Day: October 20, 2022

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

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

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

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

Jordan, Brian J.; Carroll, Joseph B.; Xu, Hao; Erdogan, Belma; Lee, Lisa; Cheng, Lily; Tiernan, Chris; Cooke, Graeme; Rotello, Vincent M. published the artcile< Site isolated redox behavior in flavin functionalized random polystyrene copolymers>, HPLC of Formula: 2244-11-3, the main research area is flavin functionalized random polystyrene copolymer.

A model system has been developed to investigate the individual redox behaviors of flavin derivatives appended onto random polystyrene copolymers through “”click”” chem. procedures. The results indicate that flavin units attached to the polymers exhibit site isolated behavior vs. free flavin, yielding unique fluorescent materials with electrochem. tunable associations upon addition of complementary diamidopyridine functionality.

Polymer Preprints (American Chemical Society, Division of Polymer Chemistry) published new progress about Cyclic voltammetry. 2244-11-3 belongs to class pyrimidines, and the molecular formula is C4H4N2O5, HPLC of Formula: 2244-11-3.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reddy, L. Srikanth; Naik, B. Eswar published the artcile< Design, synthesis and characterization of novel thieno[2,3-d]pyrimidines for anti-bacterial and anti-fungal screening>, Quality Control of 18740-39-1, the main research area is thiomorpholinothieno pyrimidine preparation antibacterial antifungal.

A series of novel 4-Substituted and different substituted heterocyclic-N-(2-thiomorpholinothieno[2,3-d]pyrimidin-4-yl)benzamide derivatives I (R = Ph, thiophen-2-yl, 2,5-difluorophenyl, etc.) was synthesized by a facile five-step procedure that afforded advantages of mild reaction conditions, simple protocol and good yields. The final compounds were screened for their antibacterial activity against Staphylococcus aureus (S. aureus) and Bacillus subtilis (B. subtilis) from Gram pos. group of bacteria and Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli) from Gram neg. group of bacteria and antifungal activity against Aspergillus niger (A. niger) and Candida albicans (C. albicans). Anti-bacterial and anti-fungal activities were evaluated and compared with the standard drugs Such as Amoxicillin and Fluconazole from anti-bacterial and antifungal activity screening results, and it has been observed that compounds I (R = thiophen-2-yl, 1-benzothiophen-2-yl, 2,5-difluorophenyl, 4-(trifluoromethyl)phenyl) possess good activity.

Pharma Innovation published new progress about Antibacterial agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Quality Control of 18740-39-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Rabal, Obdulia; Sanchez-Arias, Juan A.; Cuadrado-Tejedor, Mar; de Miguel, Irene; Perez-Gonzalez, Marta; Garcia-Barroso, Carolina; Ugarte, Ana; Estella-Hermoso de Mendoza, Ander; Saez, Elena; Espelosin, Maria; Ursua, Susana; Tan, Haizhong; Wu, Wei; Xu, Musheng; Pineda-Lucena, Antonio; Garcia-Osta, Ana; Oyarzabal, Julen published the artcile< Multitarget Approach for the Treatment of Alzheimer's Disease: Inhibition of Phosphodiesterase 9 (PDE9) and Histone Deacetylases (HDACs) Covering Diverse Selectivity Profiles>, Related Products of 89793-12-4, the main research area is Alzheimer’s disease HDAC inhibition PDE9 inhibition HDAC6 dual inhibitors; Alzheimer’s disease; HDAC6; dual inhibitors; histone deacetylase inhibition; phosphodiesterase 9 inhibition.

Here, we present a series of dual-target phosphodiesterase 9 (PDE9) and histone deacetylase (HDAC) inhibitors devised as pharmacol. tool compounds for assessing the implications of these two targets in Alzheimer’s disease (AD). These novel inhibitors were designed taking into account the key pharmacophoric features of known selective PDE9 inhibitors as well as privileged chem. structures, bearing zinc binding groups (hydroxamic acids and ortho-amino anilides) that hit HDAC targets. These substituents were selected according to rational criteria and previous knowledge from our group to explore diverse HDAC selectivity profiles (pan-HDAC, HDAC6 selective, and class I selective) that were confirmed in biochem. screens. Their functional response in inducing acetylation of histone and tubulin and phosphorylation of cAMP response element binding (CREB) was measured as a requisite for further progression into complete in vitro absorption, distribution, metabolism and excretion (ADME) and in vivo brain penetration profiling. Compound 31b, a selective HDAC6 inhibitor with acceptable brain permeability, was chosen for assessing in vivo efficacy of these first-in-class inhibitors, as well as studying their mode of action (MoA).

ACS Chemical Neuroscience published new progress about Alzheimer disease. 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

Kang, Dongwei; Fang, Zengjun; Huang, Boshi; Lu, Xueyi; Zhang, Heng; Xu, Haoran; Huo, Zhipeng; Zhou, Zhongxia; Yu, Zhao; Meng, Qing; Wu, Gaochan; Ding, Xiao; Tian, Ye; Daelemans, Dirk; De Clercq, Erik; Pannecouque, Christophe; Zhan, Peng; Liu, Xinyong published the artcile< Structure-Based Optimization of Thiophene[3,2-d]pyrimidine Derivatives as Potent HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors with Improved Potency against Resistance-Associated Variants>, Synthetic Route of 18740-39-1, the main research area is thiophene pyrimidine preparation structure based optimization antiviral HIV; HIV antiviral pharmacokinetics cardiotoxicity thiophene pyrimidine.

This work follows on from our initial discovery of a series of piperidine-substituted thiophene[3,2-d]pyrimidine HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTI) (J. Med. Chem. 2016, 59, 7991-8007). In the present study, we designed, synthesized, and biol. tested several series of new derivatives in order to investigate previously unexplored chem. space. Some of the synthesized compounds displayed single-digit nanomolar anti-HIV potencies against wild-type (WT) virus and a panel of NNRTI-resistant mutant viruses in MT-4 cells. I was exceptionally potent against the whole viral panel, affording 3-4-fold enhancement of in vitro antiviral potency against WT, L100I, K103N, Y181C, Y188L, E138K, and K103N+Y181C and 10-fold enhancement against F227L+V106A relative to the reference drug etravirine (ETV) in the same cellular assay. The structure-activity relationships, pharmacokinetics, acute toxicity, and cardiotoxicity were also examined Overall, the results indicate that I is a promising new drug candidate for treatment of HIV-1 infection.

Journal of Medicinal Chemistry published new progress about Acute toxicity. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Synthetic Route of 18740-39-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Chukwu, Roxton; Hunter, Allen D.; Santarsiero, Bernard D. published the artcile< Organometallic complexes with electronic bridges. 6. Novel organometallic complexes containing aromatic azines: synthesis and x-ray crystal structure of 4,6-bis[(η5-cyclopentadienyl)dicarbonyliron] 2-(methylthio)pyrimidine>, Category: pyrimidines, the main research area is iron azine complex; pyridine iron complex; pyrazine iron complex; pyridazine iron complex; pyrimidine iron complex; crystal structure iron pyrimidine complex; mol structure iron pyrimidine complex; safety handling mercury.

The syntheses of 13 monometallic and 4 bimetallic complexes in which (η5-C5H5)Fe(CO)2 (Fp; C5H5 = cyclopentadienyl) groups are bound to substituted pyridine, pyrazine, pyridazine, and pyrimidine rings is described. These species are prepared by metathesis reactions between the appropriate number of equivalent of NaFp and the chloro- or fluoro-substituted azine precursors in 25-95% yields and structural factors affecting these yields are discussed. These new materials have been fully characterized by conventional spectroscopic techniques and are shown to contain Fe-C σ-bonds. The x-ray crystal structure of the title complex confirms that it has the expected structure about the pyrimidine ring. It also reveals that, contrary to expectations from frontier MO theory, the (η5-C5H5)Fe(CO)2 groups shows a preference for orientations in which its mirror plane is perpendicular to that of the pyrimidine ring. The spectroscopic data provide no evidence for the existence of any electronic interaction between the metal centers of the new bimetallic azine bridged complexes having meta substitution geometries.

Organometallics published new progress about Crystal structure. 3921-01-5 belongs to class pyrimidines, and the molecular formula is C4H2Br2N2, Category: pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Zasosov, V. A.; Nikulina, T. N.; Blinova, L. S.; Onoprienko, V. S.; Sycheva, V. N.; Sokolova, G. N.; Borodina, K. S.; Denisova, K. V. published the artcile< Synthesis of 4-(p-aminobenzenesulfonamido)-5,6-dimethoxypyrimidine>, Synthetic Route of 5018-38-2, the main research area is amino benzenesulfonamido methoxy pyrimidine; sulfamide pyrimidyl.

CO2H)2 was esterified with MeOH and then treated with MeOCH2CO2CO2Me(from ClCH2CO2Me and NaOMe) to give MeO2CCH(OMe)COCO2Me, which was decarbonylated at 210° to give MeOCH(CO2Me)2. The latter reacted with NH3 and then HCONH2 in the presence of NaOEt to form the di-Na salt of 4,6-dihydroxy-5-methoxypyrimidine, which was converted to the 4,6-dichloro derivative (I) with POCl3 and PhNMe2. I reacted with NH3 in DMF to form the 4-amino derivative, which yielded 4-amino-5,6-dimethoxypyrimidine with NaOH in MeOH. The latter was converted to the title compound (II) by treatment with 4-MeO2CNHC6H4SO2Cl in pyridine, followed by hydrolysis with concentrated HCl.

Khimiko-Farmatsevticheskii Zhurnal published new progress about 5018-38-2. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Synthetic Route of 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia