pyrazoles-derivatives

Addressing species specific metabolism and solubility issues in a quinoline series of oral PDE4 inhibitors was written by Lunniss, C.;Eldred, C.;Aston, N.;Craven, A.;Gohil, K.;Judkins, B.;Keeling, S.;Ranshaw, L.;Robinson, E.;Shipley, T.;Trivedi, N.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2010.Related Products of 3528-58-3 This article mentions the following:

Species specific conversion of the lead PDE4 inhibitor 1 to the quinolone 3 was identified as the major route of metabolism in the cynomolgus monkey. Modification of the template to give the cinnoline 9 retained potency and selectivity, and greatly improved the pharmacokinetic profile in the cynomolgus monkey compared with 1. Addnl. SAR studies aimed at improving the solubility of 9 are also described. In the experiment, the researchers used many compounds, for example, 1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3Related Products of 3528-58-3).

1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3) belongs to pyrazole derivatives. Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. 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.Related Products of 3528-58-3

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

Discovery of a Potent, Selective, Orally Bioavailable, and Efficacious Novel 2-(Pyrazol-4-ylamino)-pyrimidine Inhibitor of the Insulin-like Growth Factor-1 Receptor (IGF-1R) was written by Degorce, Sebastien L.;Boyd, Scott;Curwen, Jon O.;Ducray, Richard;Halsall, Christopher T.;Jones, Clifford D.;Lach, Franck;Lenz, Eva M.;Pass, Martin;Pass, Sarah;Trigwell, Catherine. And the article was included in Journal of Medicinal Chemistry in 2016.Product Details of 5334-39-4 This article mentions the following:

Optimization of cellular lipophilic ligand efficiency (LLE) in a series of 2-anilino-pyrimidine IGF-1R kinase inhibitors led to the identification of novel 2-(pyrazol-4-ylamino)-pyrimidines with improved physicochem. properties. Replacement of the imidazo[1,2-a]pyridine group of the previously reported inhibitor 3 with the related pyrazolo[1,5-a]pyridine improved IGF-1R cellular potency. Substitution of the amino-pyrazole group was key to obtaining excellent kinase selectivity and pharmacokinetic parameters suitable for oral dosing, which led to the discovery of (2R)-1-[4-(4-{[5-chloro-4-(pyrazolo[1,5-a]pyridin-3-yl)-2-pyrimidinyl]amino}-3,5-dimethyl-1H-pyrazol-1-yl)-1-piperidinyl]-2-hydroxy-1-propanone (AZD9362, 28), a novel, efficacious inhibitor of IGF-1R. In the experiment, the researchers used many compounds, for example, 3-Methyl-4-nitro-1H-pyrazole (cas: 5334-39-4Product Details of 5334-39-4).

3-Methyl-4-nitro-1H-pyrazole (cas: 5334-39-4) 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. 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.Product Details of 5334-39-4

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

Variable Luminescence and Chromaticity of Homoleptic Frameworks of the Lanthanides together with Pyridylpyrazolates was written by Youssef, Heba;Sedykh, Alexander E.;Becker, Jonathan;Schafer, Thomas;Taydakov, Ilya V.;Li, Huanrong R.;Mueller-Buschbaum, Klaus. And the article was included in Chemistry – A European Journal in 2021.Name: 3-(1H-Pyrazol-3-yl)pyridine This article mentions the following:

Homoleptic, 3D coordination polymers of the formula ³³_{âˆ?/sub>[Ln(3-PyPz)3] and ³âˆ?/sub>[Ln(4-PyPz)3], (3-PyPz)^– = 3-(3-pyridyl)pyrazolate anion, (4-PyPz)^– = 3-(4-pyridyl)pyrazolate anion, both C8H6N3^–, Ln = Sm, Eu, Gd, Tb, Dy, were obtained as highly luminescent frameworks by reaction of the lanthanide metals (Ln) with the aromatic heterocyclic amine ligands 3-PyPzH and 4-PyPzH. The compounds form 2 isotypic series of 3D coordination polymers and exhibit fair thermal stability up to 360°. The luminescence properties of all 10 compounds were determined in the solid state, with an antenna effect through ligand-metal energy transfer leading to high efficiency of the luminescence displayed by good quantum yields of up to 74%. The emission is mainly based on ion-specific lanthanide-dependent intra 4f-4f transitions for Tb³⁺: green, Dy³⁺: yellow, Sm³⁺: orange-red, Eu³⁺: red. For the Gd³⁺-containing compounds, the yellow emission of ligand triplet-based phosphorescence is observed at room temperature and 77 K. Codoping of the Gd-containing frameworks with Eu³⁺ and Tb³⁺ allow further shifting of the chromaticity towards white light emission. In the experiment, the researchers used many compounds, for example, 3-(1H-Pyrazol-3-yl)pyridine (cas: 45887-08-9Name: 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. 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.Name: 3-(1H-Pyrazol-3-yl)pyridine

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: C5H9N3 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-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3Formula: C5H9N3).

1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3) 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. 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.Formula: C5H9N3

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

Sulfanilamidopyrazoles. IX. Chloro, methyl, and methoxy derivatives of 1-phenyl-5-sulfanilamidopyrazole was written by Alberti, Carlo;Tironi, C.. And the article was included in Farmaco, Edizione Scientifica in 1967.Application of 14678-93-4 This article mentions the following:

Pyrazoles of the general formula I are prepared; the introduction of Cl, Me, or MeO into the 1-phenyl ring decreases the bacteriostatic activity of I (R = X = H, Ar = p-H2NC6H4SO2) against Staphylococcus aureus and Escherichia coli. Thus, 2.9 g. o-ClC6H4NHNH2 in 10 ml. EtOH is treated with 3.4 g. EtOCH:C(CO2Et)CN in 10 ml. EtOH to give 65% Et α-cyano-β-[2-(o-chlorophenyl)hydrazino]acrylate (II), m. 147-8° (EtOH). Similarly prepared are (m.p. and % yield given): o-MeC6H4NHNHCH:C(CO2Et)CN, 147-8° (C6H6), 90; o-MeOC6H4NHNHCH:C(CO2Et)CN, 118-19° (C6H6), 61. A solution of 5.3 g. II in 50 ml. HOAc is refluxed 3 hrs. to give 80% Et 5-amino-1-(o-chlorophenyl)pyrazole-4-carboxylate, m. 83-4° (C6H6). Similarly prepared are (m.p. given): I (Ar = H, X = o-Me, R = CO2Et), 58-9° (EtOH-water); I (Ar = H, X = o-MeO, R = CO2Et), 78-9° (ligroine). A solution of 16.9 g. EtOCH:C(CO2Et)CN and 14.25 g. m-ClC6H4NHNH2 in 100 ml. EtOH is refluxed 3 hrs. to give 96% I (Ar = H, X = m-Cl, R = CO2Et), m. 117-18° (EtOH). Similarly prepared are the following I (Ar = H, R = CO2Et) (X and m.p. given): p-Cl, 148-9° (EtOH); m-Me, 65-6° (C6H6); p-Me, 114-15° (C6H6); m-MeO, 71-2° (ligroine); p-MeO, 110-11° (ligroine). The I (R = CO2Et) are heated with 2N NaOH to give the following I (Ar = H, R = CO2H) (X and m.p. given): o-Cl, 170-1°; m-Cl, 152-3°; p-Cl, 192-3°; o-Me, 167-8°; m-Me, 169-70°; p-Me, 178-9°; o-MeO, 154-5°; m-MeO, 166-7°; p-MeO, 184-5°. I (Ar = H, R = CO2H, X = o-Me) (4.4 g.) is heated at 170-80° to give 95% 1-(o-tolyl)-5-aminopyrazole, m. 57-8° (C6H6). Similarly prepared are the following I (Ar = R = H) (X and m.p. given): p-Me, 53-4° (ligroine); o-MeO, [HCl salt m. 216-17° (EtOH-Et2O)]; m-MeO, 65-6°; p-MeO, 87-8°. A mixture of 4.75 g. I (Ar = H, R = CO2H, X = o-Cl) and 70 ml. 75% H2SO4 is heated at 150-60° to give 78% I (Ar = R = H, X = o-Cl) (III), m. 56-7° (ligroine-ether); HOAc can also be used. Similarly prepared are the following I (Ar = R = H) (X and m.p. given): m-Cl, 91-2°; p-Cl, 82-3° (ligroine); m-Me, [HCl salt m. 217-18° (EtOH-Et2O)]. A mixture of 3.8 g. III, 4.7 g. p-AcNHC6H4SO2Cl, and 10 ml. pyridine is heated 15 min. at 40-50° and kept 12 hrs. at room temperature to give 90% 1-(o-chlorophenyl)-5-(p-acetamidobenzenesulfonamido)pyrazole (IV), m. 238-9° (dilute EtOH). Similarly prepared are the following I (Ar = p-AcNHC6H4SO2, R = H) (X and m.p. given): p-Cl, 244-5°; o-Me, 237-8°; m-Me, 209-10°; p-Me, 257-8°; o-MeO, 210-11°; m-MeO, 181-2°; p-MeO, 230-1°. A mixture of 3.9 g. IV and 40 ml. 5% NaOH is refluxed to give 87% 1-(o-chlorophenyl)-5-sulfanilamidopyrazole, m. 145-6°. Similarly prepared are the following I (Ar = p-H2NC6H4SO2, R = H) (X and m.p. given): m-Cl, 139-40°; p-Cl, 164-5°; o-Me, 166-7°; m-Me, 123-4°; p-Me, 161-2°; o-MeO, 161-2°; m-MeO, 178-9°; p-MeO, 162-3°. Phenylhydrazines are treated with mixtures of Ac2O and acrylonitrile, N1-phenyl-N2-(2-cyanoethyl)hydrazines are not obtained; the following compounds are isolated (m.p. given): o-ClC6H4NHNHAc, 119-20°; m-ClC6H4NHNHAc, 133-4°; p-ClC6H4NHNHAc, 156-7°. In the experiment, the researchers used many compounds, for example, 5-Amino-1-(p-tolyl)-1H-pyrazole-4-carboxylic acid (cas: 14678-93-4Application of 14678-93-4).

5-Amino-1-(p-tolyl)-1H-pyrazole-4-carboxylic acid (cas: 14678-93-4) 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.Application of 14678-93-4

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

A simple and efficient synthesis of pyrazoles in water was written by Wen, Jun;Fu, Yun;Zhang, Ruo-Yi;Zhang, Ji;Chen, Shan-Yong;Yu, Xiao-Qi. And the article was included in Tetrahedron in 2011.Recommanded Product: 2-(5-Methyl-1H-pyrazol-3-yl)pyridine This article mentions the following:

A simple, highly efficient, and environmentally friendly method for the synthesis of substituted 1H-pyrazoles by one-pot condensation reaction of α,β-unsaturated carbonyl compounds with tosyl hydrazide in water was developed. The reaction system exhibited tolerance with various functional groups. Aromatic moieties with both electron-rich and electron-deficient substituents gave desired products in good to excellent yields. 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. Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. Pyrazole the presence of this nucleus in pharmacological agents of diverse therapeutic categories such as celecoxib, a potent anti-inflammatory, the antidepressant agent fezolamide have proved the pharmacological potential of the pyrazole moiety. Recommanded Product: 2-(5-Methyl-1H-pyrazol-3-yl)pyridine

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

Use of pyrazoles as ligands greatly enhances the catalytic activity of titanium iso-propoxide for the ring-opening polymerization of L-lactide: a cooperation effect was written by Wang, Tzu-Fang;Kosuru, Someswara Rao;Yu, Shu-Chun;Chang, Yung-Chi;Lai, Hsin-Yu;Chang, Yu-Lun;Wu, Kuo-Hui;Ding, Shangwu;Chen, Hsuan-Ying. And the article was included in RSC Advances in 2020.Application of 15953-73-8 This article mentions the following:

Using TiOⁱPr₄ with a pyrazole ligand for one-pot LA polymerization improved catalytic activity compared with using TiOⁱPr₄ only. At 60°, TiOⁱPr₄ with ^furPz exhibited a higher catalytic activity (approx. 3-fold) than TiOⁱPr₄. At room temperature, TiOⁱPr₄ with ^BuPz exhibited a higher catalytic activity (approx. 17-fold) than TiOⁱPr₄. High mol. mass PLA (M_nGPC = 51 100, and D = 1.10) could be produced by using TiOⁱPr₄ with ^furPz in melt polymerization ([TiOⁱPr₄] : [^furPz] = 1000 : 1 : 1 at 100°, 240 min). The crystal structure of ^MePz₂Ti₂OⁱPr₇ revealed the cooperative activation between two Ti atoms during LA polymerization In the experiment, the researchers used many compounds, for example, 4-Chloro-3,5-dimethyl-1H-pyrazole (cas: 15953-73-8Application of 15953-73-8).

4-Chloro-3,5-dimethyl-1H-pyrazole (cas: 15953-73-8) belongs to pyrazole derivatives. The strategies for the synthesis of pyrazoles generally can be applied for the construction of indazoles. 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.Application of 15953-73-8

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

Interaction of sulfaphenazole derivatives with human liver cytochromes P450 2C: molecular origin of the specific inhibitory effects of sulfaphenazole on CYP 2C9 and consequences for the substrate binding site topology of CYP 2C9 was written by Mancy, Annah;Dijols, Sylvie;Poli, Sonia;Guengerich, F. Peter;Mansuy, Daniel. And the article was included in Biochemistry in 1996.Recommanded Product: 3528-58-3 This article mentions the following:

The effects of sulfaphenazole (I) on typical activities catalyzed by human cytochromes P 450 of the 1A, 3A, and 2C subfamilies expressed in yeast were studied. I acts as a strong, competitive inhibitor of CYP 2C9 (K_i = 0.3 ± 0.1 μM); it is much less potent toward CYP 2C8 and 2C18 (K_i = 63 and 29 μM, resp.) and fails to inhibit CYP 1A1, 1A2, 3A4, and 2C19. From difference visible spectroscopy experiments using microsomes of yeast expressing various human P450s, I selectively interacts only with CYP 2C9 with the appearance of a peak at 429 nm as expected for the formation of a P 450 Fe(III)-nitrogenous ligand complex (K_s = 0.4 ± 0.1 μM). Comparative studies of the spectral interaction and inhibitory effects of twelve compounds related to I with CYP 2C9 showed that the aniline function of I is responsible for the formation of the iron-nitrogen bond of the 429 nm-absorbing complex and is necessary for the inhibitory effects of I. The study of two new compounds synthesized during this work, in which the N-Ph group of I was replaced with either an Et group or a 3,4-dichlorophenyl group, showed that the presence of an hydrophobic substituent at position I of the pyrazole function of I is required for a strong interaction with CYP 2C9. A model for the binding of I in the CYP 2C9 active site is proposed; that takes into account three major interactions that should be at the origin of the high-affinity and specific inhibitory effects of I toward CYP 2C9: (i) the binding of its nitrogen atom to CYP 2C9 iron, (ii) an ionic interaction of its SO₂N^– anionic site with a cationic residue of CYP 2C9, and (iii) an interaction of its N-Ph group with an hydrophobic part of the protein active site. In the experiment, the researchers used many compounds, for example, 1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3Recommanded Product: 3528-58-3).

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. 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.Recommanded Product: 3528-58-3

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

Solvatochromism of Heteroaromatic Compounds: XX. 4(5)-Nitroimidazole was written by Vokin, A. I.;Sherstyannikova, L. V.;Krivoruchka, I. G.;Aksamentova, T. N.;Krylova, O. V.;Turchaninov, V. K.. And the article was included in Russian Journal of General Chemistry (Translation of Zhurnal Obshchei Khimii) in 2003.Related Products of 54210-32-1 This article mentions the following:

4(5)-Nitroimidazole in solution is stabilized as the 5-nitro isomer due to formation of hydrogen bond with an aprotic protophilic solvent. Amphiprotic medium favors displacement of the tautomeric equilibrium toward the 4-nitro isomer via formation of a solvate complex where 4-nitroimidazole acts as hydrogen bond acceptor. The observed specific solvatochromic effect in the UV spectrum of 4-nitroimidazole and related heterocyclic nitro compounds is determined by the electronic configuration of the excited π,π*-state. In the experiment, the researchers used many compounds, for example, 1-Methyl-3-nitro-1H-pyrazole (cas: 54210-32-1Related Products of 54210-32-1).

1-Methyl-3-nitro-1H-pyrazole (cas: 54210-32-1) 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.Related Products of 54210-32-1

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

Heterocyclic fungicides. Part IV was written by Mitra, P.;Mittra, A. S.. And the article was included in Journal of the Indian Chemical Society in 1984.Electric Literature of C4H5BrN2O This article mentions the following:

Thiazolidones I [R = Ph, C₆H₄OMe, C₆H₄NO₂, C₆H₄OH, C₆H₃(OH)OMe, CH:CHPh, C₆H₄NMe₂, furyl] condensed with bromopyrazolinones II (R¹ = H, Ph) to give thiazolidonylpyrazolinones III. At 1000 ppm, III gave 28.0-66.0% inhibition of spore germination for P. oryzae and H. oryzae. The most effective compounds were III (R = Ph, C₆H₄NO₂-2, CH:CHPh, R¹ = H, Ph; R = C₆H₄NO₂-3, C₆H₄OMe, R¹ = Ph), with 51.4-66.0% germination inhibition for both fungi at 1000 ppm. In the experiment, the researchers used many compounds, for example, 4-Bromo-3-methyl-1H-pyrazol-5(4H)-one (cas: 51395-52-9Electric Literature of C4H5BrN2O).

4-Bromo-3-methyl-1H-pyrazol-5(4H)-one (cas: 51395-52-9) 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. 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.Electric Literature of C4H5BrN2O

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