Category: 724710-02-5

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

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

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

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

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.

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.

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

Hynes, John Jr. published the artcileDiscovery of potent and efficacious pyrrolopyridazines as dual JAK1/3 inhibitors, Application In Synthesis of 724710-02-5, the publication is Bioorganic & Medicinal Chemistry Letters (2017), 27(14), 3101-3106, database is CAplus and MEDLINE.

A series of potent dual JAK1/3 inhibitors have been developed from a moderately selective JAK3 inhibitor. Substitution at the C6 position of the pyrrolopyridazine core with aryl groups provided exceptional biochem. potency against JAK1 and JAK3 while maintaining good selectivity against JAK2 and Tyk2. Translation to in vivo efficacy was observed in a murine model of chronic inflammation. X-ray co-crystal structure determination confirmed the presumed inhibitor binding orientation in JAK3. Efforts to reduce hERG channel inhibition will be described.

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, Application In Synthesis of 724710-02-5.

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

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.

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, COA of Formula: C3H5BN2O2.

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

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.

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

Carpenter, Joseph published the artcileUtilization of an Active Site Mutant Receptor for the Identification of Potent and Selective Atypical 5-HT_2C Receptor Agonists, Quality Control of 724710-02-5, the publication is Journal of Medicinal Chemistry (2017), 60(14), 6166-6190, database is CAplus and MEDLINE.

Agonism of the 5-HT_2C receptor represents one of the most well-studied and clin. proven mechanisms for pharmacol. weight reduction Selectivity over the closely related 5-HT_2A and 5-HT_2B receptors is critical as their activation has been shown to lead to undesirable side effects and major safety concerns. In this communication, we report the development of a new screening paradigm that utilizes an active site mutant D134A (D3.32) 5-HT_2C receptor to identify atypical agonist structures. We addnl. report the discovery and optimization of a novel class of nonbasic heterocyclic amide agonists of 5-HT_2C. SAR investigations around the screening hits provided a diverse set of potent agonists at 5-HT_2C with high selectivity over the related 5-HT_2A and 5-HT_2B receptor subtypes. Further optimization through replacement of the amide with a variety of five- and six-membered heterocycles led to the identification of 6-(1-ethyl-3-(quinolin-8-yl)-1H-pyrazol-5-yl)pyridazin-3-amine (69). Oral administration of 69 to rats reduced food intake in an ad libitum feeding model, which could be completely reversed by a selective 5-HT_2C antagonist.

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

Murphy-Benenato, Kerry published the artcileIdentification through structure-based methods of a bacterial NAD⁺-dependent DNA ligase inhibitor that avoids known resistance mutations, Related Products of pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2014), 24(1), 360-366, database is CAplus and MEDLINE.

In an attempt to identify novel inhibitors of NAD⁺-dependent DNA ligase (LigA) that are not affected by a known resistance mutation in the adenosine binding pocket, a detailed anal. of the binding sites of a variety of bacterial ligases was performed. This anal. revealed several similarities to the adenine binding region of kinases, which enabled a virtual screen of known kinase inhibitors. From this screen, a thienopyridine scaffold was identified that was shown to inhibit bacterial ligase. Further characterization through structure and enzymol. revealed the compound was not affected by a previously disclosed resistance mutation in Streptococcus pneumoniae LigA, Leu75Phe. A subsequent medicinal chem. program identified substitutions that resulted in an inhibitor with moderate activity across various Gram-pos. bacterial LigA enzymes.

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