Month: October 2022

Nakazawa, Junichi; Watatani, Mitsuo published the artcile< Pyrimidine derivatives. II. Transetherification in pyrimidine derivatives>, COA of Formula: C5H6ClN3O, the main research area is .

Transetherification reactions of 2-methoxy-, 2-ethoxy-4-amino-6-chloropyrimidine, and 2,6-dimethoxy- and 2,6-diethoxy-4-aminopyrimidine at the alkoxy groups at 2- and 6-position by the treatment with NaOMe or NaOEt were investigated and found that the 2-position was more reactive than 4-position and the MeO group more readily underwent transetherification reaction than the EtO group. In 5-substituted pyrimidines with an electroneg. group, the MeOH at 2-, 4-, or 6-position was readily eliminated owing to its further higher reactivity. Manufacture of the following new compounds was also described: a mixture of 38.4 g. barbituric acid 24.3 g. KCN and 144 g. urea was melted at 143-8° 4 hrs., then cooled to 100°, 240 cc. H2O added, stirred 30 min., cooled to below 50°, acidified with HCl, and filtered to give 56.5 g. 2,4,6-trihydroxy-5-pyrimidinecarboxamide (I), fiberlike crystals, m. above 360°. I (8.6 g.) was refluxed with 61 g. POCl3 and 6 g. PhNMe2 1.5 hrs., decomposed with ice, extracted with C6H6, the extract evaporated, and the residue purified by sublimation to give 2,4,6-trichloro-5-cyanopyrimidine (II), plates, m. 122-3.5°. II (1 g.) was added to a solution of 0.67 g. Na in 30 cc. MeOH, refluxed 4 hrs., filtered, the filtrate concentrated, H2O added, and the whole neutralized with HCl to give 2,4-dimethoxy-5-cyano-6-hydroxypyrimidine (III), needles, m. 217-18° (decomposition) (MeOH). III (0.3 g.) was heated 2 hrs. with 30 cc. 5% KOH solution on a steam bath, acidified with HCl, and the mixture filtered to give 2,4,6-trihydroxy-5-cyanopyrimidine, m. above 360°.

Takamine Kenkyusho Nenpo published new progress about Alcoholysis. 3286-55-3 belongs to class pyrimidines, and the molecular formula is C5H6ClN3O, COA of Formula: C5H6ClN3O.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Kickinger, Stefanie; Al-Khawaja, Anas; Haugaard, Anne Staehr; Lie, Maria E. K.; Bavo, Francesco; Loeffler, Rebekka; Damgaard, Maria; Ecker, Gerhard F.; Froelund, Bente; Wellendorph, Petrine published the artcile< Exploring the molecular determinants for subtype-selectivity of 2-amino-1,4,5,6-tetrahydropyrimidine-5-carboxylic acid analogs as betaine/GABA transporter 1 (BGT1) substrate-inhibitors>, Application of C7H7ClN2O2, the main research area is amino tetrahydropyrimidine carboxylic acid betaine GABA transporter substrate inhibitor.

We have previously identified 2-amino-1,4,5,6-tetrahydropyrimidine-5-carboxylic acid (ATPCA) as the most potent substrate-inhibitor of the betaine/GABA transporter 1 (BGT1) (IC50 2.5 μM) reported to date. Herein, we characterize the binding mode of 20 novel analogs and propose the mol. determinants driving BGT1-selectivity. A series of N1-, exocyclic-N-, and C4-substituted analogs was synthesized and pharmacol. characterized in radioligand-based uptake assays at the four human GABA transporters (hGATs) recombinantly expressed in mammalian cells. Overall, the analogs retained subtype-selectivity for hBGT1, though with lower inhibitory activities (mid to high micromolar IC50 values) compared to ATPCA. Further characterization of five of these BGT1-active analogs in a fluorescence-based FMP assay revealed that the compounds are substrates for hBGT1, suggesting they interact with the orthosteric site of the transporter. In silico-guided mutagenesis experiments showed that the non-conserved residues Q299 and E52 in hBGT1 as well as the conformational flexibility of the compounds potentially contribute to the subtype-selectivity of ATPCA and its analogs. Overall, this study provides new insights into the mol. interactions governing the subtype-selectivity of BGT1 substrate-inhibitors. The findings may guide the rational design of BGT1-selective pharmacol. tool compounds for future drug discovery.

Scientific Reports published new progress about Aminopyrimidines Role: PAC (Pharmacological Activity), PRP (Properties), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), PREP (Preparation), USES (Uses). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Application of C7H7ClN2O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Woodring, Jennifer L.; Bachovchin, Kelly A.; Brady, Kimberly G.; Gallerstein, Mitchell F.; Erath, Jessey; Tanghe, Scott; Leed, Susan E.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Sciotti, Richard J.; Pollastri, Michael P. published the artcile< Optimization of physicochemical properties for 4-anilinoquinazoline inhibitors of trypanosome proliferation>, Product Details of C4H2Br2N2, the main research area is anilinoquinazoline trypanosome inhibitor antimalarial malaria trypanosomiasis trypanosomicide; Human African trypanosomiasis; Leishmania major; Neglected tropical disease; Plasmodium falciparum; Target class repurposing; Trypanosoma brucei; Trypanosoma cruzi.

Human African trypanosomiasis (HAT) is a deadly disease in need of new chemotherapeutics that can cross into the central nervous system. The authors previously reported the discovery of (NEU-617), a small mol. with activity against T. brucei bloodstream proliferation. Further optimization of NEU-617 to improve the physicochem. properties (LogP, LLE, [1], and MPO score) [2] have led us to twelve sub-micromolar compounds, most importantly the headgroup variants I and II, and the linker variant III. Although these 3 compounds had reduced potency compared to NEU-617, they all had improved LogP, LLE and MPO scores. Cross-screening these analogs against other protozoan parasites uncovered IV with potent activity towards T. brucei, T. cruzi and L. major, while four others compounds showed activity towards P. falciparum D6. This reinforces the effectiveness of lead repurposing for the discovery of new protozoan disease therapeutics.

European Journal of Medicinal Chemistry published new progress about Antimalarials. 3921-01-5 belongs to class pyrimidines, and the molecular formula is C4H2Br2N2, Product Details of C4H2Br2N2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Bellenie, Benjamin R.; Cheung, Kwai-Ming J.; Varela, Ana; Pierrat, Olivier A.; Collie, Gavin W.; Box, Gary M.; Bright, Michael D.; Gowan, Sharon; Hayes, Angela; Rodrigues, Matthew J.; Shetty, Kartika N.; Carter, Michael; Davis, Owen A.; Henley, Alan T.; Innocenti, Paolo; Johnson, Louise D.; Liu, Manjuan; de Klerk, Selby; Le Bihan, Yann-Vai; Lloyd, Matthew G.; McAndrew, P. Craig; Shehu, Erald; Talbot, Rachel; Woodward, Hannah L.; Burke, Rosemary; Kirkin, Vladimir; van Montfort, Rob L. M.; Raynaud, Florence I.; Rossanese, Olivia W.; Hoelder, Swen published the artcile< Achieving In Vivo Target Depletion through the Discovery and Optimization of Benzimidazolone BCL6 Degraders>, Formula: C5H4Cl2N2S, the main research area is preparation benzimidazolone inhibitor BCL6 interaction repressor lymphoma.

Deregulation of the transcriptional repressor BCL6 enables tumorigenesis of germinal center B-cells, and hence BCL6 has been proposed as a therapeutic target for the treatment of diffuse large B-cell lymphoma (DLBCL). Herein we report the discovery of a series of benzimidazolone inhibitors of the protein-protein interaction between BCL6 and its co-repressors. A subset of these inhibitors were found to cause rapid degradation of BCL6, and optimization of pharmacokinetic properties led to the discovery of 5-((5-chloro-2-((3R,5S)-4,4-difluoro-3,5-dimethylpiperidin-1-yl)pyrimidin-4-yl)amino)-3-(3-hydroxy-3-methylbutyl)-1-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one (CCT369260), which reduces BCL6 levels in a lymphoma xenograft mouse model following oral dosing.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 99469-85-9 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2S, Formula: C5H4Cl2N2S.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Sodum, Rama S.; Klein, Robert S.; Otter, Brian A. published the artcile< Chemistry of 4-pyrimidinones: acetylation and ring-opening reactions>, Name: 5-Hydroxypyrimidin-4(3H)-one, the main research area is pyrimidinone acetylation ring cleavage.

4(3H)-Pyrimidinone (I), as well as its 5-acetoxy and 5-methoxy derivatives, undergoes selective acetylation at N-1 when treated with acetic anhydride. In the presence of water, these 1-acetylpyrimidines undergo spontaneous covalent hydration at C-2 and cleavage of the 1,2-bond to give crystalline cis-3-acetylamino-N-formylacrylamides, generally in good yield. In contrast, the 6-Me derivative of 4(3H)-pyrimidinone forms an equilibrium mixture of acetylated products that undergo the ring opening process to only a very limited extent, the major product (11%) being 3-formylamino-N-acetylacrylamide derivative formed via N-3 acetylation and cleavage of the 2,3-bond.

Journal of Heterocyclic Chemistry published new progress about Acetylation. 15837-41-9 belongs to class pyrimidines, and the molecular formula is C4H4N2O2, Name: 5-Hydroxypyrimidin-4(3H)-one.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Matyugina, Elena; Novikov, Mikhail; Babkov, Denis; Ozerov, Alexander; Chernousova, Larisa; Andreevskaya, Sofia; Smirnova, Tatiana; Karpenko, Inna; Chizhov, Alexander; Muthu, Pravin; Lutz, Stefan; Kochetkov, Sergei; Seley-Radtke, Katherine L.; Khandazhinskaya, Anastasia L. published the artcile< 5-Arylaminouracil Derivatives: New Inhibitors of Mycobacterium tuberculosis>, HPLC of Formula: 4956-05-2, the main research area is arylaminouracil preparation Mycobacterium tuberculosis tuberculostatic; Mycobacterium tuberculosis; carbocyclic nucleosides; uracil derivatives.

Three series of 5-arylaminouracil derivatives, including 5-(phenylamino)uracils, 1-(4′-hydroxy-2′-cyclopenten-1′-yl)-5-(phenylamino)uracils, and 1,3-di-(4′-hydroxy-2′-cyclopenten-1′-yl)-5-(phenylamino)uracils, were synthesized and screened for potential antimicrobial activity. Most of compounds had a neg. effect on the growth of the Mycobacterium tuberculosis H37Rv strain, with 100% inhibition observed at concentrations between 5 and 40 μg/mL. Of those 1-(4′-hydroxy-2′-cyclopenten-1′-yl)-3-(4”’-hydroxy-2”’-cyclopenten-1”’-yl)-5-(4”-butyloxyphenylamino)uracil proved to be the most active among tested compounds against the M. tuberculosis multidrug-resistant strain MS-115 (MIC90 5 μg/mL). In addition, the thymidylate kinase of M. tuberculosis was evaluated as a possible enzymic target.

Chemical Biology & Drug Design published new progress about Mycobacterium tuberculosis. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, HPLC of Formula: 4956-05-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Xu, Hongtao; Gu, Yuang; Zhang, Shuning; Xiong, Huan; Ma, Fei; Lu, Fengping; Ji, Qun; Liu, Lili; Ma, Peixiang; Hou, Wei; Yang, Guang; Lerner, Richard A. published the artcile< A Chemistry for Incorporation of Selenium into DNA-Encoded Libraries>, COA of Formula: C7H7ClN2O2, the main research area is selenium DNA encoded library preparation; C−H activation; DNA-encoded library; benzoselenazolone; rhodium; selenylation.

Conventional direct C-H selenylation suffers from simple selenation with limited atom economy and complicated reaction system. The authors designed benzoselenazolone as a novel bifunctional selenide reagent for both off- and on-DNA C-H selenylation under rhodium(III) catalysis. Using benzoselenazolone gave a series of selenylation products containing an adjacent aminoacyl group in a fast and efficient way, with high atom economy. The synthetic application of this method was demonstrated by taking advantage of the amide functionality as a nucleophile, directing group, and amide coupling partner. This work shows great potential in facilitating rapid construction of selenium-containing DNA-encoded chem. libraries (SeDELs), and lays the foundation for the development of selenium-containing drugs.

Angewandte Chemie, International Edition published new progress about Azoles Role: RCT (Reactant), RACT (Reactant or Reagent) (benzoselenazolones). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, COA of Formula: C7H7ClN2O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Vorbrueggen, Helmut; Ruh-Pohlenz, Carmen published the artcile< Synthesis of nucleosides>, Name: 4-Methoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine, the main research area is review Synthesis; review Nucleosides.

A review of the article Synthesis of nucleosides.

Organic Reactions (Hoboken, NJ, United States) published new progress about Organic synthesis. 84955-32-8 belongs to class pyrimidines, and the molecular formula is C7H8N4O, Name: 4-Methoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Makita, Yoshimasa; Kawaguchi, Shin-ichi; Fujiwara, Shin-ichi published the artcile< Characterization and antitumor activity of furazano[3,4-g]pteridine-2,4(1H,3H)-dione>, Product Details of C4H4N2O5, the main research area is furazanopteridinedione preparation antitumor crystal structure emission absorption spectra.

Structural characterization and properties of furazano[3,4-g]pteridine-2,4(1H,3H)-dione by X-ray crystal structure anal. was reported and evaluated for its antitumor activity. The IC50 value of furazano[3,4-g]pteridine-2,4(1H,3H)-dione was 172μM, as determined using HeLa cells.

Heterocycles published new progress about Absorption spectra. 2244-11-3 belongs to class pyrimidines, and the molecular formula is C4H4N2O5, Product Details of C4H4N2O5.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Cleaves, H. James II published the artcile< The Reactions of Nitrogen Heterocycles with Acrolein: Scope and Prebiotic Significance>, Name: 5-Hydroxypyrimidin-4(3H)-one, the main research area is acrolein nucleobase adduct Michael addition prebiotic evolution.

It was suggested that life began with a self-replicating RNA mol. However, after much research into the prebiotic synthesis of RNA, the difficulties encountered have lead some to hypothesize that RNA was preceded by a simpler mol., 1 more easily synthesized prebiotically. Many of the proposed alternative mols. are based on acrolein, since it reacts readily with nucleophiles, such as the nucleobases, via Michael addition and is readily synthesized from formaldehyde and acetaldehyde. Reports regarding the reactions of nucleobases with concentrated acrolein solutions suggest that this is a plausible reaction mechanism, though there are also reports that the “”incorrect”” isomers are obtained. The scope and kinetics of the reaction of acrolein with various nitrogen heterocycles are reported here. Reactions of pyrimidines often give N1 adducts as the major products. Reactions of purines often give N9 adducts in good yield. The reactions are rapid under neutral to slightly alk. conditions, and proceed at low temperatures and dilutions The implications of these findings for the origin of life are discussed.

Astrobiology published new progress about Addition compounds. 15837-41-9 belongs to class pyrimidines, and the molecular formula is C4H4N2O2, Name: 5-Hydroxypyrimidin-4(3H)-one.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia