M.W=100-150 | Page 5 of 51 | pyrazoles-derivatives

Wang, Zhen’s team published research in Journal of Medicinal Chemistry in 64 | CAS: 724710-02-5

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 C12H9NO, HPLC of Formula: 724710-02-5.

Wang, Zhen published the artcileDiscovery of an Orally Bioavailable Small-Molecule Inhibitor for the β-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction, HPLC of Formula: 724710-02-5, the publication is Journal of Medicinal Chemistry (2021), 64(16), 12109-12131, database is CAplus and MEDLINE.

Aberrant activation of Wnt/β-catenin signaling is strongly associated with many diseases including cancer invasion and metastasis. Small-mol. targeting of the central signaling node of this pathway, β-catenin, is a biol. rational approach to abolish hyperactivation of β-catenin signaling but has been demonstrated to be a difficult task. Herein, we report a drug-like small mol., ZW4864, that binds with β-catenin and selectively disrupts the protein-protein interaction (PPI) between B-cell lymphoma 9 (BCL9) and β-catenin while sparing the β-catenin/E-cadherin PPI. ZW4864 dose-dependently suppresses β-catenin signaling activation, downregulates oncogenic β-catenin target genes, and abrogates invasiveness of β-catenin-dependent cancer cells. More importantly, ZW4864 shows good pharmacokinetic properties and effectively suppresses β-catenin target gene expression in the patient-derived xenograft mouse model. This study offers a selective chem. probe to explore β-catenin-related biol. and a drug-like small-mol. β-catenin/BCL9 disruptor for future drug development.

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

Wang, Zhen’s team published research in Journal of Medicinal Chemistry in 64 | CAS: 724710-02-5

Wang, Zhen published the artcileDiscovery of 2-(3-(3-Carbamoylpiperidin-1-yl)phenoxy)acetic Acid Derivatives as Novel Small-Molecule Inhibitors of the β-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction, Computed Properties of 724710-02-5, the publication is Journal of Medicinal Chemistry (2021), 64(9), 5886-5904, database is CAplus and MEDLINE.

The β-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction (PPI) is a potential target for the suppression of hyperactive Wnt/β-catenin signaling that is vigorously involved in cancer initiation and development. Herein, we describe the medicinal chem. optimization of a screening hit to yield novel small-mol. inhibitors of the β-catenin/BCL9 interaction. The best compound 30 can disrupt the β-catenin/BCL9 interaction with a K_i of 3.6μM in AlphaScreen competitive inhibition assays. Cell-based experiments revealed that 30 selectively disrupted the β-catenin/BCL9 PPI, while leaving the β-catenin/E-cadherin PPI unaffected, dose-dependently suppressed Wnt signaling transactivation, downregulated oncogenic Wnt target gene expression, and on-target selectively inhibited the growth of cancer cells harboring aberrant Wnt signaling. This compound with a new chemotype can serve as a lead compound for further optimization of inhibitors for β-catenin/BCL9 PPI.

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

Wang, Zhen’s team published research in ACS Medicinal Chemistry Letters in 13 | CAS: 763120-58-7

ACS 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 C9H6N2O2, Computed Properties of 763120-58-7.

Wang, Zhen published the artcileNew ZW4864 Derivatives as Small-Molecule Inhibitors for the β-Catenin/BCL9 Protein-Protein Interaction, Computed Properties of 763120-58-7, the publication is ACS Medicinal Chemistry Letters (2022), 13(5), 865-870, database is CAplus and MEDLINE.

A series of 1-(3-(2-amino-2-oxoethoxy)phenyl)piperidine-3-carboxamide derivatives I [R¹ = 2,7-diazaspiro[4.4]nonan-2-ium, 2,7-diazaspiro[4.4]nonan-2-ium, piperazin-1-ium, etc.; R² = R³ = Me, R² R³ = -CH₂-CH₂-, -CH₂-CH₂-CH₂-, etc.], II[R⁴ = H, Me, iso-Pr, etc.], III[R⁵ = 3-indolyl, indazol-4-yl, 1H-pyrrolo[2,3-b]pyridin-5-yl, etc.] were reported as new small-mol. β-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction (PPI) inhibitors. Compounds II were discovered to inhibit the β-catenin/BCL9 PPI with Ki = 0.85-2.7μM. The effects of III[R⁵ =1H-pyrrolo[2,3-b]pyridin-5-yl] on the β-catenin/BCL9 PPI in cellular context were demonstrated by β-catenin/BCL9 pull-down inhibition and dose-dependent suppression of Wnt/β-catenin signal transactivation. Notably, compound III[R⁵ =1H-pyrrolo[2,3-b]pyridin-5-yl] is more potent than ZW4864, a previously reported analog, in modulating transcription and expression of β-catenin target genes and suppressing survival of β-catenin-dependent cancer cells. The cellular on-target efficacy of III[R⁵ =1H-pyrrolo[2,3-b]pyridin-5-yl] was demonstrated by β-catenin rescue experiments Compound III[R⁵ =1H-pyrrolo[2,3-b]pyridin-5-yl] represents a promising starting point for further optimization of β-catenin/BCL9 PPI inhibitors.

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

Wang, Zhen’s team published research in Journal of Medicinal Chemistry in 64 | CAS: 763120-58-7

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 C22H12F6O6S2, Product Details of C3H5BN2O2.

Wang, Zhen published the artcileDiscovery of an Orally Bioavailable Small-Molecule Inhibitor for the β-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction, Product Details of C3H5BN2O2, the publication is Journal of Medicinal Chemistry (2021), 64(16), 12109-12131, database is CAplus and MEDLINE.

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

Wang, Zhen’s team published research in Journal of Medicinal Chemistry in 64 | CAS: 763120-58-7

Wang, Zhen published the artcileDiscovery of 2-(3-(3-Carbamoylpiperidin-1-yl)phenoxy)acetic Acid Derivatives as Novel Small-Molecule Inhibitors of the β-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction, Product Details of C3H5BN2O2, the publication is Journal of Medicinal Chemistry (2021), 64(9), 5886-5904, database is CAplus and MEDLINE.

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

Liu, Mei’s team published research in Bioorganic & Medicinal Chemistry Letters in 16 | CAS: 724710-02-5

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, Safety of (1H-Pyrazol-5-yl)boronic acid.

Liu, Mei published the artcileSynthesis and SAR of 1,9-dihydro-9-hydroxypyrazolo[3,4-b]quinolin-4-ones as novel, selective c-Jun N-terminal kinase inhibitors, Safety of (1H-Pyrazol-5-yl)boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2006), 16(10), 2590-2594, database is CAplus and MEDLINE.

A novel class of 1,9-dihydro-9-hydroxypyrazolo[3,4-b]quinolin-4-ones I [R¹ = Me, Me₂CH, MeOCH₂CH₂, HO₂C(CH₂)₃, MeCONHCH₂CH₂, etc.; R² = Me, Et, Ph, HO₂CCH₂, HOCH₂CH₂, etc.; R³ = H, Cl, Ph, 3-pyrazolyl] as c-Jun-N-terminal kinase (JNK) inhibitors is described. These compounds were synthesized via the condensation of 2-nitrobenzaldehydes and hydroxypyrazoles. The structure-activity relationships (SAR) and kinase selectivity profile of the inhibitors are also discussed. Compound II was identified as a potent JNK inhibitor with good cellular potency.

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

Oka, Naoki’s team published research in Organic Letters in 24 | CAS: 763120-58-7

Organic 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, Name: 1H-Pyrazole-4-boronic acid.

Oka, Naoki published the artcileAryl Boronic Esters Are Stable on Silica Gel and Reactive under Suzuki-Miyaura Coupling Conditions, Name: 1H-Pyrazole-4-boronic acid, the publication is Organic Letters (2022), 24(19), 3510-3514, database is CAplus and MEDLINE.

A wide range of aryl boronic 1,1,2,2-tetraethylethylene glycol esters [ArB(Epin)s] were readily synthesized. Purifying aryl boronic esters by conventional silica gel chromatog. is generally challenging; however, these introduced derivatives were easily purified on silica gel and isolated in excellent yields. The purified ArB(Epin) was subjected to Suzuki-Miyaura couplings, which provided higher yields of the desired biaryl products than those obtained using the corresponding aryl boronic acids or pinacol esters.

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

Reed, Carson W.’s team published research in Bioorganic & Medicinal Chemistry Letters in 29 | CAS: 763120-58-7

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, HPLC of Formula: 763120-58-7.

Reed, Carson W. published the artcileSurveying heterocycles as amide bioisosteres within a series of mGlu₇ NAMs: Discovery of VU6019278, HPLC of Formula: 763120-58-7, the publication is Bioorganic & Medicinal Chemistry Letters (2019), 29(10), 1211-1214, database is CAplus and MEDLINE.

This letter describes a diversity-oriented library approach to rapidly assess diverse heterocycles as bioisosteric replacements for a metabolically labile amide moiety within a series of mGlu₇ neg. allosteric modulators (NAMs). SAR rapidly honed in on either a 1,2,4- or 1,3,4-oxadizaole ring system as an effective bioisostere for the amide. Further optimization of the southern region of the mGlu₇ NAM chemotype led to the discovery of VU6019278, a potent mGlu₇ NAM (IC₅₀ = 501 nM, 6.3% L-AP₄ Min) with favorable plasma protein binding (rat f_u = 0.10), low predicted hepatic clearance (rat CL_hep = 27.7 mL/min/kg) and high CNS penetration (rat K_p = 4.9, K_p,uu = 0.65).

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

Johns, Brian A.’s team published research in Bioorganic & Medicinal Chemistry Letters in 19 | CAS: 724710-02-5

Johns, Brian A. published the artcile1,3,4-Oxadiazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 2: SAR of the C5 position, Related Products of pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2009), 19(6), 1807-1810, database is CAplus and MEDLINE.

The use of a 1,3,4-oxadiazole in combination with an 8-hydroxy-1,6-naphthyridine ring system has been shown to deliver potent enzyme and antiviral activity through inhibition of viral DNA integration. This report presents a detailed structure-activity investigation of the C5 position resulting in low nM potency for several analogs with an excellent therapeutic index.

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

Heffron, Timothy P.’s team published research in Journal of Medicinal Chemistry in 54 | CAS: 724710-02-5

Heffron, Timothy P. published the artcileRational Design of Phosphoinositide 3-Kinase α Inhibitors That Exhibit Selectivity over the Phosphoinositide 3-Kinase β Isoform, COA of Formula: C3H5BN2O2, the publication is Journal of Medicinal Chemistry (2011), 54(22), 7815-7833, database is CAplus and MEDLINE.

Of the four class I phosphoinositide 3-kinase (PI3K) isoforms, PI3Kα has justly received the most attention for its potential in cancer therapy. Herein we report our successful approaches to achieve PI3Kα vs PI3Kβ selectivity for two chem. series. In the thienopyrimidine series of inhibitors, we propose that select ligands achieve selectivity derived from a hydrogen bonding interaction with Arg770 of PI3Kα that is not attained with the corresponding Lys777 of PI3Kβ. In the benzoxepin series of inhibitors, the selectivity observed can be rationalized by the difference in electrostatic potential between the two isoforms in a given region rather than any specific interaction.

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