Pyrimidines

Liu, Zhiqing; Ai, Jing; Peng, Xia; Song, Zilan; Wu, Kui; Zhang, Jing; Yao, Qizheng; Chen, Yi; Ji, Yinchun; Yang, Yanhong; Geng, Meiyu; Zhang, Ao published the artcile< Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent c-Met/ALK Multikinase Inhibitory Activities>, Formula: C6H2Cl2N2S, the main research area is arylaminopyrimidine preparation SAR cMet ALK multikinase inhibitor antitumor; 2,4-diarylaminopyrimidine analogues; C1-Substituted-N3-benzazepine; c-Met/ALK dual inhibitor; structure repurposing.

By repurposing a typical dopamine D1/D5 receptor agonist motif, C1-substituted-N3-benzazepine or benzazecine, into the classical RTK inhibitor 2,4-diaminopyrimidine skeleton, a series of new 2,4-diarylaminopyrimidine analogs (DAAPalogues) were developed. Two compounds were identified possessing high potency against both c-Met and ALK kinases. Compound (I) displayed appreciable antitumor efficacy at the dose of 1 mg/kg in the ALK-driven BF3/EML4-ALK xenograft mice model.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Formula: C6H2Cl2N2S.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Krasavin, Mikhail; Mujumdar, Prashant; Parchinsky, Vladislav; Vinogradova, Tatiana; Manicheva, Olga; Dogonadze, Marine published the artcile< Library of diversely substituted 2-(quinolin-4-yl)imidazolines delivers novel non-cytotoxic antitubercular leads>, COA of Formula: C4H2Cl2N2, the main research area is quinolinylimidazoline derivative preparation antitubercular antimalarial; 2-imidazoline; Antimalarial; Buchwald–Hartwig; antitubercular; microwave chemistry; non-cytotoxic; quinoline.

A novel library based on quinolin-4-ylimidazoline core was designed to incorporate a general quinoline antimicrobial pharmacophore. A synthesis of the well-characterized library of 36 compounds was achieved using the Pd-catalyzed Buchwald-Hartwig-type imidazoline arylation chem. developed earlier. Compounds were tested for biol. activity and were found to possess no antimalarial activity. However, the library delivered two promising antitubercular leads, which are non-cytotoxic and can be further optimized with respect to antimycobacterial potency.

Journal of Enzyme Inhibition and Medicinal Chemistry published new progress about Antimalarials. 6554-61-6 belongs to class pyrimidines, and the molecular formula is C4H2Cl2N2, COA of Formula: C4H2Cl2N2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Hornillo-Araujo, Ana R.; Burrell, Adam J. M.; Aiertza, Miren K.; Shibata, Takayuki; Hammond, David M.; Edmont, Dolores; Adams, Harry; Margison, Geoffrey P.; Williams, David M. published the artcile< The syntheses and properties of tricyclic pyrrolo[2,3-d]pyrimidine analogues of S6-methylthioguanine and O6-methylguanine>, Formula: C7H8N4O, the main research area is tricyclic pyrrolopyrimidine analog thioguanine methylguanine preparation; thiopyran tricyclic pyrrolopyrimidine analog thioguanine methylguanine preparation; thiepane tricyclic pyrrolopyrimidine analog thioguanine methylguanine preparation; DNA cross linking tricyclic pyrrolopyrimidine analog thioguanine methylguanine preparation; oligonucleotide pseudosubstrate DNA linking tricyclic pyrrolopyrimidine analog thioguanine methylguanine.

The syntheses of novel tricyclic pyrrolo[2,3-d]pyrimidine analogs of S6-methylthioguanine are described. The crystal structures and pKa values of these and related O6-methylguanine analogs are reported. All compounds display higher pKa values than O6-methylguanine with the sulfur-containing analogs being the more basic and exhibiting higher stability in aqueous solution In a standard substrate assay with the human repair protein O6-methylguanine-DNA methyltransferase (MGMT) only the oxygen-containing analog displayed activity.

Organic & Biomolecular Chemistry published new progress about Crystal structure. 84955-32-8 belongs to class pyrimidines, and the molecular formula is C7H8N4O, Formula: C7H8N4O.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

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