Tag: 100-200

Quality Control of 2,4,6-TrichloropyrimidineIn 2015 ,《Design, synthesis, and biological evaluation of pyrimidine-2-carboxamide analogs: investigation for novel RAGE inhibitors with reduced hydrophobicity and toxicity》 appeared in Archives of Pharmacal Research. The author of the article were Kim, Seok-Ho; Han, Young Taek. The article conveys some information:

This paper describes an investigation of novel RAGE inhibitors with improved drug-like properties. To identify the improved drug-like RAGE inhibitor, the authors designed and synthesized pyrimidine-2-carboxamide analogs based on the previous work. Several potent analogs with improved hydrophilicity were identified by evaluation of RAGE inhibitory activity. In particular, one of the potent (diethylamino)ethoxymethoxy analogs did not exhibit undesired cytotoxicity in contrast with the parent RAGE inhibitors. In the experimental materials used by the author, we found 2,4,6-Trichloropyrimidine(cas: 3764-01-0Quality Control of 2,4,6-Trichloropyrimidine)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Quality Control of 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application In Synthesis of 2,4-DichloropyrimidineIn 2019 ,《Structure-based design and synthesis of pyrimidine-4,6-diamine derivatives as Janus kinase 3 inhibitors》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Yu, Ru-Nan; Chen, Cheng-Juan; Shu, Lei; Yin, Yuan; Wang, Zhi-Jian; Zhang, Tian-Tai; Zhang, Da-Yong. The article conveys some information:

Janus kinases (JAKs) play a key role in the proliferation, apoptosis and differentiation of immune cells, and JAKs are considered as an attractive target for the treatment of inflammatory and autoimmune diseases. Here we show the design and optimization of pyrimidine-4,6-diamine derivatives as selectivity JAK3 inhibitors. Compound I, which might interact with unique cysteine (Cys909) residue in JAK3, exhibited excellent JAK3 inhibitory activity (IC50 = 2.1 nM) and high JAK kinase selectivity. In cellular assay, I showed moderate potency inhibiting IL-2-stimulated T cell proliferation. The data supports the further development of novel JAKs inhibitors. The experimental part of the paper was very detailed, including the reaction process of 2,4-Dichloropyrimidine(cas: 3934-20-1Application In Synthesis of 2,4-Dichloropyrimidine)

2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Application In Synthesis of 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Discovery of Novel Dual Poly(ADP-ribose)polymerase and Phosphoinositide 3-Kinase Inhibitors as a Promising Strategy for Cancer Therapy》 was published in Journal of Medicinal Chemistry in 2020. These research results belong to Wang, Junwei; Li, Hui; He, Guangchao; Chu, Zhaoxing; Peng, Kewen; Ge, Yiran; Zhu, Qihua; Xu, Yungen. Safety of 2,4,6-Trichloropyrimidine The article mentions the following:

Concomitant inhibition of PARP and PI3K pathways has been recognized as a promising strategy for cancer therapy, which may expand the clin. utility of PARP inhibitors. Herein, we report the discovery of dual PARP/PI3K inhibitors that merge the pharmacophores of PARP and PI3K inhibitors. Among them, compound 15 stands out as the most promising candidate with potent inhibitory activities against both PARP-1/2 and PI3Kα/δ with pIC50 values greater than 8. Compound 15 displayed superior antiproliferative profiles against both BRCA-deficient and BRCA-proficient cancer cells in cellular assays. The prominent synergistic effects produced by the concomitant inhibition of the two targets were elucidated by comprehensive biochem. and cellular mechanistic studies. In vivo, 15 showed more efficacious antitumor activity than the corresponding drug combination (Olaparib + BKM120) in the MDA-MB-468 xenograft model with a tumor growth inhibitory rate of 73.4% without causing observable toxic effects. All of the results indicate that 15, a first potent dual PARP/PI3K inhibitor, is a highly effective anticancer compound In addition to this study using 2,4,6-Trichloropyrimidine, there are many other studies that have used 2,4,6-Trichloropyrimidine(cas: 3764-01-0Safety of 2,4,6-Trichloropyrimidine) was used in this study.

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Safety of 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2019,Journal of Medicinal Chemistry included an article by Huang, Boshi; Chen, Wenmin; Zhao, Tong; Li, Zhenyu; Jiang, Xiangyi; Ginex, Tiziana; Vilchez, David; Luque, Francisco Javier; Kang, Dongwei; Gao, Ping; Zhang, Jian; Tian, Ye; Daelemans, Dirk; De Clercq, Erik; Pannecouque, Christophe; Zhan, Peng; Liu, Xinyong. Safety of 2,4-Dichloropyrimidine. The article was titled 《Exploiting the Tolerant Region I of the Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Binding Pocket: Discovery of Potent Diarylpyrimidine-Typed HIV-1 NNRTIs against Wild-Type and E138K Mutant Virus with Significantly Improved Water Solubility and Favorable Safety Profiles》. The information in the text is summarized as follows:

Diarylpyrimidine derivatives (DAPYs) exhibit robust anti-HIV-1 potency, although they have been compromised by E138K variant and severe side-effects and been suffering from poor water solubility In the present work, hydrophilic morpholine or methylsulfonyl and sulfamide-substituted piperazine/piperidines were introduced into the right wing of DAPYs targeting the solvent-exposed tolerant region I. The anti-HIV-1 activities of 11c (EC50(WT) = 0.0035 μM, EC50(E138K) = 0.0075 μM) were the same as and 2-fold better than that of the lead etravirine against the wild-type and E138K mutant HIV-1, resp., with a relative low cytotoxicity (CC50 ≥ 173 μM). Further test showed a significant improvement in the water solubility of 11c. Besides, 11c displayed no significant inhibition on main cytochrome P 450 enzymes and exhibited no acute/subacute toxicities at doses of 2000 mg·kg-1/50 mg·kg-1 in mice. Taken together, we consider that 11c is a promising lead for further structural optimization. The results came from multiple reactions, including the reaction of 2,4-Dichloropyrimidine(cas: 3934-20-1Safety of 2,4-Dichloropyrimidine)

2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.Safety of 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2018,Murthy Bandaru, Siva Sankar; Bhilare, Shatrughn; Chrysochos, Nicolas; Gayakhe, Vijay; Trentin, Ivan; Schulzke, Carola; Kapdi, Anant R. published 《Pd/PTABS: Catalyst for Room Temperature Amination of Heteroarenes》.Organic Letters published the findings.Quality Control of 2,4,6-Trichloropyrimidine The information in the text is summarized as follows:

A mild and highly efficient catalytic amination procedure for chloroheteroarenes at ambient temperature using the Pd/PTABS catalytic system is reported. The protocol is selective for the amination of chloroheteroarenes using secondary amines such as piperidine, pyrrolidine, and several others. The exceptional mildness of the developed protocol is beneficial for the synthesis of a crucial Buparlisib intermediate as well as the formal synthesis of Alogliptin in competitive yields. The experimental part of the paper was very detailed, including the reaction process of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Quality Control of 2,4,6-Trichloropyrimidine)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Quality Control of 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Category: pyrimidinesIn 2021 ,《Discovery and Synthesis of a Pyrimidine-Based Aurora Kinase Inhibitor to Reduce Levels of MYC Oncoproteins》 appeared in Journal of Medicinal Chemistry. The author of the article were Chi, Ya-Hui; Yeh, Teng-Kuang; Ke, Yi-Yu; Lin, Wen-Hsing; Tsai, Chia-Hua; Wang, Wan-Ping; Chen, Yen-Ting; Su, Yu-Chieh; Wang, Pei-Chen; Chen, Yan-Fu; Wu, Zhong-Wei; Yeh, Jen-Yu; Hung, Ming-Chun; Wu, Mine-Hsine; Wang, Jing-Ya; Chen, Ching-Ping; Song, Jen-Shin; Shih, Chuan; Chen, Chiung-Tong; Chang, Chun-Ping. The article conveys some information:

The design and synthesis of a series of pyrimidine-based derivatives I (R1 = phenylcarbonyl, (3-chloro-2-fluorophenyl)carbonyl, (6-chloro-2-fluoropyridin-3-yl)carbonyl, etc.; R2 = 4-ethylpiperazin-1-yl, 3-(dimethylamino)azetidin-1-yl, (3S)-3-(dimethylamino)pyrrolidin-1-yl, etc.), which able to inhibit Aurora A kinase activity and reduce levels of cMYC and MYCN were described. Through structure-based drug design of a small mol. that induces the DFG-out conformation of Aurora A kinase, lead compound I (R1 = (4-chloro-2-fluorophenyl)carbonyl; R2 = 4-ethylpiperazin-1-yl) was identified, which potently (IC50 <200 nM) inhibited the proliferation of high-MYC expressing small-cell lung cancer (SCLC) cell lines. Pharmacokinetic optimization of I (R1 = (4-chloro-2-fluorophenyl)carbonyl; R2 = 4-ethylpiperazin-1-yl) by prodrug strategies resulted in orally bioavailable II, which demonstrated an 8-fold higher oral AUC (F = 62.3%). Pharmacodynamic studies of II showed it to effectively reduce cMYC protein levels, leading to >80% tumor regression of NCI-H446 SCLC xenograft tumors in mice. These results support the potential of II for the treatment of MYC-amplified cancers including SCLC. The experimental process involved the reaction of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Category: pyrimidines)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

HPLC of Formula: 3934-20-1In 2021 ,《Structural modifications on indole and pyrimidine rings of osimertinib lead to high selectivity towards L858R/T790M double mutant enzyme and potent antitumor activity》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Liu, Qiao; Luo, Yanli; Li, Zerui; Chen, Chen; Fang, Lei. The article conveys some information:

Utilizing osimertinib as the lead compound, this work has explored the structural modifications on the indole and pyrimidine rings of osimertinib to generate novel osimertinib derivatives I (R = acetyl, cyclopropyl, prop-2-en-1-yl, oxetan-3-yl, etc; R1 = H, CF3). The in vitro enzymic and cellular studies showed that the derivatives I possessed high selectivity towards double mutant EGFR and potent antitumor activity. Particularly, compound I (R = cyclopropyl, R1 = H), the most active compound, exhibited excellent inhibitory activity against double mutant EGFR (IC50 = 0.18 nM) and wild-type EGFR (IC50 = 2.89 nM) as well as H1975 cells (IC50 = 1.44 nM). Western blot anal. showed that I (R = cyclopropyl, R1 = H) completely inhibited double mutant EGFR and Erk phosphorylation. In vivo test using xenograft model indicated that compound I (R = cyclopropyl, R1 = H) had better antitumor efficacy than osimertinib. More importantly, I (R = cyclopropyl, R1 = H) displayed many advantages in the pharmacokinetic study, including better oral bioavailability and metabolism character.2,4-Dichloropyrimidine(cas: 3934-20-1HPLC of Formula: 3934-20-1) was used in this study.

2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.HPLC of Formula: 3934-20-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Gao, Ping; Song, Shu; Wang, Zhao; Sun, Lin; Zhang, Jian; Pannecouque, Christophe; De Clercq, Erik; Zhan, Peng; Liu, Xinyong published their research in Bioorganic & Medicinal Chemistry in 2021. The article was titled 《Design, synthesis and anti-HIV evaluation of novel 5-substituted diarylpyrimidine derivatives as potent HIV-1 NNRTIs》.Application of 3934-20-1 The article contains the following contents:

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are widely used in combination therapies against HIV-1. As a continuation of authors’ efforts to discover and develop ”me-better” drugs of DAPYs, novel diarylpyrimidine derivatives I (R = Ph, 2-furyl, 3-pyridyl, etc.) were designed, synthesized and evaluated for their anti-HIV activities in MT-4 cells. All the compounds demonstrated strong inhibition activity against wide-type HIV-1 strain (IIIB) with EC50 values in the range of 2.5 nM ~0.93μM. Among them, compounds I (R = 4-pyridyl, 3-pyridyl) were the most potent ones which showed anti-HIV-1IIIB activity much superior than that of nevirapine, comparable to efavirenz and etravirine. What’s more, some compounds also showed low nanomole activity against some mutant strains such as K103N and E138K. The selected compound I (R = 4-pyridyl) was also evaluated for the activity against reverse transcriptase (RT), and exhibited submicromolar IC50 values indicating that this series compounds are specific RT inhibitors. Preliminary structure-activity relationships and modeling studies of these new analogs provide valuable avenues for future mol. optimization. In the experiment, the researchers used 2,4-Dichloropyrimidine(cas: 3934-20-1Application of 3934-20-1)

2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.Application of 3934-20-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2015,Satz, Alexander Lee; Cai, Jianping; Chen, Yi; Goodnow, Robert; Gruber, Felix; Kowalczyk, Agnieszka; Petersen, Ann; Naderi-Oboodi, Goli; Orzechowski, Lucja; Strebel, Quentin published 《DNA Compatible Multistep Synthesis and Applications to DNA Encoded Libraries》.Bioconjugate Chemistry published the findings.Reference of 2,4,6-Trichloropyrimidine The information in the text is summarized as follows:

Complex mixtures of DNA encoded small mols. may be readily interrogated via high-throughput sequencing. These DNA encoded libraries (DELs) are commonly used to discover mols. that interact with pharmaceutically relevant proteins. The chem. diversity displayed by the library is key to successful discovery of potent, novel, and drug-like chem. matter. The small mol. moieties of DELs are generally synthesized though a multistep process, and each chem. step is accomplished while it is simultaneously attached to an encoding DNA oligomer. Hence, library chem. diversity is often limited to DNA compatible synthetic reactions. Herein, protocols for 24 reactions are provided that have been optimized for high-throughput production of DELs. These protocols detail the multistep synthesis of benzimidazoles, imidazolidinones, quinazolinones, isoindolinones, thiazoles, and imidazopyridines. Addnl., protocols are provided for a diverse range of useful chem. reactions including BOC deprotection (under pH neutral conditions), carbamylation, and Sonogashira coupling. Last, step-by-step protocols for synthesizing functionalized DELs from trichloronitropyrimidine and trichloropyrimidine scaffolds are detailed. After reading the article, we found that the author used 2,4,6-Trichloropyrimidine(cas: 3764-01-0Reference of 2,4,6-Trichloropyrimidine)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.Reference of 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Ryabova, O. B.; Khmel’nitskaya, E. Yu.; Makarov, V. A.; Alekseeva, L. M.; Grigor’ev, N. B.; Granik, V. G. published their research in Russian Chemical Bulletin on December 31 ,2005. The article was titled 《4-[(Dialkylthiocarbamoyl)thio]-5-nitropyrimidines as new potential nitric oxide donors》.Name: 4-Chloro-6-methoxy-5-nitropyrimidine The article contains the following contents:

On heating at pH 6.86, the title compounds (I; X = H, Me; R = OMe, OPh, NHMe, NMe2, etc.; NR1R2 = 1-pyrrolidinyl, piperidino, hexahydro-1-azepinyl, NMeEt, etc.) are transformed into dithiolopyrimidines, which are either oxidized to bis(dialkylthiocarbamoylpyrimidin-5-yl) disulfides (II; n = 1, 2, 3) or converted to aminonitropyrimidines (III; n = 1, 2) with carbon disulfide elimination. The direction of the reaction is determined by the nature of the substituent in position 2 of the pyrimidine and the bulk of the thiocarbamate substituent. Mechanistic schemes for these processes are proposed. Refluxing most I in EtOH containing a phosphate buffer (pH 6.86) resulted in degradation to form nitrite anion, a measure of NO-donor ability. In the part of experimental materials, we found many familiar compounds, such as 4-Chloro-6-methoxy-5-nitropyrimidine(cas: 52854-14-5Name: 4-Chloro-6-methoxy-5-nitropyrimidine)

4-Chloro-6-methoxy-5-nitropyrimidine(cas: 52854-14-5) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Name: 4-Chloro-6-methoxy-5-nitropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia