Day: October 17, 2022

Computed Properties of C11H18BN3O2On October 13, 2011 ,《Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer》 was published in ACS Medicinal Chemistry Letters. The article was written by Burger, Matthew T.; Pecchi, Sabina; Wagman, Allan; Ni, Zhi-Jie; Knapp, Mark; Hendrickson, Thomas; Atallah, Gordana; Pfister, Keith; Zhang, Yanchen; Bartulis, Sarah; Frazier, Kelly; Ng, Simon; Smith, Aaron; Verhagen, Joelle; Haznedar, Joshua; Huh, Kay; Iwanowicz, Ed; Xin, Xiaohua; Menezes, Daniel; Merritt, Hanne; Lee, Isabelle; Wiesmann, Marion; Kaufman, Susan; Crawford, Kenneth; Chin, Michael; Bussiere, Dirksen; Shoemaker, Kevin; Zaror, Isabel; Maira, Sauveur-Michel; Voliva, Charles F.. The article contains the following contents:

Phosphoinositide-3-kinases (PI3Ks) are important oncol. targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrimidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clin. trials for the treatment of cancer. In addition to this study using 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine, there are many other studies that have used 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine(cas: 944401-55-2Computed Properties of C11H18BN3O2) was used in this study.

4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine(cas: 944401-55-2) 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 C11H18BN3O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 1970,Chemical & Pharmaceutical Bulletin included an article by Nishigaki, Sadao; Senga, Keitaro; Aida, Kyoko; Takabatake, Toyomi; Yoneda, Fumio. Synthetic Route of C7H10N4O2. The article was titled 《Condensation reactions of ethyl ethoxymethylenecyanoacetate with amidines》. The information in the text is summarized as follows:

The pyrimidine synthesis from ethyl ethoxymethylenecyanoacetate (EMCE) and amidines is significantly influenced by the mole ratios of reacting components. In general the use of excess amidine gives better yields. Condensation of EMCE with excess acetamidine gives 4-hydroxy-2-methyl-5-pyrimidinecarbonitrile acetamidinate as the main product in good yield. Reaction between EMCE and excess 2-ethyl-2-thiopseudourea gives 2-ethylthio-4-hydroxy-5-pyrimidinecarbonitrile 2-ethyl-2-thiopseudoureate rather than 3-[3 – [[amino(ethylthio)methylene]amino] – 2 – cyanoacryloyl] – 2 – ethyl-2-thiopseudourea originally claimed. The condensation reactions of EMCE with other amidines such as guanidine and benzamidine have been studied.Ethyl 2,4-diaminopyrimidine-5-carboxylate(cas: 15400-54-1Synthetic Route of C7H10N4O2) was used in this study.

Ethyl 2,4-diaminopyrimidine-5-carboxylate(cas: 15400-54-1) belongs to anime. Halogenation, in which one or more hydrogen atoms of an amine is replaced by a halogen atom, occurs with chlorine, bromine, and iodine, as well as with some other reagents, notably hypochlorous acid (HClO). With primary amines the reaction proceeds in two stages, producing N-chloro- and N,N-dichloro-amines, RNHCl and RNCl2, respectively. With tertiary amines, an alkyl group may be displaced by a halogen.Synthetic Route of C7H10N4O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Seganish, W. Michael; Fischmann, Thierry O.; Sherborne, Brad; Matasi, Julius; Lavey, Brian; McElroy, William T.; Tulshian, Deen; Tata, James; Sondey, Christopher; Garlisi, Charles G.; Devito, Kristine; Fossetta, James; Lundell, Daniel; Niu, Xiaoda published their research in ACS Medicinal Chemistry Letters on August 13 ,2015. The article was titled 《Discovery and Structure Enabled Synthesis of 2,6-Diaminopyrimidin-4-one IRAK4 Inhibitors》.Computed Properties of C4H2Cl2N2O The article contains the following contents:

We report the identification and synthesis of a series of aminopyrimidin-4-one IRAK4 inhibitors. Through high throughput screening, an aminopyrimidine hit was identified and modified via structure enabled design to generate a new, potent, and kinase selective pyrimidin-4-one chemotype. This chemotype is exemplified by compound 16 (XVI), which has potent IRAK4 inhibition activity (IC50 = 27 nM) and excellent kinase selectivity (>100-fold against 99% of 111 tested kinases), and compound 31 (XXXI), which displays potent IRAK4 activity (IC50 = 93 nM) and good rat bioavailability (F = 42%). In addition to this study using 4,6-Dichloropyrimidin-2(1H)-one, there are many other studies that have used 4,6-Dichloropyrimidin-2(1H)-one(cas: 6297-80-9Computed Properties of C4H2Cl2N2O) was used in this study.

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.Computed Properties of C4H2Cl2N2O

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2019,Reaction Chemistry & Engineering included an article by Hone, Christopher A.; Boyd, Alistair; O’Kearney-McMullan, Anne; Bourne, Richard A.; Muller, Frans L.. Name: 2,4-Dichloropyrimidine. The article was titled 《Definitive screening designs for multistep kinetic models in flow》. The information in the text is summarized as follows:

Currently, rate-based understanding of organic reactions employed in the manufacture of active pharmaceutical ingredients (APIs) is often not obtained. In many cases, the generation of kinetic models is still seen as a specialised and time intensive activity, which can only be justified at certain instances in development. In this Communication, we report the application of a definitive screening design (DSD) in combination with reaction profiling for the efficient collection of kinetic data. The exptl. data (10 profiles, 40 exptl. data points) were collected within a short time frame (< 1 wk) within a continuous flow reactor. The data were fitted to a multistep kinetic model consisting of 3 fitted rate constants and 3 fitted activation energies. The approach is demonstrated on a Friedel-Crafts type reaction used in the synthesis of an important API. Our approach enables early identification of the sensitivity of product quality to parameter changes and the early use of process models to identify optimal process-equipment combinations in silico, significantly reducing development time and scale-up risks. After reading the article, we found that the author used 2,4-Dichloropyrimidine(cas: 3934-20-1Name: 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.Name: 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2019,Journal of Organic Chemistry included an article by Perez-Caaveiro, Cristina; Oliva, Maria Moreno; Lopez Navarrete, Juan T.; Perez Sestelo, Jose; Martinez, M. Montserrat; Sarandeses, Luis A.. Application In Synthesis of 4,6-Dichloropyrimidine. The article was titled 《Synthesis of D-A-A and D-A-D Pyrimidine π-Systems Using Triorganoindium Reagents: Optical, Vibrational, and Electrochemical Studies》. The information in the text is summarized as follows:

A series of donor-acceptor-acceptor (D-A-A) and donor-acceptor-donor (D-A-D) systems based on a pyrimidine π-spacer with various substituents at the C-2 position has been successfully prepared The synthesis involved site-selective palladium cross-coupling reactions of chloropyrimidines with triorganoindium reagents and proceed in good yields and with atom economy. 4-(N,N-Diphenylamino)phenyl was chosen as the donor group and thien-2-yl dicyanovinylene as the acceptor one. The optical, vibrational, electrochem., and d. functional theory (DFT) calculations of these mol. systems were analyzed, and exptl. values show the important role of the substituents at the C-2 position of the pyrimidine with stronger electron accepting ability, absorption in a wide range of UV/vis, acceptable fluorescence lifetime, and effective intramol. charge transfer (ICT) properties. The ICT was observed in both series by the bathochromic shift on increasing the polarity of the solvent. In addition, DFT calculations found lower lowest unoccupied MOs of D-A-A mols. that suggest good electron ejection and transportation, being good properties for their application in various organic optoelectronic devices. After reading the article, we found that the author used 4,6-Dichloropyrimidine(cas: 1193-21-1Application In Synthesis of 4,6-Dichloropyrimidine)

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.Application In Synthesis of 4,6-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《In situ click chemistry-based rapid discovery of novel HIV-1 NNRTIs by exploiting the hydrophobic channel and tolerant regions of NNIBP》 was published in European Journal of Medicinal Chemistry in 2020. These research results belong to Kang, Dongwei; Feng, Da; Jing, Lanlan; Sun, Yanying; Wei, Fenju; Jiang, Xiangyi; Wu, Gaochan; De Clercq, Erik; Pannecouque, Christophe; Zhan, Peng; Liu, Xinyong. Related Products of 3764-01-0 The article mentions the following:

HIV-1 RT has been considered as one of the most important targets for the development of anti-HIV-1 drugs for their well-solved three-dimensional structure and well-known mechanism of action. In this study, with HIV-1 RT as target, we used miniaturized parallel click chem. synthesis via CuAAC reaction followed by in situ biol. screening to discover novel potent HIV-1 NNRTIs. A 156 triazole-containing inhibitor library was assembled in microtiter plates and in millimolar scale. The enzyme inhibition screening results showed that 22 compounds exhibited improved inhibitory activity. Anti-HIV-1 activity results demonstrated that A3N19 effected the most potent activity against HIV-1 IIIB (EC50 = 3.28 nM) and mutant strain RES056 (EC50 = 481 nM). The mol. simulation anal. suggested that the hydrogen bonding interactions of A3N19 with the main chain of Lys101 and Lys104 was responsible for its potency. Overall, the results indicated the in situ click chem.-based strategy was rational and might be amenable for the future discovery of more potent HIV-1 NNRTIs.2,4,6-Trichloropyrimidine(cas: 3764-01-0Related Products of 3764-01-0) 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.Related Products of 3764-01-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Discovery of 2,4-diaminopyrimidine derivatives targeting p21-activated kinase 4: Biological evaluation and docking studies》 was published in Archiv der Pharmazie (Weinheim, Germany) in 2020. These research results belong to Qin, Qiaohua; Wu, Tianxiao; Yin, Wenbo; Sun, Yixiang; Zhang, Xiangyu; Wang, Ruifeng; Guo, Jing; Zhao, Dongmei; Cheng, Maosheng. Synthetic Route of C4HCl3N2 The article mentions the following:

In this study, novel 2,4-diaminopyrimidine derivatives targeting p21-activated kinase 4 (PAK4) were discovered and evaluated for their biol. activity against PAK4. Among the derivatives studied, promising compounds A2, B6, and B8 displayed the highest inhibitory activities against PAK4 (IC50 = 18.4, 5.9, and 20.4 nM, resp.). From the cellular assay, compound B6 exhibited the highest potency with an IC50 value of 2.533μM against A549 cells. Some compounds were selected for computational ADME (absorption, distribution, metabolism, and elimination) properties and mol. docking studies against PAK4. The detailed structure-activity relationship based on the biochem. activities and mol. docking studies were explored. According to the docking studies, compound B6 had the lowest docking score (docking energy: -7.593 kcal/mol). The mol. docking simulation indicated the binding mode between compound B6 and PAK4. All these results suggest compound B6 as a useful candidate for the development of a PAK4 inhibitor. In the experiment, the researchers used 2,4,6-Trichloropyrimidine(cas: 3764-01-0Synthetic Route of C4HCl3N2)

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.Synthetic Route of C4HCl3N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Mycobacterium tuberculosis Decaprenylphosphoryl-β-D-ribose Oxidase Inhibitors: Expeditious Reconstruction of Suboptimal Hits into a Series with Potent in Vivo Activity》 was written by Borthwick, Jennifer A.; Alemparte, Carlos; Wall, Ian; Whitehurst, Benjamin C.; Argyrou, Argyrides; Burley, Glenn; de Dios-Anton, Paco; Guijarro, Laura; Monteiro, Maria Candida; Ortega, Fatima; Suckling, Colin J.; Pichel, Julia Castro; Cacho, Monica; Young, Robert J.. Product Details of 1193-21-1 And the article was included in Journal of Medicinal Chemistry in 2020. The article conveys some information:

Decaprenylphosphoryl-β-D-ribose 2′-epimerase (DprE1) is an essential enzyme in Mycobacterium tuberculosis and has recently been studied as a potential drug target, with inhibitors progressing to clin. studies. Here we describe the identification of a novel series of morpholino-pyrimidine DprE1 inhibitors. These were derived from a phenotypic high-throughput screening (HTS) hit with suboptimal physicochem. properties. Optimization strategies included scaffold-hopping, synthesis, and evaluation of fragments of the lead compounds and property-focused optimization. The resulting optimized compounds had much improved physicochem. properties and maintained enzyme and cellular potency. These mols. demonstrated potent efficacy in an in vivo tuberculosis murine infection model. 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. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.Product Details of 1193-21-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Design, synthesis and evaluation of phenylthiazole and phenylthiophene pyrimidindiamine derivatives targeting the bacterial membrane》 was written by Fan, Tingting; Guo, Weikai; Shao, Ting; Zhou, Wenbo; Hu, Pan; Liu, Mingyao; Chen, Yihua; Yi, Zhengfang. Application of 3934-20-1 And the article was included in European Journal of Medicinal Chemistry in 2020. The article conveys some information:

A series of phenylthiazole and phenylthiophene pyrimidindiamine derivatives l [R1 = ethylamino, propylamino, butylamino, pyrrolidino; R2 = H, OMe, F, Cl, Br, etc.] were designed and synthesized by modifying the hit compound (N2-isobutyl-N4-((4-methyl-2-phenylthiazol-5-yl)methyl) pyrimidine-2,4-diamine) and their antibacterial activities were evaluated both in-vitro and in-vivo was reported. Among the tested compounds, compound I [R1 = isobutylamino; R2 = 3-bromo] displayed the best antibacterial activities, which was not only capable of inhibiting E. coli and S. aureus growth at concentrations as low as 2 and 3μg/mL in-vitro, but also efficacious in a mice model of bacteremia in vivo. Unlike conventional antibiotics, compound I [R1 = isobutylamino; R2 = 3-bromo] was elucidated to mainly destroy the bacterial cell membrane, with the dissipation of membrane potential and leakage of contents, ultimately leading to cell death. The destruction of cell structure was challenging to induce bacterial resistance, which suggested that compound I [R1 = isobutylamino; R2 = 3-bromo] was a promising alternatives to antibiotics against bacteria. 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. 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

Huang, Daowei; Yang, Jixia; Zhang, Qingwei; Wang, Guan; Zhang, Zixue; Zhang, Yue; Li, Jianqi published an article in 2021. The article was titled 《Structure-guided design and development of novel N-phenylpyrimidin-2-amine derivatives as potential c-Met inhibitors》, and you may find the article in European Journal of Medicinal Chemistry.Recommanded Product: 3934-20-1 The information in the text is summarized as follows:

The HGF/Met signaling pathway is over-expressed in many types of cancers and closely related to oncogenesis and metastasis. Thus, we developed novel N-phenylpyrimidin-2-amine derivatives to test their inhibitory activities towards c-Met kinase, and most of the compounds (15a-i, 15o-r, 20 and 34a-c) could inhibit the target with IC50 values from 550.8 nM to 15.0 nM. Subsequently, compound 15b, 15d, 15f, 15i, 15o, 15r, 20, 34a and 34b also showed high antiproliferative activities in c-Met sensitive tumor cell lines (PC-3, Panc-1, HepG2, HCT116 and Caki-1) with IC50 values from 0.53 to 1.37 μM. The lead compound 34a displayed outstanding c-Met inhibitory activity (IC50: 15.0 nM) and antiproliferative activities. Furthermore, 34a also performed favorable pharmacokinetic properties in mice (F%: 59.3) and an acceptable safety profile in preclin. studies. Further docking studies showed a common interaction of 34a with c-Met at the ATP-binding site, which indicated that 34a could be a potential candidate for c-Met inhibitors. In the part of experimental materials, we found many familiar compounds, such as 2,4-Dichloropyrimidine(cas: 3934-20-1Recommanded Product: 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.Recommanded Product: 3934-20-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia