Month: October 2022

Formula: C5H6N2O2In 1994 ,《Thermal and photochemical evolution of triazolines obtained by addition of diazo compounds to methyl esters of oximino-malonodinitriles, oximino-cyanoacetates and oximino-malonates》 was published in Canadian Journal of Chemistry. The article was written by Perrocheau, Jacques; Carrie, Robert; Fleury, Jean-Pierre. The article contains the following contents:

Thermolysis of 1,2,3-triazolines I [R = Ts, COC6H4Z-4, Ac; R1 = H, Me, Ph, (MeO)2CH] leads to the corresponding aziridines only when X = Y = CO2Me, and then with a very low yield. However, photolysis or evolution in the presence of trifluoroacetic acid gives good results when carried out at sufficiently low temperature The thermolysis study of I shows a new route to 1,2,3-triazoline decomposition that has not yet been mentioned in the literature. The easy elimination of the p-toluenesulfonate or benzoate group explains this particular behavior. The experimental part of the paper was very detailed, including the reaction process of Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4Formula: C5H6N2O2)

Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4) 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.Formula: C5H6N2O2

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

SDS of cas: 474432-62-7On October 10, 2002 ,《Interactive SAR Studies: Rational Discovery of Super-Potent and Highly Selective Dopamine D3 Receptor Antagonists and Partial Agonists》 was published in Journal of Medicinal Chemistry. The article was written by Bettinetti, Laura; Schlotter, Karin; Huebner, Harald; Gmeiner, Peter. The article contains the following contents:

Starting from dopamine receptor ligand BP897, an interactive drug discovery process leading to heterocyclic bioisosteres is demonstrated. The four step strategy involved a careful optimization of geometric and electronic properties by systematic modification of the attachment points and heteroatoms, resp. Efficacy tuning by modification of the Ph substituents led to both D3 partial agonists and full antagonists. The benzothiophenes FAUC346 and FAUC365 revealed outstanding D3 affinity and subtype selectivity.Pyrazolo[1,5-a]pyridine-7-carboxylic acid(cas: 474432-62-7SDS of cas: 474432-62-7) was used in this study.

Pyrazolo[1,5-a]pyridine-7-carboxylic acid(cas: 474432-62-7) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, monoamine oxidase inhibitory, anti-inflammatory, antidiabetic and antibacterial activities. SDS of cas: 474432-62-7

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

Electric Literature of C6H8N2O2On October 31, 1991 ,《Synthesis of 5-chloropyrazoles by chlorodediazoniation with sulfur dioxide》 appeared in Journal of Heterocyclic Chemistry. The author of the article were Yamamoto, Susumu; Morimoto, Katsushi; Sato, Toshiaki. The article conveys some information:

A facile synthesis of 5-chloropyrazoles I (R = Cl, R1 = Me, R2 = H, R3 = CO2Me, CO2Et, CN; R1 = Ph, R2 = H, R3 = CO2Et; R1 = R2 = Me, R3 = CO2Et) from 5-aminopyrazoles I (R = NH2) via diazotization followed by chlorodediazoniation is described. A new application of sulfur dioxide as a catalyst for the chlorodediazoniation of diazonium chlorides I (R% = N2+Cl-). In the experiment, the researchers used Methyl 1-methyl-1H-pyrazole-4-carboxylate(cas: 5952-93-2Electric Literature of C6H8N2O2)

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. Electric Literature of C6H8N2O2

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

HPLC of Formula: 847818-72-8On May 12, 2016 ,《Discovery of a Highly Potent and Selective Indenoindolone Type 1 Pan-FLT3 Inhibitor》 appeared in ACS Medicinal Chemistry Letters. The author of the article were Hatcher, John M.; Weisberg, Ellen; Sim, Taebo; Stone, Richard M.; Liu, Suiyang; Griffin, James D.; Gray, Nathanael S.. The article conveys some information:

For a subpopulation of acute myeloid leukemia (AML) patients, the mutationally activated tyrosine kinase FLT3, has emerged as a promising target for therapy. The development of drug resistance due to mutation is a growing concern for mutant FLT3 inhibitors, such as PKC412, Quizartinib, PLX3397, and Crenolanib. Thus, there is a need to develop novel FLT3 inhibitors that overcome these mutations. Here the authors report the development of a novel type I ATP competitive inhibitor, I, that is extremely potent and selective for FLT3. I also has the highest affinity for three constitutively active isoforms of FLT3 (FLT3-ITD, FLT3-N841I, and FLT3-D835V) compared to a panel 456 other kinases. The unique and specific kinase inhibition profile suggests that this chemotype may represent an attractive starting point for the development of further improved FLT3 inhibitors with therapeutic potential in tumors harboring deregulated FLT3 activity. In the experimental materials used by the author, we found N,N-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-propanamine(cas: 847818-72-8HPLC of Formula: 847818-72-8)

N,N-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-propanamine(cas: 847818-72-8) 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. HPLC of Formula: 847818-72-8

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

Name: Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylateOn March 27, 2008, Silvestri, Romano; Cascio, Maria Grazia; La Regina, Giuseppe; Piscitelli, Francesco; Lavecchia, Antonio; Brizzi, Antonella; Pasquini, Serena; Botta, Maurizio; Novellino, Ettore; Di Marzo, Vincenzo; Corelli, Federico published an article in Journal of Medicinal Chemistry. The article was 《Synthesis, cannabinoid receptor affinity, and molecular modeling studies of substituted 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides》. The article mentions the following:

The new 1-phenyl-5-(1H-pyrrol-1-yl)pyrazole-3-carboxamides were compared with the reference compounds AM251 and SR144528 for cannabinoid hCB1 and hCB2 receptor affinity. Compounds bearing 2,4-dichlorophenyl or 2,4-difluorophenyl groups at position 1 and 2,5-dimethylpyrrole moiety at position 5 of the pyrazole nucleus were generally more selective for hCB1. On the other hand, the N-cyclohexyl group at the 3-carboxamide was the determinant for the hCB2 selectivity, in particular when a 3,4-dichlorophenyl group was also present at position 1. Compound I was the most selective ligand for the hCB1 receptor (Ki (CB2)/Ki (CB1) = 140.7). Derivative II, the most potent hCB1 ligand (Ki = 5.6 nM), was equipotent to AM251 and behaved as an inverse agonist in the cAMP assay (EC50 ∼1 nM). The carbonyl oxygen of both I and II formed a H-bond with K3.28(192), while the substituents at the nitrogen fitted in a pocket formed by lipophilic residues. This H-bonding interaction was proposed to account for the high affinity for receptors’ inactive state and the inverse agonist activity. The experimental part of the paper was very detailed, including the reaction process of Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9Name: Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate)

Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9) belongs to anime. To avoid the problem of multiple alkylation, methods have been devised for “blocking” substitution so that only one alkyl group is introduced. The Gabriel synthesis is one such method; it utilizes phthalimide, C6H4(CO)2NH, whose one acidic hydrogen atom has been removed upon the addition of a base such as KOH to form a salt.Name: Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate

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

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

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

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

《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