Day: November 21, 2022

Procopiou, Panayiotis A. published the artcileDiscovery of (S)-3-(3-(3,5-Dimethyl-1H-pyrazol-1-yl)phenyl)-4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic Acid, a Nonpeptidic α_vβ₆ Integrin Inhibitor for the Inhaled Treatment of Idiopathic Pulmonary Fibrosis, Quality Control of 1025735-46-9, the publication is Journal of Medicinal Chemistry (2018), 61(18), 8417-8443, database is CAplus and MEDLINE.

A series of 3-aryl-(pyrrolidin-1-yl)butanoic acids were synthesized using a diastereoselective route, which involved rhodium catalyzed asym. 1,4-addition of arylboronic acids in the presence of (R)-BINAP to a crotonate ester to provide the (S) absolute configuration for the major product. A variety of aryl substituents including morpholine, pyrazole, triazole, imidazole and cyclic ether were screened in cell adhesion assays for affinity against αvβ1, αvβ3, αvβ5, αvβ6 and αvβ8 integrins. Several analogs with high affinity and selectivity for the αvβ6 integrin were identified. The analog I·HCl was found to have high affinity for αvβ6 integrin in a radioligand binding assay (pKi = 11), a long dissociation half-life (7 h) , high solubility in saline at pH 7 (>71 mg/mL) and pharmacokinetic properties commensurate with inhaled dosing by nebulization. It was selected for further investigation as a potential therapeutic agent for the treatment of idiopathic pulmonary fibrosis.

Journal of Medicinal Chemistry published new progress about 1025735-46-9. 1025735-46-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Benzene,Boronic Acids, name is 3-(3,5-Dimethyl-1H-pyrazol-1-yl)phenylboronic acid, and the molecular formula is C11H13BN2O2, Quality Control of 1025735-46-9.

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

Borthwick, Jennifer A. published the artcileStructurally Diverse Mitochondrial Branched Chain Aminotransferase (BCATm) Leads with Varying Binding Modes Identified by Fragment Screening, Synthetic Route of 724710-02-5, the publication is Journal of Medicinal Chemistry (2016), 59(6), 2452-2467, database is CAplus and MEDLINE.

Inhibitors of mitochondrial branched chain aminotransferase (BCATm), identified using fragment screening, are described. This was carried out using a combination of STD-NMR, thermal melt (T_m), and biochem. assays to identify compounds that bound to BCATm, which were subsequently progressed to X-ray crystallog., where a number of exemplars showed significant diversity in their binding modes. The hits identified were supplemented by searching and screening of addnl. analogs, which enabled the gathering of further X-ray data where the original hits had not produced liganded structures. The fragment hits were optimized using structure-based design, with some transfer of information between series, which enabled the identification of ligand efficient lead mols. with micromolar levels of inhibition, cellular activity, and good solubility

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

Bayat, Mohammad published the artcileChemoselective synthesis of novel spiropyrano acenaphthylene derivatives via one-pot four-component reaction, Recommanded Product: 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone, the publication is Tetrahedron Letters (2017), 58(45), 4260-4263, database is CAplus.

An efficient one-pot four-component condensation reaction of acenaphthoquinone, pyrazolones or barbituric acid and 1,1-bis(methylthio)-2-nitroethene and alkylamines in ethanol for the synthesis of novel spiro[acenaphthylene-1,4′-pyrano[2,3-c]pyrazol]-2-one and spiro[acenaphthylene-1,5′-pyrano[2,3-d]pyrimidine]trione is described. The significant features of this method include, readily available starting materials, operational simplicity, green solvent, catalyst-free condition, no column chromatog. purification and good to high yields. Thus, e.g., acenaphthoquinone I + pyrazolone II + ketene thioacetal III + MeNH₂ afforded IV (81%) when the reaction was conducted in EtOH at 80° (90% in presence of nano SiO₂ catalyst).

Tetrahedron Letters 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, Recommanded Product: 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone.

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

Gerstenberger, Brian S. published the artcileDiscovery of Tyrosine Kinase 2 (TYK2) Inhibitor (PF-06826647) for the Treatment of Autoimmune Diseases, Computed Properties of 930-36-9, the publication is Journal of Medicinal Chemistry (2020), 63(22), 13561-13577, database is CAplus and MEDLINE.

Tyrosine kinase 2 (TYK2) is a member of the JAK kinase family that regulates signal transduction downstream of receptors for the IL-23/IL-12 pathways and type I interferon family, where it pairs with JAK2 or JAK1, resp. On the basis of human genetic and emerging clin. data, a selective TYK2 inhibitor provides an opportunity to treat autoimmune diseases delivering a potentially differentiated clin. profile compared to currently approved JAK inhibitors. The discovery of an ATP-competitive pyrazolopyrazinyl series of TYK2 inhibitors was accomplished through computational and structurally enabled design starting from a known kinase hinge binding motif. With understanding of PK/PD relationships, a target profile balancing TYK2 potency and selectivity over off-target JAK2 was established. Lead optimization involved modulating potency, selectivity, and ADME properties which led to the identification of the clin. candidate PF-06826647 (22).

Journal of 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, Computed Properties of 930-36-9.

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

de Oliveira, Marcelo T. published the artcilePrediction of ¹⁵N NMR chemical shifts for nitrogenated aromatic compounds, Recommanded Product: 1-Methylpyrazole, the publication is ARKIVOC (Gainesville, FL, United States) (2020), 113-122, database is CAplus.

Building on recent developments, we compare performance of two distinct protocols, namely SMD-mPW1PW91/6-311+G(2d,p) and CPCM-OLYP/pcSseg-2, for the computation of ¹⁵N chem. shifts of nitrogenated aromatic compounds The latter shows best overall performance (MAD 5.3 ppm) albeit results in chloroform favors the former.

ARKIVOC (Gainesville, FL, United States) 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, Recommanded Product: 1-Methylpyrazole.

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

Revelant, Germain published the artcileExploring S1 plasticity and probing S1′ subsite of mammalian aminopeptidase N/CD13 with highly potent and selective aminobenzosuberone inhibitors, Safety of 1-Methylpyrazole, the publication is Bioorganic & Medicinal Chemistry (2015), 23(13), 3192-3207, database is CAplus and MEDLINE.

In order to probe the S1 and S1′ mammalian aminopeptidase N subsites, racemic 1- or 4-substituted 7-aminobenzocyclohepten-6-ones, e.g. I [R = Br, Cl, Ph, etc.] were synthesized and evaluated for their ability to inhibit mammalian aminopeptidase N. The authors focused on improving the physicochem. and ADME properties of this series by targeting lipophilicity and LELP score. Some 4-heteroaryl substituted analogs displayed reduced lipophilicity and enhanced inhibition potency with K_i values in the nanomolar range.

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, Safety of 1-Methylpyrazole.

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

Fukuzumi, Takeo published the artcileSynthesis of 8-substituted adenine and adenosine libraries and the binding to pre-miR-29a, SDS of cas: 763120-58-7, the publication is Bulletin of the Chemical Society of Japan (2014), 87(9), 1013-1015, database is CAplus.

A small chem. library of 8-substituted adenine and adenosine derivatives was synthesized and examined for binding to pre-miR-29a. We found that one compound showed the affinity with 61 nM of K_d and a 10-fold stronger binding than the double-stranded RNA.

Bulletin of the Chemical Society of Japan 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, SDS of cas: 763120-58-7.

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

Li, Chunpu published the artcileDesign, Synthesis, and Biological Evaluation of Novel Imidazo[1,2-a]pyridine Derivatives as Potent c-Met Inhibitors, Recommanded Product: (1-(1-(tert-Butoxycarbonyl)piperidin-4-yl)-1H-pyrazol-4-yl)boronic acid, the publication is ACS Medicinal Chemistry Letters (2015), 6(5), 507-512, database is CAplus and MEDLINE.

A series of imidazo[1,2-a]pyridine derivatives against c-Met was designed by means of bioisosteric replacement. In this study, a selective, potent c-Met inhibitor, I was identified, with IC₅₀ values of 3.9 nM against c-Met kinase and 45.0 nM against c-Met-addicted EBC-1 cell proliferation, resp. Compound I inhibited c-Met phosphorylation and downstream signaling across different oncogenic forms in c-Met overactivated cancer cells and model cells. Compound I significantly inhibited tumor growth (TGI = 75%) with good oral bioavailability (F = 29%) and no significant hERG inhibition. On the basis of systematic metabolic study, the pathway of all possible metabolites of I in liver microsomes of different species has been proposed, and a major NADPH-dependent metabolite was generated by liver microsomes. To block the metabolic site, II was designed and synthesized for further evaluation. Taken together, the imidazo[1,2-a]pyridine scaffold showed promising pharmacol. inhibition of c-Met and warrants further investigation.

ACS Medicinal Chemistry Letters published new progress about 1190875-39-8. 1190875-39-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Piperidine,Boronic acid and ester,Amide,Boronic Acids,Boronic Acids,Boronic acid and ester,, name is (1-(1-(tert-Butoxycarbonyl)piperidin-4-yl)-1H-pyrazol-4-yl)boronic acid, and the molecular formula is C13H22BN3O4, Recommanded Product: (1-(1-(tert-Butoxycarbonyl)piperidin-4-yl)-1H-pyrazol-4-yl)boronic acid.

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

Hartz, Richard A. published the artcileDiscovery, Structure-Activity Relationships, and In Vivo Evaluation of Novel Aryl Amides as Brain Penetrant Adaptor Protein 2-Associated Kinase 1 (AAK1) Inhibitors for the Treatment of Neuropathic Pain, Application of 1H-Pyrazole-4-boronic acid, the publication is Journal of Medicinal Chemistry (2021), 64(15), 11090-11128, database is CAplus and MEDLINE.

Effective treatment of chronic pain, in particular neuropathic pain, without the side effects that often accompany currently available treatment options is an area of significant unmet medical need. A phenotypic screen of mouse gene knockouts led to the discovery that adaptor protein 2-associated kinase 1 (AAK1) is a potential therapeutic target for neuropathic pain. The synthesis and optimization of structure-activity relationships of a series of aryl amide-based AAK1 inhibitors led to the identification of 59, a brain penetrant, AAK1-selective inhibitor that proved to be a valuable tool compound Compound 59 was evaluated in mice for the inhibition of μ2 phosphorylation. Studies conducted with 59 in pain models demonstrated that this compound was efficacious in the phase II formalin model for persistent pain and the chronic-constriction-injury-induced model for neuropathic pain in rats. These results suggest that AAK1 inhibition is a promising approach for the treatment of neuropathic pain.

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, Application of 1H-Pyrazole-4-boronic acid.

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

Wagner-Griffin, Sarah published the artcileA Druglike Small Molecule that Targets r(CCUG) Repeats in Myotonic Dystrophy Type 2 Facilitates Degradation by RNA Quality Control Pathways, Recommanded Product: (1H-Pyrazol-5-yl)boronic acid, the publication is Journal of Medicinal Chemistry (2021), 64(12), 8474-8485, database is CAplus and MEDLINE.

Myotonic dystrophy type 2 (DM2) is one of >40 microsatellite disorders caused by RNA repeat expansions. The DM2 repeat expansion, r(CCUG)^exp (where “exp” denotes expanded repeating nucleotides), is harbored in intron 1 of the CCHC-type zinc finger nucleic acid binding protein (CNBP). The expanded RNA repeat causes disease by a gain-of-function mechanism, sequestering various RNA-binding proteins including the pre-mRNA splicing regulator MBNL1. Sequestration of MBNL1 results in its loss-of-function and concomitant deregulation of the alternative splicing of its native substrates. Notably, this r(CCUG)^exp causes retention of intron 1 in the mature CNBP mRNA. Herein, we report druglike small mols. that bind the structure adopted by r(CCUG)^exp and improve DM2-associated defects. These small mols. were optimized from screening hits from an RNA-focused small-mol. library to afford a compound that binds r(CCUG)^exp specifically and with nanomolar affinity, facilitates endogenous degradation of the aberrantly retained intron in which it is harbored, and rescues alternative splicing defects.

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 C9H12O, Recommanded Product: (1H-Pyrazol-5-yl)boronic acid.

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