Day: October 17, 2022

Sanemitsu, Yuzuru; Nakayama, Yoshinori; Tanabe, Yoo; Matsumoto, Hiroshi; Hashimoto, Shunichi published the artcile< 5-Substituted amino-3,6-dichloro-1,2,4-triazines as new potential herbicides>, Safety of 6-Bromo-1,2,4-triazine-3,5(2H,4H)-dione, the main research area is herbicide triazine structure activity.

5-Substituted 3,6-dichloro-1,2,4-triazines were tested for their preemergent herbicidal activity against 3 weeds, Echinochloa crus-galli, Scirpus juncoides, and Eleocharia acicularis. The activity was related to the structure, e.g., 5-tert-butylamino- and 5-anilino-3,6-dichloro-1,2,4-triazine derivatives exhibited strong herbicidal activity, whereas, Me, OMe, PhO at the 5-position decreased the activity. Also, derivatives with substitution at the 3- and/or 6-position failed to product activity. 5-Diisopropylamino- and 2,6-dimethylpiperidino-1,2,4-triazines were selected as promising new herbicides.

Agricultural and Biological Chemistry published new progress about Echinochloa crus-galli. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Safety of 6-Bromo-1,2,4-triazine-3,5(2H,4H)-dione.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Rai, Roopali; Pandey, Pramod S. published the artcile< Comparative binding study of steroidal adenine with flavin and uracil derivatives>, Product Details of C4H4N2O5, the main research area is steroidal adenine flavin uracil derivative preparation.

A comparative binding study of a steroidal adenine derivative based on lithocholic acid with N10-benzylisoalloxazine (flavin) and N1-iso-propyluracil has been described.

Bioorganic & Medicinal Chemistry Letters published new progress about Drug design. 2244-11-3 belongs to class pyrimidines, and the molecular formula is C4H4N2O5, Product Details of C4H4N2O5.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Dexheimer, Thomas S.; Rosenthal, Andrew S.; Luci, Diane K.; Liang, Qin; Villamil, Mark A.; Chen, Junjun; Sun, Hongmao; Kerns, Edward H.; Simeonov, Anton; Jadhav, Ajit; Zhuang, Zhihao; Maloney, David J. published the artcile< Synthesis and Structure-Activity Relationship Studies of N-Benzyl-2-phenylpyrimidin-4-amine Derivatives as Potent USP1/UAF1 Deubiquitinase Inhibitors with Anticancer Activity against Nonsmall Cell Lung Cancer>, Safety of 2,4-Dichlorothieno[2,3-d]pyrimidine, the main research area is benzylphenylpyrimidinamine antitumor neoplasm deubiquitinase.

Deregulation of ubiquitin conjugation or deconjugation has been implicated in the pathogenesis of many human diseases including cancer. The deubiquitinating enzyme USP1 (ubiquitin-specific protease 1), in association with UAF1 (USP1-associated factor 1), is a known regulator of DNA damage response and has been shown as a promising anticancer target. To further evaluate USP1/UAF1 as a therapeutic target, the authors conducted a quant. high throughput screen of >400000 compounds and subsequent medicinal chem. optimization of small mols. that inhibit the deubiquitinating activity of USP1/UAF1. Ultimately, these efforts led to the identification of ML323 (70) and related N-benzyl-2-phenylpyrimidin-4-amine derivatives, which possess nanomolar USP1/UAF1 inhibitory potency. Moreover, the authors demonstrate a strong correlation between compound IC50 values for USP1/UAF1 inhibition and activity in nonsmall cell lung cancer cells, specifically increased monoubiquitinated PCNA (Ub-PCNA) levels and decreased cell survival. The results establish the druggability of the USP1/UAF1 deubiquitinase complex and its potential as a mol. target for anticancer therapies.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 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

Toledo-Sherman, Leticia M.; Prime, Michael E.; Mrzljak, Ladislav; Beconi, Maria G.; Beresford, Alan; Brookfield, Frederick A.; Brown, Christopher J.; Cardaun, Isabell; Courtney, Stephen M.; Dijkman, Ulrike; Hamelin-Flegg, Estelle; Johnson, Peter D.; Kempf, Valerie; Lyons, Kathy; Matthews, Kimberly; Mitchell, William L.; O’Connell, Catherine; Pena, Paula; Powell, Kendall; Rassoulpour, Arash; Reed, Laura; Reindl, Wolfgang; Selvaratnam, Suganathan; Friley, Weslyn Ward; Weddell, Derek A.; Went, Naomi E.; Wheelan, Patricia; Winkler, Christin; Winkler, Dirk; Wityak, John; Yarnold, Christopher J.; Yates, Dawn; Munoz-Sanjuan, Ignacio; Dominguez, Celia published the artcile< Development of a Series of Aryl Pyrimidine Kynurenine Monooxygenase Inhibitors as Potential Therapeutic Agents for the Treatment of Huntington's Disease>, Formula: C5H4Cl2N2O, the main research area is arylpyrimidine kynurenine monooxygenase inhibitor preparation SAR Huntingtons disease.

We report on the development of a series of pyrimidine carboxylic acids that are potent and selective inhibitors of kynurenine monooxygenase and competitive for kynurenine. We describe the SAR for this novel series and report on their inhibition of KMO activity in biochem. and cellular assays and their selectivity against other kynurenine pathway enzymes. We describe the optimization process that led to the identification of a program lead compound with a suitable ADME/PK profile for therapeutic development. We demonstrate that systemic inhibition of KMO in vivo with this lead compound provides pharmacodynamic evidence for modulation of kynurenine pathway metabolites both in the periphery and in the central nervous system.

Journal of Medicinal Chemistry published new progress about Central nervous system agents. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Formula: C5H4Cl2N2O.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Miyakawa, Shin; Yamanashi, Hiroto; Kobayashi, Kensei; Cleaves, H. James; Miller, Stanley L. published the artcile< Prebiotic synthesis from CO atmospheres: implications for the origins of life>, Related Products of 15837-41-9, the main research area is carbon monoxide primordial atm prebiotic amino acid life origin.

Most models of the primitive atm. around the time life originated suggest that the atm. was dominated by carbon dioxide, largely based on the notion that the atm. was derived via volcanic outgassing, and that those gases were similar to those found in modern volcanic effluent. These models tend to downplay the possibility of a strongly reducing atm., which had been thought to be important for prebiotic synthesis and thus the origin of life. However, there is no definitive geol. evidence for the oxidation state of the early atm. and bioorganic compounds are not efficiently synthesized from CO2 atmospheres. In the present study, proton-beam irradiation of equimol. mixtures of CO and N2 in the presence of water induced abiotic synthesis of uracil, orotic acid, 5-hydroxyuracil, nicotinic acid, and 4,5-dihydroxypyrimidine. This and similar previous observations suggest that a CO-CO2-N2-H2O atm. can give a variety of bioorganic compounds with yields comparable to those obtained from a strongly reducing atm. Atmospheres containing carbon monoxide might therefore have been conducive to prebiotic synthesis and perhaps the origin of life. CO-dominant atmospheres could have existed if the production rate of CO from impacts of extraterrestrial materials were high or if the upper mantle had been more reduced than today.

Proceedings of the National Academy of Sciences of the United States of America published new progress about Life, origin. 15837-41-9 belongs to class pyrimidines, and the molecular formula is C4H4N2O2, Related Products of 15837-41-9.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Shih, Chuan; Gossett, L. S. published the artcile< The synthesis of N-{2-amino-4-substituted [(pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic acids as antineoplastic agents>, Computed Properties of 84955-32-8, the main research area is neoplasm inhibitor aminopyrrolopyrimidinylethylbenzoylglutamic acid; pyrrolopyrimidine folate antagonist antitumor; LY 231514 analog neoplasm inhibitor.

A variety of 4-substituted pyrrolo[2,3-d]pyrimidine based folate antagonists, e.g. I (R = Cl, H, OMe, NH2, SH, NEt2) which are closely related to the novel thymidylate synthase inhibitor LY231514 were prepared 2-Amino-4-chloropyrrolo[2,3-d]pyrimidine (II; R = Cl, R1 = R2 = H) was selected as an important precursor for the preparation of key intermediates such as II (R = Cl, OMe, NEt2, NHCH2Ph, R1 = iodo, CCH, R2 = Me3CCO) (III). Pyrrolopyrimidines III were coupled with either 4-ethynylbenzoylglutamate or 4-iodobenzoylglutamate in a Pd-catalyzed Heck reaction to provide the basic skeleton of the targeted mols. The availability of the chlorine atom allowed the efficient introduction of different substituents at the 4-position of the pyrrolopyrimidine ring. In vitro anal. demonstrated that some I are highly cytotoxic against human leukemic cells (CCRF-CEM) in culture.

Heterocycles published new progress about Antitumor agents. 84955-32-8 belongs to class pyrimidines, and the molecular formula is C7H8N4O, Computed Properties of 84955-32-8.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Casimiro-Garcia, Agustin; Allais, Christophe; Brennan, Agnes; Choi, Chulho; Dower, Gabriela; Farley, Kathleen A.; Fleming, Margaret; Flick, Andrew; Frisbie, Richard K.; Hall, Justin; Hepworth, David; Jones, Hannah; Knafels, John D.; Kortum, Steve; Lovering, Frank E.; Mathias, John P.; Mohan, Sashi; Morgan, Paul M.; Parng, Chuenlei; Parris, Kevin; Pullen, Nick; Schlerman, Franklin; Stansfield, John; Strohbach, Joseph W.; Vajdos, Felix F.; Vincent, Fabien; Wang, Hong; Wang, Xiaolun; Webster, Robert; Wright, Stephen W. published the artcile< Discovery of a Series of Pyrimidine Carboxamides as Inhibitors of Vanin-1>, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is pyrimidine carboxamide vanin inhibitor pharmacokinetic ADME.

A diaryl ketone series was identified as vanin-1 inhibitors from a high-throughput screening campaign. While this novel scaffold provided valuable probe 2 that was used to build target confidence, concerns over the ketone moiety led to the replacement of this group. The successful replacement of this moiety was achieved with pyrimidine carboxamides derived from cyclic secondary amines that were extensively characterized using biophys. and crystallog. methods as competitive inhibitors of vanin-1. Through optimization of potency and physicochem. and ADME properties, and guided by co-crystal structures with vanin-1, 3 was identified with a suitable profile for advancement into preclin. development.

Journal of Medicinal Chemistry published new progress about Crystal structure. 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

Hin, Niyada; Duvall, Bridget; Ferraris, Dana; Alt, Jesse; Thomas, Ajit G.; Rais, Rana; Rojas, Camilo; Wu, Ying; Wozniak, Krystyna M.; Slusher, Barbara S.; Tsukamoto, Takashi published the artcile< 6-Hydroxy-1,2,4-triazine-3,5(2H,4H)-dione Derivatives as Novel D-Amino Acid Oxidase Inhibitors>, Quality Control of 4956-05-2, the main research area is hydroxytriazinedione preparation amino acid oxidase inhibitor.

A series of 2-substituted 6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione derivatives were synthesized as inhibitors of D-amino acid oxidase (DAAO). Many compounds in this series were found to be potent DAAO inhibitors, with IC50 values in the double-digit nanomolar range. The 6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione pharmacophore appears metabolically resistant to O-glucuronidation unlike other structurally related DAAO inhibitors. Among them, compound I was found to be selective over a number of targets and orally available in mice. Furthermore, oral coadministration of D-serine with I enhanced the plasma levels of D-serine in mice compared to the oral administration of D-serine alone, demonstrating its ability to serve as a pharmacoenhancer of D-serine.

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

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Zhi, Yanle; Li, Baoquan; Yao, Chao; Li, Hongmei; Chen, Puzhou; Bao, Jiyin; Qin, Tianren; Wang, Yue; Lu, Tao; Lu, Shuai published the artcile< Discovery of the selective and efficacious inhibitors of FLT3 mutations>, Quality Control of 18740-39-1, the main research area is pyrazole carboxamide preparation FLT3 inhibitor mutation antitumor leukemia; AML; Acute myeloid; FLT3; FMS-Like tyrosine kinase 3 inhibitors; Leukemia.

Fms-like tyrosine kinase 3 (FLT3) is among the most frequently mutated protein in acute myeloid leukemia (AML), which has been confirmed as an important drug target for AML chemotherapy. Starting from the lead compound LT-106-175, a series of 1-H-pyrazole-3-carboxamide derivatives were synthesized to improve the FLT3 inhibitory potency and selectivity. Among them, compound 50 (4-((2-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)-N-(4-(piperazin-1-yl)phenyl)-1H-pyrazole-3-carboxamide) was identified as a highly potent and selective FLT3 inhibitor (IC50 = 0.213 nM), which showed equal activities against various mutants of FLT3 including FLT3 (ITD)-D835V and FLT3 (ITD)-F691L that is resistant to quizartinib. Compound 50 also exhibited efficacy against the human AML cell line MV4-11 (IC50 = 16.1 nM) harboring FLT3-ITD mutants. Inversely, compound 50 displayed no cytotoxicity to FLT3-independent cells, and the biochem. analyses showed that its effects were related to the inhibition of FLT3 signal pathways. Addnl., compound 50 induced apoptosis in MV4-11 cell as demonstrated by flow cytometry. Moreover, compound 50 showed enhanced metabolic stability. Altogether, it was concluded that compound 50 could be a promising FLT3 inhibitor for further developing therapeutic remedy of AML.

European Journal of Medicinal Chemistry published new progress about Acute myeloid leukemia. 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

Ife, Robert J.; Brown, Thomas H.; Blurton, Peter; Keeling, David J.; Leach, Colin A.; Meeson, Malcolm L.; Parsons, Michael E.; Theobald, Colin J. published the artcile< Reversible Inhibitors of the Gastric (H+/K+)-ATPase. 5. Substituted 2,4-Diaminoquinazolines and Thienopyrimidines>, Related Products of 18740-39-1, the main research area is quinazolinamine thienopyrimidinamine quinazolinediamine.

Quinazolines bearing a secondary [4-(arylamino)] substituent demonstrate a structure-activity relationship for inhibition of the gastric (H+/K+)-ATPase different from the previously described 3-acylquinolines, suggesting that, although these compounds are also K+-competitive, they probably bind to the enzyme in a different orientation. Compounds bearing a tertiary 4-(arylamino) substituent, however, in particular 4-(N-methylarylamino), appear to possess an structure-activity relationship quite similar to the 3-acylquinolines. Compounds possessing both a 4-(N-methylarylamino) substituent and a 2-(arylamino) substituent proved to be very potent, K+-competitive inhibitors of K+-stimulated ATPase activity with Ki values down to 12 nM. Some compounds also proved to be effective inhibitors of stimulated acid secretion in both the rat and dog when dosed i.v. However, although a number of these demonstrated activity after oral administration in dogs, the level and variability precluded further evaluation.

Journal of Medicinal Chemistry published new progress about Structure-activity relationship, ATPase-inhibiting. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Related Products of 18740-39-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia