pyrazoles-derivatives

Erra, Montse published the artcileDiscovery of a Novel Inhaled PI3Kδ Inhibitor for the Treatment of Respiratory Diseases, Name: 1H-Pyrazole-4-boronic acid, the publication is Journal of Medicinal Chemistry (2018), 61(21), 9551-9567, database is CAplus and MEDLINE.

Oral PI3Kδ inhibitors such as Idelalisib and Duvelisib have shown efficacy as anticancer agents and Idelalisib has been approved for the treatment of three B-cell cancers. However, Idelalisib has a black box warning on its product label regarding the risks of fatal and serious toxicities including hepatic toxicity, severe diarrhea, colitis, pneumonitis, infections, and intestinal perforation. Some of these side effects are mechanism-related and could hinder the development of Idelalisib for less severe conditions. For respiratory diseases, compounds administered by inhalation are delivered directly to the site of action and may improve the therapeutic index of a drug, minimizing undesired side effects. This work describes the discovery and optimization of inhaled PI3Kδ inhibitors intended for the treatment of severe asthma and COPD. Once the potency was in the desired range, efforts were focused on identifying the particular physicochem. properties that could translate into better lung retention. This medicinal chem. exercise led to the identification of LAS195319 as a candidate for clin. development.

Journal of Medicinal Chemistry published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, Name: 1H-Pyrazole-4-boronic acid.

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

Hayashi, Hiroki published the artcileSynthesis of difluoroglycine derivatives from amines, difluorocarbene, and CO₂: computational design, scope, and applications, Application of 1-Methylpyrazole, the publication is Chemistry – A European Journal (2021), 27(39), 10040-10047, database is CAplus and MEDLINE.

A three-component reaction (3CR) for the synthesis of difluoroglycine derivatives has been achieved by using amines, difluorocarbene (generated in situ), and the abundant, inexpensive, and nontoxic C₁ source CO₂. Various tert-amines and pyridine, (iso)quinoline, imidazole, thiazole, and pyrazole derivatives were incorporated, and the corresponding products were isolated in solid form without purification by column chromatog. on silica gel. Detailed reaction profiles of the 3CR were obtained from computational anal. using DFT calculations, and the results critically suggest that simple ammonia is not applicable to this reaction. In addition, as strongly supported by computational predictions, a new reagent that can generate difluorocarbene at 0°C without any additives was discovered. Finally, radical substitution reactions of the obtained difluoroglycine derivatives under photoredox conditions, as well as a synthetic application as an N-heterocyclic carbene ligand are shown.

Chemistry – A European Journal published new progress about 930-36-9. 930-36-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole, name is 1-Methylpyrazole, and the molecular formula is C4H6N2, Application of 1-Methylpyrazole.

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

Katoh, Taisuke published the artcileDiscovery and optimization of 1,7-disubstituted-2,2-dimethyl-2,3-dihydroquinazolin-4(1H)-ones as potent and selective PKCθ inhibitors, Product Details of C3H5BN2O2, the publication is Bioorganic & Medicinal Chemistry (2016), 24(11), 2466-2475, database is CAplus and MEDLINE.

A high-throughput screening campaign helped us to identify an initial lead compound (1) as a protein kinase C-θ (PKCθ) inhibitor. Using the docking model of compound 1 bound to PKCθ as a model, structure-based drug design was employed and two regions were identified that could be explored for further optimization, i.e., (a) a hydrophilic region around Thr442, unique to PKC family, in the inner part of the hinge region, and (b) a lipophilic region at the forefront of the Et moiety. Optimization of the hinge binder led us to find 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one as a potent and selective hinge binder, which resulted in the discovery of compound 5. Filling the lipophilic region with a suitable lipophilic substituent boosted PKCθ inhibitory activity and led to the identification of compound 10. The co-crystal structure of compound 10 bound to PKCθ confirmed that both the hydrophilic and lipophilic regions were fully utilized. Further optimization of compound 10 led us to compound 14, which demonstrated an improved pharmacokinetic profile and inhibition of IL-2 production in a mouse.

Bioorganic & Medicinal Chemistry published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, Product Details of C3H5BN2O2.

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

Katoh, Taisuke published the artcileDiscovery and optimization of 1,7-disubstituted-2,2-dimethyl-2,3-dihydroquinazolin-4(1H)-ones as potent and selective PKCθ inhibitors, Category: pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry (2016), 24(11), 2466-2475, database is CAplus and MEDLINE.

A high-throughput screening campaign helped us to identify an initial lead compound (1) as a protein kinase C-θ (PKCθ) inhibitor. Using the docking model of compound 1 bound to PKCθ as a model, structure-based drug design was employed and two regions were identified that could be explored for further optimization, i.e., (a) a hydrophilic region around Thr442, unique to PKC family, in the inner part of the hinge region, and (b) a lipophilic region at the forefront of the Et moiety. Optimization of the hinge binder led us to find 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one as a potent and selective hinge binder, which resulted in the discovery of compound 5. Filling the lipophilic region with a suitable lipophilic substituent boosted PKCθ inhibitory activity and led to the identification of compound 10. The co-crystal structure of compound 10 bound to PKCθ confirmed that both the hydrophilic and lipophilic regions were fully utilized. Further optimization of compound 10 led us to compound 14, which demonstrated an improved pharmacokinetic profile and inhibition of IL-2 production in a mouse.

Bioorganic & Medicinal Chemistry published new progress about 1009071-34-4. 1009071-34-4 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester, name is tert-Butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate, and the molecular formula is C15H25BN2O4, Category: pyrazoles-derivatives.

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

Asghar, Soneela published the artcileCobalt-Catalyzed Suzuki Biaryl Coupling of Aryl Halides, Synthetic Route of 14580-22-4, the publication is Angewandte Chemie, International Edition (2017), 56(51), 16367-16370, database is CAplus and MEDLINE.

Readily accessed cobalt pre-catalysts with N-heterocyclic carbene ligands catalyze the Suzuki cross-coupling of aryl chlorides and bromides with alkyllithium-activated arylboronic pinacolate esters. Preliminary mechanistic studies indicate that the cobalt species is reduced to Co⁰ during the reaction.

Angewandte Chemie, International Edition published new progress about 14580-22-4. 14580-22-4 belongs to pyrazoles-derivatives, auxiliary class Organic Pigment, name is 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone, and the molecular formula is C10H9ClN2O, Synthetic Route of 14580-22-4.

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

Liu, Zheng published the artcileC-3 benzoic acid derivatives of C-3 deoxybetulinic acid and deoxybetulin as HIV-1 maturation inhibitors, Application In Synthesis of 724710-02-5, the publication is Bioorganic & Medicinal Chemistry (2016), 24(8), 1757-1770, database is CAplus and MEDLINE.

A series of C-3 phenyl- and heterocycle-substituted derivatives of C-3 deoxybetulinic acid and C-3 deoxybetulin was designed and synthesized as HIV-1 maturation inhibitors (MIs) and evaluated for their antiviral activity and cytotoxicity in cell culture. A 4-subsituted benzoic acid moiety was identified as an advantageous replacement for the 3’3′-dimethylsuccinate moiety present in previously disclosed MIs that illuminates new aspects of the topog. of the pharmacophore. The new analogs exhibit excellent in vitro antiviral activity against wild-type (wt) virus and a lower serum shift when compared with the prototypical HIV-1 MI bevirimat (1, BVM), the first MI to be evaluated in clin. studies. Compound 9a exhibits comparable cell culture potency toward wt virus as 1 (WT EC₅₀ = 16 nM for 9a compared to 10 nM for 1). However, the potency of 9a is less affected by the presence of human serum, while the compound displays a similar pharmacokinetic profile in rats to 1. Hence 9a, the 4-benzoic acid derivative of deoxybetulinic acid, represents a new starting point from which to explore the design of a 2nd generation MI.

Bioorganic & Medicinal Chemistry published new progress about 724710-02-5. 724710-02-5 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Pyrazole,Boronic Acids,Boronic acid and ester, name is (1H-Pyrazol-5-yl)boronic acid, and the molecular formula is C3H5BN2O2, Application In Synthesis of 724710-02-5.

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

Fuse, Shinichiro published the artcileDesign, synthesis, and evaluation of indeno[2,1-c]pyrazolones for use as inhibitors against hypoxia-inducible factor (HIF)-1 transcriptional activity, Application of 1-Methylpyrazole, the publication is Bioorganic & Medicinal Chemistry (2020), 28(1), 115207, database is CAplus and MEDLINE.

In this study, indeno[2,1-c]pyrazolones, compounds I [Y = C, N; R¹ = H, Me; R² = H, Me, Ph, etc] were designed as readily available synthetic inhibitors of HIF-1 transcriptional activity. Nine compounds were synthesized in 4-5 steps from com. available starting materials. In evaluations of the ability to inhibit the hypoxia-induced transcriptional activity of HIF-1, compound I [Y = C, R¹ = H, R² = 4-MeC₆H₄] showed a higher level compared with that of known inhibitor, YC-1. The compound I [Y = C, R¹ = H, R² = 4-MeC₆H₄] suppressed HIF-1α protein accumulation without affecting the levels of HIF-1α mRNA.

Bioorganic & Medicinal Chemistry published new progress about 930-36-9. 930-36-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole, name is 1-Methylpyrazole, and the molecular formula is C4H6N2, Application of 1-Methylpyrazole.

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

Karthik, Murugan published the artcileGraphene Oxide as a Carbocatalyst for Sustainable ipso-Hydroxylation of Arylboronic Acids: A Simple and Straightforward Strategy To Access Phenols, Category: pyrazoles-derivatives, the publication is ACS Sustainable Chemistry & Engineering (2019), 7(9), 9028-9034, database is CAplus.

A metal-free and straightforward protocol for the synthesis of phenols from aryl and heteroaryl boronic acids has been demonstrated using graphene oxide as a carbocatalyst. This sustainable ipso-hydroxylation takes place under mild conditions using aqueous H₂O₂ as an oxidant in a water medium in a short time under organocatalytic and base-free conditions. The control experiments reveal that the presence of carboxyl groups promotes ipso-hydroxylation. The developed methodol. offers GO as a benign solid-acid catalyst with good sustainability which can be reused several times without significant loss in its catalytic activities; this was proven by the Fourier transform IR and powder X-ray diffraction studies of the reused catalyst.

ACS Sustainable Chemistry & Engineering published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, Category: pyrazoles-derivatives.

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

Song, Song published the artcileEfficient and Practical Oxidative Bromination and Iodination of Arenes and Heteroarenes with DMSO and Hydrogen Halide: A Mild Protocol for Late-Stage Functionalization, COA of Formula: C4H6N2, the publication is Organic Letters (2015), 17(12), 2886-2889, database is CAplus and MEDLINE.

An efficient and practical system for inexpensive bromination and iodination of arenes as well as heteroarenes by using readily available DMSO (DMSO) and HX (X = Br, I) reagents is reported. This mild oxidative system demonstrates a versatile protocol for the synthesis of aryl halides. HX (X = Br, I) are employed as halogenating reagents when combined with DMSO which participates in the present chem. as a mild and inexpensive oxidant. This oxidative system is amenable to late-stage bromination of natural products. The kilogram-scale experiment (>95% yield) shows great potential for industrial application.

Organic Letters published new progress about 930-36-9. 930-36-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole, name is 1-Methylpyrazole, and the molecular formula is C3H5BN2O2, COA of Formula: C4H6N2.

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