Tag: 200-300

COA of Formula: C11H8N2O4On October 21, 2004 ,《HCV NS5b RNA-Dependent RNA Polymerase Inhibitors: From α,γ-Diketoacids to 4,5-Dihydroxypyrimidine- or 3-Methyl-5- hydroxypyrimidinonecarboxylic Acids. Design and Synthesis》 was published in Journal of Medicinal Chemistry. The article was written by Summa, Vincenzo; Petrocchi, Alessia; Matassa, Victor G.; Taliani, Marina; Laufer, Ralph; De Francesco, Raffaele; Altamura, Sergio; Pace, Paola. The article contains the following contents:

A new class of the HCV NS5b RNA-dependent RNA polymerase inhibitors, the dihyroxypyrimidinecarboxylic acid derivative, was designed from a diketoacid and meconic acid derivative discovered by screening. Mechanism of action and essential moieties required for activity were identified. The corresponding N-methylpyrimidinone was also prepared; both classes are novel, reversible, and selective inhibitors of the HCV NS5b polymerase with improved druglike characteristics. The results came from multiple reactions, including the reaction of 5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2COA of Formula: C11H8N2O4)

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. COA of Formula: C11H8N2O4They 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

Wang, Yujie; Rong, Jie; Zhang, Bin; Hu, Liming; Wang, Xiaoli; Zeng, Chengchu published an article on February 15 ,2015. The article was titled 《Design and synthesis of N-methylpyrimidone derivatives as HIV-1 integrase inhibitors》, and you may find the article in Bioorganic & Medicinal Chemistry.Application In Synthesis of Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate The information in the text is summarized as follows:

A series of novel β-diketo derivatives which combined the virtues of dihydroxypyrimidine carboxamide derived from the evolution of diketo acids and polyhydroxylated aromatics moieties were designed and synthesized as potential HIV-1 integrase (IN) inhibitors and their inhibition to the strand transfer process of HIV-1 integrase and anti-HIV-1 activity evaluated. The result indicates that 3,4,5-trihydroxylated aromatic derivatives exhibit good inhibition to HIV-1 integrase, but dihydroxylated aromatic derivatives show little inhibition to HIV-1 integrase. In addition, the preliminary structure-activity relationship (SAR) of these new derivatives was rationalized by docking studies.Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6Application In Synthesis of Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate) was used in this study.

Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6) 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. Application In Synthesis of Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

SDS of cas: 519032-07-6On November 16, 2006 ,《4,5-Dihydroxypyrimidine Carboxamides and N-Alkyl-5-hydroxypyrimidinone Carboxamides Are Potent, Selective HIV Integrase Inhibitors with Good Pharmacokinetic Profiles in Preclinical Species》 appeared in Journal of Medicinal Chemistry. The author of the article were Summa, Vincenzo; Petrocchi, Alessia; Matassa, Victor G.; Gardelli, Cristina; Muraglia, Ester; Rowley, Michael; Paz, Odalys Gonzalez; Laufer, Ralph; Monteagudo, Edith; Pace, Paola. The article conveys some information:

The dihydroxypyrimidine carboxamide 4a was discovered as a potent and selective HIV integrase strand transfer inhibitor. The optimization of physicochem. properties, pharmacokinetic profiles, and potency led to the identification of (I) in the dihydroxypyrimidine series and (II) in the N-methylpyrimidinone series having low nanomolar activity in the cellular HIV spread assay in the presence of 50% normal human serum and very good pharmacokinetics in preclin. species. After reading the article, we found that the author used Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6SDS of cas: 519032-07-6)

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. SDS of cas: 519032-07-6They 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

Norman, Mark H.; Zhu, Jiawang; Fotsch, Christopher; Bo, Yunxin; Chen, Ning; Chakrabarti, Partha; Doherty, Elizabeth M.; Gavva, Narender R.; Nishimura, Nobuko; Nixey, Thomas; Ognyanov, Vassil I.; Rzasa, Robert M.; Stec, Markian; Surapaneni, Sekhar; Tamir, Rami; Viswanadhan, Vellarkad N.; Treanor, James J. S. published an article in Journal of Medicinal Chemistry. The title of the article was 《Novel Vanilloid Receptor-1 Antagonists: 1. Conformationally Restricted Analogues of trans-Cinnamides》.Computed Properties of C11H6ClF3N2 The author mentioned the following in the article:

The vanilloid receptor-1 (VR1 or TRPV1) is a member of the transient receptor potential (TRP) family of ion channels and plays a role as an integrator of multiple pain-producing stimuli. From a high-throughput screening assay, measuring calcium uptake in TRPV1-expressing cells, we identified an N-aryl trans-cinnamide (AMG9810, compound 9) that acts as a potent TRPV1 antagonist. We have demonstrated the antihyperalgesic properties of 9 in vivo and have also reported the discovery of novel, orally bioavailable cinnamides derived from this lead. Herein, we expand our investigations and describe the synthesis and biol. evaluation of a series of conformationally constrained analogs of the s-cis conformer of compound 9. These investigations resulted in the identification of 4-amino- and 4-oxopyrimidine cores as suitable isosteric replacements for the trans-acrylamide moiety. The best examples from this series, pyrimidines 79 and 74 (I), were orally bioavailable and exhibited potent antagonism of both rat (IC50 = 4.5 and 0.6 nM, resp.) and human TRPV1 (IC50 = 7.4 and 3.7 nM, resp.). In addition, compound 74 was shown to be efficacious at blocking a TRPV1-mediated physiol. response in vivo in the capsaicin-induced hypothermia model in rats; however, it was ineffective at preventing thermal hyperalgesia induced by complete Freund’s adjuvant in rats. The experimental part of the paper was very detailed, including the reaction process of 4-Chloro-6-(4-(trifluoromethyl)phenyl)pyrimidine(cas: 659729-09-6Computed Properties of 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. Computed Properties of C11H6ClF3N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《Photodehydrocyclization of 1-styrylimidazoles; an HMO study》 were Copper, Geoffrey; Irwin, William J.. And the article was published in Journal of the Chemical Society in 1976. Application of 62222-38-2 The author mentioned the following in the article:

Photodehydrocyclization of 4,5-diphenyl-1-styrylimidazole gave the phenanthroimidazoisoquinoline I via the phenanthroimidazole II. Synthesis and photocyclization of the imidazoisoquinoline III, another possible intermediate, and HMO calculations, especially the resulting localization energies, support the intermediacy of II. The results came from multiple reactions, including the reaction 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. 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

SDS of cas: 944401-55-2On September 14, 2017 ,《5-(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology》 was published in Journal of Medicinal Chemistry. The article was written by Beaufils, Florent; Cmiljanovic, Natasa; Cmiljanovic, Vladimir; Bohnacker, Thomas; Melone, Anna; Marone, Romina; Jackson, Eileen; Zhang, Xuxiao; Sele, Alexander; Borsari, Chiara; Mestan, Jurgen; Hebeisen, Paul; Hillmann, Petra; Giese, Bernd; Zvelebil, Marketa; Fabbro, Doriano; Williams, Roger L.; Rageot, Denise; Wymann, Matthias P.. The article contains the following contents:

Phosphoinositide 3-kinase (PI3K) is deregulated in a wide variety of human tumors and triggers activation of protein kinase B (PKB/Akt) and mammalian target of rapamycin (mTOR). Here we describe the preclin. characterization of compound 1 (PQR309, bimiralisib), a potent 4,6-dimorpholino-1,3,5-triazine-based pan-class I PI3K inhibitor, which targets mTOR kinase in a balanced fashion at higher concentrations No off-target interactions were detected for 1 in a wide panel of protein kinase, enzyme, and receptor ligand assays. Moreover, 1 did not bind tubulin, which was observed for the structurally related 4 (BKM120, buparlisib). Compound 1 is orally available, crosses the blood-brain barrier, and displayed favorable pharmacokinetic parameters in mice, rats, and dogs. Compound 1 demonstrated efficiency in inhibiting proliferation in tumor cell lines and a rat xenograft model. This, together with the compound’s safety profile, identifies 1 as a clin. candidate with a broad application range in oncol., including treatment of brain tumors or CNS metastasis. Compound 1 is currently in phase II clin. trials for advanced solid tumors and refractory lymphoma. 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: 944401-55-2SDS of cas: 944401-55-2)

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 derivatives also play an important role in drug development, either in concert with other compounds or on their own. SDS of cas: 944401-55-2They 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

Synthetic Route of C11H8N2O4On May 1, 2018 ,《Pharmacophore requirements for HIV-1 reverse transcriptase inhibitors that selectively “”Freeze”” the pre-translocated complex during the polymerization catalytic cycle》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Lacbay, Cyrus M.; Menni, Michael; Bernatchez, Jean A.; Gotte, Matthias; Tsantrizos, Youla S.. The article conveys some information:

Reverse transcriptase (RT) is responsible for replicating the HIV-1 genome and is a validated therapeutic target for the treatment of HIV infections. During each cycle of the RT-catalyzed DNA polymerization process, inorganic pyrophosphate is released as the byproduct of nucleotide incorporation. Small mols. were identified that act as bioisosteres of pyrophosphate and can selectively freeze the catalytic cycle of HIV-1 RT at the pre-translocated stage of the DNA- or RNA-template-primer-enzyme complex. In the experiment, the researchers used 5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2Synthetic Route of C11H8N2O4)

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. Synthetic Route of C11H8N2O4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

HPLC of Formula: 944401-55-2On October 11, 2018 ,《Discovery and Structure-Based Optimization of Benzimidazole-Derived Activators of SOS1-Mediated Nucleotide Exchange on RAS》 was published in Journal of Medicinal Chemistry. The article was written by Hodges, Timothy R.; Abbott, Jason R.; Little, Andrew J.; Sarkar, Dhruba; Salovich, James M.; Howes, Jennifer E.; Akan, Denis T.; Sai, Jiqing; Arnold, Allison L.; Browning, Carrie; Burns, Michael C.; Sobolik, Tammy; Sun, Qi; Beesetty, Yugandhar; Coker, Jesse A.; Scharn, Dirk; Stadtmueller, Heinz; Rossanese, Olivia W.; Phan, Jason; Waterson, Alex G.; McConnell, Darryl B.; Fesik, Stephen W.. The article contains the following contents:

Son of sevenless homolog 1 (SOS1) is a guanine nucleotide exchange factor that catalyzes the exchange of GDP for GTP on RAS. In its active form, GTP-bound RAS is responsible for numerous critical cellular processes. Aberrant RAS activity is involved in ∼30% of all human cancers; hence, SOS1 is an attractive therapeutic target for its role in modulating RAS activation. Here, we describe a new series of benzimidazole-derived SOS1 agonists. Using structure-guided design, we discovered small mols. that increase nucleotide exchange on RAS in vitro at submicromolar concentrations, bind to SOS1 with low double-digit nanomolar affinity, rapidly enhance cellular RAS-GTP levels, and invoke biphasic signaling changes in phosphorylation of ERK 1/2. These compounds represent the most potent series of SOS1 agonists reported to date. The experimental part of the paper was very detailed, including the reaction process of 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine(cas: 944401-55-2HPLC of Formula: 944401-55-2)

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. HPLC of Formula: 944401-55-2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Coordination Polymers from Functionalized Bipyrimidine Ligands and Silver(I) Salts》 was written by Beaulieu-Houle, Guillaume; White, Nicholas G.; MacLachlan, Mark J.. Formula: C9H6N4O2 And the article was included in Crystal Growth & Design on April 4 ,2018. The article conveys some information:

Readily functionalizable bipyrimidine compounds were prepared for the first time, and their coordination chem. with silver salts was explored. Solution 1H NMR spectroscopy experiments indicated that the ligands rapidly form complexes with silver(I) salts, and coordination at a first site inhibits coordination of a second cation to the ligand, thus favoring 1:1 complexes in solution These 1:1 units self-assemble into one-dimensional chains in the solid state, even in the presence of excess Ag(I). Structurally diverse coordination polymers exhibiting different coordination numbers and geometry were characterized by single crystal X-ray crystallog. Our results demonstrate that a modification to the ligand, distal from the binding site, affects the coordination chem. and supramol. structure of these complexes. The results came from multiple reactions, including the reaction of 2-(Pyrimidin-2-yl)pyrimidine-5-carboxylic acid(cas: 933191-25-4Formula: C9H6N4O2)

2-(Pyrimidin-2-yl)pyrimidine-5-carboxylic acid(cas: 933191-25-4) 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. Formula: C9H6N4O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Discovery of Clinical Development Candidate GDC-0084, a Brain Penetrant Inhibitor of PI3K and mTOR》 was written by Heffron, Timothy P.; Ndubaku, Chudi O.; Salphati, Laurent; Alicke, Bruno; Cheong, Jonathan; Drobnick, Joy; Edgar, Kyle; Gould, Stephen E.; Lee, Leslie B.; Lesnick, John D.; Lewis, Cristina; Nonomiya, Jim; Pang, Jodie; Plise, Emile G.; Sideris, Steve; Wallin, Jeffrey; Wang, Lan; Zhang, Xiaolin; Olivero, Alan G.. Quality Control of 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine And the article was included in ACS Medicinal Chemistry Letters on April 14 ,2016. The article conveys some information:

Inhibition of phosphoinositide 3-kinase (PI3K) signaling is an appealing approach to treat brain tumors, especially glioblastoma multiforme (GBM). The authors previously disclosed the successful approach to prospectively design potent and blood-brain barrier (BBB) penetrating PI3K inhibitors. The previously disclosed mols. were ultimately deemed not suitable for clin. development due to projected poor metabolic stability in humans. The authors, therefore, extended the studies to identify a BBB penetrating inhibitor of PI3K that was also projected to be metabolically stable in human. These efforts required identification of a distinct scaffold for PI3K inhibitors relative to the authors’ previous efforts and ultimately resulted in the identification of GDC-0084. The discovery and preclin. characterization of this mol. are described within. 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: 944401-55-2Quality Control of 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine) 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. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Quality Control of 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amineThey 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