Tag: 200-300

《Discovery of the Clinical Candidate MAK683: An EED-Directed, Allosteric, and Selective PRC2 Inhibitor for the Treatment of Advanced Malignancies》 was written by Huang, Ying; Sendzik, Martin; Zhang, Jeff; Gao, Zhenting; Sun, Yongfeng; Wang, Long; Gu, Justin; Zhao, Kehao; Yu, Zhengtian; Zhang, Lijun; Zhang, Qiong; Blanz, Joachim; Chen, Zijun; Dubost, Valerie; Fang, Douglas; Feng, Lijian; Fu, Xingnian; Kiffe, Michael; Li, Ling; Luo, Fangjun; Luo, Xiao; Mi, Yuan; Mistry, Prakash; Pearson, David; Piaia, Alessandro; Scheufler, Clemens; Terranova, Remi; Weiss, Andreas; Zeng, Jue; Zhang, Hailong; Zhang, Jiangwei; Zhao, Mengxi; Dillon, Michael P.; Jeay, Sebastien; Qi, Wei; Moggs, Jonathan; Pissot-Soldermann, Carole; Li, En; Atadja, Peter; Lingel, Andreas; Oyang, Counde. Application of 69696-35-1 And the article was included in Journal of Medicinal Chemistry on April 14 ,2022. The article conveys some information:

Polycomb Repressive Complex 2 (PRC2) plays an important role in transcriptional regulation during animal development and in cell differentiation, and alteration of PRC2 activity has been associated with cancer. On a mol. level, PRC2 catalyzes methylation of histone H3 lysine 27 (H3K27), resulting in mono-, di-, or trimethylated forms of H3K27, of which the trimethylated form H3K27me3 leads to transcriptional repression of polycomb target genes. Previously, we have shown that binding of the low-mol.-weight compound EED226 to the H3K27me3 binding pocket of the regulatory subunit EED can effectively inhibit PRC2 activity in cells and reduce tumor growth in mouse xenograft models. Here, we report the stepwise optimization of the tool compound EED226 toward the potent and selective EED inhibitor MAK683 (compound 22) and its subsequent preclin. characterization. Based on a balanced PK/PD profile, efficacy, and mitigated risk of forming reactive metabolites, MAK683 has been selected for clin. development.5-Bromo-4-chloro-2,6-dimethylpyrimidine(cas: 69696-35-1Application of 69696-35-1) was used in this study.

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.Application of 69696-35-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2022,Nucleic Acids Research included an article by Baddock, Hannah T.; Brolih, Sanja; Yosaatmadja, Yuliana; Ratnaweera, Malitha; Bielinski, Marcin; Swift, Lonnie P.; Cruz-Migoni, Abimael; Fan, Haitian; Keown, Jeremy R.; Walker, Alexander P.; Morris, Garrett M.; Grimes, Jonathan M.; Fodor, Ervin; Schofield, Christopher J.; Gileadi, Opher; McHugh, Peter J.. Electric Literature of C11H8N2O4. The article was titled 《Characterization of the SARS-CoV-2 ExoN (nsp14ExoN-nsp10) complex: implications for its role in viral genome stability and inhibitor identification》. The information in the text is summarized as follows:

The SARS-CoV-2 coronavirus is the causal agent of the current global pandemic. SARS-CoV-2 belongs to an order, Nidovirales, with very large RNA genomes. It is proposed that the fidelity of coronavirus (CoV) genome replication is aided by an RNA nuclease complex, comprising the non-structural proteins 14 and 10 (nsp14-nsp10), an attractive target for antiviral inhibition. Our results validate reports that the SARS-CoV-2 nsp14-nsp10 complex has RNase activity. Detailed functional characterization reveals nsp14-nsp10 is a versatile nuclease capable of digesting a wide variety of RNA structures, including those with a blocked 3′-terminus. Consistent with a role in maintaining viral genome integrity during replication, we find that nsp14-nsp10 activity is enhanced by the viral RNA-dependent RNA polymerase complex (RdRp) consisting of nsp12-nsp7-nsp8 (nsp12-7-8) and demonstrate that this stimulation is mediated by nsp8. We propose that the role of nsp14-nsp10 in maintaining replication fidelity goes beyond classical proofreading by purging the nascent replicating RNA strand of a range of potentially replication-terminating aberrations. Using our developed assays, we identify drug and drug-like mols. that inhibit nsp14-nsp10, including the known SARS-CoV-2 major protease (Mpro) inhibitor ebselen and the HIV integrase inhibitor raltegravir, revealing the potential for multifunctional inhibitors in COVID-19 treatment. The experimental process involved the reaction of 5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2Electric Literature of C11H8N2O4)

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. Electric Literature of C11H8N2O4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application In Synthesis of Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylateOn March 9, 2006, Koch, Uwe; Attenni, Barbara; Malancona, Savina; Colarusso, Stefania; Conte, Immacolata; Di Filippo, Marcello; Harper, Steven; Pacini, Barbara; Giomini, Claudia; Thomas, Steven; Incitti, Ilario; Tomei, Licia; De Francesco, Raffaele; Altamura, Sergio; Matassa, Victor G.; Narjes, Frank published an article in Journal of Medicinal Chemistry. The article was 《2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as Inhibitors of the Hepatitis C Virus NS5B Polymerase: Discovery, SAR, Modeling, and Mutagenesis》. The article mentions the following:

Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. The polymerase of HCV is responsible for the replication of viral RNA. The authors recently disclosed dihydroxypyrimidine carboxylates as novel, reversible inhibitors of the HCV NS5B polymerase. This series was further developed into 5,6-dihydroxy-2-(2-thienyl)pyrimidine-4-carboxylic acids such as (I) (EC50 9.3 μM), which now show activity in the cell-based HCV replication assay. The structure-activity relation of these inhibitors is discussed in the context of their physicochem. properties and of the polymerase crystal structure. We also report the results of mutagenesis experiments which support the proposed binding model, which involves pyrophosphate-like chelation of the active site Mg ions. In addition to this study using Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate, there are many other studies that have used 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. 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 Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《2-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid with inbuilt β-N-hydroxy-γ-keto-acid pharmacophore as HCV NS5B polymerase inhibitors》 were Deore, R. R.; Chen, G. S.; Chen, C.-S.; Chang, P.-T.; Chuang, M.-H.; Chern, T.-R.; Wang, H.-C.; Chern, J.-W.. And the article was published in Current Medicinal Chemistry in 2012. Computed Properties of C11H8N2O4 The author mentioned the following in the article:

The inbuilt 2-N-hydroxy-1-oxo-3-carboxylic acid of isoquinolone was designed as pyrophosphate mimic for hepatitis C NS5B polymerase. Various 2-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid derivatives 11a-p were synthesized and evaluated as HCV NS5B polymerase inhibitors. Compound 11c exhibited moderate inhibitory potency based on the inorganic pyrophosphate generation (IC50 = 9.5 μM) and based on NTP incorporation by NS5B enzyme (IC50 = 5.9 μM). Compound 11c demonstrated antiviral activity (EC50 = 15.7 μM) and good selectivity in HCV genotype 1b replicon Ava.5 cells. Compound 11c reduced the interaction of NTP to NS5B polymerase. Docking model showed that 11c situated in similar orientation to the bound uridine triphosphate in the active site of NS5B polymerase. As a result, 2-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid was disclosed as a novel inbuilt β-N-hydroxy-γ-keto-acid pharmacophore for HCV NS5B polymerase inhibitors. In the part of experimental materials, we found many familiar compounds, such as 5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2Computed Properties of C11H8N2O4)

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. Computed Properties of C11H8N2O4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

HPLC of Formula: 519032-07-6On May 3, 2007 ,《Dihydroxypyrimidine-4-carboxamides as Novel Potent and Selective HIV Integrase Inhibitors》 appeared in Journal of Medicinal Chemistry. The author of the article were Pace, Paola; Di Francesco, M. Emilia; Gardelli, Cristina; Harper, Steven; Muraglia, Ester; Nizi, Emanuela; Orvieto, Federica; Petrocchi, Alessia; Poma, Marco; Rowley, Michael; Scarpelli, Rita; Laufer, Ralph; Gonzalez Paz, Odalys; Monteagudo, Edith; Bonelli, Fabio; Hazuda, Daria; Stillmock, Kara A.; Summa, Vincenzo. The article conveys some information:

Human immunodeficiency virus type-1 (HIV-1) integrase, one of the three constitutive viral enzymes required for replication, is a rational target for chemotherapeutic intervention in the treatment of AIDS that has also recently been confirmed in the clin. setting. We report here on the design and synthesis of N-benzyl-5,6-dihydroxypyrimidine-4-carboxamides as a class of agents which exhibits potent inhibition of the HIV-integrase-catalyzed strand transfer process. In the current study, structural modifications on these mols. were made in order to examine effects on HIV-integrase inhibitory potencies. One of the most interesting compounds for this series is 2-[1-(dimethylamino)-1-methylethyl]-N-(4-fluorobenzyl)-5,6-dihydroxypyrimidine-4-carboxamide, with a CIC95 of 78 nM in the cell-based assay in the presence of serum proteins. The compound has favorable pharmacokinetic properties in preclin. species (rats, dogs, and monkeys) and shows no liabilities in several counterscreening assays, highlighting its potential as a clin. useful antiviral agent. The experimental process involved the reaction of Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6HPLC of Formula: 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. HPLC of Formula: 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

Related Products of 519032-07-6On November 21, 2018 ,《Discovery and Structure-Activity-Relationship Study of N-Alkyl-5-hydroxypyrimidinone Carboxamides as Novel Antitubercular Agents Targeting Decaprenylphosphoryl-β-D-ribose 2′-Oxidase》 appeared in Journal of Medicinal Chemistry. The author of the article were Oh, Sangmi; Park, Yumi; Engelhart, Curtis A.; Wallach, Joshua B.; Schnappinger, Dirk; Arora, Kriti; Manikkam, Michelle; Gac, Brian; Wang, Hongwu; Murgolo, Nicholas; Olsen, David B.; Goodwin, Michael; Sutphin, Michelle; Weiner, Danielle M.; Via, Laura E.; Boshoff, Helena I. M.; Barry, Clifton E.. The article conveys some information:

Magnesium plays an important role in infection with Mycobacterium tuberculosis (Mtb) as a signal of the extracellular environment, as a cofactor for many enzymes, and as a structural element in important macromols. Raltegravir, an antiretroviral drug that inhibits HIV-1 integrase is known to derive its potency from selective sequestration of active-site magnesium ions in addition to binding to a hydrophobic pocket. In order to determine if essential Mtb-related phosphoryl transfers could be disrupted in a similar manner, a directed screen of known mols. with integrase inhibitor-like pharmacophores (N-alkyl-5-hydroxypyrimidinone carboxamides) was performed. Initial hits afforded compounds with low-micromolar potency against Mtb, acceptable cytotoxicity and PK characteristics, and robust SAR. Elucidation of the target of these compounds revealed that they lacked magnesium dependence and instead disappointingly inhibited a known promiscuous target in Mtb, decaprenylphosphoryl-β-D-ribose 2′-oxidase (DprE1, Rv3790).Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6Related Products of 519032-07-6) 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. Related Products of 519032-07-6

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On February 5, 1998, Murugesan, Natesan; Barrish, Joel C.; Stein, Philip D. published a patent.Computed Properties of 160377-42-4 The title of the patent was Preparation of heterocyclyl-substituted biphenylsulfonamide as endothelin antagonists. And the patent contained the following:

Compounds of formula (I; R1 and R2 are directly bonded to a ring carbon and are each independently hydrogen, alkyl or alkoxy, hydroxyl, halo, or amino; one of X and Y is N and the other is O: R3 and R4 are each directly bonded to a ring carbon and are each independently hydrogen, alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl or aralkoxy, any of which may be substituted or R3 and R4 together may also be alkylene or alkenylene, either of which may be substituted, completing a 4- to 8-membered saturated, unsaturated or aromatic ring together with the carbon atoms to which they are attached; R11 – R14 are each independently are hydrogen alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl, aralkoxy, or heterocyclyl, any of which may be substituted, halo, OH, cyano, NO2, CHO, CO2H, etc.; J, K, L, T, and U are each independently N or C, provided that at least one is N, and at most two are N; and when only one of J, K, L, T, and U is N, the N may be substituted with O- so that N-oxide is formed), which inhibit the activity of endothelin (no data), are prepared Also claimed is a method for treating endothelin-related disorders in a mammal, such as (1) hypertension, (2) pulmonary hypertension, (3) renal, glomerular, or mesangial cell disorders, (4) endotoxemia, (5) ischemia, (6) atherosclerosis, (7) restenosis, (8) subarachnoid hemorrhage, (9) prostatic hypertrophy, and (10) congestive heart failure, and a method for inhibiting cell growth. Said compound I is used in combination with at least one angiotensin II receptor antagonist, renin inhibitor, angiotensin converting enzyme (ACE) inhibitor, or a dual neutral endopeptidase-ACE inhibitor for treating the endothelin-related disorder. A pharmaceutical composition for the treating the endothelin-related disorders comprises said compound optionally in combination with at least one angiotensin II receptor antagonist, renin inhibitor, angiotensin converting enzyme (ACE) inhibitor, or a dual neutral endopeptidase-ACE inhibitor. Thus, 2-(4-bromophenyl)pyrimidine is coupled with 2-borono-N-(3,4-dimethyl-5-isoxazolyl)-N-[(2-methoxyethoxy)methyl]benzenesulfonamide in the presence of (Ph3P)4Pd in a mixture of toluene, 2 M aqueous Na2CO3, and 95% ethanol under reflux for 1.5 h to give the title compound, N-isoxazolylpyrimidinylbiphenylsulfonamide (II). The experimental process involved the reaction of 5-(4-Bromophenyl)pyrimidine(cas: 160377-42-4).Computed Properties of 160377-42-4

The Article related to angiotensin ii receptor antagonists, antiatherosclerotics, antihypertensives, benign prostatic hyperplasia, cell (renal, glomerular, or mesangial cell disorders), endotoxemia, growth inhibitors, animal role: spn (synthetic preparation), thu (therapeutic use), prep (preparation), biol (biological study), uses (uses), heart failure, ischemia, mesangium (disorders), subarachnoid hemorrhage and other aspects.Computed Properties of 160377-42-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

COA of Formula: C13H12N2O4On November 12, 2009 ,《Coordination Chemistry Based Approach to Lipophilic Inhibitors of 1-Deoxy-D-xylulose-5-phosphate Reductoisomerase》 appeared in Journal of Medicinal Chemistry. The author of the article were Deng, Lisheng; Sundriyal, Sandeep; Rubio, Valentina; Shi, Zheng-zheng; Song, Yongcheng. The article conveys some information:

1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate pathway found in most bacteria is a validated anti-infective drug target. Fosmidomycin, a potent DXR inhibitor, is active against Gram-neg. bacteria. A coordination chem. and structure based approach was used to discover a novel, lipophilic DXR inhibitor with an IC50 of 1.4 μM. It exhibited a broad spectrum of activity against Gram-neg. and -pos. bacteria with minimal inhibition concentrations of 20-100 μM (or 3.7-19 μg/mL). In the part of experimental materials, we found many familiar compounds, such as Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6COA of Formula: C13H12N2O4)

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. COA of Formula: C13H12N2O4They 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 《Reactions of pyrimidin-5-yllithium compounds》 were Caton, M. P. L.; Grant, M. S.; Pain, D. L.; Slack, R.. And the article was published in Journal of the Chemical Society in 1965. Category: pyrimidines The author mentioned the following in the article:

Pyrimidin-5-yllithium compounds, mostly having alkoxy substituents, reacted with CO2, HCONMe2, and S, forming, resp., carboxylic acids, aldehydes, and polysulfides. The last were reduced and converted in situ into (pyrimidin-5-ylthio)alkanoic acids. Preparations of pyrimidin-5-ylacetic acids and of 5-bromo-2-formylpyrimidine are also described. The experimental process involved the reaction of 5-Bromo-4,6-dimethoxy-2-methylpyrimidine(cas: 4319-83-9Category: pyrimidines)

5-Bromo-4,6-dimethoxy-2-methylpyrimidine(cas: 4319-83-9) is a member of ether. When aromatic ethers are exposed to halogen in the presence or absence of a catalyst, they undergo halogenation, such as bromination.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Edo, Kiyoto; Sakamoto, Takao; Yamanaka, Hiroshi published their research in Chemical & Pharmaceutical Bulletin on December 31 ,1978. The article was titled 《Studies on pyrimidine derivatives. IX. Coupling reaction of mono-substituted acetylenes with iodopyrimidines》.Synthetic Route of C6H6BrClN2 The article contains the following contents:

Pyrimidine derivatives containing an acetylenic side chain were prepared by reaction of alkyl or Ph acetylenes with 2-, 4-, and 5-iodopyrimidines in the presence of Pd(PPh3)2Cl2. When HCCCH2OH was used, the reaction yield decreased. The reaction proceeded with 2,4-diiodo- and 4,6-diiodopyrimidines to give dialkynyl derivatives This acetylene coupling reaction was applicable to the preparation of 4-quinazoline derivatives The results came from multiple reactions, including the reaction of 5-Bromo-4-chloro-2,6-dimethylpyrimidine(cas: 69696-35-1Synthetic Route of 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.Synthetic Route of C6H6BrClN2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia