Month: October 2022

Crocker, Leander; Koehler, Philipp; Bernhard, Patrick; Kerbs, Antonina; Euser, Tijmen; Fruk, Ljiljana published the artcile< Enzyme-inspired flavin-polydopamine as a biocompatible nanoparticle photocatalyst>, Category: pyrimidines, the main research area is flavin polydopamine biocompatibility nanoparticle photocatalyst.

A new approach aimed at designing an enzyme-inspired photocatalyst is presented that exploits the inherent photocatalytic activity of flavin and the facile polymerization of dopamine to afford hybrid cofactor-containing nanoparticles. The flavin-polydopamine system benefits from ease of synthesis, tunability in terms of size and activity, and excellent temporal control over the catalyzed reactions. This novel, versatile photocatalyst exhibits both photooxidation and photoreduction of chromogenic enzymic substrates. In addition, the prepared hybrid nanoparticles are shown to be non-toxic, paving the way to their use in a wider range of applications beyond green catalysis, such as antioxidant adjuvants to various therapeutic approaches.

Nanoscale Horizons published new progress about Antioxidants. 2244-11-3 belongs to class pyrimidines, and the molecular formula is C4H4N2O5, Category: pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Liu, Chunjian; Lin, James; Langevine, Charles; Smith, Daniel; Li, Jianqing; Tokarski, John S.; Khan, Javed; Ruzanov, Max; Strnad, Joann; Zupa-Fernandez, Adriana; Cheng, Lihong; Gillooly, Kathleen M.; Shuster, David; Zhang, Yifan; Thankappan, Anil; McIntyre, Kim W.; Chaudhry, Charu; Elzinga, Paul A.; Chiney, Manoj; Chimalakonda, Anjaneya; Lombardo, Louis J.; Macor, John E.; Carter, Percy H.; Burke, James R.; Weinstein, David S. published the artcile< Discovery of BMS-986202: A Clinical Tyk2 Inhibitor that Binds to Tyk2 JH2>, Synthetic Route of 89793-12-4, the main research area is BMS986202 Tyk2 JH2 inhibitor antiinflammatory inflammation.

A search for structurally diversified Tyk2 JH2 ligands from 6 (BMS-986165), a pyridazine carboxamide-derived Tyk2 JH2 ligand as a clin. Tyk2 inhibitor currently in late development for the treatment of psoriasis, began with a survey of six-membered heteroaryl groups in place of the N-Me triazolyl moiety in 6. The x-ray co-crystal structure of an early lead (12) revealed a potential new binding pocket. Exploration of the new pocket resulted in two front-runners for a clin. candidate. The potential hydrogen bonding interaction with Thr599 in the pocket was achieved with a tertiary amide moiety, confirmed by the x-ray co-crystal structure of 29. When the diversity search was extended to nicotinamides, a single fluorine atom addition was found to significantly enhance the permeability, which directly led to the discovery of 7 (BMS-986202) as a clin. Tyk2 inhibitor that binds to Tyk2 JH2. The preclin. studies of 7, including efficacy studies in mouse models of IL-23-driven acanthosis, anti-CD40-induced colitis, and spontaneous lupus, will also be presented.

Journal of Medicinal Chemistry published new progress about Acanthosis. 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

Rankovic, Zoran; Cai, Jiaqiang; Fradera, Xavier; Dempster, Maureen; Mistry, Ashvin; Mitchell, Ann; Long, Clive; Hamilton, Emma; King, Angela; Boucharens, Sylviane; Jamieson, Craig; Gillespie, Jonathan; Cumming, Iain; Uitdehaag, Joost; van Zeeland, Mario published the artcile< Dioxo-triazines as a novel series of cathepsin K inhibitors>, Electric Literature of 4956-05-2, the main research area is dioxo triazine preparation cathepsin K inhibitor structure.

A novel dioxo-triazine series of cathepsin K inhibitors was identified from HTS. A rapid exploratory program led to the discovery of potent and selective cathepsin K inhibitors, typified by compound 24 which displayed IC50 values of 17 nM against catK and >10,000 nM in catL, catB and catS assays.

Bioorganic & Medicinal Chemistry Letters published new progress about Antiosteoporotic agents. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Electric Literature of 4956-05-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Gronowitz, S.; Hoernfeldt, A. B.; Kristjansson, V.; Musil, T. published the artcile< On the synthesis of various thienyl- and selenienylpyrimidines>, Computed Properties of 3921-01-5, the main research area is halopyrimidine coupling thiopheneboronic acid; selenopheneboronic acid coupling halopyrimdine; pyrimidineboronic acid coupling bromothiophene; bromoselenophene coupling pyrimidineboronic acid; palladium coupling catalyst halopyrimidine; thienylpyrimidine; selenienylpyrimidine.

Various thienyl- and selenienylpyrimidines, including 5-substituted uracils, were prepared by the Pd(0)-catalyzed coupling between halopyrimidines I (R = H, Cl, Br, Me3CO, PhCH2O; R1 = Br, H) and thiopheneboronic acids and selenopheneboronic acids II [R2 = B(OH)2; X = S, Se, resp.]. 5-Bromouracil had to be protected as the tert-butoxy or benzyloxy derivative in order to achieve successful coupling. The compounds could also be obtained in a reversed manner, when pyrimidineboronic acids I [R = H, Me3CO; R1 = B(OH)2] were coupled with halothiophenes and haloselenophenes II (R2 = Br; X = S, Se).

Chemica Scripta published new progress about Coupling reaction. 3921-01-5 belongs to class pyrimidines, and the molecular formula is C4H2Br2N2, Computed Properties of 3921-01-5.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Prabhakar, Virupakshi; Kondra, Sudhakar Babu; Maddula, Srinivasula Reddy; Parandhama, G.; Latha, J. published the artcile< Synthesis, structural elucidation of novel thieno [2,3-d] pyrimidine core unit containing 1,2,4-triazoles and thiophenes as potent antimicrobial activity>, Application In Synthesis of 18740-39-1, the main research area is aryl thiophenyl thienotriazolopyrimidine preparation antibacterial antifungal activity SAR.

Several new thieno[3,2-e][1,2,4]triazolo[4,3-c]pyrimidines I [R = Ph, 4-MeC6H4, 4-MeOC6H4, etc.] were synthesized starting from thieno[2,3-d]pyrimidine-2,4-diol. The characterization of the newly synthesized compounds was established by IR, 1H NMR, 13C NMR and mass spectral anal. The final compounds I were screened for their antibacterial activity against Bacillus subtilis and Staphylococcus aureus from Gram pos. group of bacteria and Escherichia coli and Klebsiella pneumonia from Gram neg. group of bacteria and antifungal activity against Candida albicans and Aspergillus flavus. Antibacterial and antifungal activities were evaluated and compared with the standard drugs. From antibacterial and antifungal activities screening results, it was observed that compounds I [R = pyridin-3-yl, 1H-indol-2-yl, 4-F3CC6H4] possessed good activity.

Organic Chemistry: Current Research published new progress about Antibacterial agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Application In Synthesis of 18740-39-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Riederer, Heinz; Huettermann, Juergen published the artcile< Matrix-isolation of free radicals from 5-halouracils. 3. Electron spin resonance of base oxidation in aqueous acidic glasses>, Computed Properties of 4956-05-2, the main research area is ESR irradiated nucleic acid base; uracil irradiated ESR; halouracil irradiated ESR; thymine irradiated ESR; nucleoside derivative irradiated ESR.

ESR of x-irradiated aqueous acidic glasses (5.3 M H2SO4, 7.2-14.7 M H3PO4) was used to study the base π-cations of the nucleic acid constituents uracil (U), thymine (T), and the range of 5-halouracils (FU, ClU, BU, IU) as well as their nucleoside derivatives, and to follow their secondary reactions. High solute concentrations (>50 mM) and the presence of electron scavengers (100-200 mM Na2S2O8 or H2O2) favored cation formation and stabilization and suppressed the formation of other solute radicals. Generation of the base cations resulted from transfer of a (possibly) excited solvent hole to the pyrimidine base during x-irradation at 77 K and from attack of the trapped solvent hole (SO4-: or HPO4-:) after thermal activation at 145-65 K. The base cations were either deprotonated at N1, as in most of the free bases, or added OH- at C6 in the nucleosides, where the deoxyribose moiety prevented deprotonation. This hydroxylation was suppressed in a water-deficient system (e.g., 14.7 M H3PO4) but very efficient in 5.3 M H2SO4. The structures of both the primary and secondary radicals were confirmed in most cases by a complete simulation of the exptl. ESR powder spectra. The ESR parameters obtained display a strong influence of the 5 substituent (i.e., the halogens) on the spin-d. distribution in the radicals. Characteristic for the π cations was the high spin d. in the halogen π orbital, ranging from 8% in FU to 40% in IU. Moreover, the amount of H2O in the environment exerts a considerable influence on the halogen spin densities in the charged cation.

Journal of Physical Chemistry published new progress about ESR (electron spin resonance). 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Computed Properties of 4956-05-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

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