Tag: 100-200

In 2016,Crawford, Terry D.; Romero, F. Anthony; Lai, Kwong Wah; Tsui, Vickie; Taylor, Alexander M.; de Leon Boenig, Gladys; Noland, Cameron L.; Murray, Jeremy; Ly, Justin; Choo, Edna F.; Hunsaker, Thomas L.; Chan, Emily W.; Merchant, Mark; Kharbanda, Samir; Gascoigne, Karen E.; Kaufman, Susan; Beresini, Maureen H.; Liao, Jiangpeng; Liu, Wenfeng; Chen, Kevin X.; Chen, Zhongguo; Conery, Andrew R.; Cote, Alexandre; Jayaram, Hariharan; Jiang, Ying; Kiefer, James R.; Kleinheinz, Tracy; Li, Yingjie; Maher, Jonathan; Pardo, Eneida; Poy, Florence; Spillane, Kerry L.; Wang, Fei; Wang, Jian; Wei, Xiaocang; Xu, Zhaowu; Xu, Zhongya; Yen, Ivana; Zawadzke, Laura; Zhu, Xiaoyu; Bellon, Steven; Cummings, Richard; Cochran, Andrea G.; Albrecht, Brian K.; Magnuson, Steven published 《Discovery of a Potent and Selective in Vivo Probe (GNE-272) for the Bromodomains of CBP/EP300》.Journal of Medicinal Chemistry published the findings.Quality Control of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole The information in the text is summarized as follows:

The single bromodomain of the closely related transcriptional regulators CBP/EP300 is a target of much recent interest in cancer and immune system regulation. A co-crystal structure of a ligand-efficient screening hit and the CBP bromodomain guided initial design targeting the LPF shelf, ZA loop, and acetylated lysine binding regions. Structure-activity relationship studies allowed the authors to identify a more potent analog. Optimization of permeability and microsomal stability and subsequent improvement of mouse hepatocyte stability afforded 59 (GNE-272, TR-FRET IC50 = 0.02 μM, BRET IC50 = 0.41 μM, BRD4(1) IC50 = 13 μM) that retained the best balance of cell potency, selectivity, and in vivo PK. GNE-272 showed a marked antiproliferative effect in hematol. cancer cell lines and modulates MYC expression in vivo that corresponds with antitumor activity in an AML tumor model. The results came from multiple reactions, including the reaction of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 844501-71-9Quality Control of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole)

3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 844501-71-9) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, antidiabetic and antibacterial activities. Quality Control of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

In 2012,Srinivas, Dharavath; Ghule, Vikas D.; Tewari, Surya P.; Muralidharan, Krishnamurthi published 《Synthesis of Amino, Azido, Nitro, and Nitrogen-Rich Azole Substituted Derivatives of 1H-Benzotriazole for High-Energy Materials Applications》.Chemistry – A European Journal published the findings.Recommanded Product: 20154-03-4 The information in the text is summarized as follows:

The amino, azido, nitro, and nitrogen-rich azole substituted derivatives of 1H-benzotriazole were synthesized for energetic material applications. The synthesized compounds were fully characterized by 1H and 13C NMR spectroscopy, IR, MS, and elemental anal. 5-Chloro-4-nitro-1H-benzo[1,2,3]triazole and 5-azido-4,6-dinitro-1H-benzo[1,2,3]triazole crystallize in the Pca21 (orthorhombic) and P21/c (monoclinic) space group, resp., as determined by single-crystal X-ray diffraction. Their densities are 1.71 and 1.77 g cm-3, resp. The calculated densities of the other compounds range between 1.61-1.98 g cm-3. The detonation velocity values calculated for these synthesized compounds range from 5.45-8.06 km s-1, and the detonation pressure ranges from 12.35-28 GPa.3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4Recommanded Product: 20154-03-4) was used in this study.

3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4) belongs to pyrazoles. The application of pyrazole derivatives in the development of anticancer agents has been thoroughly investigated and verified. Moreover, the medicinal features of a number of natural products incorporating pyrazole moiety such as pyrazofurin, pyrazofurin B, pyrazole-3(5)-carboxylic acid and 4-methylpyrazole-3(5)-carboxylic acid have been reported.Recommanded Product: 20154-03-4

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

In 2012,Murugaiah, A. M. S.; Wu, Xiongyu; Wallinder, Charlotta; Mahalingam, A. K.; Wan, Yiqian; Skoeld, Christian; Botros, Milad; Guimond, Marie-Odile; Joshi, Advait; Nyberg, Fred; Gallo-Payet, Nicole; Hallberg, Anders; Alterman, Mathias published 《From the First Selective Non-Peptide AT2 Receptor Agonist to Structurally Related Antagonists》.Journal of Medicinal Chemistry published the findings.Product Details of 20154-03-4 The information in the text is summarized as follows:

A para substitution pattern of the Ph ring is a characteristic feature of the first reported selective AT2 receptor agonist M024/C21 (1) and all the nonpeptidic AT2 receptor agonists described so far. Two series of compounds structurally related to 1 but with a meta substitution pattern have now been synthesized and biol. evaluated for their affinity to the AT1 and AT2 receptors. A high AT2/AT1 receptor selectivity was obtained with all 41 compounds synthesized, and the majority exhibited Ki ranging from 2 to 100 nM. Five compounds were evaluated for their functional activity at the AT2 receptor, applying a neurite outgrowth assay in NG108-15 cells. Notably, four of the five compounds, with representatives from both series, acted as potent AT2 receptor antagonists. These compounds were found to be considerably more effective than PD 123,319, the standard AT2 receptor antagonist used in most laboratories No AT2 receptor antagonists were previously reported among the derivatives with a para substitution pattern. Hence, by a minor modification of the agonist 1 it could be transformed into the antagonist, compound 38. These compounds should serve as valuable tools in the assessment of the role of the AT2 receptor in more complex physiol. models. In addition to this study using 3-(Trifluoromethyl)-1H-pyrazole, there are many other studies that have used 3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4Product Details of 20154-03-4) was used in this study.

3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4) belongs to pyrazoles. The application of pyrazole derivatives in the development of anticancer agents has been thoroughly investigated and verified. Moreover, the medicinal features of a number of natural products incorporating pyrazole moiety such as pyrazofurin, pyrazofurin B, pyrazole-3(5)-carboxylic acid and 4-methylpyrazole-3(5)-carboxylic acid have been reported.Product Details of 20154-03-4

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

In 2011,Micheli, Fabrizio; Cavanni, Paolo; Bettati, Michela; Bonanomi, Giorgio; Di Fabio, Romano; Fazzolari, Elettra; Marchioro, Carla; Roscic, Maja; Tarsi, Luca; Visentini, Filippo; Zonzini, Laura; Worby, Angela published 《1-Heteroaryl-6-(3,4-dichlorophenyl)-3-azabicyclo[4.1.0]heptane: Further insights into a class of triple re-uptake inhibitors》.Bioorganic & Medicinal Chemistry published the findings.Recommanded Product: 3-(Trifluoromethyl)-1H-pyrazole The information in the text is summarized as follows:

Further exploration around the recently disclosed potent triple re-uptake inhibitor 6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptane led to the identification of a new series of potent triple re-uptake inhibitors endowed with good developability characteristics. The insertion of a further aryl moiety into the template allowed the titration’ of the SERT/NET/DAT ratio leading to the identification of further tools in this important area. In the part of experimental materials, we found many familiar compounds, such as 3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4Recommanded Product: 3-(Trifluoromethyl)-1H-pyrazole)

3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4) belongs to pyrazoles. Pyrazole derivatives have been reported to exhibit a wide range of applications in medicinal chemistry and pharmacology. A large number of drugs incorporating pyrazole structure have been utilized as partial agonists for nicotinic acid receptors, antidepressants, antimicrobial agents, antiviral agents, and antifungal agents solely or along with the combination of other structural motifs.Recommanded Product: 3-(Trifluoromethyl)-1H-pyrazole

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

《Esters of phosphorus oxy-acids as alkylating agents. II. N-Alkylation of imidazole and related heterocyclic compounds with trialkyl phosphates》 was written by Yamauchi, Kiyoshi; Kinoshita, Masayoshi. Formula: C7H12N2 And the article was included in Journal of the Chemical Society in 1973. The article conveys some information:

Imidazole, benzimidazole, pyrazole, 1,2,4-triazole, and benzotriazole reacted with (RO)3PO (R = Me, Et, Bu) to give N-alkyl derivatives (41-90%). Predominant N-1 alkylation was observed in the triazoles. In the part of experimental materials, we found many familiar compounds, such as 1-Butyl-1H-pyrazole(cas: 52096-24-9Formula: C7H12N2)

1-Butyl-1H-pyrazole(cas: 52096-24-9) belongs to pyrazoles. Pyrazole derivatives have been reported to exhibit a wide range of applications in medicinal chemistry and pharmacology. A large number of drugs incorporating pyrazole structure have been utilized as partial agonists for nicotinic acid receptors, antidepressants, antimicrobial agents, antiviral agents, and antifungal agents solely or along with the combination of other structural motifs.Formula: C7H12N2

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Waszkowycz, Bohdan; Smith, Kate M.; McGonagle, Alison E.; Jordan, Allan M.; Acton, Ben; Fairweather, Emma E.; Griffiths, Louise A.; Hamilton, Niall M.; Hamilton, Nicola S.; Hitchin, James R.; Hutton, Colin P.; James, Dominic I.; Jones, Clifford D.; Jones, Stuart; Mould, Daniel P.; Small, Helen F.; Stowell, Alexandra I. J.; Tucker, Julie A.; Waddell, Ian D.; Ogilvie, Donald J. published their research in Journal of Medicinal Chemistry on December 13 ,2018. The article was titled 《Cell-Active Small Molecule Inhibitors of the DNA-Damage Repair Enzyme Poly(ADP-ribose) Glycohydrolase (PARG): Discovery and Optimization of Orally Bioavailable Quinazolinedione Sulfonamides》.Synthetic Route of C5H8N2O The article contains the following contents:

DNA damage repair enzymes are promising targets in the development of new therapeutic agents for a wide range of cancers and potentially other diseases. The enzyme poly(ADP-ribose) glycohydrolase (PARG) plays a pivotal role in the regulation of DNA repair mechanisms; however, the lack of potent drug-like inhibitors for use in cellular and in vivo models has limited the investigation of its potential as a novel therapeutic target. Using the crystal structure of human PARG in complex with the weakly active and cytotoxic anthraquinone 8a, novel quinazolinedione sulfonamides PARG inhibitors have been identified by means of structure-based virtual screening and library design. 1-Oxetan-3-ylmethyl derivatives 33d and 35d were selected for preliminary investigations in vivo. X-ray crystal structures help rationalize the observed structure-activity relationships of these novel inhibitors. After reading the article, we found that the author used (3-methyl-1H-pyrazol-5-yl)methanol(cas: 29004-73-7Synthetic Route of C5H8N2O)

(3-methyl-1H-pyrazol-5-yl)methanol(cas: 29004-73-7) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. Synthetic Route of C5H8N2O

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

In 1966,Bulletin of the Chemical Society of Japan included an article by Ito, Sho; Takase, Kahei; Kawabe, Norio; Sugiyama, Hiroshi. Product Details of 5952-93-2. The article was titled 《Pyrazolotropolones and their derivatives》. The information in the text is summarized as follows:

A suspension of 10 g. 3,5,7-tribromotropolone (I, R = H, X = Br) in 150 ml. MeOH treated with excess CH2N2 in Et2O gave 2-methoxy-3,5,7-tribromotropone (I, R = Me, X = Br) (II). II (not isolated) dissolved to give an orange-red solution and this was set aside 2 days in the dark with further additions of CH2N2. The solution evaporated with evolution of HBr yielded 2.97 g. III(X = Y = Br) (IV), m. 158° (MeOH-CHCl3). IV was similarly obtained in 53.5% yield by the action of CH2N2 upon II. IV (1.247 g.) hydrogenated over 93 mg. 5% Pd-C in a mixture of 6 ml. HOAc, 60 ml. EtOAc, and 990 mg. NaOAc, the product filtered, and the filtrate distilled gave III (X = Y = H) (V), m. 135-6° (EtOAc). The structure shown, rather than the alternate structure (Va, X = H) was assigned on the basis of uv and N.M.R. spectral data. IV (93 mg.) refluxed 3 hrs. with 9 ml. 6N HCl in 20 ml. MeOH afforded on standing 64 mg. 4(or 6)-bromo-6(or 4)-chloro-7-methoxy-8(1H)-cycloheptapyrazolone, m. 143.5-4.5° (MeOH). A solution of 679 mg. IV in 150 ml. Me2CO was treated at 65-70° with 4.5 g. KMnO4 in 100 ml. aqueous solution The temperature was maintained 6 hrs., the mixture left overnight, filtered, concentrated to dryness, and the residue extracted with Me2CO to yield 126 mg. 1-methylpyrazole-4-carboxylic acid, m. 169°; Me ester m. 62-2.5°. 4-Acetyltropolone (5.0 g.) treated with 6 g. p-MeC6H4SO2NHNH2 in 30 ml. alc. gave 10.52 g. of the p-toluenesulfonylhydrazone (VI), m. 220° (decomposition). A mixture of 3 g. KOH, 5.10 g. VI, and 60 ml. alc. refluxed 7 hrs., treated with 40 ml. H2O, acidified with 6N HCl, and left overnight deposited 1.09 g. VII (R = R1 = H) (VIII), m. 211-12° (HCONMe2). The mother liquor from this preparation was concentrated, the residue was warmed with MeOH, and the sparingly soluble component was recrystallized from HCONMe2 to give IX (R = H) (X), m. 225-6°; acetate (IX, R = Ac) m. 169-70° (HOAc). The MeOH-soluble portion afforded 0.6 g. p-tolyl p-toluenethiolsulfonate, m. 75-6° (MeOH). VII (R = R1 = Me), m. 81.5-2.0° (C6H6-petr. ether), was obtained in 84.5% yield by the action of CH2N2 upon VIII. Powd. KMnO4 (2.65 g.) was added slowly to a solution of 0.53 g. VIII in 25 ml. 4N KOH, the mixture left overnight, excess KMnO4 decomposed with MeOH, and the product filtered and acidified with 6N HCl. The filtrate was concentrated in vacuo, Me2CO added to precipitate inorganic salts, and 0.4 g. 5-methylpyrazole-3,4-dicarboxylic acid (XI) was isolated from the residue obtained on concentration of the Me2CO solution The same oxidation of 0.3 g. X also gave XI. When 100 mg. 3,5-dibromotropolone was treated with CH2N2 30 mg. of product, m. 235-6° (decomposition), was obtained. The exptl. evidence available indicated either structure XII or Va (X = Br) for this compound N.M.R., ir, and uv spectral data are reported for all the compounds prepared In the part of experimental materials, we found many familiar compounds, such as Methyl 1-methyl-1H-pyrazole-4-carboxylate(cas: 5952-93-2Product Details of 5952-93-2)

Methyl 1-methyl-1H-pyrazole-4-carboxylate(cas: 5952-93-2) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. Product Details of 5952-93-2

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Grotjahn, Douglas B.; Van, Sang; Combs, David; Lev, Daniel A.; Schneider, Christian; Rideout, Marc; Meyer, Christoph; Hernandez, Genaro; Mejorado, Lupe published their research in Journal of Organic Chemistry on December 27 ,2002. The article was titled 《New Flexible Synthesis of Pyrazoles with Different, Functionalized Substituents at C3 and C5》.Recommanded Product: 29004-73-7 The article contains the following contents:

Pyrazoles functionalized at the 3 and 5 positions without carbon substituents at nitrogen are prepared in short sequences from THP-protected 3-propyn-1-ol and 4-propyn-1-ol. Lithiation of protected alkynes THPO(CH2)nCCH (n = 1,2) followed by transmetalation with zinc chloride and addition of acid chlorides RCOCl (R = Me, Me2CH, Me3C, Ph) provides alkynones THPO(CH2)nCCCOR; the alkynones are also prepared by palladium-catalyzed coupling reactions of protected alkynols and acid chlorides RCOCl (R = Me2CH, Me3C, Ph, 1-adamantyl)in triethylamine. Exothermic addition of hydrazine hydrate to alkynones THPO(CH2)nCCCOR (n = 1,2; R = Me, Me2CH, Me3C, Ph, 1-adamantyl) provides pyrazoles I (n = 1,2; R = Me, Me2CH, Me3C, Ph, 1-adamantyl; R1 = THPO); acid deprotection followed by chlorination with thionyl chloride provides pyrazolealkyl chlorides I (n = 1,2; R = Me, Me2CH, Me3C, Ph, 1-adamantyl; R1 = Cl). Substitution of I with lithium diphenylphosphide or thiolate salts generated in situ provides I (n = 1,2; R = Me, Me2CH, Me3C, Ph, 1-adamantyl; R1 = Ph2P, MeS, PhS, HOCH2CH2S, Me3CS) with potential use as neutral monodentate ligands. Compounds such as I (n = 1; R = Me3C; R1 = Cl) have been prepared in 2 d on a 30 g scale in 71% overall yield. In the experiment, the researchers used many compounds, for example, (3-methyl-1H-pyrazol-5-yl)methanol(cas: 29004-73-7Recommanded Product: 29004-73-7)

(3-methyl-1H-pyrazol-5-yl)methanol(cas: 29004-73-7) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. Recommanded Product: 29004-73-7

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Dowling, James E.; Alimzhanov, Marat; Bao, Larry; Block, Michael H.; Chuaqui, Claudio; Cooke, Emma L.; Denz, Christopher R.; Hird, Alex; Huang, Shan; Larsen, Nicholas A.; Peng, Bo; Pontz, Timothy W.; Rivard-Costa, Caroline; Saeh, Jamal Carlos; Thakur, Kumar; Ye, Qing; Zhang, Tao; Lyne, Paul D. published their research in ACS Medicinal Chemistry Letters on August 8 ,2013. The article was titled 《Structure and Property Based Design of Pyrazolo[1,5-a]pyrimidine Inhibitors of CK2 Kinase with Activity in Vivo》.Reference of 2-(3-Amino-1H-pyrazol-1-yl)ethanol The article contains the following contents:

In this letter, we describe the design, synthesis, and structure-activity relationship of 5-anilinopyrazolo[1,5-a]pyrimidine inhibitors, e.g., I, of CK2 kinase. Property-based optimization of early leads using the 7-oxetan-3-yl amino group led to a series of matched mol. pairs with lower lipophilicity, decreased affinity for human plasma proteins, and reduced binding to the hERG ion channel. Agents in this study were shown to modulate pAKTS129, a direct substrate of CK2, in vitro and in vivo, and exhibited tumor growth inhibition when administered orally in a murine DLD-1 xenograft. In the experiment, the researchers used 2-(3-Amino-1H-pyrazol-1-yl)ethanol(cas: 84407-13-6Reference of 2-(3-Amino-1H-pyrazol-1-yl)ethanol)

2-(3-Amino-1H-pyrazol-1-yl)ethanol(cas: 84407-13-6) belongs to anime. Amine, any member of a family of nitrogen-containing organic compounds that is derived, either in principle or in practice, from ammonia (NH3). Naturally occurring amines include the alkaloids, which are present in certain plants; the catecholamine neurotransmitters (i.e., dopamine, epinephrine, and norepinephrine); and a local chemical mediator, histamine, that occurs in most animal tissues.Reference of 2-(3-Amino-1H-pyrazol-1-yl)ethanol

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

《Synthesis of halosulfuron-methyl via selective chlorination at the 3- and/or 5-position of pyrazole-4-carboxylates》 was written by Morimoto, Katsushi; Sato, Toshiaki; Yamamoto, Susumu; Takeuchi, Hiroshi. Reference of Methyl 1-methyl-1H-pyrazole-4-carboxylate And the article was included in Journal of Heterocyclic Chemistry on April 30 ,1997. The article conveys some information:

Heating Me pyrazole-4-carboxylates I (X = Cl, Y = H; X = H, Y = Cl; X = Y = H) with N-chlorosuccinimide without a solvent gave I (X = Y = Cl) in good yields. Reaction of I (X = Y = H) with NaSH led to nucleophilic substitution on the 5-position regioselectively to afford I (X = Cl, Y = SH); subsequent oxidative chlorination and amination gave I (X = Cl, Y = SO2NH2). Finally, the reaction of I (X = Cl, Y = SO2NH2) with Ph 4,6-dimethoxy-2-pyrimidinyl carbamate provided halosulfuron-Me (II), a promising herbicide for cornfields. In the experimental materials used by the author, we found Methyl 1-methyl-1H-pyrazole-4-carboxylate(cas: 5952-93-2Reference of Methyl 1-methyl-1H-pyrazole-4-carboxylate)

Methyl 1-methyl-1H-pyrazole-4-carboxylate(cas: 5952-93-2) belongs to pyrazoles. Pyrazole derivatives have been reported to exhibit a wide range of applications in medicinal chemistry and pharmacology. A large number of drugs incorporating pyrazole structure have been utilized as partial agonists for nicotinic acid receptors, antidepressants, antimicrobial agents, antiviral agents, and antifungal agents solely or along with the combination of other structural motifs.Reference of Methyl 1-methyl-1H-pyrazole-4-carboxylate

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics