Day: November 15, 2022

Miura, Takaaki published the artcileLead generation of heat shock protein 90 inhibitors by a combination of fragment-based approach, virtual screening, and structure-based drug design, Recommanded Product: 1-(2-Amino-4-methylpyrimidin-5-yl)ethanone, the main research area is HSP90 inhibitor virtual screening antitumor structure drug design cancer; anticancer CH5015765 preparation 3D Xray HSP90 complex crystal structure; aminotriazine aminopyrimidine derivative mol structure HSP90 target antitumor design.

Heat shock protein 90 (Hsp90) is a mol. chaperone which regulates maturation and stabilization of its substrate proteins, known as client proteins. Many client proteins of Hsp90 are involved in tumor progression and survival and therefore Hsp90 can be a good target for developing anticancer drugs. With the aim of efficiently identifying a new class of orally available inhibitors of the ATP binding site of this protein, we conducted fragment screening and virtual screening in parallel against Hsp90. This approach quickly identified 2-aminotriazine and 2-aminopyrimidine derivatives as specific ligands to Hsp90 with high ligand efficiency. In silico evaluation of the 3D X-ray Hsp90 complex structures of the identified hits allowed us to promptly design CH5015765, which showed high affinity for Hsp90 and antitumor activity in human cancer xenograft mouse models.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 66373-25-9 belongs to class pyrimidines, name is 1-(2-Amino-4-methylpyrimidin-5-yl)ethanone, and the molecular formula is C7H9N3O, Recommanded Product: 1-(2-Amino-4-methylpyrimidin-5-yl)ethanone.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Burger, Matthew T. published the artcileIdentification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer, Formula: C4HBr3N2, the main research area is morpholino heterocyclic pyrimidine preparation oral PI3 kinase inhibitor cancer; NVP-BKM120; PI3K/AKT3 pathway; phosphoinositide-3-kinase.

Phosphoinositide-3-kinases (PI3Ks) are important oncol. targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrimidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clin. trials for the treatment of cancer.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 36847-11-7 belongs to class pyrimidines, name is 2,4,6-Tribromopyrimidine, and the molecular formula is C4HBr3N2, Formula: C4HBr3N2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Kala, Pruthu published the artcileDesign, Synthesis, and Anticancer Activity of Substituted Styryl Incorporated Quinazoline Derivatives, Application In Synthesis of 5472-46-8, the main research area is styryl pyrimidopyrimidine preparation diastereoselective human anticancer.

A novel series of substituted aryl ethynyl incorporated quinazolines has been synthesized. The products have been tested for their preliminary anticancer activity against human cancer cell lines like MCF-7 (human breast cancer), A549 (human lung cancer), DU-145 (human prostate cancer), and MDA MB-231 (human breast cancer). All the synthesized compounds showed good to excellent activity against tested cell lines.

Russian Journal of General Chemistry published new progress about Antitumor agents. 5472-46-8 belongs to class pyrimidines, name is Ethyl 4-amino-2-methylpyrimidine-5-carboxylate, and the molecular formula is C8H11N3O2, Application In Synthesis of 5472-46-8.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Tseng, Chih-Hua published the artcileSynthesis and antiproliferative evaluation of 3-phenylquinolinylchalcone derivatives against non-small cell lung cancers and breast cancers, Category: pyrimidines, the main research area is methoxyphenylquinolinyl aryl propenone stereoselective preparation antitumor activity; structure methoxyphenylquinolinyl aryl propenone inhibition human cancer normal cell; breast non small cell lung cancer inhibition methoxyphenylquinolinyl arylpropenone; cell cycle progression cellular administration methoxyphenylquinolinyl aryl propenone; cleavage apoptotic protein cellular administration methoxyphenylquinolinyl aryl propenone; methoxyphenyl methoxyphenylquinolinyl propenone mol crystal structure.

3-(4-Methoxyphenyl)quinolinyl aryl propenones I [R = Ph, 4-FC6H4, 4-HOC6H4, 4-MeOC6H4, 2,4-(MeO)2C6H3, 2,6-(MeO)2C6H3, 3,4-(MeO)2C6H3, 3,5-(MeO)2C6H3, 4-H2NC6H4, 4-O2NC6H4, 2-furyl, 2-thienyl, 2-pyridinyl, 5-Br-2-thienyl, 3-thienyl, 2-pyrrolyl, 3-amino-2-thienyl, 2-amino-4-methyl-5-pyrimidinyl, 3-indolyl] were prepared as potential antitumor agents. I (R = Ph) inhibited the growth of H1299 non-small cell lung cancer and SKBR-3 breast cancer cells with IC50 values of 1.41 and 0.70 μM, resp., while the standard topotecan inhibited their growth with IC50 values of 6.02 and 8.91 μM, resp. I (R = 5-Br-2-thienyl) inhibited the growth of MDA-MB-231 breast cancer cells with an IC50 value of less than 0.10 μM, while inhibiting the growth of noncancerous mammary epithelial cells at an IC50 value of 9.38 μM. I (R = 5-Br-2-thienyl) induced cell cycle arrest at G2/M phase followed by activation of caspase-3, cleavage of PARP, and cell death. The structure of I [R = 2,4-(MeO)2C6H3] was determined by X-ray crystallog.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 66373-25-9 belongs to class pyrimidines, name is 1-(2-Amino-4-methylpyrimidin-5-yl)ethanone, and the molecular formula is C7H9N3O, Category: pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Easmon, Johnny published the artcileSynthesis, Cytotoxicity, and Antitumor Activity of Copper(II) and Iron(II) Complexes of 4N-Azabicyclo[3.2.2]nonane Thiosemicarbazones Derived from Acyl Diazines, Recommanded Product: 1-(6-Methylpyrimidin-4-yl)ethanone, the main research area is antitumor copper iron thiosemicarbazone complex synthesis Burkitt lymphoma.

A series of thiosemicarbazones (TSCs) (bearing a 4N-azabicyclo[3.2.2]nonane moiety) derived from 3-acylpyridazines, 4-acetylpyrimidines, and 2-acetylpyrazines were synthesized as potential antitumor agents. TSCs exhibited potent cytotoxic activity against human acute lymphoblastic leukemia CCRF-CEM cells (IC = 0.05-0.77 M) and colon adenocarcinoma HT-29 cells (IC = 0.011-2.22 M). Copper II complexes of TSCs showed significant improvement in cytotoxic activity against HT-29 cells (IC50 = 0.004-1.51 μM) by a factor of 3. However, complexation of some TSC ligands with Fe(II) results in lowering of cytotoxic activity by a factor of 7. In clonogenic assays involving human tumor cells of different tumor origins, three of the TSCs and their copper complexes exhibited remarkable cytotoxic activities with mean IC50 values of 6, 0.18, 1, 1, 0.37, and 0.37 nM, resp. In particular, the compounds were highly effective against human colon carcinoma and large and small cell lung carcinoma cells. One of the TSC derivative was evaluated in vivo in nude mice bearing LXFL 529 human large cell lung carcinoma cells. With respect to antitumor activity, application of 30 mg/kg/d resulted in moderate inhibition (42%) of tumor growth. No effect on tumor growth was observed at a dose of 10 mg/kg/d. However, a dose of 40 or 60 mg/kg/d resulted in 50 and 75% death, resp., in the treated mice, indicating the high toxicity of these compounds Using human liver microsomes, one of the TSC compound was rapidly and highly metabolized in vitro. In actual fact, only 2% of the unmetabolized compound could be detected in the incubation medium after 5 min. The IC50 for cell proliferation (0.006-0.022 μM) elicited by these compounds is much lower than that of the inhibition of [14C]cytidine incorporation into DNA (0.18-3.32 μM). These compounds are also non-cell cycle specific agents. Interestingly, three of these compounds were potent inducers of apoptosis in Burkitt’s lymphoma cells.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 67073-96-5 belongs to class pyrimidines, name is 1-(6-Methylpyrimidin-4-yl)ethanone, and the molecular formula is C7H8N2O, Recommanded Product: 1-(6-Methylpyrimidin-4-yl)ethanone.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Schinazi, Raymond F. published the artcileSynthesis of 5-(dihydroxyboryl)-2′-deoxyuridine and related boron-containing pyrimidines, Recommanded Product: 2,4,6-Tribromopyrimidine, the main research area is boryldeoxyuridine dihydroxy; uridine deoxy dihydroxyboryl; uracil dihydroxyboryl; virucide dihydroxyboryldeoxyuridine; neoplasm inhibitor dihydroxyboryldeoxyuridine.

Organoboron derivatives of pyrimidines and of 2′-deoxyribonucleosides were prepared as potential antiviral and anticancer agents. The title nucleoside (I) was prepared via a metal-halogen exchange at -50° in THF on 5-bromo-3′,5′-bis-O-(trimethylsilyl)-2′-deoxyuridine using BuLi followed by boronation at -65° with B(OBu)3 in the presence of HMPT. After hydrolysis, I was purified by column chromatog. and repeated fractional crystallization I was hydrolytically stable and showed no activity against Sarcoma 180 but inhibited herpes simplex virus type 1 at a nontoxic concentration I sensitized hamster V-79 cells to neutrons and could be of potential use in B neutron capture therapy. 5-(Dihydroxyboryl)uracil and 6-(dihydroxyboryl)uracil were similarly prepared The phys. characteristics of these analogs, as well as those of their iminodiethanol esters, are described.

Journal of Organic Chemistry published new progress about Antitumor agents. 36847-11-7 belongs to class pyrimidines, name is 2,4,6-Tribromopyrimidine, and the molecular formula is C4HBr3N2, Recommanded Product: 2,4,6-Tribromopyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Yamashita, Junichi published the artcileStudies on antitumor agents. V. Syntheses and antitumor activities of 5-fluorouracil derivatives, SDS of cas: 56177-80-1, the main research area is uracil fluoro derivative preparation antitumor; fluorouracil derivative preparation antitumor.

Six types of 5-fluorouracil (5-FU) derivatives were synthesized; namely, 2,4-di-O-substituted, 2-O-substituted, 4-O-substituted, 1,3-disubstituted, 1-substituted and 3-substituted compounds Thus, 2,4-dichloro-5-fluoropyrimidine was treated with BuONa in BuOH to give 2,4-dibutoxy-5-fluoropyrimidine. After oral administration of these compounds to rats, the blood levels of 5-FU were determined Among O-substituted derivatives, a 4-O-substituted derivative was most easily activated to 5-FU and 2-O-substituted derivatives were next most easily activated. Among N-substituted derivatives, acyl and sulfonyl derivatives showed the highest 5-FU releasing abilities and 1-alkoxymethyl substituted derivatives showed low ability. N-Alkyl substituted derivatives were not activated to 5-FU. Several compounds which gave higher blood levels of 5-FU than that obtained with 1-(tetrahydro-2-furyl)-5-fluorouracil (Thf-FU), as well as same related compounds, were selected and their antitumor activities were examined The 2-O-substituted derivatives, 2-butoxy-5-fluoro-4(1H)-pyrimidone and 2-benzyloxy-5-fluoro-4(1H)-pyrimidone, were as effective as Thf-FU. The activities of 2,4-di-O-substituted derivatives, 2,4-dibutoxy-5-fluoropyrimidine and 2,4-dibenzyloxy-5-fluoropyrimidine, against Ehrlich carcinoma and against sarcoma 180, resp., were the same as those of Thf-FU. The 1-substituted derivatives, 1-ethoxymethyl-5-fluorouracil and 1-(1-ethoxy-1-phenylmethyl)-5-fluorouracil, were found to be as effective as Thf-FU.

Chemical & Pharmaceutical Bulletin published new progress about Antitumor agents. 56177-80-1 belongs to class pyrimidines, name is 2-Ethoxy-5-fluoropyrimidin-4(3H)-one, and the molecular formula is C6H7FN2O2, SDS of cas: 56177-80-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Rode, W. published the artcileInhibition of mammalian tumor thymidylate synthetase by 5-alkylated 2′-deoxyuridine 5′-phosphates, Related Products of pyrimidines, the main research area is alkylated deoxyuridine phosphate tumor; thymidylate synthetase inhibition tumor.

Improved syntheses, based on Lewis acid-catalyzed nucleosidation, are described for the preparation of 5-alkyl-2′-deoxyuridines. These were converted to their 5′-phosphates with the use of wheat shoot phosphotransferase. The dUMP analogs 5-ethyl-dUMP  [56576-83-1] and 5-propyl-dUMP  [64374-82-9] were competitive vs. dUMP inhibitors of thymidylate synthetase  [9031-61-2] purified from mouse L1210, Ehrlich ascites, and HeLa cells, the former being the stronger inhibitor. Both analogs bind cooperatively to each of the mouse tumor enzymes, 2 mols. of inhibitor interacting with a single enzyme mol., as reflected by the parabolic character of the replots of the slope vs. inhibitor concentrations DTMP  [365-07-1] was a stronger inhibitor of the mouse tumor enzymes than its higher alkyl homologs.

Biochemical Pharmacology published new progress about Antitumor agents. 19030-75-2 belongs to class pyrimidines, name is 5-N-Propyluracil, and the molecular formula is C7H10N2O2, Related Products of pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Jeanrenaud, Alexander C. S. N. published the artcileCharacterisation of the epigenetic architecture of the major malaria vector Anopheles arabiensis (Diptera: Culicidae) after treatment with epigenetic modulators and heavy metals, Synthetic Route of 58366-64-6, the main research area is Anopheles arabiensis heavy metal epigenetic modulator treatment; Anopheles arabiensis; Epigenetics; Histones; Insecticide resistance; Methylation.

Anopheles arabiensis (a member of the An. gambiae species complex) is a major vector of malaria in sub-Saharan Africa. Despite its disease vector status, there is currently a paucity of epigenetic information for this species. The aim this study was therefore to analyze global epigenetic markers and their response to metal exposure in insecticide susceptible and resistant laboratory strains of An. arabiensis. This was done using com. available epigenetic marker quantification kits. In order to validate the efficacy of the kits, several kits were assessed to determine whether changes induced by known epigenetic modulators were detectable using these platforms. The efficacy of the dosages used were determined by examining the effect of the dosages used on insecticide resistant phenotypes. Upon confirmation that the dosages used were sufficient to induce a phenotypic change, the effect on epigenetic markers was assessed. Com. kits were used to quantify 5-methylcysteine (5-mC) and 5-hydroxymethylcysteine (5-hmC) methylation in DNA, m6A methylation in mRNA as well as Histone Acetyl Transferase (HAT) activity. There was a marked difference in the phenotypic response in adult mosquitoes of the insecticide susceptible strain compared to that of its’ resistant counterpart. For males and females of the resistant strain, exposure to nucleic acid modifying drugs typically increased their tolerance to insecticides. The patterns of changes in 5-mC methylation by epigenetic modulators was congruent with previous studies which quantified by mass spectrometry. The two strains differed in methylation patterns under control conditions and responded differentially to larval metal exposure. In the resistant strain, which previously was demonstrated to show increased detoxification enzyme activity and insecticide tolerance after the same treatment, the potential increase in transcriptional activity appeared to be modulated by reduced methylation and increased HAT activity. This study suggests that the com. epigenetic quantification kits can be used to characterize phenotypic changes in An. arabiensis, and also shows that epigenetic regulation of the response to metal exposure is regulated at the DNA as opposed to the RNA level.

Acta Tropica published new progress about Adult, mammalian. 58366-64-6 belongs to class pyrimidines, name is 5-Methylcytosinehydrochloride, and the molecular formula is C5H8ClN3O, Synthetic Route of 58366-64-6.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Arnett, Edward M. published the artcileSolvent effects in organic chemistry. VIII. Acidity function failure in different aqueous acids, Formula: C8H11N3O2, the main research area is .

cf. CA 62, 13908d. Acidity functions (H0′, H0”’, and HR) are given for primary and tertiary aromatic amines and triarylcarbinols in aqueous HCl, H3PO4, and p-toluenesulfonic acids. In all of these media, and H2SO4, the order in which the acidity functions change with acid concentration is HR > HR’ > H0”’ > H0′. Using such functions as H0”’ – H0′ (i.e., log fB’fB”’H+/fB’H+fB”’) as a criterion of acidity function failure, it is found that these terms have a roughly linear relationship to the acid molarity in these media and in HClO4, but give variously shaped curves if plotted against log aH2O. The slopes of the linear Sechenov-like plots for (HR’ – H0′) in these acids fall in the order HClO4 > H2SO4 > HePO4 > HCl, suggesting that H2SO4 and HClO4 are the worst media of the four as far as acidity function failure is concerned. The importance of factors (such as size) other than ion hydration in determining activity coefficient and, hence, acidity functions is noted. It is suggested that the failure of rates of acid-catalyzed reactions to give linear plots of log k1 vs. H0 of unit slope be treated in a similar way. Plots of (log k1 + H0) vs. molarity of acid are linear over a fair range of acidity in conformity with the Sechenov-like equation log fSfBH+ /f*fB = constant × molarity. Aqueous solutions of p-toluenesulfonic acid give a medium in which H0′ and H0”’ are very close together and might be a useful one for acidity function work. However, the solutions are only weakly acidic compared to the mineral acids and present a very limited range of acidities.

Journal of the American Chemical Society published new progress about Acidity function. 5472-46-8 belongs to class pyrimidines, name is Ethyl 4-amino-2-methylpyrimidine-5-carboxylate, and the molecular formula is C8H11N3O2, Formula: C8H11N3O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia