Month: October 2022

Liu, Kevin G.; Kim, Ji-In; Olszewski, Kellen; Barsotti, Anthony M.; Morris, Koi; Lamarque, Christophe; Yu, Xuemei; Gaffney, Jack; Feng, Xiao-Jiang; Patel, Jeegar P.; Poyurovsky, Masha V. published the artcile< Discovery and Optimization of Glucose Uptake Inhibitors>, Electric Literature of 18740-39-1, the main research area is glucose transporters inhibitors GLUT1 GLUT3 bioavailable ADME SAR.

Aerobic glycolysis, originally identified by Warburg as a hallmark of cancer, has recently been implicated in immune cell activation and growth. Glucose, the starting material for glycolysis, is transported through the cellular membrane by a family of glucose transporters (GLUTs). Therefore, targeting glucose transporters to regulate aerobic glycolysis is an attractive approach to identify potential therapeutic agents for cancers and autoimmune diseases. Herein, we describe the discovery and optimization of a class of potent, orally bioavailable inhibitors of glucose transporters, targeting both GLUT1 and GLUT3.

Journal of Medicinal Chemistry published new progress about Autoimmune disease. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Electric Literature of 18740-39-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Spiteller, G.; Bretschneider, H. published the artcile< Preparation of 2,6-disubstituted 4-sulfanilamidopyrimidines>, Related Products of 3286-55-3, the main research area is .

Crude 2,6-dichloro-4-aminopyrimidine (I) (21.2 g.) was treated portionwise with 50 ml. NaOMe (3.14 g. Na) at 35°, the mixture heated 1 hr. at 50° with stirring, MeOH distilled in vacuo at 40°, and the residue treated with 30 ml. H2O yielded after filtration 14.2 g. 2-methoxy-4-amino-6-chloropyrimidine (II), m. 130° (H2O), sublimable at 120° (0.5 mm.). CaCO3Pd catalyst (1.3 g.) hydrogenated in 10 ml. absolute MeOH was added to 798 mg. II in 35 ml. absolute methanolic NaOH and the mixture hydrogenated to yield 510 mg. 2-methoxy-4-aminopyrimidine, m. 160-7°; mixed m.p. with authentic material gave no depression. II (13.4 g.) was treated with 20 ml. NaOMe (113 mg. Na/ml.) and 10 ml. 90% EtSH, the mixture heated 2 hrs. at 100° in an autoclave, cooled, MeOH and excess EtSH distilled in vacuo, the residue treated with 20 ml. H2O, the oil obtained dissolved in 150 ml. Et2O, washed with H2O, dried, evaporated, and petr. ether added to give 13.1 g. 2-methoxy-4-amino-6-ethylthiopyrimidine (III), m. 83-4°, b0.5 140°. I (24.6 g.) was treated with 20 ml. EtSH, 48 ml. absolute MeOH, and 3.75 g. Na, the mixture heated 1 hr. in an autoclave at 50°, MeOH and excess EtSH distilled in vacuo at 50°, the residue taken up in 20 ml. H2O and 200 ml. Et2O, washed with H2O, the Et2O solution dried, and 2-ethylthio-4-amino-6-chloropyrimidine (IV) precipitated with petr. ether, m. 78-79°, b0.5 130°. Crude IV (17.5 g.) was treated with 30 ml. NaOMe solution (containing 2.1 g. Na) in an autoclave 2 hrs. at 100°, the mixture evaporated, and the residue treated with H2O to give 2-ethylthio-4-amino-6-methoxy pyrimidine (V), m. 117-18° (Et2O), b0.5 135-40°. I (8.4 g.) treated in an autoclave with 20 ml. EtSH and 38 ml. NaOMe (2.8 g. Na) and heated 6 hrs. at 110° gave 2,6-bis(ethylthio)-4-aminopyrimidine (VI), m. 72-3° (petr. ether), b0.5 155-60°. I (8.2 g.) treated with 60 ml. absolute CH2:CHCH2OH and 4 g. Na 2 hrs. at 100° yielded after evaporation in vacuo 2,6-diallyl-4-aminopyrimidine (VII), m. 48-53° (Et2O-petr. ether), b0.5 120-30°. Na (5.5 g.) in 60 ml. HOCH2CH2OMe was heated 3 hrs. at 100° with 16 g. crude I in an autoclave, the mixture evaporated in vacuo, the residue extracted with 500 ml. C6H6, the extract washed neutral with H2O, boiled with active C, filtered, and freed of solvent to give 2,6-bis(β-methoxyethoxy)-4-aminopyrimidine (VIII), m. 84-5° (MeOH-Et2O), and a compound, m. 63-4°. Freshly distilled PhNH2 (92 g.), 150 ml. Et2O, and 100 ml. H2O was treated dropwise with 108 g. ClCO2Et in 50 ml. Et2O at 5°, 54 g. ClCO2Et, then 40 g. NaOH in 60 ml. H2O added by a dropping funnel, the mixture stirred 15 min., the precipitate separated and extracted with Et2O, freed of solvent, and the residue distilled in vacuo to give 90% phenylurethan (IX), b11 145-6°, m. 53° (H2O). To 250 ml. HSO3Cl cooled with an ice-salt mixture was added in 5 g. portions 80 g. IX, the temperature was held at 5° maximum, the mixture stirred 15 min. at 5°, left overnight, heated 1 hr. at 75-80° on a water bath, cooled, poured on ice, the precipitated crystals filtered off, washed with NaHCO3 solution and H2O, extracted in 600 ml. C6H6, and the extract filtered hot gave 46 g. N4-carbethoxysulfanilic chloride (X), m. 103° (C6H6). The aminopyrimidines were converted to compounds of the general formula R3NHC6H4SO2NHC:-N.CR2:N.CR1:CH (Xa) by treatment with 5-10% excess X in 2.5 times absolute C5H5N. The mixture was kept briefly at room temperature, heated 1 hr. at 70-80°, C5H5N evaporated in vacuo, the residue treated with 10% NaHCO3, and the precipitated Na salt dissolved in excess H2O to give, after filtration and acidification of the filtrate, the acylated sulfonamide. V yielded 94% Xa (R1 = EtS, R2 = MeO, R3 = EtOCO) (XI), m. 172-3° (EtOH); III gave 82% Xa (R1 = MeO, R2 = EtS, R3 = EtOCO) (XII), m. 188-9° (EtOH); VI yielded 88% Xa (R1 = R2 = EtS, R3 = EtOCO) (XIII), m. 167-8° (EtOH); VII gave 94% Xa (R1 = R2 = CH2:CHCH2OH, R3 = EtOCO) (XIV), m. 164-5° (EtOH); and VIII yielded 60% Xa (R1 = R2 = MeOCH2CH2O, R3 = MeCO) (XV), m. 164-5° (MeOH). The acylsulfonamides were hydrolyzed by heating 1 hr. in 5 moles N NaOH on a water bath and the cooled solution neutralized by dropwise addition of 50% AcOH to give sulfonamides of the general formula H2NC6H4SO2NHC:N.CR2:N.CR’:CH (XVa). XI yielded 97% XVa (R1 = EtS, R2 = MeO), m. 178-9°; XII gave 75% XVa (R1 = MeO, R2 = EtS), m. 181-2°; XIII gave 94% XVa (R1 = R2 = EtS), m. 176-7°; XIV yielded 90% XVa (R1 = R2 = CH2:CHCH2O), m. 163-4°; and XV gave XVa (R1 = R2 = MeOCH2CH2O) (XVI). XVI was converted to the appropriate Ag salt, m. 262-4° (decomposition). The Ag salt of XVI was treated with H2S and the precipitated Ag2S filtered off, and the solution evaporated in vacuo. The residue was treated with Ac2O in C5H5N 2 days at room temperature and 20 min. on a water bath, freed of solvent, and poured into Na2CO3 solution, filtered, and the filtrate neutralized with AcOH to give XV. The Na salt of XV was not obtained in a pure form.

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

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 [Erratum to document cited in CA163:608335]>, Product Details of C3H2BrN3O2, the main research area is erratum arylaminouracil preparation Mycobacterium tuberculosis tuberculostatic.

On page 1387, the tenth author’s name was misspelled; the corrected name is Pravin Muthu.

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

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Prabhakar, Virupakshi; Babu, Sangu Jagadish; Jyothi, Sangu V. N. Lalitha Siva; Lahari, Sangu V. N.; Bandi, Venkateswarlu published the artcile< Synthesis, structural elucidation and anti-bacterial evaluation of some novel heterocyclic molecules derived from thieno[2,3-d]pyrimidine as a core unit>, Safety of 2,4-Dichlorothieno[2,3-d]pyrimidine, the main research area is thienopyrimidinepyrazole preparation antibacterial antifungal.

A series of novel 4-(3,5-dimethyl-1H-pyrazol-1-yl)-2-substituted phenyl/heterocyclic thieno[2,3-d]pyrimidine derivatives I (R = Ph, 4-MeC6H4, 4-MeOC6H4, etc.) were synthesized by a facile five-step procedure that afforded advantages of mild reaction conditions, simple protocol and good yields. The final compounds were screened for their anti-bacterial 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. Anti-bacterial and anti-fungal activities were evaluated and compared with the standard drugs such as amoxicillin and ketoconazole. From anti-bacterial and antifungal activity screening results, it has been observed that compounds I (R = thiophen-2-yl, indol-5-yl, 4-F3CC6H4, pyridin-3-yl) possess 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, Safety of 2,4-Dichlorothieno[2,3-d]pyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Farkas, Jiri published the artcile< Synthesis of 1,2,4-triazine-3,5(2H,4H)-diones containing electronegative substituents in position 6>, Application of C3H2BrN3O2, the main research area is triazinedione electroneg substituent.

Reaction of F2 with 1,2,4-triazine-3,5(2H,4H)-dione (I, R = H) afforded the fluoro derivative I (R = F) in 0.3% yield. The nitro compound I (R = NO2) was prepared by oxidation of the amino derivative of I (R = NH2) with H2O2, in 23% yield. Synthesis of the cyano compound I (R = cyano) was accomplished by treatment with CuCN. The effect of substituents on the CO frequencies of 6-substituted derivatives of I was studied.

Collection of Czechoslovak Chemical Communications published new progress about 4956-05-2. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Application of C3H2BrN3O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Regan, Collin F.; Pierre, Fabrice; Schwaebe, Michael K.; Haddach, Mustapha; Jung, Michael E.; Ryckman, David M. published the artcile< A facile synthesis of 5-halopyrimidine-4-carboxylic acid esters via a Minisci reaction>, Synthetic Route of 6554-61-6, the main research area is Minisci homolytic alkoxycarbonylation halopyrimidine; bromopyrimidinecarboxylate; pyrimidine halo Minisci homolytic alkoxycarbonylation.

This paper reports the synthesis of various 5-halopyrimidine-4-carboxylic acid esters via the Minisci homolytic alkoxycarbonylation of 5-halopyrimidines. The reaction was found to be highly regioselective, allowing the one-step synthesis of useful amounts (>10 g) of Et 5-bromopyrimidine-4-carboxylate where other methods proved difficult. Et 5-bromopyrimidine-4-carboxylate was used for the preparation of potent CK2 inhibitors including CX-5011. This work represents an interesting application of radical chem. for the preparation of pharmacol. active mols.

Synlett published new progress about Alkoxycarbonylation (Minisci homolytic). 6554-61-6 belongs to class pyrimidines, and the molecular formula is C4H2Cl2N2, Synthetic Route of 6554-61-6.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Xu, Ana; He, Feng; Zhang, Xiangna; Li, Xiaoyang; Ran, Yingying; Wei, Chao; James Chou, C.; Zhang, Rui; Wu, Jingde published the artcile< Tacrine-hydroxamate derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation>, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is tacrine hydroxamate derivative preparation anti Alzheimer; structure activity tacrine hydroxamate cholinesterase inhibitor; Alzheimer’s disease; Antioxidant; Cholinesterase inhibitor; Metal chelator; Multitarget-directed ligands.

In order to develop multitarget-directed ligands as potential treatments for Alzheimer’s disease, twenty-eight new tacrine-hydroxamate derivatives were designed, synthesized, and biol. evaluated. As expected, most of the compounds exhibited inhibitory activities against cholinesterases (ChEs) and histone deacetylase (HDACs). Among the tested compounds, I showed not only potent and selective inhibition on AChE at sub-nanomolar potency (AChEIC50 = 0.12 nM, BChEIC50 = 361.52 nM) but also potent inhibition on HDAC (IC50 = 0.23 nM). Moreover, I exhibited inhibitory activity on Aβ1-42 self-aggregation as well as disaggregation activity on pre-formed Aβ fibrils. Furthermore, I exhibited antioxidant activity and metal chelating properties. Further mechanistic studies demonstrated that I is a pan-inhibitor of HDACs and a mixed-type inhibitor for AChE. It was shown that I is a BBB penetrant by online prediction. Taken together, the results indicate that I can serve as a lead compound to develop promising candidate analogs as AD therapeutics.

Bioorganic Chemistry published new progress about Alzheimer disease. 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

Deng, Jifeng; Peng, Li; Zhang, Guicheng; Lan, Xiaobing; Li, Chufang; Chen, Fuxin; Zhou, Yayao; Lin, Zuoxian; Chen, Ling; Dai, Renke; Xu, Hongjiang; Yang, Ling; Zhang, Xiquan; Hu, Wenhui published the artcile< The highly potent and selective dipeptidyl peptidase IV inhibitors bearing a thienopyrimidine scaffold effectively treat type 2 diabetes>, Category: pyrimidines, the main research area is thienopyrimidine preparation DDP IV inhibitor treatment diabetes; aminothiophenecarboxylate cyclization chlorination oxygenation alkylation substitution.

Some dipeptidyl peptidase IV inhibitors, e.g., I, were designed based on alogliptin using a scaffold-hopping strategy. All of the compounds constructed on a thienopyrimidine scaffold demonstrated good inhibition and selectivity for DPP-IV. Compound I exhibited subnanomolar (IC50 = 0.33 nM) DPP-IV inhibitory activity, good in vivo efficacy and an acceptable pharmacokinetic profile. A pharmacokinetic-driven optimization of I may lead to a class of clin. candidate DPP-IV inhibitors.

European Journal of Medicinal Chemistry published new progress about Cyclization. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Category: pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Khmel’nitskii, R. A.; Klyuev, N. A.; Kunina, E. A.; Kropacheva, A. A. published the artcile< Mass spectra of methoxy derivatives of 4-aminopyrimidines>, Recommanded Product: 6-Chloro-2-methoxypyrimidin-4-amine, the main research area is mass spectra pyrimidinamine.

Mass spectra of the 2-methoxy-6-methyl, 6-methoxy-2-methyl, 2-methoxy-5-methyl, 2,6-dimethoxy, and 6-chloro-2-methoxy derivatives of 4-pyrimidinamine were determined and correlated with structure.

Khimiya Geterotsiklicheskikh Soedinenii published new progress about Mass spectra. 3286-55-3 belongs to class pyrimidines, and the molecular formula is C5H6ClN3O, Recommanded Product: 6-Chloro-2-methoxypyrimidin-4-amine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Okui, Kiyoshi published the artcile< Chemistry of sulfanilamidopyrimidine. Abnormal condensation products of 4-amino-6-chloro-2-methoxypyrimidine with p-nitro-benzenesulfonyl chloride>, Reference of 3286-55-3, the main research area is pyrimidine nitrobenzenesulfonyl chloride reaction; nitrobenzenesulfonamidopyrimidine; pyrimidinium betaine nitrobenzenesulfonamidopyrimidine.

Reaction of 4-amino-6-chloro-2-methoxypyrimidine with 4-ClSO2C6H4NO2 in the presence of pyridine gave the pyridinium betaines I and II in addition to the sulfonamide III. The yield of I increased with reaction time, accompanied by a corresponding decrease in III yield. I was also prepared by heating III with pyridine. The structure of II was also confirmed.

Heterocycles published new progress about 3286-55-3. 3286-55-3 belongs to class pyrimidines, and the molecular formula is C5H6ClN3O, Reference of 3286-55-3.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia