Month: December 2022

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.

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.

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.

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

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.

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.

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

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.

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 C19H17N2NaO4S, Computed Properties of 724710-02-5.

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

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.

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.

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

Zhu, Xinrui published the artcileOne-step preparation of ammonium-specified pyrazolium ionic liquids unveil the more popular pathway for the CO₂ fixation: Integrated experimental and theoretical studies, COA of Formula: C4H6N2, the publication is Journal of Molecular Liquids (2021), 115435, database is CAplus.

Amino-specified pyrazolium ionic liquid (APEPzBr) is synthesized by two steps. It is interesting that the product of the first step ([EPzPNH₃]Br₂) could also catalyze the coupling reaction of carbon dioxide and epoxides under 70°C along with 0.5 MPa CO₂ pressure, which is even more benign than APEPzBr. It is attributed to the strong ability of [EPzPNH₃]Br₂ to absorb CO2 along with robust electrophilic activation, which is testified by d. functional theory and ¹³C NMR measurement. The difference between [EPzPNH₃]Br₂ and APEPzBr is further elucidated by electron localization function (ELF) and atoms in mols. (AIM).

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 C19H42F6NP, COA of Formula: C4H6N2.

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

Musharrafieh, Rami published the artcileDiscovery of Quinoline Analogues as Potent Antivirals against Enterovirus D68 (EV-D68), Quality Control of 724710-02-5, the publication is Journal of Medicinal Chemistry (2019), 62(8), 4074-4090, database is CAplus and MEDLINE.

Enterovirus D68 (EV-D68) is an atypical nonpolio enterovirus that mainly infects the respiratory system of humans, leading to moderate-to-severe respiratory diseases. In rare cases, EV-D68 can spread to the central nervous system and cause paralysis in infected patients, especially young children and immunocompromised individuals. There is currently no approved vaccine or antiviral available for the prevention and treatment of EV-D68. In this study, we aimed to improve the antiviral potency and selectivity of a previously reported EV-D68 inhibitor, dibucaine, through structure-activity relationship studies. In total, 60 compounds were synthesized and tested against EV-D68 using the viral cytopathic effect assay. Three compounds 10a, 12a, and 12c were identified to have significantly improved potency (EC₅₀ < 1 μM) and a high selectivity index (>180) compared with dibucaine against five different strains of EV-D68 viruses. These compounds also showed potent antiviral activity in neuronal cells, such as A172 and SH-SY5Y cells, suggesting they might be further developed for the treatment of both respiratory infection as well as neuronal infection.

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, Quality Control of 724710-02-5.

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

Zhang, Rong-Mo published the artcileThe fibrillin-1 RGD motif posttranscriptionally regulates ERK1/2 signaling and fibroblast proliferation via miR-1208, Application of 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is FASEB Journal (2021), 35(5), e21598, database is CAplus and MEDLINE.

Fibrillin-1 is an extracellular matrix protein which contains one conserved RGD integrin-binding motif. It constitutes the backbone of microfibrils in many tissues, and mutations in fibrillin-1 cause various connective tissue disorders. Although it is well established that fibrillin-1 interacts with several RGD-dependent integrins, very little is known about the associated intracellular signaling pathways. Recent published evidence identified a subset of miRNAs regulated by fibrillin-1 RGD-cell adhesion, with miR-1208 among the most downregulated. The present study shows that the downregulated miR-1208 controls fibroblast proliferation. Inhibitor experiments revealed that fibrillin-1 RGD suppressed miR-1208 expression via c-Src kinase and the downstream JNK signaling. Bioinformatic prediction and exptl. target sequence validation demonstrated four miR-1208 binding sites on the ERK2 mRNA and one on the MEK1 mRNA. ERK2 and MEK1 are critical proliferation-promoting kinases. Decreased miR-1208 levels elevated the total and phosphorylated ERK1/2 and MEK1/2 protein levels and the phosphorylated to total ERK1/2 ratio. Together, the data demonstrate a novel outside-in signaling mechanism explaining how fibrillin-1 RGD-cell binding regulates fibroblast proliferation.

FASEB Journal 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 C15H20N2O2, Application of 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide.

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

Taldone, Tony published the artcilePreparation of a diverse purine-scaffold library via one-step palladium catalyzed cross-coupling, Formula: C3H5BN2O2, the publication is Heterocycles (2013), 87(1), 91-113, database is CAplus.

In an ongoing efforts to prepare Hsp90 inhibitors (heat-shock proteins HSP 90 inhibitors), various cross-coupling reactions (Suzuki, Stille, Heck, and Sonogashira) were used to construct a diverse library of substituted purines in a single step from PU-H71. The authors showed show that these reactions, particularly a Suzuki coupling, are highly efficient, do not require protection of the pendant amine and due to a wide variety of com. available substrates, allow for the rapid development of a diverse purine library. The products derived from these reactions will permit the exploration of the chem. space occupied by the key 6′-iodine of PU-H71 through mols. with diverse phys. and chem. properties with the potential to be useful for diseases in which Hsp90 is implicated. The synthesis of the target compounds was achieved using 6-amino-8-[(6-iodo-1,3-benzodioxolyl)thio]-N-(1-methylethyl)-9H-purine-9-propanamine as a key starting material in a reaction with boronic acid derivatives., alkenes, alkynes and organotin compounds (stannane compounds). The title compounds thus formed included 6-amino-N-(1-methylethyl)-8-[[6-(2-oxazolyl)-1,3-benzodioxolyl]thio]-9H-purine-9-propanamine (I) and related substances, such as derivatives of pyrimidine, pyrazine, imidazole, thiazole, alkenes, isoxazole, pyrazole , furan, pyrrole, pyridine, cyclohexane, cyclopentane, alkyne derivatives

Heterocycles 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, Formula: C3H5BN2O2.

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

De Schutter, Joris W. published the artcileNovel bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase, SDS of cas: 763120-58-7, the publication is Bioorganic & Medicinal Chemistry Letters (2010), 20(19), 5781-5786, database is CAplus and MEDLINE.

A structure-based approach was pursued in designing novel bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase (hFPPS). Preliminary SAR and structural evidence for the simultaneous binding of these inhibitors into the isopentenyl pyrophosphate (IPP) and the geranyl pyrophosphate (GPP) substrate sub-pockets of the enzyme are presented.

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, SDS of cas: 763120-58-7.

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

Xu, Ying-zi published the artcileDesign and synthesis of thiophene dihydroisoquinolines as novel BACE1 inhibitors, Computed Properties of 763120-58-7, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(10), 3075-3080, database is CAplus and MEDLINE.

Utilizing a structure based design approach, combined with extensive medicinal chem. execution, highly selective, potent and novel BACE1 inhibitor I (BACE1 Alpha assay IC₅₀ = 8 nM) was made from a weak μM potency hit in an extremely efficient way. The detailed SAR and general design approaches will be discussed.

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 C8H10S, Computed Properties of 763120-58-7.

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