Day: December 1, 2022

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, 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

Lu, Jinzhen published the artcileHeteroligand Molecular “Stirrups” Using Conformationally Flexible Ditopic Pyridyl-Pyrazolyl Ligands, Category: pyrazoles-derivatives, the publication is Inorganic Chemistry (2009), 48(16), 7525-7527, database is CAplus and MEDLINE.

Heteroligand mol. stirrups form by the self-assembly of flexible ditopic ligands in combination with 4,4′-bipyridine and [(dppp)Pd]²⁺ [dppp = 1,3-bis(diphenylphosphino)propane]. Crystallog. anal. shows that the ligands, bis[3-(4-pyridyl)pyrazolyl]-m-xylene (mXy^4py3pz) and bis[4-(4-pyridyl)pyrazolyl]-p-xylene (pXy^4py4pz) form [{(dppp)Pd}₂(4,4′-bipy)(L)](OTf)₄ (1·4OTf and 2·4OTf, resp.) in the solid state, with remarkably similar structures considering the differences in substitution patterns between the two ligands. The self-assembly of both 1⁴⁺ and 2⁴⁺ is assisted by face-to-face π interactions on the exterior of the macrocycle between the Ph rings of the dppp ligands and the pyridyl groups of the ditopic ligands.

Inorganic Chemistry 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, Category: pyrazoles-derivatives.

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

Tarr, James C. published the artcileTargeting Selective Activation of M₁ for the Treatment of Alzheimer’s Disease: Further Chemical Optimization and Pharmacological Characterization of the M₁ Positive Allosteric Modulator ML169, Computed Properties of 763120-58-7, the publication is ACS Chemical Neuroscience (2012), 3(11), 884-895, database is CAplus and MEDLINE.

The M₁ muscarinic acetylcholine receptor is thought to play an important role in memory and cognition, making it a potential target for the treatment of Alzheimer’s disease (AD) and schizophrenia. Moreover, M₁ interacts with BACE1 and regulates its proteasomal degradation, suggesting selective M₁ activation could afford both palliative cognitive benefit as well as disease modification in AD. A key challenge in targeting the muscarinic acetylcholine receptors is achieving mAChR subtype selectivity. Our lab has previously reported the M₁ selective pos. allosteric modulator ML169. Herein we describe our efforts to further optimize this lead compound by preparing analog libraries and probing novel scaffolds. We were able to identify several analogs that possessed submicromolar potency, with our best example displaying an EC₅₀ of 310 nM. The new compounds maintained complete selectivity for the M₁ receptor over the other subtypes (M₂-M₅), displayed improved DMPK profiles, and potentiated the carbachol (CCh)-induced excitation in striatal MSNs. Selected analogs were able to potentiate CCh-mediated non-amyloidogenic APPα release, further strengthening the concept that M₁ PAMs may afford a disease-modifying role in the treatment of AD.

ACS Chemical Neuroscience 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 C9H5ClO2, Computed Properties of 763120-58-7.

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, Quality Control of 763120-58-7, 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 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, Quality Control of 763120-58-7.

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

Faust, Thomas B. published the artcileControlling magnetic communication through aromatic bridges by variation in torsion angle, Formula: C8H7N3, the publication is Dalton Transactions (2012), 41(44), 13626-13631, database is CAplus and MEDLINE.

Heteroaromatic bridging ligands (L, e.g., 4,4′-bipyridine) are employed in the synthesis of a family of paramagnetic, heterometallic ring dimers derived from {Cr₇Ni(N-Et-D-glucamine)F₃(O₂CCMe₃)₁₅(H₂O)}, to give [{Cr₇Ni(N-Et-D-glucamine)F₃(O₂CCMe₃)₁₅}₂L]. The extent of spin propagation between the rings via the organic conduit was studied through micro-SQUID magnetometry and EPR spectroscopy from which conclusions over the mechanism of spin-communication are drawn.

Dalton Transactions 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, Formula: C8H7N3.

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

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

Arkhipova, Anna Alexandrovna published the artcileSorbents with non-covalently immobilized β-diketones for preconcentration of rare earth elements, HPLC of Formula: 4551-69-3, the publication is Talanta (2016), 497-502, database is CAplus and MEDLINE.

A comparison of the efficiency of sorbents obtained by different methods of non-covalent immobilization of β-diketones on some low-polar matrixes with respect to extraction of rare earth elements (REEs) was carried out. Sorbents containing reagent amounts of 1-8 mmol/g can be obtained by sorption of reagents on low-polar matrixes from aqueous and aqueous-organic solutions, and the value for the maximum capacity of the sorbent correlates with the sp. surface of the matrix. Similar sorbents were also prepared by impregnating the matrix with reagent. It was found out that, under the chosen conditions, sorbents modified by extracting reagent from the aqueous solutions are more stable and extract lanthanum with higher distribution coefficients than those obtained by impregnation. We have found conditions for quant. extraction of REEs from seawater in the proposed preconcentration systems (pH 4.0, minicolumn dimensions 2×10 mm, v=4 mL/min). All REE may be quant. recovered in both ways: on modified sorbents and as complexes with reagents on unmodified matrixes. We have proposed a sorbent for lanthanum preconcentration from large volumes of water samples (500 mL). The sorbent is stable in dynamic conditions and is based on hyper cross-linked polystyrene modified with 1-phenyl-3-methyl-4-benzoylpyrazol-5-one (PMBP). Desorption could be carried out with 1-2 M HNO₃. REEs were determined by ICP-MS, LODs achieved were in ng/l range.

Talanta published new progress about 4551-69-3. 4551-69-3 belongs to pyrazoles-derivatives, auxiliary class Benzenes, name is 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, and the molecular formula is C17H14N2O2, HPLC of Formula: 4551-69-3.

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