Day: November 21, 2022

Engers, Darren W. published the artcileSynthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of Dorsomorphin: The discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe, Recommanded Product: 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(11), 3248-3252, database is CAplus and MEDLINE.

A structure-activity relation of the 3- and 6-positions of the pyrazolo[1,5-a]pyrimidine scaffold of the known BMP inhibitors dorsomorphin, 1, LDN-193189, 2, and DMH1, 3, led to the identification of a potent and selective compound for ALK2 vs. ALK3. The potency contributions of several 3-position substituents were evaluated with subtle structural changes leading to significant changes in potency. From these studies, a novel 5-quinoline mol. was identified and designated an MLPCN probe mol., ML347, which shows >300-fold selectivity for ALK2 and presents the community with a selective mol. probe for further biol. evaluation.

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, Recommanded Product: 1H-Pyrazole-4-boronic acid.

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

Thakar, Amit S. published the artcileIsolation, characterization and X-ray structure determination of the Schiff base ligand: 5-methyl-2-phenyl-4-[phenyl-(4-phenyl-thiazol-2-ylamino)- methylene]-2,4-dihydro-pyrazol-3-one, Product Details of C17H14N2O2, the publication is South African Journal of Chemistry (2015), 39-44, database is CAplus.

The structure of the amine tautomer of the new Schiff base derived from 4-benzoyl-5-methyl-2-phenyl-2,4-dihydro-pyrazol- 3-one and 4-phenyl-thiazol-2-ylamine was confirmed by means of single crystal X-ray diffraction. The title compound was synthesized and crystals were grown from a mixture of dichloromethane and n-hexane (1:3). Single crystal X-ray diffraction anal. showed that the structure was primarily stabilized by strong intramol. N3-H3A···O1 hydrogen bonds [N3-H3A = 0.883(19) Å, H3A···O1 = 1.925(18) Å, N3···O1 = 2.6901(13) Å, with an angle for N3-H3A···O1 = 144.1(17) °] and this lead to the formation of a pseudo nine-membered hydrogen bonded pattern. Elemental anal., FTIR and NMR analyses was employed to characterize the crystal.

South African Journal of Chemistry published new progress about 4551-69-3. 4551-69-3 belongs to pyrazoles-derivatives, auxiliary class Benzenes, name is 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, and the molecular formula is C16H12O, Product Details of C17H14N2O2.

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

Forsyth, Craig M. published the artcileN,N-Dialkyl-N’-Chlorosulfonyl Chloroformamidines in Heterocyclic Synthesis. Part IX. Novel Triazolo-Fused Thiatriazoles and Pyrazolo-Fused Oxathiazines, Safety of 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone, the publication is Australian Journal of Chemistry (2010), 63(5), 785-791, database is CAplus.

[1,2,4]Triazolo[1,2-b][1,2,3,5]thiatriazole derivatives were obtained by a reaction of N,N-dialkyl-N’-chlorosulfonyl chloroformamidine derivatives with 4-substituted urazoles in a selective 1,2-NN-dinucleophilic mode of action. A reaction of the above-mentioned N,N-dialkyl-N’-chlorosulfonyl chloroformamidine derivatives with N¹-substituted 5-pyrazolones afforded pyrazolo[4,3-e][1,4,3]oxathiazine derivatives by a selective 1,3-CCO dinucleophilic substitution. [1,2,4]Triazolo[1,2-b][1,2,3,5]thiatriazole derivatives and pyrazolo[4,3-e][1,4,3]oxathiazine derivatives were the only products isolated from the resp. reactions and both represent new ring systems.

Australian Journal of Chemistry 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, Safety of 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone.

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

Fritzemeier, Russell published the artcileDiscovery of In Vivo Active Sphingosine-1-phosphate Transporter (Spns2) Inhibitors, Related Products of pyrazoles-derivatives, the publication is Journal of Medicinal Chemistry (2022), 65(11), 7656-7681, database is CAplus and MEDLINE.

Sphingosine 1-phosphate (S1P) is a pleiotropic signaling mol. that interacts with five G-protein-coupled receptors (S1P1-5) to regulate cellular signaling pathways. S1P export is facilitated by Mfsd2b and spinster homolog 2 (Spns2). While mouse genetic studies suggest that Spns2 functions to maintain lymph S1P, Spns2 inhibitors are necessary to understand its biol. and to learn whether Spns2 is a viable drug target. Herein, we report a structure-activity relationship study that identified the first Spns2 inhibitor 16d (SLF1081851)(I). In vitro studies in HeLa cells demonstrated that 16d inhibited S1P release with an IC₅₀ of 1.93 μM. Administration of 16d to mice and rats drove significant decreases in circulating lymphocyte counts and plasma S1P concentrations, recapitulating the phenotype observed in mice made deficient in Spns2. Thus, 16d has the potential for development and use as a probe to investigate Spns2 biol. and to determine the potential of Spns2 as a drug target.

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, Related Products of pyrazoles-derivatives.

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

Fritzemeier, Russell published the artcileDiscovery of In Vivo Active Sphingosine-1-phosphate Transporter (Spns2) Inhibitors, Synthetic Route of 724710-02-5, the publication is Journal of Medicinal Chemistry (2022), 65(11), 7656-7681, database is CAplus and MEDLINE.

Sphingosine 1-phosphate (S1P) is a pleiotropic signaling mol. that interacts with five G-protein-coupled receptors (S1P1-5) to regulate cellular signaling pathways. S1P export is facilitated by Mfsd2b and spinster homolog 2 (Spns2). While mouse genetic studies suggest that Spns2 functions to maintain lymph S1P, Spns2 inhibitors are necessary to understand its biol. and to learn whether Spns2 is a viable drug target. Herein, we report a structure-activity relationship study that identified the first Spns2 inhibitor 16d (SLF1081851)(I). In vitro studies in HeLa cells demonstrated that 16d inhibited S1P release with an IC₅₀ of 1.93 μM. Administration of 16d to mice and rats drove significant decreases in circulating lymphocyte counts and plasma S1P concentrations, recapitulating the phenotype observed in mice made deficient in Spns2. Thus, 16d has the potential for development and use as a probe to investigate Spns2 biol. and to determine the potential of Spns2 as a drug target.

Journal of 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, Synthetic Route of 724710-02-5.

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

Buckley, George M. published the artcileIRAK-4 inhibitors. Part III: A series of imidazo[1,2-a]pyridines, Computed Properties of 724710-02-5, the publication is Bioorganic & Medicinal Chemistry Letters (2008), 18(12), 3656-3660, database is CAplus and MEDLINE.

Following the identification of a potent IRAK inhibitor through routine project cross screening, a novel class of IRAK-4 inhibitor was established. The SAR of imidazo[1,2-a]pyridino-pyridines and benzimidazolo-pyridines was explored.

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, Computed Properties of 724710-02-5.

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

Lucera, Mark B. published the artcileHIV signaling through CD4 and CCR5 activates Rho family GTPases that are required for optimal infection of primary CD4+ T cells, HPLC of Formula: 71203-35-5, the publication is Retrovirology (2017), 4/1-4/13, database is CAplus and MEDLINE.

Background: HIV-1 hijacks host cell machinery to ensure successful replication, including cytoskeletal components for intracellular trafficking, nucleoproteins for pre-integration complex import, and the ESCRT pathway for assembly and budding. It is widely appreciated that cellular post-translational modifications (PTMs) regulate protein activity within cells; however, little is known about how PTMs influence HIV replication. Previously, we reported that blocking deacetylation of tubulin using histone deacetylase inhibitors promoted the kinetics and efficiency of early postentry viral events. To uncover addnl. PTMs that modulate entry and early post-entry stages in HIV infection, we employed a flow cytometric approach to assess a panel of small mol. inhibitors on viral fusion and LTR promoterdriven gene expression. Results: While viral fusion was not significantly affected, early post-entry viral events were modulated by drugs targeting multiple processes including histone deacetylation, methylation, and bromodomain inhibition. Most notably, we observed that inhibitors of the Rho GTPase family of cytoskeletal regulators-including RhoA, Cdc42, and Rho-associated kinase signaling pathways-significantly reduced viral infection. Using phosphoproteomics and a biochem. GTPase activation assay, we found that virion-induced signaling via CD4 and CCR5 activated Rho family GTPases including Rac1 and Cdc42 and led to widespread modification of GTPase signaling-associated factors. Conclusions: Together, these data demonstrate that HIV signaling activates members of the Rho GTPase family of cytoskeletal regulators that are required for optimal HIV infection of primary CD4+ T cells.

Retrovirology 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, HPLC of Formula: 71203-35-5.

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

Kapara, Anastasia published the artcileDetection of Estrogen Receptor Alpha and Assessment of Fulvestrant Activity in MCF-7 Tumor Spheroids Using Microfluidics and SERS, Quality Control of 19959-71-8, the publication is Analytical Chemistry (Washington, DC, United States) (2021), 93(14), 5862-5871, database is CAplus and MEDLINE.

Breast cancer is one of the leading causes of cancer death in women. Novel in vitro tools that integrate three-dimensional (3D) tumor models with highly sensitive chem. reporters can provide useful information to aid biol. characterization of cancer phenotype and understanding of drug activity. The combination of surface-enhanced Raman scattering (SERS) techniques with microfluidic technologies offers new opportunities for highly selective, specific, and multiplexed nanoparticle-based assays. Here, we explored the use of functionalized nanoparticles for the detection of estrogen receptor alpha (ERα) expression in a 3D tumor model, using the ERα-pos. human breast cancer cell line MCF-7. This approach was used to compare targeted vs. nontargeted nanoparticle interactions with the tumor model to better understand whether targeted nanotags are required to efficiently target ERα. Mixtures of targeted anti-ERα antibody-functionalized nanotags (ERα-AuNPs) and nontargeted (against ERα) anti-human epidermal growth factor receptor 2 (HER2) antibody-functionalized nanotags (HER2-AuNPs), with different Raman reporters with a similar SERS signal intensity, were incubated with MCF-7 spheroids in microfluidic devices and spectroscopically analyzed using SERS. MCF-7 cells expressed high levels of ERα and no detectable levels of HER2. 2D and 3D SERS measurements confirmed the strong targeting effect of ERα-AuNP nanotags to the MCF-7 spheroids in contrast to HER2-AuNPs (63% signal reduction). Moreover, 3D SERS measurements confirmed the differentiation between the targeted and the nontargeted nanotags. Finally, we demonstrated how the nanotag uptake on MCF-7 spheroids was affected by the drug fulvestrant, the first-in-class approved selective estrogen receptor degrader (SERD). These results illustrate the potential of using SERS and microfluidics as a powerful in vitro platform for the characterization of 3D tumor models and the investigation of SERD activity.

Analytical Chemistry (Washington, DC, United States) published new progress about 19959-71-8. 19959-71-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Pyridine, name is 4-(1H-Pyrazol-4-yl)pyridine, and the molecular formula is C8H7N3, Quality Control of 19959-71-8.

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

Li, Guangbin published the artcileDiazole and triazole inhibition of nitrification process in return activated sludge, Safety of 1-Methylpyrazole, the publication is Chemosphere (2020), 124993, database is CAplus and MEDLINE.

Azoles are emerging contaminants that are resistant to biodegradation during wastewater treatment. Their presence has been widely reported in wastewater effluents and receiving waters. In this work, the potential inhibition of nitrification process by six different azole compounds in wastewater treatment plants was investigated in batch bioassays. The azoles studied included three diazoles: pyrazole (Pz); 1-methylpyrazole (MePz); 3,5-dimethylpyrazole (DMePz); and three triazoles: 1,2,4-triazole (Tz); benzotriazole (BTz); and 5-Me benzotriazole (MeBTz). The concentration of azoles causing 50% inhibition (IC₅₀) increased (azoles became less inhibitory) in the following order (mg L^-1): BTz (1.99) < MeBTz (2.18) < Pz (2.69) < Tz (3.53) < DMePz (17.3) < MePz (49.6). No clear structure-inhibitory relationships were found using Log P and pKa as structural properties. The toxicity of any given azole may be related to the role of substituent groups on disabling/enabling binding to the active sites of metallo-enzymes in nitrifying microorganisms. This is exemplified by the low toxicity of MePz, which has a cyclic N blocked by a Me group. The observed inhibition caused to nitrifying bacteria is more severe than their cytotoxicity to other target organisms (e.g., methanogens and heterotrophic bacteria), suggesting a specific inhibition to the copper-containing enzyme, ammonium monooxygenase, in ammonia oxidizing nitrifying microorganisms.

Chemosphere 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, Safety of 1-Methylpyrazole.

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

Sun, Xiaohua published the artcileSynthesis of Quinoxaline Derivatives as Intermediates to Obtain Erdafitinib, Related Products of pyrazoles-derivatives, the publication is Pharmaceutical Chemistry Journal (2021), 55(9), 951-953, database is CAplus.

In this work, quinoxaline derivative 7-bromo-2-(1-methyl-1H-pyrazol-4-yl)quinoxaline, which is an essential intermediate to obtain drug erdafitinib, has been synthesized in reasonably good yield using 4-bromobenzene-1,2-diamine and 2-bromo-1-(1-methyl-1H-pyrazol-4-yl)ethan-1-one as raw materials, triethylene diamine (DABCO) as catalyst, and THF as solvent. To the best of authors’ knowledge, this is the first time 7-bromo-2-(1-methyl-1H-pyrazol-4-yl)quinoxaline has been acquired by the proposed method.

Pharmaceutical Chemistry 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 C10H14N2O, Related Products of pyrazoles-derivatives.

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