Tag: 200-300

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

Formula: C6H6BrClN2On October 31, 1989 ,《Studies on pyrimidine derivatives. XLI. Palladium-catalyzed cross-coupling reaction of halopyrimidines with aryl- and vinyltributylstannanes》 appeared in Chemical & Pharmaceutical Bulletin. The author of the article were Kondo, Yoshinori; Watanabe, Ryo; Sakamoto, Takao; Yamanaka, Hiroshi. The article conveys some information:

The arylation of 2-, 4-, and 5-halopyrimidines with aryltributylstannanes in the presence of dichlorobis(triphenylphosphine)palladium was investigated with successful results. The reaction can be expanded to the synthesis of 2-, 4-, and 5-vinylpyrimidines with generality. Thus the reaction of pyrimidine I (R = Cl) with R1SnBu3 (R1 = Ph, 2-thienyl, vinyl) gave I (R = R1). After reading the article, we found that the author used 5-Bromo-4-chloro-2,6-dimethylpyrimidine(cas: 69696-35-1Formula: C6H6BrClN2)

5-Bromo-4-chloro-2,6-dimethylpyrimidine(cas: 69696-35-1) 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.Formula: C6H6BrClN2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Sutherlin, Daniel P.; Sampath, Deepak; Berry, Megan; Castanedo, Georgette; Chang, Zhigang; Chuckowree, Irina; Dotson, Jenna; Folkes, Adrian; Friedman, Lori; Goldsmith, Richard; Heffron, Tim; Lee, Leslie; Lesnick, John; Lewis, Cristina; Mathieu, Simon; Nonomiya, Jim; Olivero, Alan; Pang, Jodie; Prior, Wei Wei; Salphati, Laurent; Sideris, Steve; Tian, Qingping; Tsui, Vickie; Wan, Nan Chi; Wang, Shumei; Wiesmann, Christian; Wong, Susan; Zhu, Bing-Yan published an article on February 11 ,2010. The article was titled 《Discovery of (Thienopyrimidin-2-yl)aminopyrimidines as Potent, Selective, and Orally Available Pan-PI3-Kinase and Dual Pan-PI3-Kinase/mTOR Inhibitors for the Treatment of Cancer》, and you may find the article in Journal of Medicinal Chemistry.Application In Synthesis of 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine The information in the text is summarized as follows:

The PI3K/AKT/mTOR pathway has been shown to play an important role in cancer. Starting with compounds I and 2 (GDC-0941) as templates, (thienopyrimidin-2-yl)aminopyrimidines were discovered as potent inhibitors of PI3K or both PI3K and mTOR. Structural information derived from PI3Kγ-ligand cocrystal structures of I and 2 were used to design inhibitors that maintained potency for PI3K yet improved metabolic stability and oral bioavailability relative to I. The addition of a single Me group to the optimized 5 resulted in 21, which had significantly reduced potency for mTOR. The lead compounds 5 (GNE-493) and 21 (GNE-490) have good pharmacokinetic (PK) parameters, are highly selective, demonstrate knock down of pathway markers in vivo, and are efficacious in xenograft models where the PI3K pathway is deregulated. Both compounds were compared in a PI3Kα mutated MCF7.1 xenograft model and were found to have equivalent efficacy when normalized for exposure. In the experiment, the researchers used many compounds, for example, 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine(cas: 944401-55-2Application In Synthesis of 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine)

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

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Doherty, Elizabeth M.; Fotsch, Christopher; Bannon, Anthony W.; Bo, Yunxin; Chen, Ning; Dominguez, Celia; Falsey, James; Gavva, Narender R.; Katon, Jodie; Nixey, Thomas; Ognyanov, Vassil I.; Pettus, Liping; Rzasa, Robert M.; Stec, Markian; Surapaneni, Sekhar; Tamir, Rami; Zhu, Jiawang; Treanor, James J. S.; Norman, Mark H. published an article in Journal of Medicinal Chemistry. The title of the article was 《Novel Vanilloid Receptor-1 Antagonists: 2. Structure-Activity Relationships of 4-Oxopyrimidines Leading to the Selection of a Clinical Candidate》.Related Products of 659729-09-6 The author mentioned the following in the article:

A series of novel 4-oxopyrimidine TRPV1 antagonists was evaluated in assays measuring the blockade of capsaicin or acid-induced influx of calcium into CHO cells expressing TRPV1. The investigation of the structure-activity relationships in the heterocyclic A-region revealed the optimum pharmacophoric elements required for activity in this series and resulted in the identification of subnanomolar TRPV1 antagonists. The most potent of these antagonists were thoroughly profiled in pharmacokinetic assays. Optimization of the heterocyclic A-region led to the design and synthesis of 23 (I), a compound that potently blocked multiple modes of TRPV1 activation. Compound 23 was shown to be effective in a rodent “”on-target”” biochem. challenge model (capsaicin-induced flinch, ED50 = 0.33 mg/kg p.o.) and was antihyperalgesic in a model of inflammatory pain (CFA-induced thermal hyperalgesia, MED = 0.83 mg/kg, p.o.). Based on its in vivo efficacy and pharmacokinetic profile, compound 23 (N-{4-[6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzothiazol-2-yl}-acetamide; AMG 517) was selected for further evaluation in human clin. trials. The experimental part of the paper was very detailed, including the reaction process of 4-Chloro-6-(4-(trifluoromethyl)phenyl)pyrimidine(cas: 659729-09-6Related Products of 659729-09-6)

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. Related Products of 659729-09-6

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reference of 6-Bromothieno[2,3-d]pyrimidin-4(3H)-oneOn March 15, 2020, Miao, Zhuang; Sun, Yu-meng; Zhao, Lan-ying; Li, Yue-shan; Wang, Yi-fei; Nan, Jin-shan; Qiao, Ze-en; Li, Lin-li; Yang, Sheng-yong published an article in Bioorganic & Medicinal Chemistry Letters. The article was 《Discovery of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors》. The article mentions the following:

Herein, we report the discovery of a series of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors. Structure-activity relationship studies of these compounds led to the identification of the most potent compound, 3-(3-methoxybenzyl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)thieno[2,3-d]pyrimidin-4(3H)-one (8k), which showed IC50 values of 0.004μM and 0.001μM against ROCK I and ROCK II, resp. In vitro, 8k significantly reduced the phosphorylation level of ROCK downstream signaling protein and induce changes in cell morphol. and migration. Overall, this study provides a promising lead compound for drug discovery targeting ROCKs. After reading the article, we found that the author used 6-Bromothieno[2,3-d]pyrimidin-4(3H)-one(cas: 56844-40-7Reference of 6-Bromothieno[2,3-d]pyrimidin-4(3H)-one)

6-Bromothieno[2,3-d]pyrimidin-4(3H)-one(cas: 56844-40-7) 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. Reference of 6-Bromothieno[2,3-d]pyrimidin-4(3H)-one

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application In Synthesis of Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylateOn October 8, 2009 ,《RNase H Active Site Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase: Design, Biochemical Activity, and Structural Information》 was published in Journal of Medicinal Chemistry. The article was written by Kirschberg, Thorsten A.; Balakrishnan, Mini; Squires, Neil H.; Barnes, Tiffany; Brendza, Katherine M.; Chen, Xiaowu; Eisenberg, Eugene J.; Jin, Weili; Kutty, Nilima; Leavitt, Stephanie; Liclican, Albert; Liu, Qi; Liu, Xiaohong; Mak, John; Perry, Jason K.; Wang, Michael; Watkins, William J.; Lansdon, Eric B.. The article contains the following contents:

Pyrimidinol carboxylic acids were designed as inhibitors of HIV-1 RNase H function. These mols. can coordinate to two divalent metal ions in the RNase H active site. Inhibition of enzymic activity was measured in a biochem. assay, but no antiviral effect was observed Binding was demonstrated via a solid state structure of the isolated p15-Ec domain of HIV-1 RT showing inhibitor and two Mn(II) ions bound to the RNase H active site. The experimental part of the paper was very detailed, including the reaction process of Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6Application In Synthesis of Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate)

Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Application In Synthesis of Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylateThey 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

Degorce, Sebastien L.; Aagaard, Anna; Anjum, Rana; Cumming, Iain A.; Diene, Coura R.; Fallan, Charlene; Johnson, Tony; Leuchowius, Karl-Johan; Orton, Alexandra L.; Pearson, Stuart; Robb, Graeme R.; Rosen, Alan; Scarfe, Graeme B.; Scott, James S.; Smith, James M.; Steward, Oliver R.; Terstiege, Ina; Tucker, Michael J.; Turner, Paul; Wilkinson, Stephen D.; Wrigley, Gail L.; Xue, Yafeng published their research in Bioorganic & Medicinal Chemistry on December 1 ,2020. The article was titled 《Improving metabolic stability and removing aldehyde oxidase liability in a 5-azaquinazoline series of IRAK4 inhibitors》.Electric Literature of C11H17BN2O2 The article contains the following contents:

In this article, we report our efforts towards improving in vitro human clearance in a series of 5-azaquinazolines through a series of C4 truncations and C2 expansions. Extensive DMPK studies enabled us to tackle high Aldehyde Oxidase (AO) metabolism and unexpected discrepancies in human hepatocyte and liver microsomal intrinsic clearance. Our efforts culminated with the discovery of 5-azaquinazoline I, which also displayed exquisite selectivity for IRAK4, and showed synergistic in vitro activity against MyD88/CD79 double mutant ABC-DLBCL in combination with the covalent BTK inhibitor acalabrutinib. The experimental process involved the reaction of 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine(cas: 1370001-96-9Electric Literature of C11H17BN2O2)

4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine(cas: 1370001-96-9) 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.Electric Literature of C11H17BN2O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 62222-38-2On November 30, 1979 ,《Synthesis of methyl 5,6-dihydroxy-2-phenyl-4-pyrimidinecarboxylate: a corrected structure》 appeared in Journal of Heterocyclic Chemistry. The author of the article were Culbertson, Townley P.. The article conveys some information:

Pyrolysis of the adduct of H2NCPh:NOH and MeO2CCCCO2Me leads to Me 5,6-dihydroxy-2-phenyl-4-pyrimidinecarboxylate rather than Me 4,5-dihydro-α,4-dioxo-2-phenyl-1H-imidazole-5-acetate. The experimental part of the paper was very detailed, including the reaction process of 5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2Application of 62222-38-2)

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. Application of 62222-38-2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 62222-38-2On November 1, 2009 ,《2-(3-Thienyl)-5,6-dihydroxypyrimidine-4-carboxylic acids as inhibitors of HCV NS5B RdRp》 appeared in Bioorganic & Medicinal Chemistry Letters. The author of the article were Pacini, Barbara; Avolio, Salvatore; Ercolani, Caterina; Koch, Uwe; Migliaccio, Giovanni; Narjes, Frank; Pacini, Laura; Tomei, Licia; Harper, Steven. The article conveys some information:

A series of 2-(3-thienyl)-5,6-dihydroxypyrimidine-4-carboxylic acid inhibitors of the hepatitis C virus (HCV) NS5B polymerase enzyme are reported. Sulfonyl urea substituted analogs in this series proved to be the most potent active site non-nucleoside inhibitors of NS5B reported to date. These compounds had low nanomolar enzyme inhibition across HCV genotypes 1-3 and showed single digit micromolar inhibition in the HCV replicon assay. This improved cell-based activity allowed the binding mode of these compounds to be probed by selection of resistant mutations against compound 21 (I). The results generated are in broad agreement with the previously proposed binding model for this compound class. In the part of experimental materials, we found many familiar compounds, such as 5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2Application of 62222-38-2)

5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Application of 62222-38-2They 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

Application In Synthesis of 5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acidOn October 18, 2004 ,《Active site inhibitors of HCV NS5B polymerase. The development and pharmacophore of 2-thienyl-5,6-dihydroxypyrimidine-4-carboxylic acid》 was published in Bioorganic & Medicinal Chemistry Letters. The article was written by Stansfield, Ian; Avolio, Salvatore; Colarusso, Stefania; Gennari, Nadia; Narjes, Frank; Pacini, Barbara; Ponzi, Simona; Harper, Steven. The article contains the following contents:

5,6-Dihydroxypyrimidine-4-carboxylic acids are a promising series of hepatitis C virus (HCV) NS5B polymerase inhibitors that bind at the active site of the enzyme. Here the authors report a simple 2-thienyl substituted analog that shows 10-fold improved activity over the original lead, and which allowed us to further delineate the key elements of the pharmacophore of this class of inhibitor. This work led to the identification of a trifluoromethyl acylsulfonamide group as a viable replacement for the C4 carboxylic acid in this series. In the part of experimental materials, we found many familiar compounds, such as 5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2Application In Synthesis of 5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid)

5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2) 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 5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia