Day: October 13, 2022

Suzuki, Haruka; Inoue, Ryo; Kawamorita, Soichiro; Komiya, Naruyoshi; Imada, Yasushi; Naota, Takeshi published the artcile< Highly Fluorescent Flavins: Rational Molecular Design for Quenching Protection Based on Repulsive and Attractive Control of Molecular Alignment>, Category: pyrimidines, the main research area is flavin fluorescence mol alignment quenching protection repulsive attractive control; flavins; fluorescence; hydrogen bonds; molecular design; steric hindrance.

Unprecedented intense fluorescent emission was observed for a variety of flavin compounds bearing a perpendicular cyclic imide moiety at the C7 position of an isoalloxazine platform. A series of alloxan-substituted flavins was prepared selectively by reduction of the corresponding N-aryl-2-nitro-5-alkoxyanilines with zinc dust and subsequent reaction with alloxan monohydrate in the presence of boric acid. Analogs bearing oxazolidine-2,4-dione functionality were obtained on methylation of the alloxan-substituted flavins with Me iodide and subsequent rearrangement in the presence of an inorganic base. The flavin compounds exhibit intense white-green fluorescent emission in the solution state under UV excitation at 298 K, with emission efficiencies Φ298 K greater than 0.55 in CH3CN, which are higher than the values for all reported flavin compounds under similar conditions. The highest Φ298 K value of 0.70 was obtained in CH3CN for isoalloxazine bearing C7-alloxan and N10-2,6-diisopropylphenyl groups. The temperature dependence of the emission intensities indicates that the pronounced emission properties at 298 K are attributable to the highly heat resistant properties towards emission decay with increasing temperature Mechanistic studies, including X-ray diffraction anal., revealed that the good emission properties and high heat resistance of the alloxan-substituted flavins are due to a synergetic effect of the associative nature of the C7-alloxan unit and the repulsive nature of the perpendicular bulky substituents at the C7 and N10 positions.

Chemistry – A European Journal published new progress about Crystal structure. 2244-11-3 belongs to class pyrimidines, and the molecular formula is C4H4N2O5, Category: pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Kang, Dongwei; Ruiz, F. Xavier; Feng, Da; Pilch, Alyssa; Zhao, Tong; Wei, Fenju; Wang, Zhao; Sun, Yanying; Fang, Zengjun; De Clercq, Erik; Pannecouque, Christophe; Arnold, Eddy; Liu, Xinyong; Zhan, Peng published the artcile< Discovery and Characterization of Fluorine-Substituted Diarylpyrimidine Derivatives as Novel HIV-1 NNRTIs with Highly Improved Resistance Profiles and Low Activity for the hERG Ion Channel>, Recommanded Product: 2,4-Dichlorothieno[2,3-d]pyrimidine, the main research area is HIV1 NNRTIs hERG inhibition half life hybridization bioisosterism cytotoxicity.

Our previous efforts have led to the development of two potent NNRTIs, K-5a2 and 25a, exhibiting effective anti-HIV-1 potency and resistance profiles compared with etravirine. However, both inhibitors suffered from potent hERG inhibition and short half-life. In this article, with K-5a2 and etravirine as leads, series of novel fluorine-substituted diarylpyrimidine derivatives were designed via mol. hybridization and bioisosterism strategies. The results indicated 24b was the most active inhibitor, exhibiting broad-spectrum activity (EC50 = 3.60-21.5 nM) against resistant strains, significantly lower cytotoxicity (CC50= 155μM), and reduced hERG inhibition (IC50 > 30μM). Crystallog. studies confirmed the binding of 24b and the role of the fluorine atom, as well as optimal contacts of a nitrile group with the main-chain carbonyl group of H235. Furthermore, 24b showed longer half-life and favorable safety properties. All the results demonstrated that 24b has significant promise in circumventing drug resistance as an anti-HIV-1 candidate.

Journal of Medicinal Chemistry published new progress about Anti-HIV agents (anti-HIV-1 agents). 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Recommanded Product: 2,4-Dichlorothieno[2,3-d]pyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Goto, Taiji; Shiina, Akiko; Yoshino, Toshiharu; Mizukami, Kiyoshi; Hirahara, Kazuki; Suzuki, Osamu; Sogawa, Yoshitaka; Takahashi, Tomoko; Mikkaichi, Tsuyoshi; Nakao, Naoki; Takahashi, Mizuki; Hasegawa, Masashi; Sasaki, Shigeki published the artcile< Identification of the fused bicyclic 4-amino-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors>, Recommanded Product: 2,4-Dichlorothieno[2,3-d]pyrimidine, the main research area is fused bicyclic aminophenylpyrimidine preparation PDE4 inhibitor SAR; anti inflammatory activity lung inflammation bicyclic aminophenylpyrimidine.

2-Phenyl-4-piperidinyl-6,7-dihydrothieno[3,4-d]pyrimidine derivative I was found to be a new PDE4 inhibitor with moderate PDE4B activity (IC50 = 150 nM). A number of derivatives with a variety of 4-amino substituents and fused bicyclic pyrimidines were synthesized. Among these, 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine derivative II showed potent PDE4B inhibitory activity (IC50 = 25 nM). Finally, N-propylacetamide derivative III (R = n-Pr) was determined to be a potent inhibitor for both PDE4B (IC50 = 7.5 nM) and TNF-α production in mouse splenocytes (IC50 = 9.8 nM) and showed good in vivo anti-inflammatory activity in the LPS-induced lung inflammation model in mice (ID50 = 18 mg/kg). The binding mode of the new inhibitor III (R = t-Bu) in the catalytic site of PDE4B is presented based on an x-ray crystal structure of the ligand-enzyme complex.

Bioorganic & Medicinal Chemistry Letters published new progress about Anti-inflammatory agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Recommanded Product: 2,4-Dichlorothieno[2,3-d]pyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Ohta, Kiminori; Kawachi, Emiko; Inoue, Noriko; Fukasawa, Hiroshi; Hashimoto, Yuichi; Itai, Akiko; Kagechika, Hiroyuki published the artcile< Retinoidal pyrimidinecarboxylic acids. Unexpected diaza-substituent effects in retinobenzoic acids>, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is retinoid heterocyclic analog preparation retinoidal activity; structure activity relationship heterocyclic retinoid analog; antileukemia heterocyclic retinoid analog preparation.

Several pyridine- and pyrimidine-carboxylic acids were synthesized as ligand candidates for retinoid nuclear receptors, retinoic acid receptors (RARs) and retinoic X receptors (RXRs). Although the pyridine derivatives, 6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]pyridine-3-carboxylic acid and 6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]pyridine-3-carboxylic acid are more potent than the corresponding benzoic acid-type retinoids, Am80 and Am580, the replacement of the benzene ring of Am580, Am555, or Am55 with a pyrimidine ring caused loss of the retinoidal activity both in HL-60 cell differentiation assay and in RAR transactivation assay using COS-1 cells. On the other hand, pyrimidine analogs (PA series) of potent RXR agonists (retinoid synergists) with a diphenylamine skeleton (DA series) exhibited potent retinoid synergistic activity in HL-60 cell differentiation assay and activated RXRs. Among the synthesized compounds, 2-[N-n-propyl-N-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)amino]pyrimidine-5-carboxylic acid (PA013) is most active retinoid synergist in HL-60 assay.

Chemical & Pharmaceutical Bulletin published new progress about Antitumor agents. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Seela, Frank; Soulimane, Tewfik; Mersmann, Karin; Juergens, Thomas published the artcile< 2,4-Disubstituted pyrrolo[2,3-d]pyrimidine α-D- and β-D-ribofuranosides related to 7-deazaguanosine>, Recommanded Product: 4-Methoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine, the main research area is pyrrolopyrimidine stereoselective glycosidation ribofuranosyl chloride; deazaguanosine related pyrrolopyrimidine ribofuranoside; guanosine deaza related pyrrolopyrimidine ribofuranoside; nucleoside.

Nucleobase-anion glycosylation [KOH, (MeOCH2CH2OCH2CH2)3N] of the pyrrolo[2,3-d]pyrimidines I (R = Cl, OMe, R1 = NH2, SMe) with ribofuranosyl chlorides gave the corresponding protected β-D-nucleosides stereoselectively. Contrary, II (R2 = Cl, R3 = H) yielded the corresponding α-D-nucleosides apart from minor amounts of the β-D-anomers. The deprotected nucleosides III (R4 = Cl) were converted into 4-substituted 2-aminopyrrolo[2,3-d]-pyrimidine β-D-ribofuranosides e.g. III (R4 = H, NH2, OMe), and into their α-D-anomers, resp.

Helvetica Chimica Acta published new progress about Glycosylation, stereoselective. 84955-32-8 belongs to class pyrimidines, and the molecular formula is C7H8N4O, Recommanded Product: 4-Methoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Darout, Etzer; Robinson, Ralph P.; McClure, Kim F.; Corbett, Matthew; Li, Bryan; Shavnya, Andrei; Andrews, Melissa P.; Jones, Christopher S.; Li, Qifang; Minich, Martha L.; Mascitti, Vincent; Guimaraes, Cristiano R. W.; Munchhof, Michael J.; Bahnck, Kevin B.; Cai, Cuiman; Price, David A.; Liras, Spiros; Bonin, Paul D.; Cornelius, Peter; Wang, Ruduan; Bagdasarian, Victoria; Sobota, Colleen P.; Hornby, Sam; Masterson, Victoria M.; Joseph, Reena M.; Kalgutkar, Amit S.; Chen, Yue published the artcile< Design and Synthesis of Diazatricyclodecane Agonists of the G-Protein-Coupled Receptor 119>, Safety of 4,6-Dichloro-5-methoxypyrimidine, the main research area is diazatricyclodecane derivative preparation agonist G protein coupled receptor 119; Hofmann Loeffler Freytag reaction formation bicyclic framework; ligand lipophilic efficiency diazatricyclodecane.

A series of GPR119 agonists based on a 2,6-diazatricyclo[3.3.1.1∼3,7∼]decane ring system is described. Also provided is a detailed account of the development of a multigram scale synthesis of the diazatricyclic ring system, which was achieved using a Hofmann-Loeffler-Freytag reaction as the key step. The basis for the use of this complex framework lies in an attempt to constrain one end of the mol. in the “”agonist conformation”” as was previously described for 3-oxa-7-aza-bicyclo[3.3.1]nonanes. Optimization of carbamate analogs of the diazatricyclic compounds led to the identification of I as a potent agonist of the GPR119 receptor with low unbound human liver microsomal clearance. The use of an agonist response weighted ligand lipophilic efficiency (LLE) termed AgLLE is discussed along with the issues of applying efficiency measures to agonist programs. Ultimately, solubility limited absorption and poor exposure reduced further interest in these mols.

Journal of Medicinal Chemistry published new progress about Crystal structure. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Safety of 4,6-Dichloro-5-methoxypyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Oka, Yoshimi; Shishino, Hisae published the artcile< Fluorescence Imaging of Disrupted Interfaces between Liquid-Ordered and Liquid-Disordered Domains by a Flavin-Labeled PNA Duplex>, Computed Properties of 2244-11-3, the main research area is fluorescence imaging interface liquid ordered disordered domain flavin PNA.

Lipid rafts and membrane-active peptides are attracting attention because they help understand basic membrane functions. In addition, the authors focus on flavoproteins playing some physiol. roles and explore the model compounds A new flavin probe, composed of palmitoylated peptide nucleic acid (PNA) and its complementary PNA labeled with flavin, targets the liquid-ordered (lo) microdomains and disrupts its interfaces to liquid-disordered (ld) microdomains of giant unilamellar vesicles and can be visualized by using confocal laser scanning microscopy. Surprisingly, as shown in time-lapse images, vesiculation and probe aggregations appear in the lo-ld interfaces, which leads to local disruption of the membrane. A possible interpretation of the data based on comparison with control experiments are discussed.

ACS Omega published new progress about Biological imaging. 2244-11-3 belongs to class pyrimidines, and the molecular formula is C4H4N2O5, Computed Properties of 2244-11-3.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Guan, Aiying; Zhao, Yu; Wang, Weiwei; Liu, Xinlei; Wang, Ming-an published the artcile< Synthesis and fungicidal activity of 3-Acetyl-4-phenyl-1-oxaspiro[4,5]dec-3-en-2-one derivatives>, COA of Formula: C5H4Cl2N2O, the main research area is fungicide acetyl phenyl oxaspiro decenone derivative synthesis.

The diversity-oriented synthesis strategy was utilized to diversely derive from the carbonyl of 3-acetyl-4-phenyl-1-oxaspiro[4,5]dec-3-en-2-one, a series of novel 3-acetyl-4-phenyl-1-oxaspiro[4,5]dec-3-en-2-one derivatives were synthesized. The preliminary in vivo and in vitro bioassay results showed that some compounds exhibited excellent fungicidal activity against phytopathagens, such as 3-allyloxyethyl-4-phenyl-1-oxaspiro[4,5]dec-3-en-2-one had 100% control rates against Pseudoperonospora cubensis and Puccinia polysora at the concentration of 400μg/mL.

Youji Huaxue published new progress about Agrochemical fungicides. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, COA of Formula: C5H4Cl2N2O.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia