Category: pyrazoles-derivatives

Synthesis, cytotoxicity, and inhibitory effects on tubulin polymerization of a new 3-heterocyclo substituted 2-styrylquinazolinones was written by Raffa, Demetrio;Edler, Michael C.;Daidone, Giuseppe;Maggio, Benedetta;Merickech, Mourad;Plescia, Salvatore;Schillaci, Domenico;Bai, Ruoli;Hamel, Ernest. And the article was included in European Journal of Medicinal Chemistry in 2004.Synthetic Route of C5H9N3 This article mentions the following:

In order to study the influence of 3-substituents on the cytotoxic activity of 2-styrylquinazolinones, a series of 6-chloro-2-styryl-3-(heteroaryl)-4(3H)-quinazolinones, e.g. I, were synthesized by refluxing equimolar amounts of the corresponding 2-methyl-quinazolinones and benzaldehyde in glacial acetic acid. At 1 μg ml^-1 concentration, almost all the synthesized compounds showed some cytotoxic activity against the L1210 and K562 leukemia cell lines. However, only compound I inhibited the growth of these cells by over 50%. It was also found to be the only member of the series that inhibited tubulin polymerization, with an IC₅₀ value of 5.8 vs. 3.2 μM for control drug colchicine. I was further examined for effects on the growth of human MCF7 breast carcinoma cells and Burkitt lymphoma CA46 cells, which had IC₅₀ values of 0.34 and 1.0 μM, resp. At 10 μM, I induced G2/M arrest (66%) in Burkitt cells, with a mitotic index of 20%. At 3.4 μM, it caused disruption of the cellular microtubule system of the MCF7 cells. Both these cellular effects are consistent with its mechanism of action resulting from its inhibitory effect on tubulin assembly. In the experiment, the researchers used many compounds, for example, 1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3Synthetic Route of C5H9N3).

1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3) belongs to pyrazole derivatives. An alternative way to synthesize multisubstituted pyrazoles is the Csingle bondH arylation of simple 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.Synthetic Route of C5H9N3

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

Solvent-Induced Structural Changes in Complexes of 1,2-Bis(3-(3-pyridyl)pyrazolyl)ethane was written by Prananto, Yuniar P.;Turner, David R.;Lu, Jinzhen;Batten, Stuart R.. And the article was included in Australian Journal of Chemistry in 2009.Recommanded Product: 3-(1H-Pyrazol-3-yl)pyridine This article mentions the following:

A series of complexes were obtained using the flexible ditopic ligand 1,2-bis(3-(3-pyridyl)pyrazolyl)ethane (L^Et) with M(SCN)₂ (M = Co, Fe) and ZnCl₂. The ligand exists in a variety of conformations with rotations around the ethane spacer and around the pyridyl/pyrazole bond. The bridging length of the ligand (i.e., distance between pyridyl nitrogen atoms) varies by 3.5 Å depending on its geometry. Three different cobalt(II) complexes of the general form [Co(L^Et)₂(SCN)₂]·Solv (Solv is a variable number/type of non-coordinated solvent) were structurally characterized and form a series of solvent dependant supramol. isomers. When Solv = 2MeCN a (4,4)-sheet is formed (1), however, when Solv = H₂O an alternate collapsed (4,4)-sheet is observed (2). Changing the solvent to two mols. of N,N-dimethylformamide (DMF) leads to a radical change in structure with a one-dimensional (1D) polymer formed (3) that contains two bridging ligands between adjacent metal atoms (i.e., maintaining the same metal/ligand ratio as in the (4,4)-sheet structures). A monomeric thiocyanate complex [Fe(L^Et)₂(SCN)₂(H₂O)₂] (4) is reported in which the bispyridyl ligands are terminal and partake in an extended hydrogen-bonded network. A 1D polymer [Zn(L^Et)Cl₂] (5) is also presented. The structures of the metal complexes are contrasted with that of the free ligand. In the experiment, the researchers used many compounds, for example, 3-(1H-Pyrazol-3-yl)pyridine (cas: 45887-08-9Recommanded Product: 3-(1H-Pyrazol-3-yl)pyridine).

3-(1H-Pyrazol-3-yl)pyridine (cas: 45887-08-9) belongs to pyrazole derivatives. An alternative way to synthesize multisubstituted pyrazoles is the Csingle bondH arylation of simple pyrazoles. Protonation of pyrazole in strong acid leads to pyrazolium cations, which undergo electrophilic substitution preferentially at C3 rather than C4. The pyrazole anion is not reactive toward nucleophiles but is mostly reactive to electrophiles.Recommanded Product: 3-(1H-Pyrazol-3-yl)pyridine

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

Design of Potent, Selective, and Orally Bioavailable Inhibitors of Cysteine Protease Cathepsin K was written by Tavares, Francis X.;Boncek, Virginia;Deaton, David N.;Hassell, Anne M.;Long, Stacey T.;Miller, Aaron B.;Payne, Alan A.;Miller, Larry R.;Shewchuk, Lisa M.;Wells-Knecht, Kevin;Willard, Derril H. Jr.;Wright, Lois L.;Zhou, Hui-Qiang. And the article was included in Journal of Medicinal Chemistry in 2004.Reference of 3528-58-3 This article mentions the following:

Osteoclast-mediated bone matrix resorption has been attributed to cathepsin K, a cysteine protease of the papain family that is abundantly and selectively expressed in osteoclast. Inhibition of cathepsin K could potentially be an effective method to prevent osteoporosis. Structure-activity studies on a series of reversible ketoamides based inhibitors of cathepsin K have led to identification of potent and selective compounds Crystallog. studies have given insights into the mode of binding of these inhibitors. A series of ketoamides with varying P1 moieties were first synthesized to find an optimum group that would fit into the S1 subsite of the cysteine protease, cathepsin K. With a desired P1 group in place a variety of heterocyclic analogs in the P’ region were synthesized to study their steric and electronic effects. In the process of exploring these P’ heterocyclic variations, excellent selectivity was gained over other highly homologous cysteine proteases, including cathepsins L, S, and V. The favorable pharmacokinetic properties of some of these cathepsin K inhibitors in rats make them suitable for evaluation in rodent osteoporosis models. A representative cathepsin K inhibitor was shown to attenuate PTH-stimulated hypercalcemia in the TPTX rat model. These inhibitors provide a viable lead series in the discovery of new therapies for the prevention and treatment of osteoporosis. In the experiment, the researchers used many compounds, for example, 1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3Reference of 3528-58-3).

1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3) belongs to pyrazole derivatives. Pyrazole is a weak base, with pKb 11.5 (pKa of the conjugated acid 2.49 at 25 °C).Pyrazole used as a ligand to prepare organometallic compounds. 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.Reference of 3528-58-3

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

Identification of Novel d-Amino Acid Oxidase Inhibitors by in Silico Screening and Their Functional Characterization in Vitro was written by Katane, Masumi;Osaka, Naoko;Matsuda, Satsuki;Maeda, Kazuhiro;Kawata, Tomonori;Saitoh, Yasuaki;Sekine, Masae;Furuchi, Takemitsu;Doi, Issei;Hirono, Shuichi;Homma, Hiroshi. And the article was included in Journal of Medicinal Chemistry in 2013.Computed Properties of C9H7BrN2 This article mentions the following:

D-Amino acid oxidase (DAO) is a degradative enzyme that is stereospecific for d-amino acids, including d-serine and d-alanine, which are potential coagonists of the N-methyl-d-aspartate (NMDA) receptor. Dysfunction of NMDA receptor-mediated neurotransmission has been implicated in the onset of various mental disorders such as schizophrenia. Hence, a DAO inhibitor that augments the brain levels of d-serine and/or d-alanine and thereby activates NMDA receptor function is expected to be an antipsychotic drug, for instance, in the treatment of schizophrenia. In the search for potent DAO inhibitor(s), a large number of compounds were screened in silico, and several compounds were estimated as candidates. These compounds were then characterized and evaluated as novel DAO inhibitors in vitro. The results reported in this study indicate that some of these compounds are possible lead compounds for the development of a clin. useful DAO inhibitor and have the potential to serve as active site probes to elucidate the structure-function relationships of DAO. In the experiment, the researchers used many compounds, for example, 3-(4-Bromophenyl)-1H-pyrazole (cas: 73387-46-9Computed Properties of C9H7BrN2).

3-(4-Bromophenyl)-1H-pyrazole (cas: 73387-46-9) belongs to pyrazole derivatives. The 1H-pyrazole provides an excellent means by which to provide the requisite hydrogen bond acceptor–donor motifs, whether as a monocyclic ring or as a fused indazole ring. Pyrazoles can be selectively lithiated at different carbons and subsequently react with electrophiles depending on the substitution patterns.Computed Properties of C9H7BrN2

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

Approach to the library of fused pyridine-4-carboxylic acids by Combes-type reaction of acyl pyruvates and electron-rich amino heterocycles was written by Volochnyuk, Dmitriy M.;Ryabukhin, Sergey V.;Plaskon, Andrey S.;Dmytriv, Yuri V.;Grygorenko, Oleksandr O.;Mykhailiuk, Pavel K.;Krotko, Dmitriy G.;Pushechnikov, Alexei;Tolmachev, Andrey A.. And the article was included in Journal of Combinatorial Chemistry in 2010.Formula: C8H15N3 This article mentions the following:

A library of fused pyridine-4-carboxylic acids (including pyrazolo[3,4-b]pyridines, isoxazolo[5,4-b]pyridines, furo[2,3-b]pyridines, thieno[2,3-b]pyridines, and pyrido[2,3-d]pyrimidines) was generated by Combes-type reaction of acyl pyruvates and electron-rich amino heterocycles followed by hydrolysis of the ester. The library members were also demonstrated to undergo the standard combinatorial transformations including amide coupling and esterification, as well as less common heterocyclizations to 1,2,4-triazoles and 1,2,4-oxadiazoles. In the experiment, the researchers used many compounds, for example, 1-(tert-Butyl)-3-methyl-1H-pyrazol-5-amine (cas: 141459-53-2Formula: C8H15N3).

1-(tert-Butyl)-3-methyl-1H-pyrazol-5-amine (cas: 141459-53-2) belongs to pyrazole derivatives. Pyrazole has two ring nitrogen atoms in which N1 is pyrrolic and N2 is pyridine-like. The N1 nitrogen is not reactive but is deprotonated in the presence of a base-forming anion. The pyrazole ring is resistant to oxidation and reduction but the groups, such as alkyl and formyl attached to the ring, are oxidized to respective acids. Only electrolytic oxidation, ozonolysis, and a strong base cause ring opening.Formula: C8H15N3

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

5-Aminopyrazoles as Dienophiles in the Inverse Electron Demand Diels-Alder Reactions of 2,4,6-Tris(ethoxycarbonyl)-1,3,5-triazine: Syntheses of Pyrazolopyrimidines was written by Dang, Qun;Brown, Brian S.;Erion, Mark D.. And the article was included in Journal of Organic Chemistry in 1996.Safety of 1-Ethyl-1H-pyrazol-5-amine This article mentions the following:

[4 + 2] Cycloaddition reactions of 2,4,6-tris(ethoxycarbonyl)-1,3,5-triazine with 5-aminopyrazoles are reported. This methodol. is suitable for the one-step synthesis of highly substituted pyrazolo[3,4-d]pyrimidines. In the experiment, the researchers used many compounds, for example, 1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3Safety of 1-Ethyl-1H-pyrazol-5-amine).

1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3) belongs to pyrazole derivatives. The strategies for the synthesis of pyrazoles generally can be applied for the construction of indazoles. Protonation of pyrazole in strong acid leads to pyrazolium cations, which undergo electrophilic substitution preferentially at C3 rather than C4. The pyrazole anion is not reactive toward nucleophiles but is mostly reactive to electrophiles.Safety of 1-Ethyl-1H-pyrazol-5-amine

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

Three Modes of Proton Transfer in One Chromophore: Photoinduced Tautomerization in 2-(1H-Pyrazol-5-yl)Pyridines, Their Dimers and Alcohol Complexes was written by Vetokhina, Volha;Dobek, Krzysztof;Kijak, Michal;Kaminska, Izabela I.;Muller, Keven;Thiel, Werner R.;Waluk, Jacek;Herbich, Jerzy. And the article was included in ChemPhysChem in 2012.Recommanded Product: 2-(5-Methyl-1H-pyrazol-3-yl)pyridine This article mentions the following:

Studies of 2-(1H-pyrazol-5-yl)pyridine (PPP) and its derivatives 2-(4-methyl-1H-pyrazol-5-yl)pyridine (MPP) and 2-(3-bromo-1H-pyrazol-5-yl)pyridine (BPP) by stationary and time-resolved UV/Vis spectroscopic methods, and quantum chem. computations show that this class of compounds provides a rare example of mols. that exhibit three types of photoreactions: (1) excited-state intramol. proton transfer (ESIPT) in the syn form of MPP, (2) excited-state intermol. double-proton transfer (ESDPT) in the dimers of PPP in nonpolar media, as well as (3) solvent-assisted double-proton transfer in hydrogen-bonded 1:1 complexes of PPP and MPP with alc. partners. The excited-state processes are manifested by the appearance of a dual luminescence and a bimodal irreversible kinetic coupling of the two fluorescence bands. Ground-state syn-anti equilibrium are detected and discussed. The fraction of the higher-energy anti form varies for different derivatives and is strongly dependent on the solvent polarity and hydrogen-bond donor or acceptor abilities. In the experiment, the researchers used many compounds, for example, 2-(5-Methyl-1H-pyrazol-3-yl)pyridine (cas: 19959-77-4Recommanded Product: 2-(5-Methyl-1H-pyrazol-3-yl)pyridine).

2-(5-Methyl-1H-pyrazol-3-yl)pyridine (cas: 19959-77-4) belongs to pyrazole derivatives. The 1H-pyrazole provides an excellent means by which to provide the requisite hydrogen bond acceptor–donor motifs, whether as a monocyclic ring or as a fused indazole ring. The presence of both electronegative nitrogen atoms in the pyrazole ring reduces the electron density of the C3- and C5-positions leaving electron density of C4-position unaltered. Thus the C4-position is vulnerable to electrophilic attack. The C3 electrophilic-position may undergo deprotonation in the presence of a strong base leading to ring opening.Recommanded Product: 2-(5-Methyl-1H-pyrazol-3-yl)pyridine

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

Overall Synthesis of GSK356278: Quick Delivery of a PDE4 Inhibitor Using a Fit-for-Purpose Approach was written by Guercio, Giuseppe;Castoldi, Damiano;Giubellina, Nicola;Lamonica, Alessandro;Ribecai, Arianna;Stabile, Paolo;Westerduin, Pieter;Dams, Riet;Nicoletti, Anna;Rossi, Sara;Bismara, Claudio;Provera, Stefano;Turco, Lucilla. And the article was included in Organic Process Research & Development in 2010.Computed Properties of C5H9N3 This article mentions the following:

The family of phosphodiesterase (PDE) enzymes hydrolyze cyclic nucleotides, cAMP and cGMP, leading to their inactivation as intracellular second messengers. Inhibition of these enzymes leads to an elevation of levels of cyclic nucleotides in the cell and prolongs their action on downstream signaling pathways. PDE4, of which there are four subtypes, is widely expressed throughout the brain but is also abundant in the periphery in inflammatory and immune cells, in the gastrointestinal tract, and in cardiac myocytes. GSK356278 (I) is a potent, selective, and competitive inhibitor of PDE4 enzymes currently under investigation for the treatment of CNS disorders. The initial synthetic route developed by Medicinal Chem. Department, used several hazardous and/or expensive reagents and harsh conditions and gave relatively low yields. By targeted process of research and development plus application of anal. techniques to identify byproduct and extensive route scouting, a novel synthetic route for I has been developed. This contribution reports the optimization of the chem. synthesis of I to develop a large-scale process suitable for its synthesis. In the experiment, the researchers used many compounds, for example, 1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3Computed Properties of C5H9N3).

1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3) belongs to pyrazole derivatives. As is the case with imidazoles, the pyrazole ring offers many opportunities to create new multiring systems that incorporate this heterocycle. Protonation of pyrazole in strong acid leads to pyrazolium cations, which undergo electrophilic substitution preferentially at C3 rather than C4. The pyrazole anion is not reactive toward nucleophiles but is mostly reactive to electrophiles.Computed Properties of C5H9N3

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

Synthesis of new heterocycles by using thiocarbohydrazide and thiosemicarbazides was written by Chande, Madhukar S.;Pankhi, Mohd Aslam;Ambhaikar, Shireesh B.. And the article was included in Indian Journal of Chemistry in 2000.Product Details of 51395-52-9 This article mentions the following:

3-Amino-2-alkyl/arylimino-5-carbethoxy-thiazolidin-4-ones, 2-hydrazino-6-carbethoxy-4H,6H-1,3,4-thiadiazin-5-one, 2-hydrazino-7-substituted, 5,7-disubstituted-4H-pyrazolo[5,4-e]1,3,4-thiadiazines and 2-hydrazino-7-phenyl-4H-isoxazolo[5,4-e]-1,3,4-thiadiazine have been synthesized. The compounds have been characterized by chem. reactions, alternate syntheses and spectral data. In the experiment, the researchers used many compounds, for example, 4-Bromo-3-methyl-1H-pyrazol-5(4H)-one (cas: 51395-52-9Product Details of 51395-52-9).

4-Bromo-3-methyl-1H-pyrazol-5(4H)-one (cas: 51395-52-9) belongs to pyrazole derivatives. As is the case with imidazoles, the pyrazole ring offers many opportunities to create new multiring systems that incorporate this heterocycle. The presence of both electronegative nitrogen atoms in the pyrazole ring reduces the electron density of the C3- and C5-positions leaving electron density of C4-position unaltered. Thus the C4-position is vulnerable to electrophilic attack. The C3 electrophilic-position may undergo deprotonation in the presence of a strong base leading to ring opening.Product Details of 51395-52-9

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

Pyrimidinone Nicotinamide Mimetics as Selective Tankyrase and Wnt Pathway Inhibitors Suitable for in Vivo Pharmacology was written by Johannes, Jeffrey W.;Almeida, Lynsie;Barlaam, Bernard;Boriack-Sjodin, P. Ann;Casella, Robert;Croft, Rosemary A.;Dishington, Allan P.;Gingipalli, Lakshmaiah;Gu, Chungang;Hawkins, Janet L.;Holmes, Jane L.;Howard, Tina;Huang, Jian;Ioannidis, Stephanos;Kazmirski, Steven;Lamb, Michelle L.;McGuire, Thomas M.;Moore, Jane E.;Ogg, Derek;Patel, Anil;Pike, Kurt G.;Pontz, Timothy;Robb, Graeme R.;Su, Nancy;Wang, Haiyun;Wu, Xiaoyun;Zhang, Hai-Jun;Zhang, Yue;Zheng, Xiaolan;Wang, Tao. And the article was included in ACS Medicinal Chemistry Letters in 2015.Product Details of 18213-75-7 This article mentions the following:

The canonical Wnt pathway plays an important role in embryonic development, adult tissue homeostasis, and cancer. Germline mutations of several Wnt pathway components, such as Axin, APC, and ss-catenin, can lead to oncogenesis. Inhibition of the poly(ADP-ribose) polymerase (PARP) catalytic domain of the tankyrases (TNKS1 and TNKS2) is known to inhibit the Wnt pathway via increased stabilization of Axin. In order to explore the consequences of tankyrase and Wnt pathway inhibition in preclin. models of cancer and its impact on normal tissue, the authors sought a small mol. inhibitor of TNKS1/2 with suitable physicochem. properties and pharmacokinetics for hypothesis testing in vivo. Starting from a 2-Ph quinazolinone hit I, the authors discovered the pyrrolopyrimidinone compound II (AZ6102), which is a potent TNKS1/2 inhibitor that has 100-fold selectivity against other PARP family enzymes and shows 5 nM Wnt pathway inhibition in DLD-1 cells. Moreover, compound II can be formulated well in a clin. relevant i.v. solution at 20 mg/mL, has demonstrated good pharmacokinetics in preclin. species, and shows low Caco2 efflux to avoid possible tumor resistance mechanisms. In the experiment, the researchers used many compounds, for example, 5-Amino-1-methyl-1H-pyrazole-4-carboxamide (cas: 18213-75-7Product Details of 18213-75-7).

5-Amino-1-methyl-1H-pyrazole-4-carboxamide (cas: 18213-75-7) belongs to pyrazole derivatives. An alternative way to synthesize multisubstituted pyrazoles is the Csingle bondH arylation of simple pyrazoles. Pyrazole rings have been used as core components of several leading non-steroidal anti-inflammatory drugs (NSAIDs) and antihypertensive drugs. It has also been found to be useful as a bifunctional ligand for metal catalysis.Product Details of 18213-75-7

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