Day: October 20, 2022

Chen, Xing; Yan, Yaoyao; Zhang, Zhaoyan; Zhang, Faming; Liu, Mingming; Du, Leran; Zhang, Haixia; Shen, Xiaobao; Zhao, Dahai; Shi, Jing Bo; Liu, Xinhua published their research in Journal of Medicinal Chemistry in 2021. The article was titled 《Discovery and In Vivo Anti-inflammatory Activity Evaluation of a Novel Non-peptidyl Non-covalent Cathepsin C Inhibitor》.Application of 3934-20-1 The article contains the following contents:

Cathepsin C (Cat C) participates in inflammation and immune regulation by affecting the activation of neutrophil serine proteases (NSPs). Therefore, cathepsin C is an attractive target for treatment of NSP-related inflammatory diseases. Here, the complete discovery process of the first potent “”non-peptidyl non-covalent cathepsin C inhibitor”” was described with hit finding, structure optimization, and lead discovery. Starting with hit 14, structure-based optimization and structure-activity relationship study were comprehensively carried out, and lead compound 54 was discovered as a potent drug-like cathepsin C inhibitor both in vivo and in vitro. Also, compound 54 (with cathepsin C Enz IC50 = 57.4 nM) exhibited effective anti-inflammatory activity in an animal model of chronic obstructive pulmonary disease. These results confirmed that the non-peptidyl and non-covalent derivative could be used as an effective cathepsin C inhibitor and encouraged us to continue further drug discovery on the basis of this finding. In the experiment, the researchers used many compounds, for example, 2,4-Dichloropyrimidine(cas: 3934-20-1Application of 3934-20-1)

2,4-Dichloropyrimidine(cas: 3934-20-1) 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.Application of 3934-20-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2022,Skaisgiris, Rokas; Serevicius, Tomas; Dodonova, Jelena; Banevicius, Dovydas; Kazlauskas, Karolis; Tumkevicius, Sigitas; Jursenas, Saulius published an article in Journal of Luminescence. The title of the article was 《Tuning of HOMO-LUMO localization for achieving thermally activated delayed fluorescence》.Safety of 4,6-Dichloropyrimidine The author mentioned the following in the article:

High emission yield and rapid reverse intersystem crossing are essential for efficient thermally activated delayed fluorescence (TADF) compounds In this paper, we show that efficient TADF can be achieved by enhancing the localization of HOMO and LUMO in carbazole-pyrimidine compounds with rather flat mol. structure. Simple carbazole-pyrimidine Cbz-PYR was selected as a reference compound due to the pronounced room-temperature phosphorescence activity. The subsequent modifications of carbazole and pyrimidine units with diphenylamine and Ph fragments resulted in weakened HOMO-LUMO communication, leading to the minimized singlet-triplet energy gap of only 111 meV. Due to the rather flat mol. geometry, TADF compounds showed remarkable radiative decay rate reaching 4.6 x 107 s-1 for the most efficient TADF-active carbazole-pyrimidine compound dCbz-pPYR, followed by high emission yield of 0.75. Efficient green electroluminescence with peak EQE of 18.3%. was shown for OLED device with dCbz-pPYR emitter. The experimental part of the paper was very detailed, including the reaction process of 4,6-Dichloropyrimidine(cas: 1193-21-1Safety of 4,6-Dichloropyrimidine)

4,6-Dichloropyrimidine(cas: 1193-21-1) 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 4,6-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Utilizing triazine/pyrimidine acceptor and carbazole-triphenylamine donor based bipolar novel host materials for highly luminescent green phosphorescent OLEDs with lower efficiency roll-off》 was written by Braveenth, Ramanaskanda; Ahn, Dae Hyun; Han, Ji-Hun; Moon, Ji Su; Kim, Si Woo; Lee, Hyuna; Qiong, Wu; Kwon, Jang Hyuk; Chai, Kyu Yun. Safety of 2,4,6-TrichloropyrimidineThis research focused ontriazine pyrimidine acceptor carbazole triphenylamine donor host material; host material luminescent green phosphorescent efficiency. The article conveys some information:

In this work, two novel bipolar host materials were designed, synthesized and applied in green phosphorescent based OLEDs. Both the host materials, 4-(2-(4,6-diphenyl-1,3,5-triazin-2-yl)-9H-carbazol-9-yl)-N,N-diphenylaniline (TRZ 1) and 4-(2-(4,6-diphenylpyrimidin-2-yl)-9H-carbazol-9-yl)-N,N-diphenylaniline (PYR 1) exhibited high thermal stability, with decomposition temperatures of 425 °C and 400 °C, resp. The triplet energy of PYR 1 (2.63 eV) was higher than that of TRZ 1 (2.44 eV), and facilitated suitable energy transfer to the green dopant. The PYR 1 based green device demonstrated an excellent maximum current efficiency of 48.7 cd/A and external quantum efficiency of 16.4%. Interestingly, the green device with PYR 1 showed an outstanding brightness of 95,870 cd/m2, which is three times greater than that of the reference CBP based device (31,370 cd/m2). The bipolar host PYR 1 is a promising material for high luminescent and low efficiency roll off applications, especially for green PhOLEDs. In the part of experimental materials, we found many familiar compounds, such as 2,4,6-Trichloropyrimidine(cas: 3764-01-0Safety 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.Safety of 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 1972,Acta Biochimica Polonica included an article by Kazimierczuk, Z.; Lipski, M.; Shugar, D.. Recommanded Product: 6297-80-9. The article was titled 《Intermediates in the synthesis of purines and pteridines. Selective hydrolysis of chloropyrimidines》. The information in the text is summarized as follows:

Alk. hydrolysis of 2,4,6-trichloropyrimidine gave 4,6-dichloro-2-hydroxypyrimidine (I), which gave 6-chlorouracil on acid hydrolysis. Treatment of I with NH3 in anhydrous EtOH gave 4,6-diamino-2-hydroxypyrimidine, but Me2NH in anhydrous EtOH gave 4,6-bis(methylamino)-2-hydroxypyrimidine. Alk. hydrolysis of 2,4-dichloropyrimidine gave 4-chloro-2-hydroxypyrimidine (II), which reacted with NH3 in anhydrous EtOH to give cytosine. Treatment of II with Na and anhydrous EtOH gave 4-ethoxy-2-hydroxypyrimidine. The experimental process involved the reaction of 4,6-Dichloropyrimidin-2(1H)-one(cas: 6297-80-9Recommanded Product: 6297-80-9)

4,6-Dichloropyrimidin-2(1H)-one(cas: 6297-80-9) 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.Recommanded Product: 6297-80-9

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

The author of 《2-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid with inbuilt β-N-hydroxy-γ-keto-acid pharmacophore as HCV NS5B polymerase inhibitors》 were Deore, R. R.; Chen, G. S.; Chen, C.-S.; Chang, P.-T.; Chuang, M.-H.; Chern, T.-R.; Wang, H.-C.; Chern, J.-W.. And the article was published in Current Medicinal Chemistry in 2012. Computed Properties of C11H8N2O4 The author mentioned the following in the article:

The inbuilt 2-N-hydroxy-1-oxo-3-carboxylic acid of isoquinolone was designed as pyrophosphate mimic for hepatitis C NS5B polymerase. Various 2-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid derivatives 11a-p were synthesized and evaluated as HCV NS5B polymerase inhibitors. Compound 11c exhibited moderate inhibitory potency based on the inorganic pyrophosphate generation (IC50 = 9.5 μM) and based on NTP incorporation by NS5B enzyme (IC50 = 5.9 μM). Compound 11c demonstrated antiviral activity (EC50 = 15.7 μM) and good selectivity in HCV genotype 1b replicon Ava.5 cells. Compound 11c reduced the interaction of NTP to NS5B polymerase. Docking model showed that 11c situated in similar orientation to the bound uridine triphosphate in the active site of NS5B polymerase. As a result, 2-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid was disclosed as a novel inbuilt β-N-hydroxy-γ-keto-acid pharmacophore for HCV NS5B polymerase inhibitors. In the part of experimental materials, we found many familiar compounds, such as 5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2Computed Properties of C11H8N2O4)

5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2) belongs to pyrimidine. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. Computed Properties of C11H8N2O4

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

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

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

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