Category: pyrimidines

Non-mitogenic fibroblast growth factor 1 enhanced angiogenesis following ischemic stroke by regulating the sphingosine-1-phosphate 1 pathway was written by Zou, Yuchi;Hu, Jian;Huang, Wenting;Ye, Shasha;Han, Fanyi;Du, Jingting;Shao, Mingjie;Guo, Ruili;Lin, Jingjing;Zhao, Yeli;Xiong, Ye;Wang, Xue. And the article was included in Frontiers in Pharmacology in 2020.HPLC of Formula: 219580-11-7 The following contents are mentioned in the article:

Ischemic strokes account for about 80% of all strokes and are associated with a high risk of mortality. Angiogenesis of brain microvascular endothelial cells may contribute to functional restoration following ischemia. Fibroblast growth factor 1 (FGF1), a member of FGF superfamily, involved in embryonic development, angiogenesis, wound healing, and neuron survival. However, the mitogenic activity of FGF1 is known to contribute to several human pathologies, thereby questioning the safety of its clin. applications. Here, we explored the effects and mechanism of action of non-mitogenic FGF1 (nmFGF1) on angiogenesis in mice after ischemia stroke and an oxygen-glucose deprivation (OGD)-induced human brain microvascular endothelial cells (HBMECs) injury model. We found that intranasal administration nmFGF1 significantly promoted angiogenesis in mice after stroke, and significantly increased the formation of matrigel tube and promoted scratch migration in a dose-dependent manner in OGD-induced HBMECs in vitro. However, the co-administration of an FGF receptor 1 (FGFR1)-specific inhibitor PD173074 significantly reversed the effects of nmFGF1 in vitro, suggesting that nmFGF1 functions via FGFR1 activation. Moreover, nmFGF1 activated sphingosine-1-phosphate receptor 1 (S1PR1, S1P1) in mice after stroke in vivo. S1P1 protein antagonist VPC23019 and agonist FTY720 were used to confirm that nmFGF1 promotes angiogenesis in vitro partially through the S1P1 pathway. OGD induced downregulation of S1P1 expression. The S1P1 antagonist VPC23019 blocked the stimulatory effects of nmFGF1, whereas the S1P1 agonist FTY720 exerted effects comparable with those of nmFGF1. Furthermore, PD173074 reversed the effect of nmFGF1 on upregulating S1P1 signaling. In conclusion, nmFGF1 enhanced angiogenesis in mice following stroke and OGD-induced HBMECs through S1P1 pathway regulation mediated via FGFR1 activation. This new discovery suggests the potential therapeutic role of nmFGF1 for the treatment of ischemic strokes. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7HPLC of Formula: 219580-11-7).

1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. Heterocyclic compounds bearing the pyrimidine core are of tremendous interest as they constitute an important class of natural and synthetic compounds exhibiting diverse useful biological activities that hold attractive potential for clinical translation as therapeutic agents in alleviation of a myriad of diseases. For example, the neurotoxin tetrodotoxin is a pyrimidine derivative. It is found in a number of species including the Japanese puffer fish, the blue-ringed octopus, and the orange-bellied newt. Tetrodotoxin prevents the transmission of nerve signals and can result in paralysis and death.HPLC of Formula: 219580-11-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

FGFR2-related pathogenesis and FGFR2-targeted therapeutics: (review) was written by Katoh, Yuriko;Katoh, Masaru. And the article was included in International Journal of Molecular Medicine in 2009.Synthetic Route of C28H41N7O3 The following contents are mentioned in the article:

A review. FGFR2 gene at human chromosome 10q26 encodes FGFR2b and FGFR2c isoforms functioning as FGF receptors with distinct expression domain and ligand specificity. FGFR2 plays oncogenic and anti-oncogenic roles in a context-dependent manner. Single nucleotide polymorphisms (SNPs) within intron 2 of FGFR2 gene are associated with breast cancer through allelic FGFR2 upregulation. Missense mutations or copy number gains of FGFR2 gene occur in breast cancer and gastric cancer to activate FGFR2 signaling. Aberrant FGFR2 signaling activation induces proliferation and survival of tumor cells. The class switch from FGFR2b to FGFR2c occurs during progression of prostate cancer and bladder cancer because of spliceosome dysregulation. In addition, epidermal Fgfr2b knockout mice show increased sensitivity to chem. carcinogenesis partly due to the failure of Nfe212 (Nrf2)-mediated detoxification of reactive oxygen species (ROS). Loss of FGFR2b signaling induces epithelial-to-mesenchymal transition (EMT) and unruly ROS. FGFR2 signaling dysregulation due to the accumulation of epigenetic modifications and genetic alterations during chronic inflammation, smoking, increased caloric uptake, and decreased exercise leads to carcinogenesis. PD173074, SU5402, AZD2171, and Ki23057 are small-mol. FGFR inhibitors. Human antibody, peptide mimetic, RNA aptamer, siRNA, and synthetic microRNA (miRNA) are emerging technologies to be applied for cancer therapeutics targeted to FGFR2. Because novel sequence technol. and peta-scale supercomputer are opening up the sequence era following the genome era, personalized medicine prescribing targeted drugs based on germline and/or somatic genomic information is coming reality. Application of FGFR2 inhibitors for cancer treatment in patients with FGFR2 mutation or gene amplification is beneficial; however, that for cancer prevention in people with FGFR2 risk allele might be disadvantageous due to the impediment of a cytoprotective mechanism against oxidative stress. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7Synthetic Route of C28H41N7O3).

1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. Heterocyclic compounds bearing the pyrimidine core are of tremendous interest as they constitute an important class of natural and synthetic compounds exhibiting diverse useful biological activities that hold attractive potential for clinical translation as therapeutic agents in alleviation of a myriad of diseases. Pyrimidine derivatives have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.Synthetic Route of C28H41N7O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Widespread molecular patterns associated with drug sensitivity in breast cancer cell lines, with implications for human tumors was written by Creighton, Chad J.. And the article was included in PLoS One in 2013.SDS of cas: 219580-11-7 The following contents are mentioned in the article:

Background: Recent landmark studies have profiled cancer cell lines for mol. features, along with measuring the corresponding growth inhibitory effects for specific drug compounds These data present a tool for determining which subsets of human cancer might be more responsive to particular drugs. To this end, the NCI-DREAM-sponsored DREAM7: Drug Sensitivity Prediction Challenge (sub-challenge 1) set out to predict the sensitivities of 18 breast cancer cell lines to 31 previously untested compounds, on the basis of mol. profiling data and a training subset of cell lines. Methods and Results: With 47 teams submitting blinded predictions, team Creighton scored third in terms of overall accuracy. Team Creighton’s method was simple and straightforward, incorporated multiple expression data types (RNA-seq, gene array, RPPA), and incorporated all profiled features (not only the “best” predictive ones). As an extension of the approach, cell line data, from public datasets of expression profiling coupled with drug sensitivities (Barretina, Garnett, Heiser) were used to “predict” the drug sensitivities in human breast tumors (using data from The Cancer Genome Atlas). Drug sensitivity correlations within human breast tumors showed differences by expression-based subtype, with many associations in line with the expected (e.g. Lapatinib sensitivity in HER2-enriched cancers) and others inviting further study (e.g. relative resistance to PI3K inhibitors in basal-like cancers) Conclusions: Mol. patterns associated with drug sensitivity are widespread, with potentially hundreds of genes that could be incorporated into making predictions, as well as offering biol. clues as to the mechanisms involved. Applying the cell line patterns to human tumor data may help generate hypotheses on what tumor subsets might be more responsive to therapies, where multiple cell line datasets representing various drugs may be used, in order to assess consistency of patterns. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7SDS of cas: 219580-11-7).

1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. Pyrimidine derivatives have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.SDS of cas: 219580-11-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Inhibition of H3K27me3 demethylases attenuates asthma by reversing the shift in airway smooth muscle phenotype was written by Yu, Qijun;Yu, Xiaowei;Zhao, Wenxue;Zhu, Manni;Wang, Zhengxia;Zhang, Jiaxiang;Huang, Mao;Zeng, Xiaoning. And the article was included in Clinical & Experimental Allergy in 2018.Product Details of 1373423-53-0 The following contents are mentioned in the article:

The shift in airway smooth muscle cells (ASMCs) phenotype between proliferation and contraction during asthma has been reported recently, highlighting a role of ASMCs plasticity in the pathophysiol. of asthma. As an event involved in epigenetic post-translational modification, histone H3 lysine27 (H3K27) demethylation has attracted significant attention with respect to the epigenetic changes in diverse cells; however, little is known about its contribution to the switching of ASMCs phenotype in asthma. To investigate the role of trimethylated H3K27 (H3k27me3) demethylation in ASM remodeling as well as the underling mechanism. Mice were exposed five times a week to house dust mite (HDM) extract for 5 wk. Lung function was measured following the final HDM challenge. Airway inflammation and remodeling were then assessed in lungs of individual mice. Human ASMCs were purchased from Sciencell Research Laboratories Proliferation, synthesis, migration and contraction of ASMCs were analyzed, resp. We observed demethylation at H3k27me3 sites in lungs harvested from mice exposed to HDM extract Administration of a selective inhibitor of H3K27 demethylase (GSK-J4) could ameliorate the classical hallmarks of asthma, such as airway hyperresponsiveness, airway inflammation and remodeling. We established a proliferative as well as a contractive model of human ASMCs to explore the impacts of H3K27 demethylase inhibition on ASMCs phenotype. Our results indicated that GSK-J4 decreased ASMCs proliferation and migration elicited by PDGF through the Akt/JNK signalling; GSK-J4 also prevented the upregulation of contractile proteins in ASMCs induced by TGF-β through the Smad3 pathway. Inhibition of H3K27me3 demethylation alleviated the development of asthmatic airway disease in vivo and modulated ASMCs phenotype in vitro. Collectively, our findings highlight a role of H3K27me3 demethylation in exptl. asthma and ASMCs phenotype switch. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0Product Details of 1373423-53-0).

Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own.Product Details of 1373423-53-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Evaluation of tyrosine kinase inhibitor combinations for glioblastoma therapy was written by Joshi, Avadhut D.;Loilome, Watcharin;Siu, I.-Mei;Tyler, Betty;Gallia, Gary L.;Riggins, Gregory J.. And the article was included in PLoS One in 2012.Reference of 219580-11-7 The following contents are mentioned in the article:

Glioblastoma multiforme (GBM) is the most common intracranial cancer but despite recent advances in therapy the overall survival remains about 20 mo. Whole genome exon sequencing studies implicate mutations in the receptor tyrosine kinase pathways (RTK) for driving tumor growth in over 80% of GBMs. In spite of various RTKs being mutated or altered in the majority of GBMs, clin. studies have not been able to demonstrate efficacy of mol. targeted therapies using tyrosine kinase inhibitors in GBMs. Activation of multiple downstream signaling pathways has been implicated as a possible means by which inhibition of a single RTK has been ineffective in GBM. In this study, we sought a combination of approved drugs that would inhibit in vitro and in vivo growth of GBM oncospheres. A combination consisting of gefitinib and sunitinib acted synergistically in inhibiting growth of GBM oncospheres in vitro. Sunitinib was the only RTK inhibitor that could induce apoptosis in GBM cells. However, the in vivo efficacy testing of the gefitinib and sunitinib combination in an EGFR amplified/PTEN wild type GBM xenograft model revealed that gefitinib alone could significantly improve survival in animals whereas sunitinib did not show any survival benefit. Subsequent testing of the same drug combination in a different syngeneic glioma model that lacked EGFR amplification but was more susceptible to sunitinib in vitro demonstrated no survival benefit when treated with gefitinib or sunitinib or the gefitinib and sunitinib combination. Although a modest survival benefit was obtained in one of two animal models with EGFR amplification due to gefitinib alone, the addition of sunitinib, to test our best in vitro combination therapy, did not translate to any addnl. in vivo benefit. Improved targeted therapies, with drug properties favorable to intracranial tumors, are likely required to form effective drug combinations for GBM. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7Reference of 219580-11-7).

1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. The pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. Therapy for fungal infections is based mainly on four classes of antifungals: azoles, echinocandins, polyenes, and pyrimidine analogs.Reference of 219580-11-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The synthesis of 5-carbethoxyuracils was written by Whitehead, Calvert W.. And the article was included in Journal of the American Chemical Society in 1952.Formula: C9H12N2O4 The following contents are mentioned in the article:

To NaOEt from 2.3 g. Na in 150 cc. EtOH was added 6.0 g. urea, then 21.6 g. EtOCH:CH(CO₂Et)₂, the mixture let stand 7 days at room temperature, the EtOH removed in vacuo, the residue dissolved in 50 cc. cold H₂O, and the solution acidified with dilute HCl to give 6 g. (21.8%) H₂NCONHCH: C(CO₂Et)₂ (I), m. 207-9° (from EtOH). I (23 g.) in 200 cc. absolute EtOH containing 0.1 mol. NaOEt let stand 12 hrs. at room temperature, refluxed 5 hrs., the EtOH removed in vacuo, and the residue in 50 cc. acidified yielded 13 g. (72%) 5-carbethoxyuracil, m. 232° (from EtOH). CO(NHMe)₂ (44 g.) and 108 g. I heated 24 hrs. at 120°, and the product recrystallized with charcoal from EtOAc gave 66 g. (62%) 1,3-dimethyl-5-carbethoxyuracil, m. 112° (from EtOH). H₂NCONHMe (14.8 g.) and 43.2 g. I gave 16 g. (41%) 3-methyl-5-carbethoxyuracil (II), m. 221° (from EtOH). II (10 g.) and 50 cc. 10% aqueous NaOH heated 2 hrs. on a steam bath, and the mixture acidified with dilute HCl gave 8.5 g. (98%) 3-methyl-5-carboxyuracil (III), m. 242° (from EtOH). III (2 g.) heated 10 min. at 225° yielded 90% 3-methyluracil, m. 174-5° (from EtOH). H₂NCONHPr (10.2 g.) and 21.6 g. I heated 12 hrs. at 110° yielded 50% PrNHCONHCH: C(CO₂Et)₂ (IV), b₁ 165-70°. IV (14.5 g.) and 2.88 g. NaOMe in 50 cc. MeOH let stand 48 hrs. at room temperature and then heated 6 hrs. at 80° gave 6 g. (56.5%) 3-propyl-5-carbomethoxyuracil, m. 205° (from EtOH). AmNHCONH₂ (13.0 g.) and 21.6 g. I heated 24 hrs. at 120°, the resulting sirup added to 200 cc. absolute EtOH containing 0.1 mol. NaOEt, the mixture let stand 24 hrs. at room temperature, the EtOH removed in vacuo, and the residue taken up in 100 cc. H₂O and 100 g. ice and acidified with dilute HCl yielded 6.2 g. (24%) 3-amyl-5-carbethoxyuracil, m. 152° (from aqueous EtOH). Similarly were prepared the following compounds (V), where R = H, R’ = Bu (VI), 53%, m. 152°, and R = H, R’ = C₆H₁₃, 50%, m. 140°. HOCH₂CHEtNHCONH₂ (11.6 g.) in 200 cc. absolute EtOH containing 0.1 mol. NaOEt and 21.6 g. I let stand 48 hrs. at room temperature and the mixture worked up as above yielded 21.0 g. (82%) 3-(1-hydroxymethylpropyl)-5-carbethoxyuracil, m. 161° (from EtOAc). Similarly were obtained the following V, where R = H (R’ given): Et, 82%, m. 219°; HO(CH₂)₂, 79%, m. 175-6°; CH₂:CHCH₂, 80%, m. 174°; iso-Bu, 62%, m. 167°; cyclohexyl, 49%, m. 282°; p-ClC₆H₄, 88%, m. 265°; p-MeOC₆H₄, 90%, m. 185-94°; p-MeC₆H₄, 97%, m. 235°; PhCH₂, 90%, m. 215°; C₇H₁₅, 49%, m. 133°; PhCHMe, 77%, m. 130°; Ph(CH₂)₂, 84%, m. 228°; and C₈H₁₇, 48%, m. 130°. PhNHCONH₂ (27.2 g.) and 43.2 g. I in 250 cc. absolute EtOH containing 0.2 mol. NaOEt let stand 3 days at room temperature, and the mixture worked up as usual yielded 46 g. (88%) 3-phenyl-5-carbethoxyuracil (VIII), m. 230-1° (from EtOH). VIII (5.2 g.) refluxed 2 hrs. with 100 cc. 5% aqueous NaOH, and the mixture cooled, filtered, and acidified yielded 2.5 g. 3-phenyl-5-carboxyuracil (IX), m. 243° (decomposition). IX (1.0 g.) heated 15 min. at 243° gave 0.6 g. 3-phenyluracil, m. 242-6° (from H₂O). VI (20 g.) stirred vigorously at 40° with 3.4 g. NaOH in 150 cc. H₂O and 12.9 g. Et₂SO₄ added dropwise during 1 hr., the mixture stirred another hr., the H₂O removed in vacuo, and the residue extracted gave 14.5 g. (65%) 1-ethyl-3-butyl-5-carbethoxyuracil, m. 41-3°. Similarly were prepared from the corresponding monoalkyl derivatives of V the following V (R and R’ given): Me, Et, 76%, m. 116°; Me, iso-Pr, 78%, m. 98°; Me, Bu, < 50%, m. 60°; Me, iso-Bu, 72%, m. 119°; Et, iso-Bu, 65%, m. 90-90.5°; Me, p-ClC₆H₄, – , m. 141°; and Me, PhCH₂, 76%, m. 79°. The above V heated 24-48 hrs. with 10% excess of an amine, the mixture cooled, and the product recrystallized from hot EtOAc gave the following 5-carbamyluracils (X) (R, R’, and Y given): Me, Me, NHMe, 100%, m. 196°; Me, Me, NHEt(XI), 95%, m. 158°; H, Pr, NHCONH₂, (50%), m. 234°; H, HO(CH₂)₂, NHEt, 75%, m. 222° Me, Me, NH(CH₂)₂OH (XII), 100%, m. 151°; H, HO(CH₂)₂, NH(CH₂)₂OH, 60%, m. 185°; Me, Et, NH(CH₂)₂OH, 57%, m. 179°; Et, Me, NH(CH₂)₂OH, 70%, m. 123°; Me, Me, NHBu, 100%, m. 125°; Me, Me, NHCH₂CHMe₂ (XIII), 100%, m. 150.5°; Me, iso-Pr, NH(CH₂)₂OH (XIV), 93%, m. 114°; Me, Me, N(CH₂CH₂OH)₂ (XV), 45%, m. 122°; Me, Me, NHAm, 100%, m. 115.5°; Me, iso-Bu, NH(CH₂)₂OH, 49%, m. 142°; Me, Me, NH(CH₂₃N Me₂, 86%, m. 89°; H, cyclohexyl, NH(CH₂)₂OH, 89%, m. 232°; Me, Me, NHC₆H₁₃, 79%, m. 121°; Me, Me, NH(CH₂)₃NEt₂, 66%, m. 69.5°; and Me, Me, NHC₇H₁₅, 87%, m. 107°. Alk. hydrolysis of the above V with refluxing 5% aqueous NaOH gave the following XVI (R and R’ given): Me, Me (XVII), 90%, m. 183°; H, Et, 70%, m. 179°; H, Pr, 90%, m. 172-3°; Me, Et, 70%, m. 172°; H, iso-Pr, 69%, m. 192°; Me, CH₂:CHCH₂, 70%, m. 161-2°; H, iso-Bu, 80%, m. 211°; H, HOCH₂CHEt, 90%, m. 166°; Me, Bu, 80%, m. 148°; Et, Bu, 95%, m. 107°; Me, Am, 74%, m. 152° H, p-ClC₆H₄, 98%, m. 255° (decomposition); H, p-MeC₆H₄, 90%, m. 240° (decomposition); and Me, C₆H₁₃, 66%, m. 151°. XII and XVII showed moderate diuresis in dogs with oral doses of 0.5-1 g.; XI, XIII, and XIV with intravenous doses of 5-10 mg.; XII caused marked diuresis with oral doses of 0.5-1 g.; and XII and XV with intravenous doses of 5-10 mg./kg. This study involved multiple reactions and reactants, such as Ethyl 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (cas: 39513-47-8Formula: C9H12N2O4).

Ethyl 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (cas: 39513-47-8) belongs to pyrimidine derivatives. The pyrimidine nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. As nucleotides in DNA and RNA, pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Formula: C9H12N2O4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Some thiopyrimidine derivatives was written by Monti, Lydia;Pacini, Carlo. And the article was included in Gazzetta Chimica Italiana in 1948.Product Details of 39083-15-3 The following contents are mentioned in the article:

By the reaction of HCHO (I), in the presence of H₂SO₄, on thiopyrimidines of the HN.CO.CH:CR.NH.CS ⇄ N:C(OH).CH:CR.N:CSH (II) and HN.CO.CR’:CMe.NH.CS ⇄ N:C(OH).CR’:CMe.N:CSH (III) types, 2 series of new derivatives were obtained. They are essentially different from those prepared by Kircher (C.A. 6, 857) and Poetsch and Behrend (C.A. 20, 2681) by the action of I on HN.CO.CH:CMe.NH.CO and HN.CO.CH:CMe.NH.CS, resp., in acid medium. With II the reactions involve the initial reaction of I with enolic II in the 5-position, following which another I mol. reacts with the newly formed OH group and the original OH group in the 6-position, with final formation of compounds of the C:CR.N:C(SH).N:C.O.CH₂.O.CH₂ (IV) type. With III, in which the H in the 5-position is replaced by an alkyl group, the formation of analogous compounds is difficult to explain, for no intermediate products could be isolated. Perhaps I reacts with III in the ketone-imide form with formation of SC.N.CO.CR’:CMe.N.CH₂.O.CH₂ compounds If so, 1,3-dimethylol compounds would be intermediate products, but none was isolated. Possibly the NH group in the 1-position (between CS and CO) is more reactive than that in the 3-position, and SC.N.CH₂.O.CH₂.O.C:CR’.CMe:N or S.CH₂.O.CH₂.N.CO.CR’:CMe.N:C compounds are formed. Or III compounds may react in a tautomeric form N:C(OH).CHR’.CMe:N.CS, with formation of N:C.O.CH₂.O.CH₂.CR’.CMe:N.CS compounds Comparative physiol. tests of these doubtful compounds and of II, III, and IV now in progress may help solve this problem. (H₂N)₂CS (2.5 g.), 6 g. AcAmCHCO₂Et, and alc. NaOEt (from 1.5 g. Na in a min. of EtOH), refluxed 30-40 min., evaporated, the residue taken up in AcOH (60 cc. AcOH + 40 cc. water), filtered, and the product purified by water, yield 60% of 4-methyl-5-amyl-2-thiouracil (V), m. 217-19°, soluble in dilute aqueous alkalies, and decomposed by boiling concentrated aqueous alkalies (evolution of H₂S and NH₃). It behaves like a weak monobasic acid. With aqueous AgNO₃, its boiling concentrated aqueous solutions deposit the Ag salt, C₁₀H₁₅ON₂SAg. The Cu and Hg salts were prepared similarly. 4-Phenyl-2-thiouracil (IV) (2 g.) in 15 cc. hot 10% aqueous NaOH, allowed to stand 24 hrs. with 4 cc. 40% I, diluted, neutralized with dilute HCl, and the precipitate purified by EtOH, yields 86% 5-(hydroxymethyl)-4-phenyl-2-thiouracil (VII), m. 250-1°, evolves I when heated; its solutions in concentrated H₂SO₄ are intensely yellow. 4-Methyl-2-thiouracil (2 g.), 16 cc. dilute H₂SO₄ (4 volumes concentrated H₂SO₄ + 1 volume water), and 3 cc. 40% I, allowed to stand 24 hrs. (with frequent agitation), diluted with 100 cc. water, neutralized with NH₄OH, filtered, and the residue purified by boiling water and CCl₄, yield the methylenic ether of 2-thio-4-methyl-6-hydroxy-5-pyrimidinemethanol (VIII), does not form an Ac derivative; its concentrated H₂SO₄ solution with a trace of gallic acid gives the green-to-blue Labat reaction; when heated with a dilute alkali, it evolves H₂S and NH₃. VII and I in dilute H₂SO₄, also under the same conditions, form VIII. VI or VII (3 g.) and 4 cc. 40% I in 16 cc. dilute H₂SO₄ (4 volumes concentrated H₂SO₄ + 1 volume water), treated as above, yield 95% of methylenic ether of 2-thio-4-phenyl-6-hydroxy-5-pyrimidinemethanol, m. 151-2°, yellow when crystallized from EtOH but colorless from CCl₄. It gives a pos. Labat reaction, and is decomposed, with evolution of H₂S and NH₃, by hot dilute alkalies. Prepared under similar conditions from 4,5-dimethyl-2-thiouracil (IX) and I in 73% yield and purified by boiling water, the methylenic ether (X) of IX m. 133-5°, does not give an Ac derivative, gives a pos. Labat reaction, and is decomposed by hot aqueous alkalies with evolution of H₂S and NH₃. 4-Methyl-5-ethyl-2-thiouracil and I give 82-3% of the methylenic ether (XI), m. 163-4°, with chem. properties similar to those of X. V (2 g.) in 22 cc. dilute H₂SO₄ (same concentration as before) and 3 cc. 40% I, allowed to stand 24 hrs., diluted, neutralized with NH₄OH, concentrated, and the product purified by boiling water, yield 41% of the methylenic ether, m. 122-5°, with chem. properties like those of X and XI. This study involved multiple reactions and reactants, such as 5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (cas: 39083-15-3Product Details of 39083-15-3).

5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (cas: 39083-15-3) belongs to pyrimidine derivatives. The pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own.Product Details of 39083-15-3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Chemotherapy. X. Antithyroid compounds. Synthesis of 5- and 6-substituted 2-thiouracils from β-oxo esters and thiourea was written by Anderson, George W.;Halverstadt, I. F.;Miller, Wilbur H.;Roblin, Richard O. Jr.. And the article was included in Journal of the American Chemical Society in 1945.Reference of 39083-15-3 The following contents are mentioned in the article:

5- and 6-Substituted 2-thiouracils have been prepared by condensing CS(NH₂)₂ with β-keto esters. The latter were prepared by one of several methods. As an example of the first, 0.84 mol of AcCHNaCO₂Et in 500 mL. ether was treated with 0.84 mol of PrCOCl during 3 h., allowed to stand overnight, treated with 200 cc. H₂O, extracted with 600 cc. ether, and treated with 40 g. NH₃ gas at 0-25°, giving 39% of Et β-ketocaproate; similarly prepared were Et γ-methyl-β-ketovalerate (41%), Et β-ketoenanthate (40%), Et β-ketocyclohexanepropionate (40%), and Et β-keto-γ-phenylbutyrate (31%). In the 2nd method the reactions involved were: RCOCl + EtOMgCH(CO₂Et)CO₂CMe₃ → RCOCH(CO₂Et)CO₂CMe₃ → RCOCH₂CO₂Et + CH₂:CMe₂ + CO₂; this method gives the best results when only small quantities are required; the limiting factor is the relative unavailability of tert-BuCH(CO₂Et)₂; prepared by this method were: Et β-ketovalerate (I) (60%), Et γ-methyl-β-ketocaproate (49%), Et β-(4-chlorophenyl)-β-ketopropionate (82%), and Et β-keto-δ-phenylvalerate (61%). The 3rd method involved the reaction of RAc with NaNH₂, followed by Et₂CO₃; Et γ-methyl-β-ketocaproate (68%), Et γ-γ-dimethyl-β-ketovalerate (43%), Et β-ketocaprylate (57%), and Et β-ketopelargonate (61%) were prepared by this method. The 4th method consisted in the reaction of RCOCH₂CO₂Et with R’X; AcCHMeCO₂Et (45%), AcCHEtCO₂Et (58%), and Et α-ethyl-β-ketovalerate, b₈ 83-5° (75%), were prepared by this method. The 5th method involved the reaction of RCO₂Et and R’CH₂CO₂Et with EtONa or Na; prepared by this method were Et α-methyl-β-ketovalerate (26%) and 2-carbethoxycyclopentanone (71%). Details are given of the reaction of EtMgBr and NCCH₂CO₂Et, which yields 58% of I. In the preparation of the uracils, 0.1 g.-atom of Na in 50 cc. anhydrous EtOH, 0.07 mol of CS(NH₂)₂, and 0.05 mol of the keto ester were heated on the steam bath for 6-7 h. and allowed to stand overnight; the solution was evaporated at 40-50°, the residue taken up in 50 cc. H₂O, and the product precipitated by addition of 7 cc. concentrated HCl and then AcOH to pH 4; the compounds were crystallized from boiling H₂O or AcOH. The m. ps. (corrected), yield (from the ester), and antithyroid activity (thiouracil = 1) are given. 6-Substituted 2-thiouracils: Me, m. above 300°, 63%, 1.0; Et, m. 228.5-30.5°, 78%, 8; Pr, m. 218-19°, 70%, 11; iso-Pr, m. 179-80°, 45%, 9; Bu, m. 207.5-9°, 31%, 3; iso-Bu, m. 220.5-1.5°, 36%, 5; sec-Bu, m. 222-4%, 55%, 6; tert-Bu, m. 178-80°, 43%, 9; Am, m. 153-4.5° and 163-4°, 33%, 1.3; hexyl, m. 144.5-5.5°, 27%, 0.18; cyclohexyl, m. 282-5°, 69%, 1.2; Ph, m. 263-4.5%, 45%, 1; p-chlorophenyl, m. 289-91°, 21%, less than 0.01; benzyl, m. 223-4°, 71%, 10; phenethyl, m. 223.5-5.5°, 41%, 1.2. 5,6-Dimethyl-2-thiouracil, m. 283-5°, 42%, 1.2; 5-methyl-6-Et homolog, m. 223-4°, 48%, 3.5; 5-ethyl-6-Me isomer, m. 216-18°, 53%, 0.9; 5,6-di-Et homolog, m. 214.5-15.5°, 41%, 2.0; trimethylene homolog, m. 336-7° (decomposition), 10%, 0.3; 5-(2-hydroxyethyl)-6-Me compound, m. 265-7, 13%, less than 0.01. BuCO₂Et (II) (28.6 g.) and 28.4 g. HCO₂Et, added during 4 h. to 4.85 g. Na in 100 cc. ether, the mixture allowed to stand overnight, evaporated in vacuo, treated with 0.75 g. CS(NH₂)₂ and 85 cc. absolute EtOH, and refluxed 7 h., give 3.4 g. (based on II) of 5-propyl-2-thiouracil, m. 161-3°, 2; 5-iso-Pr isomer, m. 242-4°, 6%, 2.5; 5-Bu homolog, m. 151.5-3.5°, 6%, 0.6; 5-Et homolog, m. 190-2°, 4%, 3.5. Et α-cyano-β-ethoxyacrylate (30 g.), added slowly to 4.22 g. Na in 200 cc. absolute EtOH and 13.5 g. CS(NH₂)₂, the mixture refluxed 1 h. and allowed to stand overnight, the solution concentrated to 75 cc., diluted with 400 cc. H₂O, neutralized to pH 7, the precipitate taken up in 350 cc. H₂O and acidified to pH 3, gives 18.9 g. of the Et ester, m. 277° (decomposition), of 2-mercapto-4-amino-5-pyrimidinecarboxylic acid, m. 276-9° (decomposition); the filtrate yields 14% of 5-cyano-2-thiouracil, m. 282-3° (decomposition), activity less than 0.01. The maximum antithyroid activity appears when the alkyl group contains 3 or 4 C atoms. The benzyl derivative was the most active of the aralkyl compounds This study involved multiple reactions and reactants, such as 5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (cas: 39083-15-3Reference of 39083-15-3).

5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (cas: 39083-15-3) belongs to pyrimidine derivatives. The pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. A Cu-catalyzed and 4-HO-TEMPO-mediated [3 + 3] annulation of commercially available amidines with saturated ketones enables an efficient and facile synthesis of structurally important pyrimidines via a cascade reaction of oxidative dehydrogenation/annulation/oxidative aromatization.Reference of 39083-15-3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthesis of pyrimidine-5-carboxaldehydes by the Reimer-Tiemann reaction was written by Wiley, Richard H.;Yamamoto, Yuzuru. And the article was included in Journal of Organic Chemistry in 1960.Application of 14160-85-1 The following contents are mentioned in the article:

Substituted pyrimidines, N:CR.N:CR¹.CX:CR² (I, X = H, R = OH. Me, OH, SH, SMe, OH, Me, H, H, OH, R¹ = OH, OH, OH, OH, OH, Me, OH, OH, OH, OH, R² = H, OH, Me, Me, Me, Me, Me, Me, H, OH) (II-XI) were submitted to the Reimer-Tiemann reaction by treatment 1 h. in dilute alc. with KOH and CHCl₃ at 80° and neutralization of the precipitate K salts with AcOH to give the corresponding 5-carboxaldehydes I (X = CHO) (XII). The monohydroxylated pyrimidines V, VI, VII, and VIII did not precipitate the K salt and were isolated through a suitable derivative Data were tabulated for the isolated XII [pyrimidine, % yield of XII, and m.p. (solvent) given)]: XI, 42, 330° (H₂O); II, 18, 304° (MeOH, H₂O); III, 29, 300° (AcOH); IV, 14, -; V, 17, 300° (H₂O); VI, 14, 300° (dilute alc.); VII, 26, -; VIII, 13, -. IX gave only 1.5% non-characterized derivative and no aldehyde or derivative was obtained from X. The data were consistent with the established difference in reactivity between IX and VIII, the less reactive nature of the pyrimidine nucleus than that of benzene, and the mechanism of the Reimer-Tiemann reaction. Various derivatives of XII were prepared and m.p. data listed [aldehyde, m.p. (solvent) of phenylhydrazone, dinitrophenylhydrazone, dimethylhydrazone, bis(2-hydroxyethyl)hydrazone, oxime, and semicarbazone of the corresponding XII given]: XI, 271-3° (AcOH), 301-2° (HCONMe₂-alc.), 283-4° (MeOH), -, 250° (H₂O),-; II, 298-300° (HCONMe₂), 270-2° (MeOH), -, above 330° (MeOH), 260° (HCONMe₂), 240° (reprecipitated from alk. solution); III, 240° (reprecipitated), above 330° (HCONMe₂-H₂O), 200° (EtOAc), -, -, 205° (reprecipitated); IV, -, -, 258-9° (MeOH), 320° (MeOH), 260° (MeOH),-; V, 276-7° (MeOH), -, 232-3° (MeOH), -, -, -; VI, 250-1° (MeOH), 283-4° (HCONMe₂), 168-70° (MeOH), -, 228-9° (MeOH), 263° (reprecipitated); VII, 229-31° (MeOH), -, -, -, -, -; VIII, 277-9° (MeOH), 305° (HCONMe₂), 192-3° (MeOH), -, 238-40° (MeOH), 265-6° (reprecipitated from alk. solution). CHCl₃ (24 mL.) and 56 g. KOH in 60 mL. H₂O added in 20 min. with stirring to 22.4 g. II and 11.2 g. KOH in 180 mL. 5:4 H₂O-alc. at 80°, the mixture refluxed 1 h., the cooled mixture filtered from KCl, kept 10 h. at 20°, the precipitated K salt suspended in H₂O, and neutralized with AcOH gave 8.6% XII (R = R¹ = OH, R² = H). The filtrate with PhNHNH₂ gave 9.4% phenylhydrazone. XII (R = R¹ = OH, R² = Me) oxime (XIII) (0.5 g.) and 10 mL. Ac₂O refluxed 30 min. and the hot filtered solution cooled to 20° gave 0.15 g. I (R = R¹ = OH, R² = Me, X = CN), m. above 330°, λ 273 mμ, also obtained (56%) by refluxing 0.5 g. XIII with 4.5 mL. POCl₃, pouring the mixture onto ice, and recrystallizing from alc. XIII (0.7 g.) in 6 mL. POCl₃ treated slowly with cooling with 3 mL. PhNMe₂, the mixture refluxed 30 min., cooled, poured onto ice, extracted with Et₂O, and the product recrystallized from ligroine (b. 60-80°) yielded 57% I (R = R¹ = OH, R² = Me, X = CN), m. 93-4°, converted by recrystallization from EtOH to I [R = Cl(EtO), R¹ = EtO(Cl), R² = Me, X = CN], m. 134-6°. The ease with which XIII was dehydrated suggested that the HO group and H atom were in the trans configuration. This study involved multiple reactions and reactants, such as 4,6-Dihydroxy-2-methylpyrimidine-5-carbaldehyde (cas: 14160-85-1Application of 14160-85-1).

4,6-Dihydroxy-2-methylpyrimidine-5-carbaldehyde (cas: 14160-85-1) belongs to pyrimidine derivatives. Pyrimidines are isomeric with two other forms of diazines: pyridazine, with the nitrogen atoms in the 1 and 2 positions; and pyrazine, with the nitrogen atoms in the 1 and 4 positions. As nucleotides in DNA and RNA, pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Application of 14160-85-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

[(N-aryl)piperazinyl]butylpyrimidine derivatives with neurotropic and actoprotective properties was written by Andronati, S. A.;Soboleva, S. G.;Zamkovat, A. V.;Karasyova, T. L.;Rakipov, I. M.;Tsymbal, D. I.. And the article was included in Zhurnal Organichnoi ta Farmatsevtichnoi Khimii in 2016.Quality Control of 5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one The following contents are mentioned in the article:

In this study the potential ligands of 5-HT1A receptors – arylpiperazines containing the residues of tetrahydropyrimidine as terminal fragments, compounds I·HCl [R¹ = Pr-i, R² = H, Me-2, Me-3, X = S; R¹ = Pr-n, R² = Me-3, X = O; R¹ = Et, R² = Me-2, X = S] and II·HCl, and dihydropyrimidine III·2HCl have been synthesized. The structures of I·HCl [R¹ = Pr-i, R² = H, Me-2, Me-3 X = S; R¹ = Pr-n, R² = Me-3 X = O;], II·HCl and III·2HCl have been confirmed by IR-spectroscopy, mass spectrometry and 1H-NMR-spectroscopy. Substances I [R¹ = Pr-i, R² = Me-2, Me-3, X = S; R¹ = Pr-n, R² = Me-3, X = O;] and III·2HCl inhibit the specific binding of the radioligand [³H]8-OH-DPAT with 5-HT1A receptors; it has been found that they have a pronounced affinity for these receptors. In the conflict situation test compounds of I·HCl [R¹ = Pr-i, R² = H, Me-2, Me-3, X = S; R¹ = Pr-n, R² = Me-3, X = O; R¹ = Et, R² = Me-2, X = S] and III·2HCl showed anxiolytic properties, whereas phenylpiperazinil- and o-tolylpiperazinilbutyl-4-methyl-5-isopropyl-1,2,3,-6-tetrahydropyrimidine-2-thio-6-ones (I·HCl; R¹ = Pr-i, R² = H, Me-2) exceeded the known drug buspirone by the level of the anxiolytic activity. The absence of this activity in compound II·HCl is probably due to the differences of substituents at N1 atom of the pyrimidine nucleus of compound II·HCl and other compounds of this series. It has been shown that on the model of hyperthermia all of these compounds in the dose range of 0.04-0.1 mg/kg possessed a high actoprotective activity increased the rat capacity work by 1.4-2.5 times compared to the control. The most active compound, I·HCl [R¹ = Pr-i, R² = Me-3, X = S;], in the ED50 dose of 0.04 mg/kg increased the duration of swimming in rats by 2.2 times (122%) compared to bemithylum. Some of the compounds (15 mg/kg) showed antihypoxic activity on the models of hemic [compounds I (R¹ = Pr-i, R² = Me-2, Me-3, S = S; R¹ = Pr-n, R² = Me-3, X = O;) and III·2HCl] and normobaric hypoxia [compounds I·HCl (R¹ = Pr-i, R² = H, Me-2, X = S) and II·HCl] and exceeded bemithylym (33.5 mg/kg) by their activity. The compounds synthesized are low toxic with the LD50 value of 150-250 mg/kg. This study involved multiple reactions and reactants, such as 5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (cas: 39083-15-3Quality Control of 5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one).

5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (cas: 39083-15-3) belongs to pyrimidine derivatives. Heterocyclic compounds bearing the pyrimidine core are of tremendous interest as they constitute an important class of natural and synthetic compounds exhibiting diverse useful biological activities that hold attractive potential for clinical translation as therapeutic agents in alleviation of a myriad of diseases. As nucleotides in DNA and RNA, pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Quality Control of 5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia