Category: 890590-91-7

Zhang, Lei published the artcileDiscovery of Novel Small-Molecule Inhibitors of NF-κB Signaling with Antiinflammatory and Anticancer Properties, Recommanded Product: 3-Isopropyl-1H-pyrazole-5-carboxylic acid, the publication is Journal of Medicinal Chemistry (2018), 61(14), 5881-5899, database is CAplus and MEDLINE.

Excessive NF-κB activation contributes to the pathogenesis of numerous diseases. Small-mol. inhibitors of NF-κB signaling have significant therapeutic potential especially in treating inflammatory diseases and cancers. In this study, we performed a cell-based high-throughput screening to discover novel agents capable of inhibiting NF-κB signaling. On the basis of two hit scaffolds from the screening, we synthesized 69 derivatives to optimize the potency for inhibition of NF-κB activation, leading to successful discovery of the most potent compound Z9j with over 170-fold enhancement of inhibitory activity. Preliminary mechanistic studies revealed that Z9j inhibited NF-κB signaling via suppression of Src/Syk, PI3K/Akt, and IKK/IκB pathways. This novel compound also demonstrated antiinflammatory and anticancer activities, warranting its further development as a potential multifunctional agent to treat inflammatory diseases and cancers.

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 C7H10O4, Recommanded Product: 3-Isopropyl-1H-pyrazole-5-carboxylic acid.

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

Gharbaoui, Tawfik published the artcileAgonist lead identification for the high affinity niacin receptor GPR109a, Safety of 3-Isopropyl-1H-pyrazole-5-carboxylic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2007), 17(17), 4914-4919, database is CAplus and MEDLINE.

A strategy for lead identification of new agonists of GPR109a, starting from known compounds shown to activate the receptor, is described. Early compound triage led to the formulation of a binding hypothesis and eventually to our focus on a series of pyrazole acid derivatives Further elaboration of these compounds provided a series of 5,5-fused pyrazoles to be used as lead compounds for further optimization.

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, Safety of 3-Isopropyl-1H-pyrazole-5-carboxylic acid.

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

Yang, Fan published the artcileHomology modelling of G-coupled protein receptor 109A and docking simulation with pyrazole agonists, Quality Control of 890590-91-7, the publication is Jisuanji Yu Yingyong Huaxue (2016), 33(5), 569-574, database is CAplus.

Niacin receptor G-coupled protein receptor 109A (GPR109A) is an important target protein of the treatment of cardiovascular diseases and disorders of lipid metabolism diseases. Since GPR109A is one membrane protein, the crystal structure of which has not been resolved, there are many challenges to drug design for the receptor. Based on the mouse PUMA-G crystal structure, the three-dimensional structure of GPR109A was built by using the homol. modeling method. The model was evaluated by using the Ramachandran Plot and Profile-3D, and the model was optimized with MMFF94 force field, membrane and method of loop, and finally one stabile model was obtained and 12 sites that might be the active sites in the optimal model were found. SYBYL-X2 software was used to build GPR109A pyrazole agonist drug mols., through the steepest descent method and the Conjugate gradient method to receive the most stable conformation of the small drugs mols. All the agonists were docked into each active site of the protein by Libdock method, receiving the interaction models. We analyzed the distribution of amino acid of each active site, and took 5-methyl-3-carboxylic acid as a reference drug mol. to explore the interaction force with each protein active site. This study has theor. significance in designing G-coupled protein receptor 109A pyrazole agonists.

Jisuanji Yu Yingyong Huaxue 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, Quality Control of 890590-91-7.

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

Bouaik, Hassan published the artcileOptimal parameters and structural composition of bio-oil and biochar from intermediate pyrolysis of red algal biomass, Related Products of pyrazoles-derivatives, the publication is Comptes Rendus Chimie (2021), 24(Spec.Iss.1), 1-15, database is CAplus.

Intermediate pyrolysis of red algal biomass was performed in a fixed-bed tubular reactor. To study the parametric effect on product distribution, the experiments were carried out at different temperatures ranging from 400 to 600 °C and different heating rates of 15, 30 and 50 °C/min. The objective of this study is to understand the effect of pyrolysis temperature and heating rate on the yields and compositions of the pyrolysis products of red algal biomass. The bio-oil, biochar and biogas yields ranged between 33 and 45 wt%, 29 and 42 wt%, and 18 and 35 wt%, resp., at different pyrolysis conditions. The highest bio-oil yield (45.02%) was obtained at 450 °C temperature at a heating rate of 50 °C/min. The bio-oil was characterized by proximate and ultimate anal., FTIR, 1H-NMR and GC-MS anal. whereas the biochar was characterized by proximate, ultimate, FTIR, SEM and BET. Higher heating value and d. of the bio-oil were 20.11 MJ/kg, 1289 kg/m³, resp. The bio-oil with relatively high fuel potential can be obtained from the pyrolysis of the red algal biomass. The characterization of bio-oil showed a high percentage of aliphatic functional groups and presence of phenolic, ketone- and nitrogen-containing groups. The characterization results showed that the bio-oil obtained from red algal biomass can be potentially valuable as a source of value-added chems. The biochar obtained with a high heating value of 22.89 MJ/kg can be used as an adsorbent as well as a solid fuel.

Comptes Rendus Chimie 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

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

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

Seki, Kunio published the artcileStudies on hypolipidemic agents. II. Synthesis and pharmacological properties of alkylpyrazole derivatives, Application of 3-Isopropyl-1H-pyrazole-5-carboxylic acid, the publication is Chemical & Pharmaceutical Bulletin (1984), 32(4), 1568-77, database is CAplus and MEDLINE.

Claisen condensation of MeCOR (R = C₁-C₁₇ alkyl) with (CO₂Et)₂ gave enolates RCOCH:C(ONa)CO₂Et, which underwent cyclocondensation with R¹NHNH₂[R¹ = H, Me, (CH₂)_nMe, C₆H₄R²-4; R² = H, Me, Cl, OMe, NH₂; n = 7, 9, 11] to give pyrazoles I (R³ = CO₂H, CO₂Et). Reduction of I (same R, R¹ = H, R² = CO₂Et) gave I (R³ = CH₂OH) and hydrolysis of I (R³ = CO₂Et) gave I (R = CO₂H). The latter compounds were chlorinated and amidated to give I [same R, R¹ = H, R³ = CONHR⁴, R⁴ = CH₂CH₂OH, CH₂CO₂Et, CH(CHMeEt)CO₂Et, H, Bu, decyl]. These pyrazoles (46 compounds) were evaluated for hypolipidemic activity in rats. Homologation of the C-5 alkyl chain led to marked increase in activity, but introduction of other substituents at other sites on the pyrazole ring failed to enhance the activity. The replacement of the pyrazole ring with an isoxazole ring resulted in a marked decrease in activity. I (R = tridecyl, R¹ = H, R² = CO₂H) was as effective as clofibrate in lowering serum triglycerides and cholesterol in rats and showed fairly low toxicity with LD₅₀ = 10.0 g/kg orally in mice.

Chemical & Pharmaceutical Bulletin 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 C48H47FeP, Application of 3-Isopropyl-1H-pyrazole-5-carboxylic acid.

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