Month: October 2022

Rabal, Obdulia; San Jose-Eneriz, Edurne; Agirre, Xabier; Sanchez-Arias, Juan Antonio; de Miguel, Irene; Ordonez, Raquel; Garate, Leire; Miranda, Estibaliz; Saez, Elena; Vilas-Zornoza, Amaia; Pineda-Lucena, Antonio; Estella, Ander; Zhang, Feifei; Wu, Wei; Xu, Musheng; Prosper, Felipe; Oyarzabal, Julen published the artcile< Design and Synthesis of Novel Epigenetic Inhibitors Targeting Histone Deacetylases, DNA Methyltransferase 1, and Lysine Methyltransferase G9a with In Vivo Efficacy in Multiple Myeloma>, Category: pyrimidines, the main research area is histone deacetylases DNA methyltransferase G9a inhibitors multiple myeloma antitumor.

Concomitant inhibition of key epigenetic pathways involved in silencing tumor suppressor genes has been recognized as a promising strategy for cancer therapy. Herein, we report a first-in-class series of quinoline-based analogs that simultaneously inhibit histone deacetylases (from a low nanomolar range) and DNA methyltransferase-1 (from a mid-nanomolar range, IC50 < 200 nM). Addnl., lysine methyltransferase G9a inhibitory activity is achieved (from a low nanomolar range) by introduction of a key lysine mimic group at the 7-position of the quinoline ring. The corresponding epigenetic functional cellular responses are observed: histone-3 acetylation, DNA hypomethylation, and decreased histone-3 methylation at lysine-9. These chem. probes, multi-target epigenetic inhibitors, were validated against the multiple myeloma cell line MM1.S, demonstrating promising in vitro activity of 12a (CM-444) with GI50 of 32 nM, an adequate therapeutic window (>1 log unit), and a suitable pharmacokinetic profile. In vivo, 12a achieved significant antitumor efficacy in a xenograft mouse model of human multiple myeloma.

Journal of Medicinal Chemistry published new progress about Acetylation (histone H3). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Category: pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Wang, Zhao; Kang, Dongwei; Feng, Da; Cherukupalli, Srinivasulu; Jiang, Xiangyi; Fu, Zhipeng; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong; Zhan, Peng published the artcile< Targeting dual tolerant regions of binding pocket: Discovery of novel morpholine-substituted diarylpyrimidines as potent HIV-1 NNRTIs with significantly improved water solubility>, Formula: C6H2Cl2N2S, the main research area is morpholine diarylpyrimidine synthesis antiHIV NNRTI HIV1 CYP450; HIV-1; Morpholine; NNRTIs; SARs; Tolerant region I; Tolerant region II.

To address the intractable issues of drug resistance and poor solubility, a novel series of morpholine-substituted diarylpyrimidines targeting the tolerant region I and tolerant region II of NNIBP were rationally designed by utilizing the available crystallog. studies. The biol. evaluation results showed that four most promising compounds (14e1, 14g1, 14g2 and 14j2) displayed excellent potency against WT HIV-1 strain with EC50 values ranging from 58 to 87 nM, being far more potent than NVP and comparable to ETV. Besides, some derivatives exhibited moderate activity in inhibiting the mutant HIV-1 strains. More encouragingly, 14d2 (RF = 0.4) possessed higher antiresistance profile than ETV (RF = 6.3) and K-5a2 (RF = 3.0) toward the double mutant strain F227L + V106A. The HIV-1 RT inhibition assay confirmed their binding target. The mol. docking studies were conducted and discussed in detail to rationalize the preliminary SARs. Further test indicated that morpholine could indeed promote the improvement of water solubility Addnl., the in silico prediction of physicochem. properties and CYP enzymic inhibitory ability were investigated to evaluate their drug-like features.

European Journal of Medicinal Chemistry published new progress about Anti-HIV agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Formula: C6H2Cl2N2S.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Wu, Tianxiao; Qin, Qiaohua; Liu, Nian; Zhang, Chu; Lv, Ruicheng; Yin, Wenbo; Sun, Yin; Sun, Yixiang; Wang, Ruifeng; Zhao, Dongmei; Cheng, Maosheng published the artcile< Rational drug design to explore the structure-activity relationship (SAR) of TRK inhibitors with 2,4-diaminopyrimidine scaffold>, SDS of cas: 18740-39-1, the main research area is diaminopyrimidine preparation tropomyosin receptor kinase inhibitor SAR mol docking; Anticancer; NTRK gene fusion; Pharmacophore model; TRK inhibitors.

Tropomyosin receptor kinase (TRK) is an ideal target for treating cancers caused by the NTRK gene fusion. In this study, more than 60 2,4-diaminopyrimidine derivatives were prepared to understand the structure-activity relationship and confirm the rationality of the pharmacophore model reported previously. Among them, compound I was found to be a potent pan-TRK inhibitor that inhibits the proliferation of Km-12 cell lines. Addnl., compound I induced the apoptosis of Km-12 cells in a concentration-dependent manner. Western blot anal. revealed that compound I inhibited the phosphorylation of TRK to block downstream pathways. Compound I also possessed outstanding plasma stability and liver microsomal stability in vitro, with half-lives greater than 289.1 min and 145 min, resp. Pharmacokinetic studies indicated that the oral bioavailability of compound I is 17.4%. These results demonstrate that compound I could serve as a novel lead compound for overcoming NTRK-fusion cancers.

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

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Mylari, Banavara L.; Miller, Max W.; Howes, Harold L. Jr.; Figdor, Sanford K.; Lynch, John E.; Koch, Richard C. published the artcile< Anticoccidial derivatives of 6-azauracil. 1. Enhancement of activity by benzylation of nitrogen-1. Observations on the design of nucleotide analogs in chemotherapy>, Related Products of 4956-05-2, the main research area is coccidiostat benzylazauracil derivative; azauracil derivative anticoccidial.

Of >100 6-azauracil derivatives prepared and tested against Eimeria tenella infections in Leghorn cockerels, the 1-benzyl derivatives were most active, with maximum activity shown by 1-benzyl derivatives with compact, electron-withdrawing substituents such as 3′- or 4′-fluorine, -chlorine, or -nitrile substituents. The most active compound was 1-(3-cyanobenzyl)-6-azauracil (I) [27414-41-1], with a potency ∼16 times that of 6-azauracil [461-89-2]. I was also effective against E. maxima, E. acervulina, E. brunetti, and E. necatrix. Metabolism experiments using C-14-labeled 1-benzyl-6-azauracil [5991-46-8] showed no cleavage of the side chain. Structure-activity relations are discussed.

Journal of Medicinal Chemistry published new progress about Coccidiosis. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Related Products of 4956-05-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Mitran, Raul-Augustin; Boscornea, Aurelian Cristian; Stancu, Izabela-Cristina; Tomas, Stefan published the artcile< Some unusual spectral properties of 6-azauracil derivatives>, Formula: C3H2BrN3O2, the main research area is fluorescence spectrometry azauracil derivative.

The optical properties of several new 6-azauracil derivatives have been obtained by means of fluorescence spectroscopy. This method allowed a rapid and accurate characterization, having high specificity and sensitivity.

Scientific Bulletin – University “Politehnica” of Bucharest, Series B: Chemistry and Materials Science published new progress about 4956-05-2. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Formula: C3H2BrN3O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Gershon, Herman; Parmegiani, Raulo published the artcile< Antifungal activity of ring poly-chlorinated pyrimidines: structure activity relations>, Formula: C4H2Cl2N2, the main research area is DRUG RESISTANCE, MICROBIAL; FUNGICIDES; PYRIMIDINES.

A total of 48 ring chlorinated pyrimidines were screened against strains of 5 fungi by the disk-plate method, liquid culture, and for activity of the vapors of the compounds Correlations of the results obtained by the 3 methods were made, and structure:activity relations were discussed. The outstanding members of this series were found to be 2,4,5-trichloropyrimidine, 4,5,6-trichloropyrimidine, and 2-chloro-methyl-4,5,6-trichloropyrimidine.

Applied Microbiology published new progress about 6554-61-6. 6554-61-6 belongs to class pyrimidines, and the molecular formula is C4H2Cl2N2, Formula: C4H2Cl2N2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Kandalkar, Sachin R.; Kaduskar, Rahul D.; Ramaiah, Parimi Atchuta; Barawkar, Dinesh A.; Bhuniya, Debnath; Deshpande, Anil M. published the artcile< Highly efficient one-pot amination of carboxylate-substituted nitrogen-containing heteroaryl chlorides via Staudinger reaction>, Related Products of 89793-12-4, the main research area is carboxylate substituted heteroaryl amine preparation; Staudinger reaction carboxylate substituted heteroaryl chloride.

An efficient one-pot method for the synthesis of tert-Bu 6-aminonicotinate I is described. The key transformation involves displacement of the chloro group in tert-Bu 6-chloronicotinate with azide followed by a Staudinger reaction. The scope of this methodol. is further extended for the synthesis of a series of carboxylate-substituted heteroaryl amines e. g., II. In particular, we synthesized tert-Bu carboxylate-substituted amino-pyridine, -pyridazine, and -pyrazine. In addition to one-pot conversion, short reaction time, simplicity of operation, ease of purification, and good yields are the key advantages of this methodol.

Tetrahedron Letters published new progress about Amination. 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

Kashiwagi, Michio published the artcile< Electron spin resonance of irradiated single crystals of alloxan monohydrate>, Related Products of 2244-11-3, the main research area is ALLOXAN IRRADIATED ESR; ESR IRRADIATED ALLOXAN.

X-ray irradiated single crystals of alloxan monohydrate were subjected to E.S.R. studies. Irradiation gives rise to radicals I by the abstraction of a hydroxyl group. The principal values of g-factors of the radicals are g1 = 2.0021, g2 = 2.0042, and g3 = 2.0060. The principal values of coupling constants with hydroxyl H are A1 = 3.1, A2 = -5.9, and A3 = -7.4 gauss. Spin ds. on the C and H atoms of •C-OH were evaluated from the 13C coupling constant Under the assumption of a planar structure for •C-OH and from consideration of the electronic structure of the radical, the directions of the principal values were concluded as follows. The directions of g1 and A2 are perpendicular to the radical plane, while that of g3 bisects the exterior angle of •COH. The direction of A1 is parallel to the OH bond.

Nippon Kagaku Zasshi published new progress about ESR (electron spin resonance). 2244-11-3 belongs to class pyrimidines, and the molecular formula is C4H4N2O5, Related Products of 2244-11-3.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Zhang, Liandi; Xin, Minhang; Shen, Han; Wen, Jun; Tang, Feng; Tu, Chongxing; Zhao, Xinge; Wei, Ping published the artcile< Five-membered heteroaromatic ring fused-pyrimidine derivatives: Design, synthesis, and hedgehog signaling pathway inhibition study>, Safety of 2,4-Dichlorothieno[2,3-d]pyrimidine, the main research area is purine pyrrolopyrimidine thienopyrimidine furopyrimidine benzamide preparation hedgehog signaling inhibition; Five-membered heteroaromatic ring fused-pyrimidine; Hedgehog signaling pathway; Inhibitors; Synthesis.

A series of novel five-membered heteroaromatic ring fused-pyrimidine derivatives I [X = N, Y = NH, NMe; X = CH, Y = NH, NMe, S; R1 = Me, R2 = H; R1 = H, R2 = 4-morpholinylmethyl, 4-methyl-1-piperazinylmethyl, 2-(4-morpholinyl)ethoxy] and II (Z = NH, NMe, O, S; the same R1 and R2), including purines, pyrrolo[2,3-d]pyrimidines, pyrrolo[3,2-d]pyrimidines, thieno[2,3-d]pyrimidines, thieno[3,2-d]pyrimidines and furo[3,2-d]pyrimidines, have been prepared and identified to be potent inhibitors of hedgehog signaling pathway. Among this new series of hedgehog signaling pathway inhibitors, most compounds exhibited significant inhibitory activity compared to vismodegib, indicating that the five-membered heteroaromatic ring fused-pyrimidines stand out as encouraging scaffolds among the currently reported structural skeletons for hedgehog signaling pathway inhibitors, deserving more exploration and further investigation.

Bioorganic & Medicinal Chemistry Letters published new progress about Hedgehog protein Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Safety of 2,4-Dichlorothieno[2,3-d]pyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Dolsak, Ana; Mrgole, Kristjan; Sova, Matej published the artcile< Microwave-assisted regioselective suzuki coupling of 2,4-dichloropyrimidines with aryl and heteroaryl boronic acids>, Application of C4H2Br2N2, the main research area is dihalopyrimidine boronic acid palladium regioselective Suzuki coupling microwave irradiation; halo arylpyrimidine preparation.

The Suzuki coupling of 2,4-dihalopyrimidines with aryl and heteroaryl boronic acids was investigated. A thorough screening of reaction conditions and the use of microwave irradiation leded to a very efficient and straightforward synthetic procedure provided arylpyrimidines in good to excellent yields. Short reaction time (15 min) and extremely low catalyst loading (0.5 mol%) were the main advantages of our tetrakis(triphenylphosphine)palladium(0) catalyzed microwave-assisted procedure, which could be used for quick and low-cost regioselective preparation of pyrimidine rings.

Catalysts published new progress about Arylboronic acids Role: RCT (Reactant), RACT (Reactant or Reagent). 3921-01-5 belongs to class pyrimidines, and the molecular formula is C4H2Br2N2, Application of C4H2Br2N2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia