Tag: M.W=150-200

Gavrilenko, B. B. published the artcileReaction of enamines with hydrazine, Safety of Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate, the publication is Zhurnal Organicheskoi Khimii (1974), 10(3), 601-4, database is CAplus.

RR1C:C(NH2)NHNH2 (I; R = CO2Me, CO2Et, CO2Pr, CO2Ph, R1 = CO2Me, CO2Et, CN) were obtained in 78-90% yields by boiling RR1C:C(CCl3)NH2 on a water bath 3-5 min. Pyrazoles (II; R1 = CO2Et, CO2Pr, CO2Ph) were obtained in 80-95% yields by cyclization of the appropriate I (R = CN) in DMF containing N2H4.H2O. Analogous obtained were 70-98% pyrazoles (III; R1 = H, CO2Et,R3 = Me). Acylaminopyrazoles (IV; R1 = H, CO2Et, CO2Pr,R3 = Me, Ph, NH2, AcNH) were addnl. obtained in 78-96% yields.

Zhurnal Organicheskoi Khimii published new progress about 23286-70-6. 23286-70-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Amine,Ester, name is Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate, and the molecular formula is C7H11N3O2, Safety of Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Ivachtchenko, Alexandre V. published the artcileSynthesis of pinacol esters of 1-alkyl-1H-pyrazol-5-yl- and 1-alkyl-1H-pyrazol-4-ylboronic acids, Quality Control of 847818-64-8, the publication is Journal of Heterocyclic Chemistry (2004), 41(6), 931-939, database is CAplus.

1-Substituted pyrazolylboronic acids and their pinacol esters were prepared by lithiation-borylation reaction sequence starting from bromopyrazoles. Alkylation of 4-bromo-1H-pyrazole gave 1-alkyl-4-bromo-1H-pyrazoles, which were lithiated at -80° and borylated with B(OMe)₃ to give 1-R-1H-pyrazole-4-boronic acids [4a–g, R = Me, Et, Pr, (CH₂)₂CHMe₂, (CH₂)₂OMe, (CH₂)₃NMe₂, (CH₂)₂CH(OEt)₂]. Lithiation of 4-bromo-1-(2-dimethylaminoethyl)-1H-pyrazole (2h) gave 5-lithio-derivative, which on borylation afforded 1-R¹-4-Br-1H-pyrazole-5-boronic acid (8). Boronic acids 4a–g are unstable and were deborylated slowly due to hydrolysis by traces of water; the stability of boryl derivatives can be greatly enhanced by converting to corresponding pinacol boronates (10a–g). Direct lithiation of 1-R²-1H-pyrazoles by BuLi at -20° afforded 5-lithio-derivatives, which were converted to corresponding 1-R²-1H-pyrazole-5-boronic acids [17a–e; R² = Me, ⁱBu, Pr, (CH₂)₂CHMe₂, (CH₂)₂CH(OEt)₂] and their pinacol boronates (18a–e, same R²). The key step in the described methodol. is the regioselective lithiation of the pyrazole ring. The synthesized pinacolates are stable under prolonged storage and can be used as convenient reagents in organic synthesis.

Journal of Heterocyclic Chemistry published new progress about 847818-64-8. 847818-64-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Pyrazole,Boronic Acids,Boronic acid and ester, name is (1-Isobutyl-1H-pyrazol-5-yl)boronic acid, and the molecular formula is C7H13BN2O2, Quality Control of 847818-64-8.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Ivachtchenko, Alexandre V. published the artcileSynthesis of pinacol esters of 1-alkyl-1H-pyrazol-5-yl- and 1-alkyl-1H-pyrazol-4-ylboronic acids, SDS of cas: 847818-66-0, the publication is Journal of Heterocyclic Chemistry (2004), 41(6), 931-939, database is CAplus.

1-Substituted pyrazolylboronic acids and their pinacol esters were prepared by lithiation-borylation reaction sequence starting from bromopyrazoles. Alkylation of 4-bromo-1H-pyrazole gave 1-alkyl-4-bromo-1H-pyrazoles, which were lithiated at -80° and borylated with B(OMe)₃ to give 1-R-1H-pyrazole-4-boronic acids [4a–g, R = Me, Et, Pr, (CH₂)₂CHMe₂, (CH₂)₂OMe, (CH₂)₃NMe₂, (CH₂)₂CH(OEt)₂]. Lithiation of 4-bromo-1-(2-dimethylaminoethyl)-1H-pyrazole (2h) gave 5-lithio-derivative, which on borylation afforded 1-R¹-4-Br-1H-pyrazole-5-boronic acid (8). Boronic acids 4a–g are unstable and were deborylated slowly due to hydrolysis by traces of water; the stability of boryl derivatives can be greatly enhanced by converting to corresponding pinacol boronates (10a–g). Direct lithiation of 1-R²-1H-pyrazoles by BuLi at -20° afforded 5-lithio-derivatives, which were converted to corresponding 1-R²-1H-pyrazole-5-boronic acids [17a–e; R² = Me, ⁱBu, Pr, (CH₂)₂CHMe₂, (CH₂)₂CH(OEt)₂] and their pinacol boronates (18a–e, same R²). The key step in the described methodol. is the regioselective lithiation of the pyrazole ring. The synthesized pinacolates are stable under prolonged storage and can be used as convenient reagents in organic synthesis.

Journal of Heterocyclic Chemistry published new progress about 847818-66-0. 847818-66-0 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic Acids,Boronic acid and ester, name is (1-Isopentyl-1H-pyrazol-5-yl)boronic acid, and the molecular formula is C8H15BN2O2, SDS of cas: 847818-66-0.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Liang, Jun published the artcileFrom a novel HTS hit to potent, selective, and orally bioavailable KDM5 inhibitors, Related Products of pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2017), 27(13), 2974-2981, database is CAplus and MEDLINE.

A high-throughput screening (HTS) of the Genentech/Roche library identified a novel, uncharged scaffold as a KDM5A inhibitor. Lacking insight into the binding mode, initial attempts to improve inhibitor potency failed to improve potency, and synthesis of analogs was further hampered by the presence of a C-C bond between the pyrrolidine and pyridine. Replacing this with a C-N bond significantly simplified synthesis, yielding pyrazole analog, [3-(4-bromo-1H-pyrazol-1-yl)-1-pyrrolidinyl][5-(1-methylethyl)-1H-pyrazol-3-yl]methanone (35), of which the authors obtained a co-crystal structure with KDM5A. Using structure-based design approach, the authors identified, N-[(3R)-1-[[5-(1-methylethyl)-1H-pyrazol-3-yl]carbonyl]-3-pyrrolidinyl]cyclopropanecarboxamide (50), with improved biochem., cell potency and reduced MW and lower lipophilicity (Log D) compared with the original hit. Furthermore, 50 showed lower clearance than [5-(1-methylethyl)-1H-pyrazol-3-yl][(3S)-3-[6-methyl-4-(1-methyl-1H-pyrazol-4-yl)-2-pyridinyl]-1-pyrrolidinyl]methanone (9) in mice. In combination with its remarkably low plasma protein binding (PPB) in mice (40%), oral dosing of 50 at 5 mg/kg resulted in unbound C_max ∼2-fold of its cell potency (PC9 H3K4Me3 0.96 μM), meeting the authors’ criteria for an in vivo tool compound from a new scaffold.

Bioorganic & Medicinal Chemistry Letters published new progress about 890590-91-7. 890590-91-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid, name is 3-Isopropyl-1H-pyrazole-5-carboxylic acid, and the molecular formula is C7H10N2O2, Related Products of pyrazoles-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Gao, Yaojun published the artcileSynthesis of Pyrazolo[5,1-d][1,2,3,5]tetrazin-4(3H)-ones, Name: Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate, the publication is Journal of Combinatorial Chemistry (2010), 12(1), 69-74, database is CAplus and MEDLINE.

A solid-phase synthesis of 5-aminopyrazoles I (R¹ = H, CN, EtO₂C, Ph; R² = H, Me, Ph) has been developed and applied to the preparation of pyrazolo[5,1-d][1,2,3,5]tetrazin-4(3H)-ones II (R³ = n-hexyl, Ph, 4-ClC₆H₄, PhCH₂, PhCH₂CH₂). In this strategy, 5-aminopyrazoles I were converted into pyrazolo[5,1-d][1,2,3,5]tetrazines II in one-pot via diazotization followed cyclocondensation with isocyanates R³NCO.

Journal of Combinatorial Chemistry published new progress about 23286-70-6. 23286-70-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Amine,Ester, name is Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate, and the molecular formula is C7H11N3O2, Name: Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Yoon, Suyoung published the artcileStructure-activity relationship of leucyladenylate sulfamate analogues as leucyl-tRNA synthetase (LRS)-targeting inhibitors of Mammalian target of rapamycin complex 1 (mTORC1), Safety of 3-Isopropyl-1H-pyrazole-5-carboxylic acid, the publication is Bioorganic & Medicinal Chemistry (2019), 27(6), 1099-1109, database is CAplus and MEDLINE.

Leucyl-tRNA synthetase (LRS) plays an important role in amino acid-dependent mTORC1 signaling, which is known to be associated with cellular metabolism and proliferation. Therefore, LRS-targeting small mols. that can suppress mTORC1 activation may provide an alternative strategy to current anticancer therapy. In this work, we developed a library of leucyladenylate sulfate analogs by extensively modifying three different pharmacophoric regions comprising adenine, ribose and leucine. Several effective compounds were identified by cell-based mTORC1 activation assays and further tested for anticancer activity. The selected compounds mostly exhibited selective cytotoxicity toward five different cancer cell lines, supporting the hypothesis that the LRS-mediated mTORC1 pathway is a promising alternative target to current therapeutic approaches.

Bioorganic & Medicinal Chemistry published new progress about 890590-91-7. 890590-91-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid, name is 3-Isopropyl-1H-pyrazole-5-carboxylic acid, and the molecular formula is C3H5BN2O2, Safety of 3-Isopropyl-1H-pyrazole-5-carboxylic acid.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Nam, Mina published the artcileDiscovery and biological evaluation of tetrahydrothieno[2,3-c]pyridine derivatives as selective metabotropic glutamate receptor 1 antagonists for the potential treatment of neuropathic pain, Application of 3-Isopropyl-1H-pyrazole-5-carboxylic acid, the publication is European Journal of Medicinal Chemistry (2015), 245-258, database is CAplus and MEDLINE.

Metabotropic glutamate receptor 1 (mGluR1) was a prime target for drug discovery due to its heavy involvement in various brain disorders. Recent studies suggested that mGluR1 is associated with chronic pain and can serve as a promising target for the treatment of neuropathic pain. In an effort to develop a novel mGluR1 antagonist, the authors designed and synthesized a library of compounds with tetrahydrothieno[2,3-c]pyridine scaffold. Among these compounds, compound 2-(Benzylamino)-6-(3-methyl-1H-pyrazole-5-carbonyl)4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carbonitrile and 2-(Benzylamino)-6-(4-fluorobenzoyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carbonitrile showed excellent antagonistic activity in vitro and demonstrated pain-suppressing activity in animal models of pain. Both compounds were orally active, and compound 2-(Benzylamino)-6-(3-methyl-1H-pyrazole-5-carbonyl)4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carbonitrile exhibited a favorable pharmacokinetic profile in rats. The authors believe that these compounds can provide a promising lead compound that is suitable for the potential treatment of neuropathic pain.

European Journal of Medicinal Chemistry published new progress about 890590-91-7. 890590-91-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid, name is 3-Isopropyl-1H-pyrazole-5-carboxylic acid, and the molecular formula is C7H10N2O2, Application of 3-Isopropyl-1H-pyrazole-5-carboxylic acid.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Richman, Jeremy G. published the artcileNicotinic Acid Receptor Agonists Differentially Activate Downstream Effectors, Synthetic Route of 890590-91-7, the publication is Journal of Biological Chemistry (2007), 282(25), 18028-18036, database is CAplus and MEDLINE.

Nicotinic acid remains the most effective therapeutic agent for the treatment and prevention of atherosclerosis resulting from low high d. lipoprotein cholesterol. The therapeutic actions of nicotinic acid are mediated by GPR109A, a G_i protein-coupled receptor, expressed primarily on adipocytes, Langerhans cells, and macrophage. Unfortunately, a severe, cutaneous flushing side effect limits its use and patient compliance. The mechanism of high d. lipoprotein elevation is not clearly established but assumed to be influenced by an inhibition of lipolysis in the adipose. The flushing side effect appears to be mediated by the release of prostaglandin D2 from Langerhans cells in the skin. We hypothesized that the signal transduction pathways mediating the anti-lipolytic and prostaglandin D2/flushing pathways are distinct and that agonists may be identified that are capable of selectively eliciting the therapeutic, anti-lipolytic pathway while avoiding the activation of the parallel flush-inducing pathway. We have identified a number of GPR109A pyrazole agonists that are capable of fully inhibiting lipolysis in vitro and in vivo and not only fail to elicit a flushing response but can antagonize the ability of nicotinic acid to elicit a flush response in vivo. In contrast to flushing agonists, exposure of cells expressing GPR109A to the non-flushing agonists fails to induce internalization of the receptor or to activate ERK 1/2 mitogen-activated protein kinase phosphorylation.

Journal of Biological Chemistry published new progress about 890590-91-7. 890590-91-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid, name is 3-Isopropyl-1H-pyrazole-5-carboxylic acid, and the molecular formula is C7H10N2O2, Synthetic Route of 890590-91-7.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Wipf, Peter published the artcileMetathesis reactions of pyrazolotriazinones generate dynamic combinatorial libraries, Product Details of C7H10N2O2, the publication is Organic Letters (2005), 7(20), 4483-4486, database is CAplus and MEDLINE.

Reversible metathesis reactions of pyrazolotriazinones and aliphatic aldehydes or ketones proceed in aqueous, phosphate-buffered media at pH 4 and 40-60 °C to generate thermodynamically controlled mixtures of heterocycles.

Organic Letters published new progress about 890590-91-7. 890590-91-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid, name is 3-Isopropyl-1H-pyrazole-5-carboxylic acid, and the molecular formula is C3H6O2, Product Details of C7H10N2O2.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Nemec, Vaclav published the artcileHighly selective inhibitors of protein kinases CLK and HIPK with the furo[3,2-b]pyridine core, COA of Formula: C9H9BN2O2, the publication is European Journal of Medicinal Chemistry (2021), 113299, database is CAplus and MEDLINE.

The furo [3,2-b]pyridine motif represents a relatively underexplored central pharmacophore in the area of kinase inhibitors. Herein, author’s report flexible synthesis of 3,5-disubstituted furo[3,2-b]pyridines that relies on chemoselective couplings of newly prepared 5-chloro-3-iodofuro[3,2-b]pyridine. This methodol. allowed efficient second-generation synthesis of the state-of-the-art chem. biol. probe for CLK1/2/4 I, and identification of the highly selective inhibitors of HIPKs II and III which are presented and characterized in this study, including the X-ray crystal structure of II in HIPK2.chem. biol. probe.

European Journal of Medicinal Chemistry published new progress about 1100095-25-7. 1100095-25-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Benzene,Boronic Acids,Boronic acid and ester, name is (3-(1H-Pyrazol-3-yl)phenyl)boronic acid, and the molecular formula is C9H9BN2O2, COA of Formula: C9H9BN2O2.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics