Day: October 12, 2022

Ognyanov, Vassil I.; Balan, Chenera; Bannon, Anthony W.; Bo, Yunxin; Dominguez, Celia; Fotsch, Christopher; Gore, Vijay K.; Klionsky, Lana; Ma, Vu V.; Qian, Yi-Xin; Tamir, Rami; Wang, Xianghong; Xi, Ning; Xu, Shimin; Zhu, Dawn; Gavva, Narender R.; Treanor, James J. S.; Norman, Mark H. published the artcile< Design of potent, orally available antagonists of the transient receptor potential vanilloid 1. Structure-activity relationships of 2-piperazin-1-yl-1H-benzimidazoles>, Category: pyrimidines, the main research area is benzimidazole piperazinyl preparation transient receptor potential vanilloid antagonist antihyperalgesic.

The vanilloid receptor-1 (VR1 or TRPV1) is a membrane-bound, nonselective cation channel that is predominantly expressed by peripheral neurons sensing painful stimuli. TRPV1 antagonists produce antihyperalgesic effects in animal models of inflammatory and neuropathic pain. The synthesis and the structure-activity relationships of a series of 2-(4-pyridin-2-ylpiperazin-1-yl)-1H-benzo[d]imidazoles I [R1 = H, Me3SiCH2CH2OCH2, PhCH2; R2 = F, Cl, Br, F3C, Me, CN, Me3C, MeO2C, etc.; R3 = H, 4-(2-thiazolyl), 4-(4-pyridyl), 5-(4-F3CC6H4), etc.; R4 = H, Me; R5 = H, H2N, MeCHOH, H2C:CH, etc.; R6 = H, Cl, F3C, etc.] and analogs as novel TRPV1 antagonists have been described. I [R1 = H; R2 = F3C; R3 = 4-(3,4,5-F3C6H2); R4 = (R)-Me; R5 = HOCH2CHOH; R6 = Cl; (II)] was among the most potent analogs in this series. This compound was orally bioavailable in rats and was efficacious in blocking capsaicin-induced flinch in rats in a dose-dependent manner. II also reversed thermal hyperalgesia in a model of inflammatory pain, which was induced by complete Freund’s adjuvant (CFA).

Journal of Medicinal Chemistry published new progress about Analgesics. 6554-61-6 belongs to class pyrimidines, and the molecular formula is C4H2Cl2N2, Category: pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Bretschneider, H.; Kloetzer, W.; Spiteller, G.; Dehler, J. published the artcile< New pyrimidines and their conversion into 6-sulfanilamidopyrimidines. Preliminary communications>, HPLC of Formula: 3286-55-3, the main research area is .

The favorable chemotherapeutic properties of 6-sulfanilamido-2,4-dimethoxypyrimidine (I) motivated the preparation of a number of 2,4-disubstituted 6-sulfanilamidopyrimidines. From II were prepared the following IIa (R, R’, and R” given): MeO, MeO, Cl (III); MeO, MeO, NMe3Cl; MeO, Cl, Cl (IV); MeO, MeO, EtS; MeO, MeO, EtSO2; MeO, MeO, PhS; MeO, MeO, PhSO2; MeO, MeO, 4-AcNHC6H4SO2; Cl, Cl, NH2; MeO, MeO, NH2; EtS, EtS, NH2; CH2:CHCH2O, CH2:CHCH2O, NH2 (V); MeOCH2CH2O, MeOCH2CH2O, NH2; MeO, Cl, NH2; EtS, Cl, NH2; MeO, H, NH2; MeO, EtS, NH2; EtS, MeO, NH2. Also prepared was Va. Two procedures were used to introduce the sulfanilamido group: (1) replacement of the 6-substituent by treatment with 4-H2NC6H4SO2NHNa (VI) or 4-AcNHC6H4SO2NHNa (VII) and (2) the standard acylation with an N4-acylaminobenzenesulfonyl chloride in pyridine followed by hydrolysis. Treatment of II with VII gave (VIII) (R” = Ac, R’ = R = Cl), converted by acid hydrolysis to VIII (R” = H, R’ = R = Cl) (IX). Partial methanolysis of IX with NaOMe gave VIII (R” = H, R’ = Cl, R = OMe) (X) and total methanolysis afforded I. X was also prepared from IV and VII to give VIII (R” = Ac, R’ = Cl, R = OMe) (XI), followed by hydrolysis. Methanolysis of XI followed by hydrolysis gave I. X treated with Me2NH gave VIII (R” = H, R’ = NMe2, R = OMe). I was also obtained from III and VI, and X from IV and VI. V was converted to VIII (R” = Ac, R’ = R = OCH2CH2OMe) and hydrolyzed to VIII (R = H, R’ = R = OCH2CH2OMe). The following VIII (R” = EtO2C) were reported (R and R’ given): MeO, MeO; EtS, EtS; CH2:CHCH2O, CH2:CHCH2O; MeO, EtS; EtS, MeO. Also prepared was XII. Hydrolysis of the above compounds gave the corresponding sulfapyrimidines. Complete details of this work are in preparation

Monatshefte fuer Chemie published new progress about 3286-55-3. 3286-55-3 belongs to class pyrimidines, and the molecular formula is C5H6ClN3O, HPLC of Formula: 3286-55-3.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Law, Robert P.; Ukuser, Sabri; Tape, Daniel T.; Talbot, Eric P. A. published the artcile< Regioselective Synthesis of 3-Aminoimidazo[1,2-a]pyrimidines with Triflic Anhydride>, Electric Literature of 89793-12-4, the main research area is regioselective synthesis aminoimidazopyrimidine cyclization pyrimidine amide triflic anhydride pyridine.

The regioselective synthesis of 3-aminoimidazo[1,2- a]pyrimidines via triflic anhydride mediated amide activation and intramol. cyclization is reported. The nature of the added pyridine base allows access to both regioisomers from a simple common precursor [e.g., treatment of pyrimidine amide I with Tf2O and pyridine bases yielded II + III (yield ratios 8:45 % using 2,6-difluoropyridine and 83:9 % using 2-fluoropyridine)]. The method tolerates a range of functional groups and provides access to novel heterocyclic scaffolds.

Synthesis published new progress about Cyclization catalysts (regioselective). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Electric Literature of 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Odingo, Joshua; O’Malley, Theresa; Kesicki, Edward A.; Alling, Torey; Bailey, Mai Ann; Early, Julie; Ollinger, Juliane; Dalai, Suryakanta; Kumar, Naresh; Singh, Ravindra Vikram; Hipskind, Philip A.; Cramer, Jeffrey W.; Ioerger, Thomas; Sacchettini, James; Vickers, Richard; Parish, Tanya published the artcile< Synthesis and evaluation of the 2,4-diaminoquinazoline series as anti-tubercular agents>, COA of Formula: C6H2Cl2N2S, the main research area is diaminoquinazoline preparation tuberculostatic Mycobacterium tuberculosis; 2,4-Diaminoquinazoline; Antibacterial activity; Dioxygenase; Mycobacterium tuberculosis; Tuberculosis.

The 2,4-diaminoquinazoline class of compounds has previously been identified as an effective inhibitor of Mycobacterium tuberculosis growth. The authors conducted an extensive evaluation of the series for its potential as a lead candidate for tuberculosis drug discovery. Three segments of the representative mol. N-(4-fluorobenzyl)-2-(piperidin-1-yl)quinazolin-4-amine were examined systematically to explore structure-activity relationships influencing potency. The authors determined that the benzylic amine at the 4-position, the piperidine at 2-position and the N-1 (but not N-3) are key activity determinants. The 3-deaza analog retained similar activity to the parent mol. Biol. activity was not dependent on iron or carbon source availability. The authors demonstrated through pharmacokinetic studies in rats that good in vivo compound exposure is achievable. A representative compound demonstrated bactericidal activity against both replicating and nonreplicating M. tuberculosis. The authors isolated and sequenced M. tuberculosis mutants resistant to this compound and observed mutations in Rv3161c, a gene predicted to encode a dioxygenase, suggesting that the compound may act as a prodrug.

Bioorganic & Medicinal Chemistry published new progress about Mycobacterium tuberculosis. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, COA of Formula: C6H2Cl2N2S.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Borgesde Melo, Eduardo; Ferreira, Marcia Miguel Castro published the artcile< Nonequivalent Effects of Diverse LogP Algorithms in Three QSAR Studies>, Quality Control of 15837-41-9, the main research area is nonequivalent algorithm QSAR.

Despite of the availability and facility of accessing several algorithms for calculation of LogP in QSA(P)R studies, articles typically do not describe the selection procedure for the method used. Therefore, three studies to verify the influence of different LogP algorithms on building QSAR models were performed. Two QSAR data sets from the literature (42 tricyclic phtalimide inhibitors of HIV-integrase and 46 TIBO derivatives inhibitors of HIV-reverse transcriptase) were used together with LogP calculated by thirteen algorithms, and several regression models were constructed and compared. A new QSAR study for 4,5-dihydroxypyrimidine carboxamides inhibitors of HIV-1 integrase was also performed. The explained and predicted variance, results from external validation, leave-N-out cross-validation and y-randomization test were analyzed for all models from the three data sets. Despite the same physicochem. meaning, LogP’s calculated by distinct methods may show different levels of contribution to the model. This observation comes out from the comparison of validated models. These results indicate that the arbitrary choice of one specific algorithm for LogP calculation, as is usual in QSA(P)R studies, does not necessarily lead to the highest quality model for the analyzed data set.

QSAR & Combinatorial Science published new progress about Algorithm. 15837-41-9 belongs to class pyrimidines, and the molecular formula is C4H4N2O2, Quality Control of 15837-41-9.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Srimongkolpithak, Nitipol; Sundriyal, Sandeep; Li, Fengling; Vedadi, Masoud; Fuchter, Matthew J. published the artcile< Identification of 2,4-diamino-6,7-dimethoxyquinoline derivatives as G9a inhibitors>, Quality Control of 18740-39-1, the main research area is diamino dimethoxyquinoline derivative histone lysine methyltransferase inhibitor identification.

G9a is a histone lysine methyltransferase (HKMT) involved in epigenetic regulation via the installation of histone methylation marks. 6,7-Dimethoxyquinazoline analogs, such as BIX-01294, are established as potent, substrate competitive inhibitors of G9a. With an objective to identify novel chemotypes for substrate competitive inhibitors of G9a, we have designed and synthesized a range of heterocyclic scaffolds, and investigated their ability to inhibit G9a. These studies have led to improved understanding of the key pharmacophoric features of BIX-01294 and the identification of a new core quinoline inhibitory scaffold, which retains excellent potency and high selectivity. Mol. docking was carried out to explain the observed in vitro data.

MedChemComm published new progress about Hydrogen bond. 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; Haizhong, Tan; Wei, Wu; Musheng, Xu; Garcia-Osta, Ana; Oyarzabal, Julen published the artcile< Design, Synthesis, and Biological Evaluation of First-in-Class Dual Acting Histone Deacetylases (HDACs) and Phosphodiesterase 5 (PDE5) Inhibitors for the Treatment of Alzheimer's Disease>, Application In Synthesis of 89793-12-4, the main research area is histone deacetylase HDAC phosphodiesterase PDE5 inhibitor antialzheimer Alzheimer.

Simultaneous inhibition of phosphodiesterase 5 (PDE5) and histone deacetylases (HDAC) has recently been validated as a potentially novel therapeutic approach for Alzheimer’s Disease (AD). To further extend this concept, the authors designed and synthesized the first chem. series of dual acting PDE5 and HDAC inhibitors, and the authors validated this systems therapeutics approach. Following the implementation of structure- and knowledge-based approaches, initial hits were designed and were shown to validate the hypothesis of dual in vitro inhibition. Then, an optimization strategy was pursued to obtain a proper tool compound for in vivo testing in AD models. Initial hits were translated into mols. with adequate cellular functional responses (histone acetylation and cAMP/cGMP response element-binding (CREB) phosphorylation in the nanomolar range), an acceptable therapeutic window (>1 log unit) and the ability to cross the blood-brain barrier, leading to the identification of 7 as a candidate for in vivo proof-of-concept testing.

Journal of Medicinal Chemistry published new progress about Alzheimer disease. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Application In Synthesis of 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia