Syntheses on the basis of 4-(Oxiran-2-ylmethyl)morpholine

Mesropyan, E. G.; Galstyan, A. S.; Avetisyan, A. A.

doi:10.1134/s1070428006120141

Cited by 11 publications

(6 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1-Chloro-3-morpholinopropan-2-ol (0.40 g, 2.2 mmol; prepared according to the literature) was added to a mixture of 3-isopropyl-7-[4-(2-pyridyl)benzyl]amino-1(2) H -pyrazolo[4,3- d ]pyrimidine-5-thiol 3 (0.38 g, 1 mmol) and K 2 CO 3 (0.17 g) in MeOH (10 mL), and the mixture was stirred at 45 °C for 24 h. The crude product was precipitated by adding water and then purified stepwise (3%, 4 and 5%) with MeOH in CHCl 3 by column chromatography. Chromatography provided (after evaporation under vacuum) an amorphous colorless glass foam (0.31 g, 60% yield).…”

Section: Methodsmentioning

confidence: 99%

3,5,7-Substituted Pyrazolo[4,3-d]pyrimidine Inhibitors of Cyclin-Dependent Kinases and Their Evaluation in Lymphoma Models

et al. 2019

View full text Add to dashboard Cite

Cyclin-dependent kinases are therapeutic targets frequently deregulated in various cancers. By convenient alkylation of the 5-sulfanyl group, we synthesized 3-isopropyl-7-[4-(2-pyridyl)benzyl]amino-1(2)H-pyrazolo[4,3-d]pyrimidines with various substitutions at position 5 with potent antiproliferative activity in non-Hodgkin lymphoma cell lines. The most potent derivative 4.35 also displayed activities across more than 60 cancer cell lines. The kinase profiling confirmed high selectivity of 4.35 toward cyclin-dependent kinases (CDKs) 2, 5, and 9, and the cocrystal with CDK2/cyclin A2 revealed its binding in the active site. Cultured lymphoma cell lines treated with 4.35 showed dephosphorylation of CDK substrates, cleavage of PARP-1, downregulation of XIAP and MCL-1, and activation of caspases, which collectively confirmed ongoing apoptosis. Moreover, 4.35 demonstrated significant activity in various cell line xenograft and patient-derived xenograft mouse models in vivo both as a monotherapy and as a combination therapy with the BCL2-targeting venetoclax. These findings support further studies of combinatorial treatment based on CDK inhibitors.

show abstract

Section: Methodsmentioning

confidence: 99%

3,5,7-Substituted Pyrazolo[4,3-d]pyrimidine Inhibitors of Cyclin-Dependent Kinases and Their Evaluation in Lymphoma Models

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The purity of the products was checked by TLC on Silufol UV-254 plates; spots were visualized by treatment with iodine vapor. N-(Oxiran-2-ylmethyl)amines III and IV were synthesized according to the procedure reported in [8]. Ethanol was dehydrated and purified as described in [9].…”

Section: Methodsmentioning

confidence: 99%

Syntheses on the basis of diethyl (2-morpholinoethyl)malonate

Mesropyan¹,

Galstyan²,

Avetisyan³

et al. 2010

Russ J Org Chem

Self Cite

View full text Add to dashboard Cite

New functionally substituted butan-4-olides were synthesized by reactions of diethyl (2-morpholinoethyl)malonate with 2-(allyloxymethyl)oxirane, 4-(oxiran-2-ylmethyl)morpholine, N-ethyl-N-(oxiran-2-ylmethyl)aniline, and 1-chloro-2,3-epoxypropane. 5-[2-(Morpholino)ethyl]barbituric and -thiobarbituric acids were also synthesized. † Deceased.Organic oxides are universal starting compounds for the synthesis of butanolides. Some publications in this field are related to syntheses of biologically active natural compounds [1][2][3][4][5]. We have developed a procedure for the preparation of diethyl (2-morpholinoethyl)-malonate (I) from diethyl malonate sodium salt and 4-(2-chloroethyl)morpholine in ethanol. Diester I may be used as a basis for the synthesis of new morpholinecontaining lactones. It is known that molecules of many biologically active compounds, in particular tranquilizers, synthetic narcotic analgesics, anticonvulsants, and antituberculous agents, include a morpholine fragment [6].By condensation of diester I with 2-(allyloxymethyl)oxirane, 4-(oxiran-2-ylmethyl)morpholine, and N-ethyl-N-(oxiran-2-ylmethyl)aniline (reactant ratio 1 : 1) in anhydrous ethanol we obtained 5-substituted 3-(2-morpholinoethyl)tetrahydrofuran-2-ones VI-VIII (Scheme 1). The reaction begins with heterolytic cleavage of the epoxide C-O bond according to the

show abstract

“…The metabolite of AMOZ was regarded as the residual marker of FTD because of its long term stability in vivo. In previous studies, E. G. Mesropyan et al 19 developed procedures for the synthesis of 4-(oxiran-2-ylmethyl) morpholine from 1-chloro-2,3-epoxypropane and morpholine. In this study, the results indicated that the AMOZ was prepared successfully with a high purity (>98%) and the recovery was notably increased.…”

Section: Preparation Of Amoz and Haptensmentioning

confidence: 99%

Synthesis of furaltadone metabolite, 3-amino-5-morpholinomethyl-2-oxazolidone (AMOZ) and novel haptens for the development of a sensitive enzyme-linked immunosorbent assay (ELISA)

Shu

Ding

et al. 2014

Anal. Methods

View full text Add to dashboard Cite

A sensitive and specific monoclonal enzyme-linked immunosorbent assay (ELISA) for the determination of tissue-bound metabolite 3-amino-5-morpholinomethyl-2-oxazolidone (AMOZ) was developed.Three different haptens of AMOZ were synthesized. The haptens (I, III) were derived from 4-carboxybenzaldehyde and ethyl 4-bromobutyrate, respectively. Hapten II was based on hapten I but a C]N bond in the parent structure was reduced. Corresponding immunogens and coating antigens were prepared to improve the assay sensitivity. The hybridomas 4 Â 10 8 secreting antibodies against CPAMOZ were obtained from immunogens I-BSA by monoclonal antibody (mAb) technology. The antibody indicated that: (1) the small molecular AMOZ cannot induce the specific response against AMOZ; (2) the weakened conjugation effect improved the recognition of AMOZ. Assessment of twelve coating antigen/ antibody combinations consequently resulted in the development of an indirect competitive enzymelinked immunosorbent assay (icELISA). The results showed that the sensitivity was highly improved about fifteen-fold for the novel heterologous coating antigen at low hapten density. The IC 50 value of the ELISA for CPAMOZ was 0.13 ng mL À1 . The cross reactivity values of the assay with NPAMOZ, AMOZ and FTD were 118%, 2.3% and 16.3%. Recoveries from AMOZ fortified animal tissues were in a range of 82.6-108.4% and the CV values were less than 12.5%. The immunoassay was further validated by a LC-MS/MS method and the two methods showed good correlation (r 2 ¼ 0.9908). The proposed icELISA could be used for an accurate monitoring of AMOZ in animal tissues.

show abstract

Syntheses on the basis of 4-(Oxiran-2-ylmethyl)morpholine

Cited by 11 publications

References 7 publications

3,5,7-Substituted Pyrazolo[4,3-d]pyrimidine Inhibitors of Cyclin-Dependent Kinases and Their Evaluation in Lymphoma Models

3,5,7-Substituted Pyrazolo[4,3-d]pyrimidine Inhibitors of Cyclin-Dependent Kinases and Their Evaluation in Lymphoma Models

Syntheses on the basis of diethyl (2-morpholinoethyl)malonate

Synthesis of furaltadone metabolite, 3-amino-5-morpholinomethyl-2-oxazolidone (AMOZ) and novel haptens for the development of a sensitive enzyme-linked immunosorbent assay (ELISA)

Contact Info

Product

Resources

About