Day: October 19, 2022

In 2017,Thorarensen, Atli; Dowty, Martin E.; Banker, Mary Ellen; Juba, Brian; Jussif, Jason; Lin, Tsung; Vincent, Fabien; Czerwinski, Robert M.; Casimiro-Garcia, Agustin; Unwalla, Ray; Trujillo, John I.; Liang, Sidney; Balbo, Paul; Che, Ye; Gilbert, Adam M.; Brown, Matthew F.; Hayward, Matthew; Montgomery, Justin; Leung, Louis; Yang, Xin; Soucy, Sarah; Hegen, Martin; Coe, Jotham; Langille, Jonathan; Vajdos, Felix; Chrencik, Jill; Telliez, Jean-Baptiste published 《Design of a Janus Kinase 3 (JAK3) Specific Inhibitor 1-((2S,5R)-5-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one (PF-06651600) Allowing for the Interrogation of JAK3 Signaling in Humans》.Journal of Medicinal Chemistry published the findings.Synthetic Route of C6H3Cl2N3 The information in the text is summarized as follows:

Significant work has been dedicated to the discovery of JAK kinase inhibitors resulting in several compounds entering clin. development and two FDA approved NMEs. However, despite significant effort during the past two decades, identification of highly selective JAK3 inhibitors has eluded the scientific community. A significant effort within the research organization has resulted in the identification of the first orally active JAK3 specific inhibitor, which achieves JAK isoform specificity through covalent interaction with a unique JAK3 residue Cys-909. The relatively rapid resynthesis rate of the JAK3 enzyme presented a unique challenge in the design of covalent inhibitors with appropriate pharmacodynamics properties coupled with limited unwanted off-target reactivity. This effort resulted in the identification of PF-06651600 I, a potent and low clearance compound with demonstrated in vivo efficacy. The favorable efficacy and safety profile of this specific JAK3 inhibitor I led to its evaluation in several human clin. studies. In the experiment, the researchers used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Synthetic Route of C6H3Cl2N3)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) 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. Synthetic Route of C6H3Cl2N3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《Early Process Development of an Irreversible Epidermal Growth Factor Receptor (EGFR) T790 M Inhibitor》 were Tao, Yong; Keene, Nandell F.; Wiglesworth, Kristin E.; Sitter, Barbara; McWilliams, J. Christopher. And the article was published in Organic Process Research & Development in 2019. Electric Literature of C6H3Cl2N3 The author mentioned the following in the article:

The original synthesis of the irreversible epidermal growth factor receptor (EGFR) T790 M inhibitor 1 (I) was enabled by successful application of ammonium hydroxide to cleanly cleave the N-hydroxymethyl group and by development of high yielding conditions for the subsequent amidation reaction. Furthermore, a protection-free and regioselective new synthetic route was developed that shortened the synthesis from the original 8 steps to 6 steps and improved the overall yield from 5% to 34% on scale. Crystallizations of 1 and intermediates were correspondingly developed to control the quality en route. After reading the article, we found that the author used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Electric Literature of C6H3Cl2N3)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Electric Literature of C6H3Cl2N3They 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

The author of 《Process Development and Scale Up of a Selective JAK3 Covalent Inhibitor PF-06651600》 were Tao, Yong; McWilliams, J. Christopher; Wiglesworth, Kristin E.; Girard, Kevin P.; Makowski, Teresa M.; Sach, Neal W.; Mustakis, Jason G.; Mehta, Ruchi; Trujillo, John I.; Chen, Xiaofeng; Li, Tangqing; Shi, Feng; Xie, Chengfu; Zhang, Qing. And the article was published in Organic Process Research & Development in 2019. Safety of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine The author mentioned the following in the article:

A scalable process for PF-06651600 was developed through successful enabling of the first generation synthesis. The synthesis highlights include the following: (1) replacement of costly PtO2 with a less expensive 5% Rh/C catalyst for a pyridine hydrogenation, (2) identification of a diasteromeric salt crystallization to isolate the enantiomerically pure cis-isomer directly from a racemic mixture of cis/trans isomers, (3) a high yielding amidation via Schotten-Baumann conditions, and (4) critical development of a reproducible crystallization procedure for a stable crystalline salt 1-((2S,5R)-5-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one p-Toluenesulfonate, which is suitable for long-term storage and tablet formulation. All chromatog. purifications, including two chiral SFC chromatog. separations, were eliminated. Combined with other improvements in each step of the synthesis, the overall yield was increased from 5% to 14%. Several multikilogram batches of the API were delivered to support clin. studies. In the experiment, the researchers used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Safety of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine)

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. Safety of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Design, synthesis, and anticancer evaluation of acetamide and hydrazine analogues of pyrimidine》 was published in Journal of Heterocyclic Chemistry in 2020. These research results belong to Khazir, Jabeena; Mir, Bilal Ahmad; Chashoo, Gousia; Maqbool, Tariq; Riley, Darren; Pilcher, Lynne. Product Details of 1193-21-1 The article mentions the following:

A library of acetamide I [R = 2-hydroxyethylamino, 1-pyrrolidinyl, N-morpholinyl, etc.] and hydrazine II [R1 = 1-pyrrolidinyl, 1-piperidinyl, N-morpholinyl, 4-propanoyl-1-piperidyl; R2 = H, 2-Br, 3,4-di-MeO, etc.] analogs were generated on the pyrimidine ring through a multistep reaction starting from 5-nitro-pyrimidine-4,6-diol and pyrimidine-4,6-diol, resp. The synthesized analogs I and II were screened for in-vitro cytotoxic activity against various human cancer cell lines like HCT-1 and HT-15 (colon), MCF-7(breast), PC-3 (prostrate), SF268 (CNS) using MTT method. From the bioassay results, it was observed that even though many of the synthesized derivatives I and II exhibited a good potency against various screened cancer cell lines, compound I [R = 1-piperidinyl] showed potent anticancer activity on all the tested cancer cell lines with IC50 value of 0.36μM on CNS cell line and 1.6μM on HT-21 cell line, and compound II [R1 = N-morpholinyl, R2 = 2-OH] showed potent activity against three tested cancer cell lines with IC50 value of 0.76μM on HT-29 cell line, 2.6μM on HCT-15 and 3.2μM on MCF-7 cell line. After reading the article, we found that the author used 4,6-Dichloropyrimidine(cas: 1193-21-1Product Details of 1193-21-1)

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.Product Details of 1193-21-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《An efficient synthesis of designed 4-thiazolidinone fused pyrimidine derivatives as potent antimicrobial agents》 was written by Patel, Janki J.; Morja, Mayur I.; Chikhalia, Kishor H.. Name: 2,4,6-Trichloropyrimidine And the article was included in Journal of Heterocyclic Chemistry in 2020. The article conveys some information:

A novel series of hybrid 2-substituted [(pyrimidin-2-yl)hydrazinyl]thiazolidin-4-one derivatives I [R = H, 3-Cl, 4-NO2, etc.] was synthesized via aromatic nucleophilic displacement of chlorine atoms/intermol. cyclization of 2-chloro-N’-[6-morpholino-4-[(substituted-phenyl)amino]pyrimidin-2-yl]acetohydrazides II with ammonium thiocyanate. I were evaluated for their antibacterial and antifungal activities against various strains of bacteria and fungi. Structure-activity relationship and HOMO-LUMO studies were also carried out for confirming structure-biol. activity. Thus, these studies suggested that hydrazinyl pyrimidine derivatives I bearing a thiazolidinone moiety are interesting scaffolds for the development of novel antimicrobial agents. After reading the article, we found that the author used 2,4,6-Trichloropyrimidine(cas: 3764-01-0Name: 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.Name: 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Introducing rigid pyrimidine ring to improve the mechanical properties and thermal-oxidative stabilities of phthalonitrile resin》 was written by Yang, Kaixiong; Chen, Xinggang; Zhang, Zhenjiang; Yu, Xiaoyan; Naito, Kimiyoshi; Zhang, Qingxin. Formula: C4H2Cl2N2 And the article was included in Polymers for Advanced Technologies in 2020. The article conveys some information:

In this study, a novel phthalonitrile monomer containing pyrimidine ring, 4,6-bis[3-(3,4-dicyanophenoxy)phenoxy]pyrimidine (BCPM), was successfully synthesized by nucleophilic substitution reaction with resorcinol, 4,6-dichloropyrimidine and 4-nitrophthalonitrile. The BCPM monomer was cured by different temperature programs with 4-(aminophenoxy)phthalonitrile (APPH) as catalyst to give the polymers. The mol. structures of the BCPM monomer and the polymers were investigated by Fourier transform IR (FTIR) spectroscopy and NMR (NMR) spectroscopy. Differential scanning calorimetric (DSC) anal. was performed to study the processability of the BCPM monomer, which showed a wide processing window of about 117°. The mech. properties and thermal-oxidative stability of the polymer were characterized by dynamic mech. anal. (DMA) and thermogravimetric anal. (TGA), resp., which indicated that the polymers exhibited excellent storage modulus, high glass transition temperature over 400°, and outstanding thermal stability. The polymers also have low water absorption capacity and are suitable for humid environments. In the experiment, the researchers used 4,6-Dichloropyrimidine(cas: 1193-21-1Formula: C4H2Cl2N2)

4,6-Dichloropyrimidine(cas: 1193-21-1) 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.Formula: C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Yang, Fan; Su, Huilin; Deng, Ji; Mou, Luohe; Wang, Huali; Li, Rong; Dai, Qing-Qing; Yan, Yu-Hang; Qian, Shan; Wang, Zhouyu; Li, Guo-Bo; Yang, Lingling published an article in 2021. The article was titled 《Discovery of new human Sirtuin 5 inhibitors by mimicking glutaryl-lysine substrates》, and you may find the article in European Journal of Medicinal Chemistry.COA of Formula: C4H2Cl2N2 The information in the text is summarized as follows:

Human sirtuin 5 (SIRT5) plays pivotal roles in metabolic pathways and other biol. processes, and is involved in several human diseases including cancer. Development of new potent and selective SIRT5 inhibitors is currently desirable to provide potential therapeutics for related diseases. Herein, we report a series of new 3-thioureidopropanoic acid derivatives, which were designed to mimic the binding features of SIRT5 glutaryl-lysine substrates. Structure-activity relationship studies revealed several compounds with low micromolar inhibitory activities to SIRT5. Computational and biochem. studies indicated that these compounds exhibited competitive SIRT5 inhibition with respect to the glutaryl-lysine substrate rather than NAD cofactor. Moreover, they showed high selectivity for SIRT5 over SIRT1-3 and 6 and could stabilize SIRT5 proteins as revealed by thermal shift analyses. This work provides an effective substrate-mimicking strategy for future inhibitor design, and offers new inhibitors to investigate their therapeutic potentials in SIRT5-associated disease models. After reading the article, we found that the author used 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

Makova, Barbara; Mik, Vaclav; Liskova, Barbora; Gonzalez, Gabriel; Vitek, Dominik; Medvedikova, Martina; Monfort, Beata; Rucilova, Veronika; Kadlecova, Alena; Khirsariya, Prashant; Gandara Barreiro, Zoila; Havlicek, Libor; Zatloukal, Marek; Soural, Miroslav; Paruch, Kamil; D’Autreaux, Benoit; Hajduch, Marian; Strnad, Miroslav; Voller, Jiri published an article in 2021. The article was titled 《Cytoprotective activities of kinetin purine isosteres》, and you may find the article in Bioorganic & Medicinal Chemistry.Electric Literature of C6H3Cl2N3 The information in the text is summarized as follows:

Kinetin (N6-furfuryladenine), a plant growth substance of the cytokinin family, has been shown to modulate aging and various age-related conditions in animal models. Here, the authors report the synthesis of kinetin isosteres with the purine ring replaced by other bicyclic heterocycles, and the biol. evaluation of their activity in several in vitro models related to neurodegenerative diseases. The findings indicate that kinetin isosteres protect Friedreichs ataxia patient-derived fibroblasts against glutathione depletion, protect neuron-like SH-SY5Y cells from glutamate-induced oxidative damage, and correct aberrant splicing of the ELP1 gene in fibroblasts derived from a familial dysautonomia patient. Although the mechanism of action of kinetin derivatives remains unclear, this data suggest that the cytoprotective activity of some purine isosteres is mediated by their ability to reduce oxidative stress. Further, the studies of permeation across artificial membrane and model gut and blood-brain barriers indicate that the compounds are orally available and can reach the central nervous system. Overall, the data demonstrate that isosteric replacement of the kinetin purine scaffold is a fruitful strategy for improving known biol. activities of kinetin and discovering novel therapeutic opportunities. In the part of experimental materials, we found many familiar compounds, such as 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Electric Literature of C6H3Cl2N3)

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. Electric Literature of C6H3Cl2N3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2022,Yuan, Kai; Kuang, Wenbin; Chen, Weijiao; Ji, Minghui; Min, Wenjian; Zhu, Yasheng; Hou, Yi; Wang, Xiao; Li, Jiaxing; Wang, Liping; Yang, Peng published an article in European Journal of Medicinal Chemistry. The title of the article was 《Discovery of novel and orally bioavailable CDK 4/6 inhibitors with high kinome selectivity, low toxicity and long-acting stability for the treatment of multiple myeloma》.Application of 3934-20-1 The author mentioned the following in the article:

Multiple myeloma (MM) ranks second in malignant hematopoietic cancers, and the most common anti-MM drugs easily generate resistance. CDK4/6 have been validated to play determinant roles in MM, but no remarkable progress has been obtained from clin. trials of CDK4/6 inhibitors for MM. To discover novel CDK6 inhibitors with better potency and high druggability, structure-based virtual screening was conducted to identify compound I. Further chem. optimization afforded a better derivative, compound II, which exhibited strong inhibition of CDK4/6 and showed high selectivity over 360+ kinases, including homologous CDKs. The in vivo evaluation demonstrated that compound II possessed low toxicity (LD50 > 10,000 mg/kg), favorable bioavailability (F% = 51%), high metabolic stability (t1/2 > 24 h) and strong anti-MM potency. In summary, we discovered a novel CDK4/6 inhibitor bearing favorable drug-like properties and offered a great candidate for MM preclin. studies. The experimental part of the paper was very detailed, including the reaction process of 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

Name: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidineIn 2012 ,《Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization》 appeared in European Journal of Medicinal Chemistry. The author of the article were Xie, Hui; Zeng, Lili; Zeng, Shaogao; Lu, Xin; Zhang, Guicheng; Zhao, Xin; Cheng, Na; Tu, Zhengchao; Li, Zhiyuan; Xu, Hongjiang; Yang, Ling; Zhang, Xiquan; Huang, Min; Zhao, Junling; Hu, Wenhui. The article conveys some information:

We previously reported a highly potent DPP-IV inhibitor 6 with low in vivo efficacy. While trying to maintain consistent in vitro and in vivo biol. activity, we initiated a pharmacokinetic property-driven optimization to improve the metabolic stability and permeability of inhibitor 6. A simple scaffold replacement of thienopyrimidine with pyrrolopyrimidine (21a) led to significantly improved metabolic stability (4% vs. 65% remaining). Further modification of the pyrrolopyrimidine scaffold to produce compound 21j resulted in much better oral bioavailability than 6. Importantly, compound 21j exhibits greater in vivo efficacy than does 6 and Alogliptin and is worthy of further development.2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Name: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine) was used in this study.

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. Name: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia