested. V (70 mg./kg. given I.P. or s.c.) had a diuretic effect, while 5-mercapto-6-azauracil (1000 mg./kg.) given intravenously had an antidiuretic effect.

Biochemical Pharmacology published new progress about Antispasmodics. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Reference of 4956-05-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Li, Yang; Yang, Gaoxia; Zhang, Jifa; Tang, Pan; Yang, Chengcan; Wang, Guan; Chen, Juncheng; Liu, Jie; Zhang, Lan; Ouyang, Liang published the artcile< Discovery, Synthesis, and Evaluation of Highly Selective Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Inhibitor for the Potential Treatment of Metastatic Triple-Negative Breast Cancer>, Name: 2,4-Dichlorothieno[2,3-d]pyrimidine, the main research area is VEGFR inhibitor preparation metastatic breast cancer.

We herein report the identification, structural optimization, and structure-activity relationship of thieno[2,3-d]pyrimidine derivatives as a novel kind of selective vascular endothelial growth factor receptor 3 (VEGFR3) inhibitors. N-(4-Chloro-3-(trifluoromethyl)phenyl)-4-(6-(4-(4-methylpiperazin-1-yl)phenyl)thieno[2,3-d]pyrimidin-4-yl)piperazine-1-carboxamide (38k) was the most potent VEGFR3 inhibitor (IC50 = 110.4 nM) among developed compounds Compared with VEGFR1 and VEGFR2, VEGFR3 was approx. 100 times more selective. Here, compound 38k significantly inhibited proliferation and migration of VEGF-C-induced human dermal lymphatic endothelial cells (HDLEC), MDA-MB-231, and MDA-MB-436 cells by inactivating the VEGFR3 signaling pathway. Addnl., 38k induced cell apoptosis and a prolonged G1/S-phase in MDA-MB-231 and MDA-MB-436 cells. It also presented acceptable pharmacokinetic characteristics in Sprague-Dawley (SD) rats with an oral bioavailability of 30.9%. In the xenograft model in vivo, 38k effectively inhibited breast cancer growth by suppressing the VEGFR3 signaling pathway. 38k pronouncedly resisted the formation of pulmonary metastatic nodules in mice. Collectively, 38k may be a promising therapeutic agent of metastatic breast cancer.

Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Name: 2,4-Dichlorothieno[2,3-d]pyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Zhang, Kehui; Lai, Fangfang; Lin, Songwen; Ji, Ming; Zhang, Jingbo; Zhang, Yan; Jin, Jing; Fu, Rong; Wu, Deyu; Tian, Hua; Xue, Nina; Sheng, Li; Zou, Xiaowen; Li, Yan; Chen, Xiaoguang; Xu, Heng published the artcile< Design, Synthesis, and Biological Evaluation of 4-Methyl Quinazoline Derivatives as Anticancer Agents Simultaneously Targeting Phosphoinositide 3-Kinases and Histone Deacetylases>, Synthetic Route of 89793-12-4, the main research area is quinazoline derivative anticancer phosphoinositide kinases histone deacetylase dual inhibitor.

Polypharmacol. is a promising paradigm in modern drug discovery. Herein, we have discovered a series of novel PI3K and HDAC dual inhibitors in which the hydroxamic acid moiety as the zinc binding functional group was introduced to a quinazoline-based PI3K pharmacophore through an appropriate linker. Systematic structure-activity relationship studies resulted in lead compounds 23 (shown in graphical abstract and duplicated as I) and 36 (II) that simultaneously inhibited PI3K and HDAC with nanomolar potencies and demonstrated favorable antiproliferative activities. Compounds 23 and 36 efficiently modulated the expression of p-AKT and Ac-H3, arrested the cell cycle, and induced apoptosis in HCT116 cancer cells. Following pharmacokinetic studies, 23 was further evaluated in HCT116 and HGC-27 xenograft models to show significant in vivo anticancer efficacies with tumor growth inhibitions of 45.8% (po, 150 mg/kg) and 62.6% (i.p., 30 mg/kg), resp. Overall, this work shows promise in discovering new anticancer therapeutics by the approach of simultaneously targeting PI3K and HDAC pathways with a single mol.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Synthetic Route of 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Tzeng, Cherng Chyi; Rychlewska, Urszula; Hodgson, Derek J.; Panzica, Raymond P. published the artcile< 4-Azapteridines. 2. Spectral, chromatographic, and x-ray crystallographic studies concerning the mode of covalent addition to the pyrazino[2,3-e]-as-triazine ring system>, HPLC of Formula: 4956-05-2, the main research area is pyrazinotriazine dihydroxy crystal structure; aminotriazine cyclocondensation glyoxal.

The first examples of the unknown pyrazino[2,3-e]-as-triazine ring system, i.e., the 6,7-dihydroxy-5,6,7,8-tetrahydropyrazino[2,3,-e]-as-triazines, have been prepared by ring closure of selected 5,6-diamino-as-triazines with 40% aq glyoxal. These 4-azapteridines experience a novel exchange process with alcs. at the C(7)-position. When dissolved in alc. and stirred at room temperature, the 7-alkoxy, 6-hydroxy analogs are formed and isolated. If alcs. are used as the solvent during ring closure, only the latter compounds are obtained. Initially, cyclization of the ortho-diamino-as-triazines with glyoxal proceeds in a stereoselective manner giving rise to both the cis and trans adducts. A single-crystal x-ray diffraction study of the pyrazinotriazine I has determined the predominant and most stable adduct to be the trans (R,R or S,S)-isomer. NMR spectroscopy has verified the intermediacy of the cis adduct, but because of the aforementioned exchange process only the trans isomer is isolated. The site of exchange on these σ-adducts has been rigorously established as C(7). A plausible reaction mechanism by which this exchange process occurs is presented.

Journal of Heterocyclic Chemistry published new progress about Crystal structure. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, HPLC of Formula: 4956-05-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Wei, Wei; Feng, Zhanzhan; Liu, Zhihao; Li, Xinyue; He, Hualong; Ran, Kai; Shi, Yaojie; Zhu, Yongxia; Ye, Tinghong; Gao, Chao; Wang, Ningyu; Yu, Luoting published the artcile< Design, synthesis and biological evaluation of 7-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)-2,3-dihydro-1H-inden-1-one derivatives as potent FAK inhibitors for the treatment of ovarian cancer>, Computed Properties of 18740-39-1, the main research area is pyrrolopyrimidinyloxydihydroindenone derivative focal adhesion kinase inhibitor ovarian cancer antitumor; Anti-Tumor; FAK; Kinase inhibitor; Ovarian cancer; Structure-activity relationship.

Focal adhesion kinase (FAK) promotes tumor progression by intracellular signal transduction and regulation of gene expression and protein turnover, which is a compelling therapeutic target for various cancer types, including ovarian cancer. However, the clin. responses of FAK inhibitors remain unsatisfactory. Here, we describe the discovery of FAK inhibitors using a scaffold hopping strategy. Structure-activity relationship (SAR) exploration identified 3-Methoxy-4-((4-((3-oxo-2,3-dihydro-1H-inden-4-yl)oxy)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-N-(piperidin-4-yl)benza-mide as a potent FAK inhibitor, which exhibited inhibitory activities against FAK signaling in vitro. Treatment with 3-Methoxy-4-((4-((3-oxo-2,3-dihydro-1H-inden-4-yl)oxy)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-N-(piperidin-4-yl)benza-mide not only decreased migration and invasion of PA-1 cells, but also reduced expression of MMP-2 and MMP-9. Moreover, 3-Methoxy-4-((4-((3-oxo-2,3-dihydro-1H-inden-4-yl)oxy)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-N-(piperidin-4-yl)benza-mide inhibited tumor growth and metastasis, and no obvious adverse effects were observed during the in vivo study. These results revealed the potential of FAK inhibitor 3-Methoxy-4-((4-((3-oxo-2,3-dihydro-1H-inden-4-yl)oxy)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-N-(piperidin-4-yl)benza-mide for treatment of ovarian cancer.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Computed Properties of 18740-39-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Ferris, J. P.; Joshi, P. C.; Edelson, E. H.; Lawless, J. G. published the artcile< Chemical evolution. XXX. Hydrogen cyanide: a plausible source of purines, pyrimidines and amino acids on the primitive earth>, Recommanded Product: 5-Hydroxypyrimidin-4(3H)-one, the main research area is hydrocyanate chem evolution; amino acid formation hydrocyanate prebiotic; pyrimidine formation hydrocyanate prebiotic; purine formation hydrocyanate prebiotic.

Dilute (0.1M) solutions of HCN condense to oligomers at pH 9.2. Hydrolysis of these oligomers yields 4,5-dihydroxypyrimidine, orotic acid, 5-hydroxyuracil, adenine, 4-aminoimidazole-5-carboxamide, and amino acids. These results, together with the earlier data, demonstrate that the 3 main classes of N-containing biomols., purines, pyrimidines, and amino acids may have originated from HCN on the primitive earth. The observation of orotic acid and 4-aminoimidazole-5-carboxamide suggests that the contemporary biosynthetic pathways for nucleotides may have evolved from the compounds released on hydrolysis of HCN oligomers.

Journal of Molecular Evolution published new progress about Amino acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 15837-41-9 belongs to class pyrimidines, and the molecular formula is C4H4N2O2, Recommanded Product: 5-Hydroxypyrimidin-4(3H)-one.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Seela, Frank; Winkeler, Heinz Dieter published the artcile< 2-Amino-7-β-D-arabinofuranosyl-4-methoxy-7H-pyrrolo[2,3-d]pyrimidine: a facile preparation and anomerization of a 7-deazapurine nucleoside>, Reference of 84955-32-8, the main research area is arabinofuranosylpyrrolopyrimidine amino; pyrrolopyrimidine arabinofuranosyl amino; deazapurine nucleoside preparation anomerization; glycosylation aminopyrrolopyrimidine arabinofuranosyl bromide.

Phase-transfer glycosylation of 2-amino-4-methoxy-7H-pyrrolo[2,3-d]pyrimidine with 2,3,5-tri-O-benzyl-D-arabinofuranosyl bromide in C6H6-50% aqueous NaOH-tetrabutylammonium hydrogen sulfate gave two anomeric glycosylation products I and II (R = PhCH2). Removal of the benzyl groups with BCl3 yielded I and II (R = H). Treatment of I and II (R = H) with 2M HCl under N caused anomerization and demethylation without glycosylic cleavage, and reflected the extraordinary stability of pyrrolo[2,3-d]pyrimidine nucleosides towards hydrolysis. The conversion of I and II (R = H) into ara-7-deazaguanosine or its a anomer was accomplished with anhydrous acid.

Carbohydrate Research published new progress about Glycosylation. 84955-32-8 belongs to class pyrimidines, and the molecular formula is C7H8N4O, Reference of 84955-32-8.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia