Category: pyrimidines

Tupitsyn, I. F.; Zatsepina, N. N.; Kolodina, N. S.; Kirova, A. V. published the artcile< Nuclear quadrupole resonance and infrared spectroscopic studies of electron interactions in polysubstituted azines>, HPLC of Formula: 6554-61-6, the main research area is NQR nitrogen heterocycle chlorine; pyridine pyrimidine NQR IR; substituent effect NQR IR pyridine.

35Cl NQR frequencies (νCl) and integral intensities (A) of ir absorption bands of stretching vibrations of aromatic C-H bonds of polysubstituted N heterocycles, e.g., chloropyridines, chloropyrimidines, were correlated with inductive and resonance substituent constants Electronic effects of the heteroatoms and substituents on νCl and A were additive.

Reaktsionnaya Sposobnost Organicheskikh Soedinenii published new progress about IR spectra. 6554-61-6 belongs to class pyrimidines, and the molecular formula is C4H2Cl2N2, HPLC of Formula: 6554-61-6.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Khamouli, Saida; Belaidi, Salah; Zinebalmi; Medjahed, Sihem; Belaidi, Houmam published the artcile< Property/activity relationships and drug likeness for pyrimidine derivatives as serine/threonine protein kinase B inhibitors>, Related Products of 6554-61-6, the main research area is pyrimidine derivative serine threonine protein kinase inhibitor drug property.

The equilibrium geometry and electronic structures of the pyrimidine, were determined and analyzed with ab initio/HF, and DFT method. In the present work, the calculated values, namely net charges, MESP contours/surfaces has also been drawn to explain the electronic activity of Pyrimidine. QSAR properties, Lipinski′s parameters, Lipophilic Efficiency (LipE), are reported and discussed to understand the biol. activity of the Pyrimidine Derivatives

Journal of Bionanoscience published new progress about Absorption. 6554-61-6 belongs to class pyrimidines, and the molecular formula is C4H2Cl2N2, Related Products of 6554-61-6.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Semin, G. K.; Babushkina, T. A.; Mamaev, V. P.; Krivopalov, V. P. published the artcile< Chlorine-35 nuclear quadrupole resonance in chloropyrimidines>, Category: pyrimidines, the main research area is nuclear quadrupole resonance chloropyrimidine.

The nuclear quadrupole resonance (NQR) spectra of 35Cl in 2- and 5-chloro-, 2,4-, 4,6-, 4,5-, and 2,5-dichloro-, 4,5,6-, 2,4,5-, and 2,4,6-trichloropyrimidines and tetrachloropyrimidine were measured at 77°K and calculated by the published additivity method to study the electron d. distribution on C atom of the ring and effect of the substituents. The additivity method of calculating the NQR frequencies of 35Cl is valid for the chloro substituted pyrimidines. It was used to determine electron d. distribution on various C atoms in the pyrimidine ring. The relative role of various mechanisms of the transmission throughout the ring of the effect of substituents is discussed.

Izvestiya Sibirskogo Otdeleniya Akademii Nauk SSSR, Seriya Khimicheskikh Nauk published new progress about Electron configuration. 6554-61-6 belongs to class pyrimidines, and the molecular formula is C4H2Cl2N2, Category: pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Wang, Manjiong; Tang, Tongke; Li, Ruoxi; Huang, Zhenghui; Ling, Dazheng; Zheng, Lulu; Ding, Yan; Liu, Taiping; Xu, Wenyue; Zhu, Feng; Min, Hui; Boonhok, Rachasak; Mao, Fei; Zhu, Jin; Li, Xiaokang; Jiang, Lubin; Li, Jian published the artcile< Drug Repurposing of Quisinostat to Discover Novel Plasmodium falciparum HDAC1 Inhibitors with Enhanced Triple-Stage Antimalarial Activity and Improved Safety>, HPLC of Formula: 89793-12-4, the main research area is quisinostat derivative preparation resistant malaria drug repurposing.

Our previous work found that the clin. histone deacetylase (HDAC) inhibitor quisinostat exhibited a significant antimalarial effect but with severe toxicity. In this work, 35 novel derivatives were designed and synthesized based on quisinostat as the lead compound, and their in vitro antimalarial activities and cytotoxicities were systematically evaluated. Among them, JX35 showed potent inhibition against both wild-type and multidrug-resistant parasite strains and displayed a significant in vivo killing effect against all life cycles of parasites, including the blood stage, liver stage, and gametocyte stage, indicating its potential for the simultaneous treatment, chemoprevention, and blockage of malaria transmission. Compared with quisinostat, JX35 exhibited stronger antimalarial efficacy, more adequate safety, and good pharmacokinetic properties. Addnl., mechanistic studies via mol. docking studies, induced PfHDAC1/2 knockdown assays, and PfHDAC1 enzyme inhibition assays jointly indicated that the antimalarial target of JX35 was PfHDAC1. In summary, we discovered the promising candidate PfHDAC1 inhibitor JX35, which showed stronger triple-stage antimalarial effects and lower toxicity than quisinostat.

Journal of Medicinal Chemistry published new progress about Antimalarials. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, HPLC of Formula: 89793-12-4.

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

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

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

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

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

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