Day: October 21, 2022

In 2014,Gehringer, Matthias; Forster, Michael; Pfaffenrot, Ellen; Bauer, Silke M.; Laufer, Stefan A. published 《Novel hinge-binding motifs for janus kinase 3 inhibitors: a comprehensive structure-activity relationship study on tofacitinib bioisosteres》.ChemMedChem published the findings.Related Products of 90213-66-4 The information in the text is summarized as follows:

The Janus kinases (JAKs) are a family of cytosolic tyrosine kinases crucially involved in cytokine signaling. JAKs have been demonstrated to be valid targets in the treatment of inflammatory and myeloproliferative disorders, and two inhibitors, tofacitinib and ruxolitinib, recently received their marketing authorization. Despite this success, selectivity within the JAK family remains a major issue. Both approved compounds share a common 7H-pyrrolo[2,3-d]pyrimidine hinge binding motif, and little is known about modifications tolerated at this heterocyclic core. In the current study, a library of tofacitinib bioisosteres was prepared and tested against JAK3. The compounds possessed the tofacitinib piperidinyl side chain, whereas the hinge binding motif was replaced by a variety of heterocycles mimicking its pharmacophore. In view of the promising expectations obtained from mol. modeling, most of the compounds proved to be poorly active. However, strategies for restoring activity within this series of novel chemotypes were discovered and crucial structure-activity relationships were deduced. The compounds presented may serve as starting point for developing novel JAK inhibitors and as a valuable training set for in silico models. In the experimental materials used by the author, we found 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Related Products of 90213-66-4)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) 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. Related Products of 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2022,Han, Shuwen; Zhou, Wei; Zhuang, Chunlin; Chen, Fener published an article in Bioorganic Chemistry. The title of the article was 《Structure-Based design of Marine-derived Meridianin C derivatives as glycogen synthase kinase 3β inhibitors with improved oral bioavailability: From aminopyrimidyl-indoles to the sulfonyl analogues》.COA of Formula: C4H2Cl2N2 The author mentioned the following in the article:

Glycogen synthase kinase 3β (GSK-3β) has become an attractive target for the treatment of diabetes. Compound I is an indole-based GSK-3β inhibitor designed from the Meridianin C, a marine natural product (MNP) isolated from Aplidium meridianum. However, this compound has a moderate inhibitory activity toward GSK-3β (IC50 = 24.4 μM), moderate glucose uptake (38%), and especially, a low oral bioavailability (F = 11.4%). In the present study, applying the structure-based design strategy, a series of derivatives modified on the indole moiety were synthesized based on the lead compound I, followed by evaluating their cytotoxic activity, antihyperglycemic activity, and kinase inhibitory activity. Among this series, compound 6x with a sulfonyl group displayed the highest glucose uptake (83.5%) in muscle L6 cells, showing much higher inhibitory activity against GSK-3β (IC50 = 5.25 μM). Mol. docking indicated that compound 6x was properly inserted into the ATP-binding binding pocket of GSK-3β with a higher docking score (-8.145 kcal/mol) compared with that of compound I (-6.950 kcal/mol), interpreting the higher kinase inhibitory activity toward GSK-3β. Remarkably, compound 6x showed favorable drug-like properties, including significantly better oral bioavailability (F = 47.4%) and no two-week acute toxicity at a dose of 1g/kg. Our findings suggest that these MNP-derived sulfonyl indole derivatives could be used as lead compounds for the development of anti-hyperglycemic drugs. The experimental process involved the reaction of 2,4-Dichloropyrimidine(cas: 3934-20-1COA of Formula: C4H2Cl2N2)

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.COA of Formula: C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Formula: C11H6ClF3N2On March 31, 2018, Hu, Wei-Kang; Li, Si-Hua; Ma, Xiu-Fang; Zhou, Shi-Xiong; Zhang, Qian-feng; Xu, Jing-Yu; Shi, Peng; Tong, Bi-Hai; Fung, Man-Keung; Fu, Lianshe published an article in Dyes and Pigments. The article was 《Blue-to-green electrophosphorescence from iridium(III) complexes with cyclometalated pyrimidine ligands》. The article mentions the following:

A series of 4, 6-disubstituted pyrimidine based iridium(III) complexes (1-5), has been synthesized with a simple method. Single X-ray structural analyses were conducted on 5 to reveal their coordination arrangement. These complexes exhibit almost single peak emission with the peak wavelength located in the range of 468-505 nm and quantum yields of over 75%. The relationship between photophys. properties and the substituent nature of the complexes was discussed by d. functional theory. Organic light-emitting diodes (OLEDs) were also fabricated using these complexes as dopants in 15 wt%. The green device based on 1 shows a maximum external quantum efficiency, current efficiency, and power efficiency of 9.7%, 46.5 cd A-1 and 29.0 lm W-1, resp., while the blue device based on 5 exhibits an external quantum efficiency of up to 14.5%, peak luminance efficiency of 28.0 cd A-1 and power efficiency of 19.5 lm W-1. Moreover, the Commission Internationale de L’Eclairage (CIE) coordinates of 5 are (0.15, 0.30) which is closer to blue emission than that of FIrpic. After reading the article, we found that the author used 4-Chloro-6-(4-(trifluoromethyl)phenyl)pyrimidine(cas: 659729-09-6Formula: C11H6ClF3N2)

4-Chloro-6-(4-(trifluoromethyl)phenyl)pyrimidine(cas: 659729-09-6) 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. Formula: C11H6ClF3N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 86443-51-8On May 31, 2017, Jarusiewicz, Jamie A.; Jeon, Jae Yoon; Connelly, Michele C.; Chen, Yizhe; Yang, Lei; Baker, Sharyn D.; Guy, R. Kiplin published an article in ACS Omega. The article was 《Discovery of a Diaminopyrimidine FLT3 Inhibitor Active against Acute Myeloid Leukemia》. The article mentions the following:

Profiling of the kinase-binding capabilities of an aminopyrimidine analog detected in a cellular screen of the St. Jude small-mol. collection led to the identification of a novel series of FMS-like tyrosine kinase 3 (FLT3) inhibitors. Structure-activity relationship studies led to the development of compounds exhibiting good potency against MV4-11 and MOLM13 acute myelogenous leukemia cells driven by FLT3, regardless of their FLT3 mutation status. In vitro pharmacol. profiling demonstrated that compound 5e shows characteristics suitable for further preclin. development. The experimental process involved the reaction of 2-Chloro-N-ethylpyrimidin-4-amine(cas: 86443-51-8Related Products of 86443-51-8)

2-Chloro-N-ethylpyrimidin-4-amine(cas: 86443-51-8) belongs to anime. Aniline, ethanolamines, and several other amines are major industrial commodities used in making rubber, dyes, pharmaceuticals, and synthetic resins and fibres and for a host of other applications. Most of the numerous methods for the preparation of amines may be broadly divided into two groups: (1) chemical reduction (replacement of oxygen with hydrogen atoms in the molecule) of members of several other classes of organic nitrogen compounds and (2) reactions of ammonia or amines with organic compounds.Related Products of 86443-51-8

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

De Abrew, K. Nadira; Shan, Yuqing K.; Wang, Xiaohong; Krailler, Jesse M.; Kainkaryam, Raghunandan M.; Lester, Cathy C.; Settivari, Raja S.; LeBaron, Matthew J.; Naciff, Jorge M.; Daston, George P. published an article in Toxicology. The title of the article was 《Use of connectivity mapping to support read across: A deeper dive using data from 186 chemicals, 19 cell lines and 2 case studies》.Application In Synthesis of 7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine The author mentioned the following in the article:

The authors previously demonstrated that the Connectivity Map (CMap) (Lamb et al., 2006) concept can be successfully applied to a predictive toxicol. paradigm to generate meaningful MoA-based connections between chems. (De Abrew et al., 2016). Here the authors expand both the chem. and biol. (cell lines) domain for the method and demonstrate two applications, both in the area of read across. In the first application the authors demonstrate CMap’s utility as a tool for testing biol. relevance of source chems. (analogs) during a chem. led read across exercise. In the second application CMap can be used to identify functionally relevant source chems. (analogs) for a structure of interest (SOI)/target chem. with minimal knowledge of chem. structure. Finally, the authors highlight four factors: promiscuity of chem., dose, cell line and timepoint as having significant impact on the output. The authors discuss the biol. relevance of these four factors and incorporate them into a work flow. The experimental part of the paper was very detailed, including the reaction process of 7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine(cas: 213743-31-8Application In Synthesis of 7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine)

7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine(cas: 213743-31-8) belongs to pyrimidine. 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 In Synthesis of 7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Kawakami, Hiroshi; Ebata, Takashi; Koseki, Koshi; Matsumoto, Katsuya; Matsushita, Hajime; Naoi, Yoshitake; Itoh, Kazuo published their research in Heterocycles on December 1 ,1991. The article was titled 《Synthesis of 2′,3′-didehydro-2′,3′-dideoxynucleosides utilizing coupling reactions between nucleic bases and phenylthio-substituted 2,3-dideoxyribose》.Formula: C17H16N2O5 The article contains the following contents:

Stereoselectivities in coupling reactions between silylated pyrimidine bases I (X = O, R = H, Me; X = NAc, R = H) and 3- or 2-α-phenylthio-2,3-dideoxyribose derivatives, e.g., II (R1 = Cl, OAc) and III, resp., was examined In the former case, no stereoselectivities were observed when the coupling reactions were performed either with 1-chloro sugar in an SN2 mode or in the presence of Lewis acids as catalyst in an SN1 mode. Coupling reaction with 2-α-phenylthio-2,3-dideoxyribose in the presence of Lewis acids, especially SnCl4, proceeded with good stereoselectivity to give anomeric mixtures of nucleosides, e.g. IV, α:β = 1:9. All these nucleosides were converted to 2′,3′-didehydro-2′,3′-dideoxynucleosides, such as V, by oxidation to sulfoxides followed by thermal elimination of sulfenic acid. In the experimental materials used by the author, we found ((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate(cas: 122567-97-9Formula: C17H16N2O5)

((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate(cas: 122567-97-9) belongs to pyrimidine. 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: C17H16N2O5

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Wang, Xiao-Jun; Xu, Yibo; Zhang, Li; Krishnamurthy, Dhileepkumar; Senanayake, Chris H. published an article in Organic Letters. The title of the article was 《Mild Iodine-Magnesium Exchange of Iodoaromatics Bearing a Pyrimidine Ring with Isopropylmagnesium Chloride》.Reference of 3-(Pyrimidin-5-yl)benzaldehyde The author mentioned the following in the article:

(Iodo)arenes bearing a reactive pyrimidine ring underwent a clean iodine-magnesium exchange with isopropylmagnesium chloride in the presence of bis[2-(dimethylamino)ethyl] ether to provide the corresponding Grignard reagents. The presence of bis[2-(dimethylamino)ethyl] ether prevented reduction of the pyrimidine ring and addition by isopropylmagnesium chloride. As a result, the newly formed reactive Grignard reagents were allowed to react with electrophiles in a highly selective manner to afford adducts in excellent yields. In the experimental materials used by the author, we found 3-(Pyrimidin-5-yl)benzaldehyde(cas: 640769-70-6Reference of 3-(Pyrimidin-5-yl)benzaldehyde)

3-(Pyrimidin-5-yl)benzaldehyde(cas: 640769-70-6) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Reference of 3-(Pyrimidin-5-yl)benzaldehydeThey 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.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Feng, Da; Wei, Fenju; Sun, Yanying; Sharma, Prem Prakash; Zhang, Tao; Lin, Hao; Rathi, Brijesh; De Clercq, Erik; Pannecouque, Christophe; Kang, Dongwei; Zhan, Peng; Liu, Xinyong published their research in Chinese Chemical Letters in 2021. The article was titled 《Boronic acid-containing diarylpyrimidine derivatives as novel HIV-1 NNRTIs: Design, synthesis and biological evaluation》.Synthetic Route of C4H2Cl2N2 The article contains the following contents:

Drug resistance remains to be a serious problem with type I human immunodeficiency virus (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs). A series of novel boronic acid-containing diarylpyrimidine (DAPY) derivatives were designed via bioisosterism and scaffold-hopping strategies, taking advantage of the ability of a boronic acid group to form multiple hydrogen bonds. The target compounds were synthesized and evaluated for their anti-HIV activities and cytotoxicity in MT-4 cells. Compound 10j yielded the most potent activity and turned out to be a single-digit nanomolar inhibitor towards the HIV-1 IIIB [wild-type (WT) strain], L100I and K103N strains, with 50% effective concentration (EC50) values of 7.19-9.85 nmol/L. Moreover, 10j inhibited the double-mutant strain RES056 with an EC50 value of 77.9 nmol/L, which was 3.3-more potent than that of EFV (EC50 = 260 nmol/L) and comparable to that of ETR (EC50 = 32.2 nmol/L). 10J acted like classical NNRTIs with high affinity for WT HIV-1 reverse transcriptase (RT) with 50% inhibition concentration (IC50) value of 0.1837μmol/L. Furthermore, mol. dynamics simulation indicated that 10j was proposed as a promising mol. for fighting against HIV-1 infection through inhibiting RT activity. Overall, the results demonstrated that 10j could serve as a lead mol. for further modification to address virus-drug resistance. In the experimental materials used by the author, we found 2,4-Dichloropyrimidine(cas: 3934-20-1Synthetic Route of C4H2Cl2N2)

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.Synthetic Route of C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2022,Scattolin, Thomas; Gharbaoui, Tawfik; Chen, Cheng-yi published an article in Organic Letters. The title of the article was 《A Nucleophilic Deprotection of Carbamate Mediated by 2-Mercaptoethanol》.Synthetic Route of C4H2Cl2N2 The author mentioned the following in the article:

Carbamates, typically used for the protection of amines, including Cbz, Alloc, and Me carbamate, was readily deprotected by treatment with 2-mercaptoethanol in the presence of potassium phosphate tribasic in N,N-dimethylacetamide at 75°C. This nucleophilic deprotection protocol was superior to the standard hydrogenolysis or Lewis acid-mediated deprotection conditions for substrates bearing a functionality sensitive to these more traditional methods.2,4-Dichloropyrimidine(cas: 3934-20-1Synthetic Route of C4H2Cl2N2) was used in this study.

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.Synthetic Route of C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2022,Wang, Xinran; Zhang, Cai; Zhang, Xiangyu; Wang, Jiming; Zhao, Liyu; Zhao, Dongmei; Cheng, Maosheng published an article in Bioorganic Chemistry. The title of the article was 《Design, synthesis and biological evaluation of 2-aminopyrimidine-based LSD1 inhibitors》.Safety of 2,4-Dichloropyrimidine The author mentioned the following in the article:

AZD9291, with excellent pharmaceutical properties, has been reported to have certain LSD1 inhibitory activity. Therefore, we carried out structural optimization based on the AZD9291 skeleton to increase the LSD1 inhibitory potential of the compound Then, a series of 2-aminopyrimidine derivatives were designed and synthesized as LSD1 inhibitors, and their structure-activity relationships were studied. The most promising compound, X43, with an IC50 of 0.89 μM showed remarkable LSD1 selectivity not only to EGFRwt (>100-fold) but also to MAO-A/B (>50-fold). Further studies showed that X43 inhibited LSD1 activity and induced the apoptosis of A549 cells in a dose-dependent manner. Meanwhile, compound X43 showed a superior ability to inhibit the proliferation of A549 and THP-1 cells, with IC50 values of 1.62 μM and 1.21 μM, resp. Then, analyses of the stability of human liver microsomes, CYP inhibition and in vivo pharmacokinetics in rats showed that X43 had favorable profiles in vitro and in vivo and the potential for further study. Our findings suggested that a 2-aminopyrimidine-based LSD1 inhibitor deserves further investigation as a treatment for LSD1-overexpressing cancer.2,4-Dichloropyrimidine(cas: 3934-20-1Safety of 2,4-Dichloropyrimidine) was used in this study.

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