cas 53554-29-3, 1,4-DIHYDRO-2-(METHYLTHIO)-4-OXO-5-PYRIMIDINE-CARBOXYLATE ACID ETHYL ESTER

Articles about 53554-29-3Total 12 be found

Article title
Article abstract
Author
Journal number and time
Download

Antibacterial activity of 2-amino-4-hydroxypyrimidine-5-carboxylates and binding to Burkholderia pseudomallei 2-C-methyl-D-erythritol-2,4-cyclodiphosphate synthase
Enzymes in the methylerythritol phosphate pathway make attractive targets for antibacterial activity due to their importance in isoprenoid biosynthesis and the absence of the pathway in mammals. The fifth enzyme in the pathway, 2-C-methyl-D-erythritol-2,4-cyclodiphosphate synthase (IspF), contains a catalytically important zinc ion in the active site. A series of de novo designed compounds containing a zinc binding group was synthesized and evaluated for antibacterial activity and interaction with IspF from Burkholderia pseudomallei, the causative agent of Whitmore's disease. The series demonstrated antibacterial activity as well as protein stabilization in fluorescence-based thermal shift assays. Finally, the binding of one compound to Burkholderia pseudomallei IspF was evaluated through group epitope mapping by saturation transfer difference NMR.
Watkins, Sydney M.,Ghose, Debarati,Blain, Joy M.,Grote, Dakota L.,Luan, Chi-Hao,Clare, Michael,Meganathan,Horn, James R.,Hagen, Timothy J.
(2019)
Read Online

Synthesis and Antifungal Activity Evaluation of Novel Substituted Pyrimidine-5-Carboxamides Bearing the Pyridine Moiety
A series of novel N-(substituted phenyl/benzyl)-2-methylthio-4-((pyridin-3-ylmethyl)amino)pyrimidine-5-carboxamides were synthesized by multistep reactions. The structures of the target compounds were characterized by IR, 1H NMR, 13C NMR, and elemental analysis. Their in vitro antifungal activities against two kinds of plant pathogenic fungi were evaluated by the mycelial growth rate method. The result showed that at the dosage of 100 μg/mL, several of these compounds exhibited moderate activity against Botrytis cinerea with inhibition rates of ~70%, and most compounds (e.g., 5a, 5c, 5e, 5f, and 5h) possessed excellent activity against Sclerotinia Sclerotiorum with more than 90% inhibition rate.
Wang, Shi-Chun,Wan, Fu-Xian,Liu, Si,Zhang, Shuai,Jiang, Lin
p. 445 - 451
(2018/01/15)

Method for synthesizing high-purity 4-chloro-2-methylthiopyrimidine-5-ethyl carboxylate
The invention discloses a method for synthesizing high-purity 4-chloro-2-methylthiopyrimidine-5-ethyl carboxylate. The method comprises the following steps: reacting S-methylisothiourea sulfate and diethyl ethoxy-methylene malonate in an ethanol-sodium hydroxide solution, concentrating to remove ethanol and regulating the pH to be acidic to obtain an intermediate, namely 4-hydroxy-2-hydroxyhydroxypyrimidine-5-carboxylic acid ethyl ester, wherein the molar ratio of the S-methylisothiourea sulfate to the diethyl ethoxy-methylene malonate is 1 to 1.9-2.4; enabling the obtained 4-hydroxy-2-hydroxyhydroxy pyrimidine-5-carboxylic acid ethyl ester to react with thionyl chloride to obtain a target product, wherein the molar ratio of the 4-hydroxy-2-hydroxyhydroxy pyrimidine-5-carboxylic acid ethyl ester to the thionyl chloride is 1 to 1-1.8. The improved method provided by the invention can improve the yield, increase the reaction safety and reduce the cost.
-
Paragraph 0012-0014

(2018/06/26)

Preparation method of avanafil
The invention provides a preparation method of avanafil, and specifically relates to the technical field of pharmaceutical chemistry. The preparation method of avanafil comprises the following steps:sequentially carrying out cyclization and chlorination reactions on methyl thiourea sulfuric acid and diethyl ethoxymethylene malonate which serve as initial raw materials to obtain 4-chloro-2-methylthiopyrimidine-5-carboxylic acid ethyl ester; then substituting and hydrolyzing with 3-chloro-4-methoxybenzylamine; condensing with 2-pyrimidinemethanamine to obtain a key intermediate, namely, 4-[(3-chloro-methoxybenzyl)amino]-2-methylthio-N-(2-pyrimidine methyl)-5-pyrimidine formamide; oxidizing the intermediate and reacting with L-prolinol to generate the avanafil. The preparation method has theadvantages of easy availability of raw materials, easiness and convenience in operation, mild reaction conditions and higher product yield.
-
Paragraph 0027; 0028; 0029; 0038; 0047

(2018/11/22)

Design, synthesis, and biological evaluation of novel catecholopyrimidine based PDE4 inhibitor for the treatment of atopic dermatitis
Selective inhibition of phosphodiesterase (PDE) 4B favorably suppresses the synthesis of inflammatory cytokines and subsequently arrest the development of atopic dermatitis via modulating the intracellular cAMP levels. Considering the side effects of corticosteroids, selective PDE4 inhibition could constitute an effective alternative therapy for the treatment of atopic dermatitis (AD). In this study, a series of novel catechol based compounds bearing pyrimidine as the core have been synthesized and screened for the PDE4 inhibitory properties. The PDE4 selectivity of the active compounds over other PDEs has been investigated. Compound 23 bearing pyrimidine core functionalized with catechol, pyridine and trifluoromethyl groups can effectively inhibit the PDE4B with IC50 value in nanomolar range (IC50 = 15 ± 0.4 nM). Compound 23 exhibited seven fold higher selectivity towards PDE4B over PDE4D. Molecular Docking study confirmed its stronger affinity towards catalytic domain of PDE4B. In-vivo analysis confirmed that compound 23 effectively alleviated the symptoms of atopic dermatitis in DNCB–treated Balb/c mice by suppressing the synthesis of inflammatory mediators such as TNF-α and Ig-E. Taken together, this study suggested that compound 23 could be an effective PDE4 inhibitor for the potential treatment of AD.
Purushothaman, Baskaran,Arumugam, Parthasarathy,Kulsi, Goutam,Song, Joon Myong
supporting information
p. 673 - 690
(2018/01/26)

PROCESS FOR THE PREPARATION OF (S)-4-[(3-CHLORO-4-METHOXYBENZYL)AMINO]-2-[2- (HYDROXYMETHYL)-1-PYRROLIDINYL]-N-(2-PYRIMIDINYL METHYL-5-PYRIMIDINE CARBOXAMIDE
The present invention relates to an improved process for the preparation of (S)-4-[(3- chloro-4-methoxybenzyl)amino]-2-[2-(hydroxymethyl)-1-pyrrolidinyl]-N-(2-pyrimidinyl ethyl)- 5-pyrimidine carboxamide compound of formula-1 represented by the following structural formula.
-
Page/Page column 23

(2015/01/16)

DESIGN AND SYNTHESIS OF NOVEL INHIBITORS OF ISOPRENOID BIOSYNTHESIS
Antibacterial IspF inhibitor compounds and compositions are described. Methods include administering described compounds and compositions to treat bacterial or parasitic infections and to inhibit or parasite or bacterial growth.
-
Paragraph 00083

(2013/11/18)

Synthesis of 4-unsubstituted dihydropyrimidines. Nucleophilic substitution at position-2 of dihydropyrimidines
Synthesis of novel 4-unsubstituted dihydropyrimidines (DPs) was performed. Subsequently, a variety of 4-unsubstituted 1,4(3,4)-DPs with amino moieties at position-2 were obtained in excellent yields by activation of position-2 owing to regioselective alkoxycarbonylation at position-3 of the DP skeleton. 3-Oxo-2-phenyl-2,3,5,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrimidine was obtained using phenylhydrazine instead of amines. Individual tautomers of 1,4(3,4)-DP were observed in the 1H NMR spectra of one derivative depending on temperature and concentration. On the other hand, only 1,4-DP was found in the solid state by single-crystal X-ray crystallography.
Cho, Hidetsura,Nishimura, Yoshio,Yasui, Yoshizumi,Kobayashi, Satoshi,Yoshida, Shin-Ichiro,Kwona, Eunsang,Yamaguchi, Masahiko
experimental part
p. 2661 - 2669
(2011/04/25)

ENZYME MODULATORS AND TREATMENTS
Novel compounds and methods of using those compounds for the treatment of inflammatory conditions, hyperproliferative diseases, cancer, and diseases characterized by hypervascularization are provided. In a preferred embodiment, modulation of the activation state of p38 kinase protein ab1 kinase protein, bcr-ab1 kinase protein, braf kinase protein, VEGFR kinase protein, or PDGFR kinase protein comprises the step of contacting said kinase protein with the novel compounds.
-
Page/Page column 354

(2008/06/13)

PYRIMIDINE-5-CARBOXAMIDE COMPOUNDS, PROCESS FOR PRODUCING THE SAME AND USE THEREOF
A compound of the formula wherein R1 is a heterocycle having a skeleton consisting of 3 to 15 atoms including 1 to 5 nitrogen atom(s), which heterocycle is attached by a secondary nitrogen atom constituting the heterocycle; X is an oxygen atom, a nitrogen atom optionally substituted by a hydrocarbon group having 1 to 5 carbon atom(s) or a sulfur atom optionally oxidized with 1 or 2 oxygen, Y is a bond or a C1-5 alkylene group, R2 is (1) a hydrogen atom, (2) a hydroxy group, (3) a C1-5 alkoxy group, (4) a C1-5 alkylthio group, (5) a carbocycle having 3 to 15 carbon atoms or (6) a heterocycle having a skeleton consisting of 3 to 15 atoms including 1 to 5 heteroatom(s), provided that when Y is a bond, R2 is a carbocycle having 3 to 15 carbon atoms or a heterocycle having a skeleton consisting of 3 to 15 atoms including 1 to 5 heteroatom(s) and; one of R3 and R4 is a hydrogen atom or a group of the formula: -Z-R5 (Z is a bond or C1-10 alkylene group optionally having substituent(s) and R5 is (1) a hydrogen atom, (2) a hydroxy group, (3) a C1-5 alkoxy group, (4) a nitrile group, (5) a C1-5 alkoxy-carbonyl group, (6) a carboxyl group, (7) a carbamoyl group, (8) a (mono or di-C1-5 alkyl)carbamoyl group, (9) an amino group, (10) a (di or mono-C1-5 alkyl)amino group, (11) a (C1-5 alkoxy-carbonyl)amino group, (12) a C1-5 alkylthio group, (13) a carbocycle having 3 to 15 carbon atoms or (14) a heterocycle having a skeleton consisting of 3 to 15 atoms including 1 to 5 heteroatom(s)); the other is a group of the formula: -Z-R5 (Z and R5 are as defined above); and R3 and R4 may form, together with the adjacent nitrogen atom, a heterocycle having a skeleton consisting of 3 to 15 atoms, which heterocycle is attached by a secondary nitrogen atom constituting the heterocycle, wherein the above-mentioned heterocycle and a carbocycle having 3 to 15 carbon atoms are each optionally substituted by substituent(s) selected from the group consisting of C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C7-16 aralkyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, C6-14 aryl, C1-8 alkoxy, C1-3 alkylenedioxy, hydroxy, halogen atom, amino, (di or mono-C1-5 alkyl)amino, (C1-5 alkoxy-carbonyl)amino, (C1-5 acyl)amino, (C1-5 acyl) (C1-5 alkyl)amino, C1-5 alkylthio, nitrile, nitro, C1-5 alkoxy-carbonyl, carboxyl, C1-5 alkyl-carbonyloxy, oxo, thioxo, C1-6 acyl group, sulfamoyl and (di or mono-C1-5 alkyl)sulfamoyl, or a salt thereof or a prodrug thereof have a superior cGMP specific phosphodiesterase (PDE) inhibitory activity, and can be used as an agent for the prophylaxis or treatment of cardiovascular diseases such as angina pectoris, heart failure, cardiac infarction, hypertension, arteriosclerosis and the like, allergic diseases such as asthma, or disorders of male or female genital function and the like.
-
(2008/06/13)

Cationic 1,3-diazadienes in annulation reactions. Synthesis of pyrimidine, thiadiazinedioxide and triazine derivatives
Triazapentadienium iodides 2 prepared from N'-thiocarbamoylformamidines 1 are efficient intermediates in heterocyclic synthesis. They react with ketenes, sulfenes, phenyl isocyanate or isothiocyanate and dimethyl acetylenedicarboxylate affording the corre
Landreau,Deniaud,Reliquet,Reliquet,Meslin
p. 93 - 98
(2007/10/03)

Novel inhibitors of AP-1 and NF-κB mediated gene expression: Structure-activity relationship studies of ethyl 4-[(3-methyl-2,5-dioxo(3-pyrrolinyl))amino]-2-(trifluoromethyl)pyrimidine-5-carb oxylate
In an effort to identify novel inhibitors of AP-1 and NF-κB mediated transcriptional activation, several analogues of ethyl 4-[(3-methyl-2,5-dioxo(3-pyrrolinyl))amino]-2-(trifluoromethyl)pyrimidine-5-carb oxylate (1) were synthesized and tested in two in vitro assays. The 2-(2'-thienyl) substituted compound (11) was identified as the most potent in this series. (C) 2000 Elsevier Science Ltd. All rights reserved.
Palanki, Moorthy S.S.,Erdman, Paul E.,Manning, Anthony M.,Ow, Arnold,Ransone, Lynn J.,Spooner, Cheryl,Suto, Carla,Suto, Mark
p. 1645 - 1648
(2007/10/03)