Tag: M.W=100-150

Szymanska, Ewa published the artcileAryl- and heteroaryl-substituted phenylalanines as AMPA receptor ligands, Computed Properties of 763120-58-7, the publication is Chemical Biology & Drug Design (2017), 90(6), 1271-1281, database is CAplus and MEDLINE.

A series of racemic unnatural amino acids was rationally designed on the basis of recently published X-ray structures of the GluA2 LBD with bound phenylalanine-based antagonists. Twelve new diaryl- or aryl/heteroaryl-substituted phenylalanine derivatives were synthesized and evaluated in vitro in radioligand binding assays at native rat ionotropic glutamate receptors. The most interesting compound in this series, (RS)-2-amino-3-(3′-hydroxy-5-(1H-pyrazol-4-yl)-[1,1′-biphenyl]-3-yl)propanoic acid 7e, showed the binding affinity of 4.6 μM for native AMPA receptors and over fourfold lower affinity for kainic acid receptors. Furthermore, 7e was evaluated at recombinant homomeric rat GluA2 and GluA3 receptors. Recently reported X-ray structures 5CBR and 5CBS, representing two distinct antagonist binding modes, were used as templates for mol. docking of the synthesized series. Binding data supported with mol. modeling confirmed that aryl/heteroaryl-substituted phenylalanine analogs effectively bind to AMPA receptors with low micromolar affinity and high selectivity over native NMDA and kainate receptors. These properties make 7e a promising lead for the further development of new AMPA receptor ligands.

Chemical Biology & Drug Design 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 C14H28O5S, Computed Properties of 763120-58-7.

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

Otrubova, Katerina published the artcileN-Acyl pyrazoles: Effective and tunable inhibitors of serine hydrolases, Recommanded Product: 1H-Pyrazole-1-carbonyl chloride, the publication is Bioorganic & Medicinal Chemistry (2019), 27(8), 1693-1703, database is CAplus and MEDLINE.

A series of N-acyl pyrazoles was examined as candidate serine hydrolase inhibitors in which the active site acylating reactivity and the leaving group ability of the pyrazole could be tuned not only through the nature of the acyl group (reactivity: amide > carbamate > urea), but also through pyrazole C4 substitution with electron-withdrawing or electron-donating substituents. Their impact on enzyme inhibitory activity displayed pronounced effects with the activity improving substantially as one alters both the nature of the reacting carbonyl group (urea > carbamate > amide) and the pyrazole C4 substituent (CN > H > Me). It was further demonstrated that the acyl chain of the N-acyl pyrazole ureas can be used to tailor the potency and selectivity of the inhibitor class to a targeted serine hydrolase. Thus, elaboration of the acyl chain of pyrazole-based ureas provided remarkably potent, irreversible inhibitors of fatty acid amide hydrolase (FAAH, apparent K_i = 100-200 pM), dual inhibitors of FAAH and monoacylglycerol hydrolase (MGLL), or selective inhibitors of MGLL (IC₅₀ = 10-20 nM) while simultaneously minimizing off-target activity (e.g., ABHD6 and KIAA1363).

Bioorganic & Medicinal Chemistry published new progress about 53355-55-8. 53355-55-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Chloride,acyl chloride,Amide, name is 1H-Pyrazole-1-carbonyl chloride, and the molecular formula is C4H3ClN2O, Recommanded Product: 1H-Pyrazole-1-carbonyl chloride.

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

Hornberger, Keith R. published the artcileDiscovery and optimization of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1, Application of 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(16), 4517-4522, database is CAplus and MEDLINE.

The discovery and potency optimization of a series of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1 is described. Micromolar hits taken from high-throughput screening were optimized for biochem. and cellular mechanistic potency to ∼10 nM, as exemplified by compound 12az. Application of structure-based drug design aided by co-crystal structures of TAK1 with inhibitors significantly shortened the number of iterations required for the optimization.

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, Application of 1H-Pyrazole-4-boronic acid.

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

Harris, Philip A. published the artcileDiscovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases, Name: (1H-Pyrazol-5-yl)boronic acid, the publication is Journal of Medicinal Chemistry (2017), 60(4), 1247-1261, database is CAplus and MEDLINE.

RIP1 regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. Small-mol. inhibitors of RIP1 kinase that are suitable for advancement into the clinic have yet to be described. Herein, the authors report the lead optimization of a benzoxazepinone hit from a DNA-encoded library and the discovery and profile of clin. candidate GSK2982772 (compound I), currently in phase 2a clin. studies for psoriasis, rheumatoid arthritis, and ulcerative colitis. Compound I potently binds to RIP1 with exquisite kinase specificity and has excellent activity in blocking many TNF-dependent cellular responses. Highlighting its potential as a novel anti-inflammatory agent, the inhibitor was also able to reduce spontaneous production of cytokines from human ulcerative colitis explants. The highly favorable physicochem. and ADMET properties of I, combined with high potency, led to a predicted low oral dose in humans.

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

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

Hosseini, Simin S. published the artcileSynthesis, carbohydrate- and DNA-binding studies of cationic 2,2′:6′,2”-terpyridineplatinum(II) complexes containing N- and S-donor boronic acid ligands, HPLC of Formula: 763120-58-7, the publication is Dalton Transactions (2011), 40(2), 506-513, database is CAplus and MEDLINE.

Platinum(II) complexes [Pt(trpy)L](NO₃)_n (L = 3- or 4-pyridineboronic acid (3- or 4-pyB, resp.), n = 2; HL = 4-mercaptophenylboronic acid (HmpB), n = 1; trpy = 2,2′:6′,2”-terpyridine) and [{Pt(trpy)}₂(μ-pzB)](NO₃)₃ (HpzB = 4-pyrazoleboronic acid) were synthesized and fully characterized by multinuclear (¹H, ¹³C, ¹¹B, and ¹⁹⁵Pt) 1-dimensional- and 2-dimensional-NMR spectroscopy and elemental anal. The triflate derivatives [Pt(trpy)(4-pyB)](OTf)₂ and [{Pt(trpy)}₂(μ-pzB)](OTf)₃ were also prepared, and their mol. structures were confirmed by x-ray crystallog. Variable pH ¹H NMR spectroscopy showed that hydroxylation of the boronic acid group occurs in aqueous solution at pH > 5 and the pK_a values for the complexes were determined In buffered aqueous solution (pH 7.4), the complexes bind strongly to simple diols such as catechol and monosaccharides including D-fructose, D-ribose, D-sorbitol and D-mannitol, as determined by isothermal titration calorimetry (ITC). The equilibrium binding constants for these reactions were determined and were found to exceed those of organic boronic acids such as phenylboronic acid by an order of magnitude or greater, an effect that can be directly attributed to the cationic charge of the complexes. Two-dimensional-NMR methods (HSQC and HMBC) were used to elucidate the structures of the carbohydrate adducts [Pt(trpy)(3-pyB)]·D-fructose·NO₃ and [Pt(trpy)(4-pyB)]·D-fructose·NO₃ in aqueous solution DNA-binding experiments with calf-thymus DNA (CT-DNA) indicate an avid DNA-binding interaction by the mononuclear complexes, as determined using thermal melting methods and ITC, but the behavior of dinuclear [{Pt(trpy)}₂(μ-pzB)](NO₃)₃ is complicated and could not be modeled adequately; higher ionic strength solutions and lower temperatures resulted in a similar DNA binding interaction to the mononuclear complexes. The presence of excess D-fructose did not significantly affect the binding of the platinum(II)-trpy complexes to CT-DNA.

Dalton Transactions 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, HPLC of Formula: 763120-58-7.

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

Chen, Pei published the artcileDiscovery of 6,7-dihydro-5H-pyrrolo[3,4-d] pyrimidine derivatives as a new class of ATR inhibitors, HPLC of Formula: 724710-02-5, the publication is Bioorganic & Medicinal Chemistry Letters (2022), 128651, database is CAplus and MEDLINE.

Ataxia telangiectasia and Rad3-related (ATR) kinase is a key regulating protein within the DNA damage response (DDR), responsible for sensing replication stress (RS), and has been considered as a potential target for cancer therapy. Herein, we report the discovery of a series of 6,7-dihydro-5H-pyrrolo[3,4-d]-pyrimidine derivatives as a new class of ATR inhibitors. Among them, compound 5g exhibits an IC50 value of 0.007 μM against ATR kinase. In vitro, 5g displays good anti-tumor activity and could significantly reduce the phosphorylation level of ATR and its downstream signaling protein. Overall, this study provides a promising lead compound for subsequent drug discovery targeting ATR kinase.

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, HPLC of Formula: 724710-02-5.

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

Large, Jonathan M. published the artcilePotent inhibitors of malarial P. Falciparum protein kinase G: Improving the cell activity of a series of imidazopyridines, Synthetic Route of 763120-58-7, the publication is Bioorganic & Medicinal Chemistry Letters (2019), 29(3), 509-514, database is CAplus and MEDLINE.

Development of a class of bicyclic inhibitors of the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG), starting from known compounds with activity against a related parasite PKG orthologue, is reported. Examination of key sub-structural elements led to new compounds with good levels of inhibitory activity against the recombinant kinase and in vitro activity against the parasite. Key examples were shown to possess encouraging in vitro ADME properties, and computational anal. provided valuable insight into the origins of the observed activity profiles.

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, Synthetic Route of 763120-58-7.

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

Barraclough, Paul published the artcileInotropic polyazapentalene sulmazole analogs, COA of Formula: C5H7N3O, the publication is Archiv der Pharmazie (Weinheim, Germany) (1992), 325(4), 225-34, database is CAplus and MEDLINE.

Aryl substituted 1H-imidazo[1,2-a]imidazole I, imidazo[2,1-b]thiazole II (X = S), 1,4-dihydroimidazo[4,5-d]imidazole III, and 1(2),4-dihydroimidazo[4,5-c]pyrazoles IV (Y = SOMe, SMe, cyano, CONH₂) and V (Z = cyano, CONH₂) have been prepared Thus, 2-aminoimidazole reacted with 2-bromo-2′,4′-dimethoxyacetophenone to give II (X = NCH₂R¹, R¹ = 2′,4′-dimethoxybenzoyl) which was treated with Zn in aqueous HOAc to give I in 70% yield. An x-ray crystallog. study confirmed the structure of I and showed this analog to exist as the 1H-tautomer. These heterocycles were evaluated as inotropic agents and analogs IV (Y = SOMe, CONH₂) and V (Z = CONH₂) displayed inotropic properties which were less potent in vitro, but more potent in vivo, than those of sulmazole. Structure-activity relationships are discussed.

Archiv der Pharmazie (Weinheim, Germany) published new progress about 3553-12-6. 3553-12-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Amine,Amide, name is 3-Acetamidopyrazole, and the molecular formula is C5H7N3O, COA of Formula: C5H7N3O.

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

Harris, Philip A. published the artcileDiscovery of Small Molecule RIP1 Kinase Inhibitors for the Treatment of Pathologies Associated with Necroptosis, Category: pyrazoles-derivatives, the publication is ACS Medicinal Chemistry Letters (2013), 4(12), 1238-1243, database is CAplus and MEDLINE.

Potent inhibitors of RIP1 kinase from three distinct series, 1-aminoisoquinolines, pyrrolo-[2,3-b]-pyridines, and furo-[2,3-d]-pyrimidines, all of the type II class recognizing a DLG-out inactive conformation, were identified from screening of our inhouse kinase focused sets. An exemplar from the furo-[2,3-d]-pyrimidine series showed a dose proportional response in protection from hypothermia in a mouse model of TNFα induced lethal shock.

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 C3H5BN2O2, Category: pyrazoles-derivatives.

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

Romagnoli, Romeo published the artcileSynthesis and biological evaluation of novel 2-amino-3-aroyl-4-neopentyl-5-substituted thiophene derivatives as allosteric enhancers of the A₁ adenosine receptor, SDS of cas: 763120-58-7, the publication is Bioorganic & Medicinal Chemistry (2014), 22(1), 148-166, database is CAplus and MEDLINE.

2-Amino-3-benzoyl thiophenes have been widely reported to act as allosteric enhancers at the A₁ adenosine receptor. Their activity can be increased considerably by appropriate substitutions at the 4- and 5-positions of the thiophene ring. Substituent size at the thiophene C-4 position seemed to be a factor closely related to activity, with the 4-neopentyl (2,2-dimethylpropyl) substitution showing the greatest enhanced activity. A wide series of 2-amino-3-aroyl-4-neopentylthiophene derivatives with general structure I, characterized by the presence of different substituents (bromine, aryl and heteroaryl) at the 5-position of the thiophene ring, have been identified as potent AEs at the A₁AR. With only one exception, all of the synthesized compounds proved to be superior to the reference compound PD 81,723 in a functional assay. Derivatives I (R = Ph, R¹ = 4-Me; R = 4-OMePh, R¹ = 4-Me; R = 3-OMePh, R¹ = 4-Cl; R = 3,4-(O-CH₂-O)Ph, R¹ = 4-Cl; and R = 4-MePh, R¹ = 4-Cl) were the most active compounds in binding (saturation and competition) and functional cAMP studies, being able to potentiate agonist [³H]CCPA binding to the A₁ receptor.

Bioorganic & 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, SDS of cas: 763120-58-7.

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