Tag: M.W=100-150

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

Liu, Qingsong published the artcileDiscovery of 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer, Name: 1H-Pyrazole-4-boronic acid, the publication is Journal of Medicinal Chemistry (2011), 54(5), 1473-1480, database is CAplus and MEDLINE.

The mTOR mediated PI3K/AKT/mTOR signal transduction pathway has been demonstrated to play a key role in a broad spectrum of cancers. Starting from the mTOR selective inhibitor 1 (Torin1), a focused medicinal chem. effort led to the discovery of an improved mTOR inhibitor 3 (Torin2, I), which possesses an EC₅₀ of 0.25 nM for inhibiting cellular mTOR activity. Compound 3 exhibited 800-fold selectivity over PI3K (EC₅₀: 200 nM) and over 100-fold binding selectivity relative to 440 other protein kinases. Compound 3 has significantly improved bioavailability (54%), metabolic stability, and plasma exposure relative to compound 1.

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

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

Liu, Qingsong published the artcileDiscovery and optimization of potent and selective benzonaphthyridinone analogs as small molecule mTOR inhibitors with improved mouse microsome stability, Recommanded Product: 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2011), 21(13), 4036-4040, database is CAplus and MEDLINE.

Starting from small mol. mTOR inhibitor Torin1, replacement of the piperazine ring with a Ph ring resulted in a new series of mTOR inhibitors (as exemplified by 10) that showed superior potency and selectivity for mTOR, along with significantly improved mouse liver microsome stability and a longer in vivo half-life.

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

Burdick, Daniel J. published the artcileFragment-based discovery of potent ERK2 pyrrolopyrazine inhibitors, Category: pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2015), 25(21), 4728-4732, database is CAplus and MEDLINE.

A fragment-based lead discovery approach was used to discover novel ERK2 inhibitors. The crystal structure of N-benzyl-9H-purin-6-amine (compound 1) in complex with ERK2 elucidated its hinge-binding mode. In addition, the simultaneous binding of an imidazole mol. adjacent to (1) suggested a direction for fragment expansion. Structure-based core hopping applied to (1) led to 5H-pyrrolo[3,2-b]pyrazine that afforded direct vectors to probe the pockets of interest while retaining the essential hinge binding elements. Utilizing the new vectors for SAR exploration, the new core (I) was quickly optimized to 7-(1-benzyl-1H-pyrazol-4-yl)-2-(pyridin-4-yl)-5H-pyrrolo[3,2-b]pyrazine (compound 39) resulting in a greater than 6600-fold improvement in potency.

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, Category: pyrazoles-derivatives.

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

Gu, Zheng-Song published the artcileSynthesis and antidepressant effect of novel aralkyl piperazine and piperidine derivatives targeting SSRI/5-HT_1A/5-HT₇, Category: pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2019), 29(23), 126703, database is CAplus and MEDLINE.

A series of novel aralkyl piperazine and piperidine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT_1A/5-HT₇ receptors affinities activity. Antidepressant activities in vivo of the selective compound were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compound 19a (I) exhibited high affinities for the 5-HT_1A/5-HT₇ receptors (5-HT_1A, K_i = 12 nM; 5-HT₇, K_i = 3.2 nM) coupled with potent serotonin reuptake inhibition (IC₅₀ = 14 nM) and showed a marked antidepressant-like effect in the FST and TST models.

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, Category: 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

Lu, Jinzhen published the artcileOctapi Interactions: Self-Assembly of a Pd-Based [2]Catenane Driven by Eightfold π Interactions, Related Products of pyrazoles-derivatives, the publication is Journal of the American Chemical Society (2009), 131(30), 10372-10373, database is CAplus and MEDLINE.

An unprecedented 2.5 nm array of π interactions between eight aromatic rings drives the formation of a [2]catenane, {[Pd(dppp)]₂L²}₂⁸⁺ (L = 1,2-bis(4-(4-pyridyl)pyrazolyl)ethane; dppp = 1,3-bis(diphenylphosphino)propane). Disruption of this array through the use of longer ligands gave only single, uncatenated rings as observed in {[Pd(dppp)₂]₂L¹}⁴⁺ (L = 1,3-bis(4-(4-pyridyl)pyrazolyl)propane). The catenated complex persists in solution alongside its constituent metallomacrocycles.

Journal of the American Chemical Society 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, Related Products of pyrazoles-derivatives.

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

Wang, Tao published the artcileDiscovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir, Product Details of C3H5BN2O2, the publication is Journal of Medicinal Chemistry (2018), 61(14), 6308-6327, database is CAplus and MEDLINE.

The optimization of the 4-methoxy-6-azaindole series of HIV-1 attachment inhibitors (AIs) that originated with 1 to deliver temsavir (3, BMS-626529) is described. The most beneficial increases in potency and pharmacokinetic (PK) properties were attained by incorporating N-linked, sp²-hybridized heteroaryl rings at the 7-position of the heterocyclic nucleus. Compounds that adhered to a coplanarity model afforded targeted antiviral potency, leading to the identification of 3 with characteristics that provided for targeted exposure and PK properties in three preclin. species. However, the phys. properties of 3 limited plasma exposure at higher doses, both in preclin. studies and in clin. trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir). An extended-release formulation of 4 is currently in phase III clin. trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.

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 C3H7NO2, Product Details of C3H5BN2O2.

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

Lemurell, Malin published the artcileNovel Chemical Series of 5-Lipoxygenase-Activating Protein Inhibitors for Treatment of Coronary Artery Disease, HPLC of Formula: 724710-02-5, the publication is Journal of Medicinal Chemistry (2019), 62(9), 4325-4349, database is CAplus and MEDLINE.

5-Lipoxygenase (5-LO)-activating protein (FLAP) inhibitors have proven to attenuate 5-LO pathway activity and leukotriene production in human clin. trials. However, previous clin. candidates have been discontinued and the link between FLAP inhibition and outcome in inflammatory diseases remains to be established. We here describe a novel series of FLAP inhibitors identified from a screen of 10k compounds and the medicinal chem. strategies undertaken to progress this series. Compound I showed good overall properties and a pIC₅₀ hWB_free of 8.1 and an lipophilic ligand efficiency of 5.2. Target engagement for I was established in dogs using ex vivo measurement of leukotriene B₄ (LTB₄) levels in blood with good correlation to in vitro potency. A predicted human dose of 280 mg b.i.d. suggests a wide margin to any identified in vitro off-target effects and sufficient exposure to achieve an 80% reduction of LTB₄ levels in humans. Compound I is progressed to preclin. in vivo safety studies.

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, HPLC of Formula: 724710-02-5.

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

Liang, Jun published the artcileLead Optimization of a 4-Aminopyridine Benzamide Scaffold To Identify Potent, Selective, and Orally Bioavailable TYK2 Inhibitors, Synthetic Route of 763120-58-7, the publication is Journal of Medicinal Chemistry (2013), 56(11), 4521-4536, database is CAplus and MEDLINE.

Herein the authors report the authors’ lead optimization effort to identify potent, selective, and orally bioavailable TYK2 inhibitors, starting with lead mol. 2,6-dichloro-N-(2-(cyclopropanecarboxamido)pyridin-4-yl)benzamide. The authors used structure-based design to discover 2,6-dichloro-4-cyanophenyl and (1R,2R)-2-fluorocyclopropylamide modifications, each of which exhibited improved TYK2 potency and JAK1 and JAK2 selectivity relative to 2,6-dichloro-N-(2-(cyclopropanecarboxamido)pyridin-4-yl)benzamide. Further optimization eventually led to 2-Chloro-4-cyano-6-fluoro-N-(2-((1R,2R)-2-fluorocyclopropanecarboxamido)pyridin-4-yl)benzamide that showed good TYK2 enzyme and interleukin-12 (IL-12) cell potency, as well as acceptable cellular JAK1 and JAK2 selectivity and excellent oral exposure in mice. When tested in a mouse IL-12 PK/PD model, 2-Chloro-4-cyano-6-fluoro-N-(2-((1R,2R)-2-ffluorocyclopropanecarboxamido)pyridin-4-yl)benzamide showed statistically significant knockdown of cytokine interferon-γ (IFNγ), suggesting that selective inhibition of TYK2 kinase activity might be sufficient to block the IL-12 pathway in vivo.

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, Synthetic Route of 763120-58-7.

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