Day: November 23, 2022

Qian, Yimin published the artcileDiscovery of Highly Selective and Orally Active Lysophosphatidic Acid Receptor-1 Antagonists with Potent Activity on Human Lung Fibroblasts, Related Products of pyrazoles-derivatives, the publication is Journal of Medicinal Chemistry (2012), 55(17), 7920-7939, database is CAplus and MEDLINE.

Lysophosphatidic acid is a class of bioactive phospholipid that mediates most of its biol. effects through LPA receptors, of which six isoforms have been identified. The recent results from LPA1 knockout mice suggested that blocking LPA1 signaling could provide a potential novel approach for the treatment of idiopathic pulmonary fibrosis. Here, we report the design and synthesis of pyrazole- and triazole-derived carbamates as LPA1-selective and LPA1/3 dual antagonists. In particular, compound I, the most selective LPA1 antagonist reported, inhibited proliferation and contraction of normal human lung fibroblasts (NHLF) following LPA stimulation. Oral dosing of compound I to mice resulted in a dose-dependent reduction of plasma histamine levels in a murine LPA challenge model. Furthermore, we applied our novel antagonists as chem. probes and investigated the contribution of LPA1/2/3 in mediating the pro-fibrotic responses. Our results suggest LPA1 as the major receptor subtype mediating LPA-induced proliferation and contraction of NHLF.

Journal of Medicinal Chemistry published new progress about 105675-85-2. 105675-85-2 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Bromide,Amine, name is 4-Bromo-1-methyl-1H-pyrazol-5-amine, and the molecular formula is C4H6BrN3, Related Products of pyrazoles-derivatives.

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

Li, Chaomin published the artcileSulfone Displacement Approach for Large-Scale Synthesis of 4-Chloro-N-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-amine, Quality Control of 1462286-01-6, the publication is Organic Process Research & Development (2022), 26(1), 137-143, database is CAplus.

Route evaluation, process development, and large-scale manufacturing of title compound I were described. The improved route consists of two linear chem. steps: oxidation of 4-chloro-2-(methylthio)pyrimidine to 4-chloro-2-(methylsulfonyl)pyrimidine and displacement of the sulfonyl with N-(1-methyl-1H-pyrazol-4-yl)formamide under basic conditions followed by in situ hydrolysis of the N-formyl intermediate to deliver compound I. N-(1-Methyl-1H-pyrazol-4-yl)formamide was readily prepared from 1-methyl-1H-pyrazol-4-amine via reaction with formic acid.

Organic Process Research & Development published new progress about 1462286-01-6. 1462286-01-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazoles, name is 4-Chloro-N-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-amine, and the molecular formula is C8H8ClN5, Quality Control of 1462286-01-6.

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

Kim, Hyun Tae published the artcileLigand-controlled Regiodivergent C-H Alkenylation of Pyrazoles and its Application to the Synthesis of Indazoles, HPLC of Formula: 930-36-9, the publication is Angewandte Chemie, International Edition (2017), 56(51), 16262-16266, database is CAplus and MEDLINE.

Regioselective C4-, C5-, and di-alkenylations of pyrazoles were achieved. An electrophilic Pd catalyst generated by trifluoroacetic acid (TFA) and 4,5-diazafluoren-9-one (DAF) leads to C4-alkenylation, whereas KOAc and mono-protected amino acid (MPAA) ligand Ac-Val-OH give C5-alkenylation. A combination of palladium acetate, silver carbonate, and pivalic acid affords dialkenylation products. Annulation through sequential alkenylation, thermal 6π-electrocyclization, and oxidation gives functionalized indazoles. This comprehensive strategy greatly expands the range of readily accessible pyrazole and indazole derivatives, enabling useful regiodivergent C-H functionalization of pyrazoles and other heteroaromatic systems.

Angewandte Chemie, International Edition 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, HPLC of Formula: 930-36-9.

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

Ochiana, Stefan O. published the artcileSynthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 2. Tadalafil analogs, Related Products of pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(7), 2582-2584, database is CAplus and MEDLINE.

In this Letter we describe our ongoing target repurposing efforts focused on discovery of inhibitors of the essential trypanosomal phosphodiesterase TbrPDEB1. This enzyme has been implicated in virulence of Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). We outline the synthesis and biol. evaluation of analogs of tadalafil, a human PDE5 inhibitor currently utilized for treatment of erectile dysfunction, and report that these analogs are weak inhibitors of TbrPDEB1.

Bioorganic & Medicinal Chemistry Letters 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, Related Products of pyrazoles-derivatives.

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

Zhang, Tong-wei published the artcileMeasurement and correlation of solubility of 1-methyl-3,4,5-trinitropyrazole in twelve pure solvents at temperatures from 283.15 K to 323.15 K, Synthetic Route of 930-36-9, the publication is Journal of Molecular Liquids (2020), 113895, database is CAplus.

In the present study, the solubility of 1-methyl-3,4,5-trinitropyrazole (MTNP) was determined by a dynamic laser monitoring at T = (283.15, 288.15, 293.15, 298.15, 303.15, 308.15, 313.15, 318.15 and 323.15) K in twelve pure solvents, including water, benzene (Ph), di-Me sulfate (DMS), methylbenzene (PhMe), THF (THF), methanol (MeOH), ethanol (EtOH), 1,2-dichloroethane (DCE), nitromethane (NM), acetonitrile (ACN), Et acetate (EA) and formic acid (FA), at atm. pressure (P = 0.1 MPa). In the temperature range from 283.15 K to 323.15 K, the mole fraction solubility values of MTNP in water, Ph, DMS, PhMe, THF, MeOH, EtOH, DCE, NM, ACN, EA and FA were 0.000008-0.000072, 0.003495-0.025271, 0.002153-0.037197, 0.001602-0.012304, 0.002103-0.074525, 0.000318-0.001625, 0.003752-0.048205, 0.017836-0.047105, 0.008408-0.016783, 0.003579-0.012367, 0.004460-0.022006 and 0.220917-0.443206. As revealed from the exptl. results, the solubility of MTNP in twelve pure solvents increased with the increase in the temperature The solubility behaviors of MTNP in investigated solvents were analyzed with the Hansen solubility parameter. The Kamlet-Taft parameters were calculated to delve into the solvent effect. Subsequently, the measured solubility data was correlated with five thermodn. models, i.e., the modified Apelblat equation, λh equation, NRTL model, Wilson model and Two-Suffix Margules model. Overall, the NRTL model provided the most satisfactory fitting results. As revealed from the results, the min. average values of relative mean deviation (10⁴ARD) and root-mean square deviation (10⁴RMSD) were determined with the NRTL model that achieved the values of 2.06 and 1.49. Furthermore, the dissolution thermodn. parameters, including mixing enthalpy (ΔmixH), mixing entropy (ΔmixS) and mixing Gibbs energy (ΔmixG) were calculated according to the Wilson model, and the relative contributions of enthalpy %ζH and entropy %ζS were also calculated It can be seen that the dissolution of MTNP in a given solvent is spontaneous and entropy driven.

Journal of Molecular Liquids 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 C7H11Br, Synthetic Route of 930-36-9.

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

Johns, Brian A. published the artcilePyrazolo[1,5-a]pyridine antiherpetics: Effects of the C3 substituent on antiviral activity, Category: pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2007), 17(10), 2858-2862, database is CAplus and MEDLINE.

A recently disclosed series of pyrazolo[1,5-a]pyridine inhibitors of herpes virus replication has been closely examined herein for effects of the C3 substituent on antiviral activity. Significant changes in activity are observed by alterations of the heteroatom basicity and orientation of the group at C3. These results in combination with previous studies have served to further elaborate the minimal pharmacophore required for potency of this novel series of antiviral agents. During the course of these studies, several novel synthetic approaches were developed and are described.

Bioorganic & Medicinal Chemistry Letters 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

Ambati, Srinivasa Rao published the artcileFacile Synthesis of Novel 3-(4-phenylisothiazol-5-yl)-2H-chromen-2-one Derivatives as Potential Anticancer Agents, Related Products of pyrazoles-derivatives, the publication is Journal of Heterocyclic Chemistry (2017), 54(4), 2333-2341, database is CAplus.

A series of 3-(4-phenylisothiazol-5-yl)-2H-chromen-2-one derivatives was efficiently synthesized by straightforward sequential reactions. Tandem Vilsmeier Hack reaction/cyclization/bromination/Suzuki cross-coupling reactions were successfully applied to the preparation of title compounds in good-to-high yields. In the synthetic sequences, 3-chloro-3-(2-oxo-2H-chromen-3-yl)acrylaldehydes react with ammonium thiocyanate to yield the corresponding 3-(isothiazol-5-yl)-2H-chromen-2-ones. These derivatives were brominated with N-bromo succinamide to yield the corresponding regioselective 3-(4-bromoisothiazol-5-yl)-2H-chromen-2-one. Finally, compound 3-(4-bromoisothiazol-5-yl)-2H-chromen-2-one was treated with various phenyl/pyrazole/7H-pyrrolo[2,3-d]pyrimidinyl boronic acids in the presence of K₂CO₃ and Pd catalyst in DMF to yield the corresponding title derivatives All the synthesized compounds were characterized by anal. and spectral studies. All the final compounds were screened against different cancer cell lines (A549, PC3, SKOV3, and B16F10), and among these compounds, 3-(4-phenylisothiazol-5-yl)-2H-chromen-2-one, 6-bromo-3-(4-(4-chlorophenyl)isothiazol-5-yl)2H-chromen-2-one, 6-bromo-3-(4-phenylisothiazol-5-yl)-2H-chromen-2-one , and 3-(4-(7H-pyrrolo[2,3-d]pyrimidine-4-yl)isothiazole-5-yl)-6-bromo-2H-chromen-2-one displayed moderate cytotoxic activity against the tested cell lines.

Journal of Heterocyclic 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, Related Products of pyrazoles-derivatives.

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

Vicentini, C. B. published the artcilePotential of pyrazolooxadiazinone derivatives as serine protease inhibitors, Recommanded Product: Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate, the publication is Journal of Enzyme Inhibition (2001), 16(1), 15-34, database is CAplus and MEDLINE.

As a part of an investigation on mol. hybrids as new serine protease inhibitors, the pyrazolo [4,3-c][1,2,5]oxadiazin-3(5H)-one ring system was selected as a model of potential mechanism-based inhibitors. Due to the inherent reactivity of this system an optimal balance between susceptibility to nucleophilic attack and stability in solvents was sought prior to development as therapeutic agents. Substitutions on N5 and C7 of the supporting pyrazole ring with either aliphatic or aromatic groups and the replacement of the carbonyl oxygen on the reactive oxadiazinone ring with sulfur were explored. Two members of this class of inhibitors displayed time-dependent inhibition of human leukocyte elastase (HLE) suggesting mechanism-based inhibition. The observation that HLE generated a product(s) which displayed an identical UV-Visible spectrum to that observed during non-enzymic hydrolysis further supports this proposal. FlexX-based docking of these compounds into a model of HLE active site produced a mol. model of the inhibitor-enzyme interaction.

Journal of Enzyme Inhibition 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 C11H13N3, Recommanded Product: Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate.

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

Guha, Rajarshi published the artcileRanking differential drug activities from dose-response synthetic lethality screens, Category: pyrazoles-derivatives, the publication is Journal of Biomolecular Screening (2016), 21(9), 942-955, database is CAplus and MEDLINE.

Synthetic lethal screens are used to discover new combination treatments for cancer. In traditional high-throughput synthetic lethal screens, compounds are tested at a single dose, and hit selection is based on threshold activity values from the variance of the efficacy of the compounds tested. The limitation of the single-dose screening for synthetic lethal screens is that it does not allow for the robust detection of differential activities from compound collections with a broad range of potencies and efficacies. There is therefore a need to develop screening approaches that enable the identification of compounds with synthetic lethal effects based on changes in both potency and efficacy. Here we describe the implementation of a dose response-based synthetic lethal screen to find drugs that enhance or mitigate the cytotoxic effect of an immunotoxin protein (HA22). We developed a data anal. framework for the selection of compounds with enhancing or mitigating cytotoxic activities based on the use of dose-response parameters. The data anal. framework includes an ensemble ranking approach that allows the use of multiple dose-response parameters in a nonparametric fashion. Quant. high-throughput screening (HTS) enables the identification of compounds with synthetic lethal activity not identified by single-dose HTS.

Journal of Biomolecular Screening published new progress about 71203-35-5. 71203-35-5 belongs to pyrazoles-derivatives, auxiliary class GPCR/G Protein,Ras, name is 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C22H21N3O3S, Category: pyrazoles-derivatives.

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