Category: 5018-38-2

Zasosov, V. A.; Nikulina, T. N.; Blinova, L. S.; Onoprienko, V. S.; Sycheva, V. N.; Sokolova, G. N.; Borodina, K. S.; Denisova, K. V. published the artcile< Synthesis of 4-(p-aminobenzenesulfonamido)-5,6-dimethoxypyrimidine>, Synthetic Route of 5018-38-2, the main research area is amino benzenesulfonamido methoxy pyrimidine; sulfamide pyrimidyl.

CO2H)2 was esterified with MeOH and then treated with MeOCH2CO2CO2Me(from ClCH2CO2Me and NaOMe) to give MeO2CCH(OMe)COCO2Me, which was decarbonylated at 210° to give MeOCH(CO2Me)2. The latter reacted with NH3 and then HCONH2 in the presence of NaOEt to form the di-Na salt of 4,6-dihydroxy-5-methoxypyrimidine, which was converted to the 4,6-dichloro derivative (I) with POCl3 and PhNMe2. I reacted with NH3 in DMF to form the 4-amino derivative, which yielded 4-amino-5,6-dimethoxypyrimidine with NaOH in MeOH. The latter was converted to the title compound (II) by treatment with 4-MeO2CNHC6H4SO2Cl in pyridine, followed by hydrolysis with concentrated HCl.

Khimiko-Farmatsevticheskii Zhurnal published new progress about 5018-38-2. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Synthetic Route of 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Bretschneider, H.; Richter, W.; Kloetzer, W. published the artcile< New reactions of sulfonamides. XV. Syntheses of 4-sulfanilamido-5,6-dimethoxypyrimidine>, SDS of cas: 5018-38-2, the main research area is .

4,6-Dihydroxy-5-methoxypyrimidine (I), m. 275-80°, was prepared (a) as the Na salt from di-Me α-methoxymalonate (II) and HC-(:NH)NH2 in MeOH-NaOMe, (b) by desulfurizing the 2-mercapto- derivative, m. 215° (decomposition) (from II and CS(NH2)2]. In 4,6-dichloro-5-methoxypyrimidine (III), m. 57-8° (from I and POCl3), one Cl atom reacts readily with nucleophiles; III with liquid NH3 at 20 atm. gave 4-amino- (IV), m. 178-80°, with Na sulfanilamide in HCONMe2 at 100° 4-sulfanilamido- (V), m. 198-202° (190°, labile form), with Na N-4-acetylsulfanilamide in HCONMe2 at 100° 4-(N-4-acetylsulfanilamido)-5-methoxy-6-chloropyrimidine (VI), m. 210-12°, and with NaOMe-MeOH at 20° 4-chloro-5,6-dimethoxypyrimidine (VII), m. 53-5°. V autoclaved at 125° with NaOMe-MeOH gave the title compound (VIII), m. 192-4° (4:1 MeOH-H2O). VI was hydrolyzed by boiling 0.5N NaOH to V, and by NaOMe-MeOH at 115-25° (autoclave) to VIII. VII in EtOH with PhSNa or EtSNa gave 4-phenylthio; b0.001 160-70°, or 4-ethylthio-5,6-dimethoxypyrimidine, b0.05, 84°, oxidized by peracetic acid to the corresponding 4-phenylsulfonyl-, m. 96-100° (EtOH-H2O, 1:1) and 4-ethylsulfonyl-5,6-dimethoxypyrimidine, m. 87-8° (EtOH-H2O); both sulfones yielded VIII when heated with Na sulfanilamide. Autoclaved at 130° with NaOMe-MeOH III was converted to 4,5,6-trimethoxypyrimidine, m. 56-8°. Other routes to VIII started from Me 2-methoxy-2-cyanoacetate (from the bromo ester and CuCN), b25 99°, n20D 1.4170, which with CS(NH2)2 afforded 2-mercapto-4-amino-5-methoxy-6-hydroxypyrimidine (IX), m. 275-80° (decomposition); desulfurized IX, m. 230-1°, with POCl3 gave IV, converted by p-acetamidobenzenesulfonyl chloride via the disulfonyl derivative (not isolated) to VIII. Alternatively, IX was S-methylated by MeI-NaOMe and the 2-methylthio derivative, m. 203°, treated with PhMe3N toluenesulfonate to give (beside an N-Me derivative, m. 206-7°) 2-methylthio-4-amino-5,6-di-methoxypyrimidine, m. 115-17°, the p-acetamidobenzenesulfonyl derivative, m. 220-1°, which was desulfurized (Raney Ni) and deacetylated to VIII. VIII was investigated as a potential antibacterial agent with prolonged action similar to its 2,6-dimethoxy congener.

Monatshefte fuer Chemie published new progress about Sulfonamides. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, SDS of cas: 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Le, Phuong T.; Richardson, Paul F.; Sach, Neal W.; Xin, Shuibo; Ren, Shijian; Xiao, Jiezhan; Xue, Liangliang published the artcile< Development of a Scalable Synthesis of 4-Aminopyrimidin-5-ol, a Versatile Intermediate>, SDS of cas: 5018-38-2, the main research area is aminopyrimidinol preparation green chem.

A robust process for the preparation of multigram quantities of 4-aminopyrimidin-5-ol in good yield from an inexpensive and readily available 4,6-dichloro-5-methoxypyrimidine starting material is described. An initial evaluation of the reported literature route for this material utilizing a de novo pyrimidine synthesis provided safety concerns over the scalability of several intermediates. In addition, a number of steps proceeded in mediocre yield, and involved chromatog. separations for the desired products. The newly developed route mitigates the safety concerns, reduces the number of steps from five to three, avoids column chromatog., leads to an 8-fold improvement in yield, and utilizes reagents, which are recognized to be more environmentally benign.

Organic Process Research & Development published new progress about Green chemistry. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, SDS of cas: 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Mwalwisi, Yonah H.; Hoellein, Ludwig; Kaale, Eliangiringa; Holzgrabe, Ulrike published the artcile< Development of a simple, rapid, and robust liquid chromatographic method for the simultaneous determination of sulfalene, sulfadoxine, and pyrimethamine in tablets>, Category: pyrimidines, the main research area is liquid chromatog sulfalene sulfadoxine pyrimethamine tablet quality control; Counterfeit and substandard medicines; Developing countries; Fixed dose combination; Malaria; Quality control; RP-HPLC.

A simple, cost effective, accurate, and precise RP-HPLC method was developed for the simultaneous determination of sulfalene and sulfadoxine in fixed dose dual combinations with pyrimethamine together with their related substances. Proprietary products containing these combinations are often being prescribed in malaria endemic countries. Quantification of the active compounds and impurity profiling was achieved using two standard C18 columns with a mobile phase being composed of 60% (volume/volume) of a 0.05 M KH2PO4 buffer solution (pH = 2.6) and 40% (volume/volume) of methanol, applying an isocratic elution mode and a detection wavelength of 215 nm. The method allows a quick quant. determination of sulfadoxine and sulfalene and the separation of the resp. impurities within a total runtime of approx. 15 min and was validated with respect to specificity, linearity, precision, accuracy, limits of detection and quantification, robustness, and stability of the standard and sample solutions The method is simpler than the corresponding method described in the International Pharmacopoeia and the United States Pharmacopoeia in terms of being easy to apply, being less time consuming, and utilizing reagents and chems. which are cost efficient.

Journal of Pharmaceutical and Biomedical Analysis published new progress about Combination chemotherapy. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Category: pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Jayne, Charles L.; Andreani, Teresa; Chan, Tin-Yau; Chelliah, Mariappan V.; Clasby, Martin C.; Dwyer, Michael; Eagen, Keith A.; Fried, Steve; Greenlee, William J.; Guo, Zhuyan; Hawes, Brian; Hruza, Alan; Ingram, Richard; Keertikar, Kartik M.; Neelamkavil, Santhosh; Reichert, Paul; Xia, Yan; Chackalamannil, Samuel published the artcile< Discovery of hydroxy pyrimidine Factor IXa inhibitors>, Recommanded Product: 4,6-Dichloro-5-methoxypyrimidine, the main research area is hydroxypyrimidine preparation Factor IXa inhibitor structure activity; Factor IXa; Factor IXa inhibition; Pyrimidine; Thrombosis.

The synthesis and structure activity relationship development of a pyrimidine series of heterocyclic Factor IXa inhibitors, I and II [R = Q, Q1, Q2, etc.], is described. Increased selectivity over Factor Xa inhibition was achieved through SAR expansion of the P1 element. Select compounds were evaluated in vivo to assess their plasma levels in rat.

Bioorganic & Medicinal Chemistry Letters published new progress about Blood coagulation factor inhibitors (factor IXa). 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Recommanded Product: 4,6-Dichloro-5-methoxypyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Rzasa, Robert M.; Hu, Essa; Rumfelt, Shannon; Chen, Ning; Andrews, Kristin L.; Chmait, Samer; Falsey, James R.; Zhong, Wenge; Jones, Adrie D.; Porter, Amy; Louie, Steven W.; Zhao, Xiaoning; Treanor, James J. S.; Allen, Jennifer R. published the artcile< Discovery of selective biaryl ethers as PDE10A inhibitors: Improvement in potency and mitigation of Pgp-mediated efflux>, Related Products of 5018-38-2, the main research area is biaryl ether PDE10A inhibitor preparation Pgp efflux structure.

We report the discovery of a novel series of biaryl ethers as potent and selective PDE10A inhibitors. Structure-activity studies improved the potency and decreased Pgp-mediated efflux found in the initial compound 4. X-ray crystallog. studies revealed two novel binding modes to the catalytic site of the PDE10A enzyme.

Bioorganic & Medicinal Chemistry Letters published new progress about Antipsychotics. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Related Products of 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Guan, Aiying; Wang, Mingan; Yang, Jinlong; Wang, Lizeng; Xie, Yong; Lan, Jie; Liu, Changling published the artcile< Discovery of a New Fungicide Candidate through Lead Optimization of Pyrimidinamine Derivatives and Its Activity against Cucumber Downy Mildew>, Formula: C5H4Cl2N2O, the main research area is fungicide pyrimidinamine derivative preparation lead optimization cucumber downy mildew; development of resistance; downy mildew; pyrimidinamine fungicide candidate; unique mode of action.

Downy mildew is one of the most highly destructive of the diseases that cause damage to fruits and vegetables. Because of the continual development of resistance, it is important to discover new fungicides with different modes of action from existing fungicides for the control of downy mildew. This study is a continuation of our previous work on the novel pyrimidinamine lead compound, (I), and includes field trials for the identification of the optimal candidate. A new compound, 5-Chloro-N-(2-(6-(4-chlorophenoxy)pyridin-3yl)ethyl)-6-(difluoromethyl)pyrimidin-4-amine, (II), was obtained from 4,5-Dichloro-6-(difluoromethyl)pyrimidine and 2-(6-(4-chlorophenoxy)pyridin-3-yl)ethanamine, which gave a lower EC50 value (0.10 mg/L) against downy mildew than lead compound I (0.19 mg/L) and the com. fungicides diflumetorim, dimethomorph, and cyazofamid (1.01-23.06 mg/L). Compound II displayed similar broad-spectrum fungicidal activity to compound I but better field efficacy than compound I, cyazofamid, and flumorph. The present work indicates that pyrimidinamine compound II is a candidate for further development as a com. fungicide for the control of downy mildew.

Journal of Agricultural and Food Chemistry published new progress about Agrochemical fungicides. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Formula: C5H4Cl2N2O.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Zhang, Haoyang; Wu, Wenkui; Feng, Chao; Liu, Zhaogang; Bai, Enhe; Wang, Xueyuan; Lei, Meng; Cheng, Hao; Feng, Huayun; Shi, Jingmiao; Wang, Jia; Zhang, Zhao; Jin, Tao; Chen, Shanshan; Hu, Shihe; Zhu, Yongqiang published the artcile< Design, synthesis, SAR discussion, in vitro and in vivo evaluation of novel selective EGFR modulator to inhibit L858R/T790M double mutants>, Application In Synthesis of 5018-38-2, the main research area is dihydropyrroloquinoline preparation anticancer EGFR modulator; 5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinoline derivatives; EGFR modulator; L858R/T790M double mutants; Non-small cell lung cancer.

Based upon the modeling binding mode of marketed AZD9291 (I) with T790M, a series of 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline derivatives were designed and synthesized with the purpose to overcome the drug resistance resulted from T790M/L858R double mutations. The most potent compound II showed excellent enzyme inhibitory activities and selectivity with sub nanomolar IC50 values for both the single L858R and double T790M/L858R mutant EGFRs, and was more than 8-fold selective for wild type EGFR. Compound II exhibited good microsomes stabilities and pharmacokinetic properties and lower binding affinity to hERG ion channel than AZD9291 and displayed strong antiproliferative activity against the H1975 non-small cell lung cancer (NSCLC) cells bearing T790M/L858R and in vivo anticancer efficacy in a human NSCLC (H1975) xenograft mouse model.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Application In Synthesis of 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Li, Jian-Yuan; Miklossy, Gabriella; Modukuri, Ram K.; Bohren, Kurt M.; Yu, Zhifeng; Palaniappan, Murugesan; Faver, John C.; Riehle, Kevin; Matzuk, Martin M.; Simmons, Nicholas published the artcile< Palladium-Catalyzed Hydroxycarbonylation of (Hetero)aryl Halides for DNA-Encoded Chemical Library Synthesis>, Application of C5H4Cl2N2O, the main research area is palladium catalyzed hydroxycarbonylation heteroaryl halide DNA encoded library synthesis.

A strategy for DNA-compatible, palladium-catalyzed hydroxycarbonylation of (hetero)aryl halides on DNA-chem. conjugates has been developed. This method generally provided the corresponding carboxylic acids in moderate to very good conversions for (hetero)aryl iodides and bromides, and in poor to moderate conversions for (hetero)aryl chlorides. These conditions were further validated by application within a DNA-encoded chem. library synthesis and subsequent discovery of enriched features from the library in selection experiments against two protein targets.

Bioconjugate Chemistry published new progress about Carbonylation. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Application of C5H4Cl2N2O.

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