Category: 724710-02-5

Pham, Thanh Truc published the artcileNovel 1,2-dihydroquinazolin-2-ones: Design, synthesis, and biological evaluation against Trypanosoma brucei, Name: (1H-Pyrazol-5-yl)boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2017), 27(16), 3629-3635, database is CAplus and MEDLINE.

In 2014, a published report of the high-throughput screen of >42,000 kinase inhibitors from GlaxoSmithKline against T. brucei identified 797 potent and selective hits. From this rich data set, the authors selected NEU-<0001101≥(1) for hit-to-lead optimization. Through the authors’ preliminary compound synthesis and SAR studies, the authors confirmed the previously reported activity of 4-phenyl-6-(pyridin-4-yl)quinazolin-2(1H)-one in a T. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 4-phenyl-6-(pyridin-4-yl)quinazolin-2(1H)-one. Pyrazole 24 achieves improvements in both potency and lipophilicity relative to 4-phenyl-6-(pyridin-4-yl)quinazolin-2(1H)-one , while also showing good in vitro metabolic stability. The SAR developed on 24 provides new directions for further optimization of this novel scaffold for anti-trypanosomal drug discovery.

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, Name: (1H-Pyrazol-5-yl)boronic acid.

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

Caldwell, John J. published the artcileDesign and synthesis of 2(1H)-pyrazinones as inhibitors of protein kinases, Category: pyrazoles-derivatives, the publication is Tetrahedron (2012), 68(47), 9713-9728, database is CAplus.

Kinase enzymes play a key role in the development and progression of cancer. Inhibitors of deregulated kinases are effective small mol. anticancer drugs. The 2(1H)-pyrazinone heterocycle is a previously unexploited motif that can fulfil the structural requirements for ATP-competitive inhibition of kinases. Rapid solution-phase syntheses of novel 3,5- and 3,6-disubstituted-2(1H)-pyrazinones were developed through selective, sequential substitution of 2,5-dihalo-3-benzyloxypyrazine and 3,5-dihalo-2(1H)-pyrazinone intermediates. Palladium-catalyzed cross-couplings and S_NAr reactions were used to introduce substituents chosen on the basis of the calculated physicochem. properties of the target pyrazinones. Representative compounds, e.g., I, demonstrated good solubility, kinase inhibitory activity and antiproliferative activity in human tumor cells, confirming the suitability of this chem. class as a kinase-focused library.

Tetrahedron 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, Category: pyrazoles-derivatives.

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

Nasir Baig, R. B. published the artcileOrganic synthesis via magnetic attraction: benign and sustainable protocols using magnetic nanoferrites, Product Details of C3H5BN2O2, the publication is Green Chemistry (2013), 15(2), 398-417, database is CAplus.

Magnetic nano-catalysts have been prepared using simple modification of iron ferrites. The nm size range of these particles facilitates the catalysis process, as an increased surface area is available for the reaction; the easy separation of the catalysts by an external magnet and their recovery and reuse are addnl. beneficial attributes. Glutathione bearing nano-ferrites have been used as organocatalysts for the Paal-Knorr reaction and homocoupling of boronic acids. Nanoferrites, post-synthetically modified by ligands, were used to immobilize nanometals (Cu, Pd, Ru, etc.) which enabled the development of efficient, sustainable and green procedures for azide-alkynes-cycloaddition (AAC) reactions, C-S coupling, O-allylation of phenol, Heck-type reactions and hydration of nitriles.

Green 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, 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

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

Lu, Rong-Jian published the artcileHeterobiaryl Human Immunodeficiency Virus Entry Inhibitors, Formula: C3H5BN2O2, the publication is Journal of Medicinal Chemistry (2009), 52(14), 4481-4487, database is CAplus and MEDLINE.

Previously disclosed HIV (human immunodeficiency virus) attachment inhibitors, exemplified by BMS 806 (formally BMS 378806), are characterized by a substituted indole or azaindole ring linked to a benzoylpiperazine via a ketoamide or sulfonamide group. In the present report, we describe the discovery of a novel series of potent HIV entry inhibitors in which the indole or azaindole ring of previous inhibitors is replaced by a heterobiaryl group. Several of these analogs exhibited IC₅₀ values of less than 5 nM in a pseudotyped antiviral assay, and a methylisoxazolylphenyloxoacetyl piperazine was demonstrated to exhibit potency and selectivity similar to those of BMS 378806 against a panel of clin. viral isolates. Moreover, current structure-activity relation studies of these novel biaryl gp120 inhibitors revealed that around the biaryl, a fine crevice might exist in the gp120 binding site. Taken in sum, these data reveal a hitherto unsuspected flexibility in the structure-activity relationships for these inhibitors and suggest new avenues for exploration and gp120 inhibitor design.

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, Formula: C3H5BN2O2.

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

Lizarzaburu, Mike published the artcileDiscovery and optimization of a novel series of GPR142 agonists for the treatment of type 2 diabetes mellitus, SDS of cas: 724710-02-5, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(18), 5942-5947, database is CAplus and MEDLINE.

N-alkylphenylalaninamides of pyridinylphenyl- and oxobipyridinylamines such as I were prepared as GPR142 agonists for potential use as antidiabetic agents for type 2 diabetes and tested for their agonism of GPR142 in vitro and in human plasma and their inhibition of cytochrome P 450 enzymes such as isoforms 3A4 and 2D6. Optimization of the original lead compound gave agonists 90 times more potent against human GPR142. Inhibition of cytochrome P 450 isoforms 3A4 and 2D6 was reduced by increasing the polarity of the biarylamine moiety. The pharmacokinetics of I and a thiazolylmethyl phenylalaninamide of an aminopyridinylbenzoate were determined in rats.

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, SDS of cas: 724710-02-5.

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

Lu, Rong-Jian published the artcileDesign and Synthesis of Human Immunodeficiency Virus Entry Inhibitors: Sulfonamide as an Isostere for the α-Ketoamide Group, Safety of (1H-Pyrazol-5-yl)boronic acid, the publication is Journal of Medicinal Chemistry (2007), 50(26), 6535-6544, database is CAplus and MEDLINE.

The crystal structures of many tertiary α-ketoamides reveal an orthogonal arrangement of the two carbonyl groups. Based on the hypothesis that the α-ketoamide HIV attachment inhibitor BMS 806 (formally BMS378806, 26) might bind to its gp120 target via a similar conformation, we designed and synthesized a series of analogs in which the ketoamide group is replaced by an isosteric sulfonamide group. The most potent of these analogs, 14i (I), demonstrated antiviral potency comparable to 26 in the M33 pseudotyped antiviral assay. Flexible overlay calculations of a ketoamide inhibitor with a sulfonamide inhibitor revealed a single conformation of each that gave significantly better overlap of key pharmacophore features than other conformations and thus suggest a possible binding conformation for each class.

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

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

Kharbanda, Anupreet published the artcileDiscovery of 4-aminoquinolines as highly selective TGFβR1 inhibitors with an attenuated MAP4K4 profile for potential applications in immuno-oncology, Formula: C3H5BN2O2, the publication is European Journal of Medicinal Chemistry (2021), 113763, database is CAplus and MEDLINE.

The tumor microenvironment contains high concentrations of TGFβ, a crucial immunosuppressive cytokine. TGFβ stimulates immune escape by promoting peripheral immune tolerance to avoid tumoricidal attack. Small-mol. inhibitors of TGFβR1 are a prospective method for next-generation immunotherapies. In the present study, we identified selective 4-aminoquinoline-based inhibitors of TGFβR1 through structural and rational-based design strategies. This led to the identification of [N-(2-(2,5-difluorophenyl)pyridin-4-yl)-7-(4-(methylsulfonyl)phenyl)quinolin-4-amine], which was found to be selective for TGFβR1 with the exception of MAP4K4 in the kinase profiling assay. The compound was then further optimized to remove MAP4K4 activity, since MAP4K4 is vital for proper T-cell function and its inhibition could exacerbate tumor immunosuppression. Optimization efforts led to [7-(4-(methylsulfonyl)phenyl)-N-(2-(m-tolyl)pyridin-4-yl)quinolin-4-amine] that inhibited TGFβR1 at an IC₅₀ of 0.79 ± 0.19 nM with 2000-fold selectivity against MAP4K4. 7-(4-(Methylsulfonyl)phenyl)-N-(2-(m-tolyl)pyridin-4-yl)quinolin-4-amine, represents a highly selective TGFβR1 inhibitor that has potential applications in immuno-oncol.

European 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, Formula: C3H5BN2O2.

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

Lim, Jongwon published the artcileDiscovery of 1-Amino-5H-pyrido[4,3-b]indol-4-carboxamide Inhibitors of Janus Kinase 2 (JAK2) for the Treatment of Myeloproliferative Disorders, Synthetic Route of 724710-02-5, the publication is Journal of Medicinal Chemistry (2011), 54(20), 7334-7349, database is CAplus and MEDLINE.

The JAK-STAT pathway mediates signaling by cytokines, which control survival, proliferation, and differentiation of a variety of cells. In recent years, a single point mutation (V617F) in the tyrosine kinase JAK2 was found to be present with a high incidence in myeloproliferative disorders (MPDs). This mutation led to hyperactivation of JAK2, cytokine-independent signaling, and subsequent activation of downstream signaling networks. The genetic, biol., and physiol. evidence suggests that JAK2 inhibitors could be effective in treating MPDs. De novo design efforts of new scaffolds identified 1-amino-5H-pyrido[4,3-b]indol-4-carboxamides as a new viable lead series. Subsequent optimization of cell potency, metabolic stability, and off-target activities of the leads led to the discovery of 7-(2-aminopyrimidin-5-yl)-1-{[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]amino}-5H-pyrido[4,3-b]indole-4-carboxamide (65). Compound 65 is a potent, orally active inhibitor of JAK2 with excellent selectivity, PK profile, and in vivo efficacy in animal models.

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