Tag: M.W=100-150

Fernandes, Celia published the artcileRe(I) and ^99mTc(I) tricarbonyl complexes with ether-containing pyrazolyl-based chelators: Chemistry, biodistribution and metabolism, Application of 4-(methoxymethyl)-1H-pyrazole, the publication is Journal of Organometallic Chemistry (2014), 138-148, database is CAplus.

Tris(pyrazolyl)methane chelators, L1-L3, containing one or two ether groups at different positions of the azole rings, were synthesized and fully characterized. These chelators enabled the synthesis of fac-[^99mTc(CO)₃{HC[4-(ROCH₂)pz]₃}]⁺ (R = Me (Tc1), Et (Tc2)) and fac-[^99mTc(CO)₃{HC[3,5-(EtOCH₂)₂pz]₃}]⁺ (Tc3) which were identified by HPLC in comparison with the rhenium counterparts. The evaluation of Tc1-Tc3 in CD-1 mice showed that the number and/or nature of the ether groups greatly influence the biodistribution profile, pharmacokinetics and metabolic stability of these complexes. Tc1 and Tc2, bearing a unique ether substituent at the 4-position of the pyrazolyl ring, undergo metabolic transformation in vivo while Tc3 is not metabolized. The metabolization of Tc1 and Tc2 enhanced their rate of excretion but, most probably, also justify their negligible heart uptake in contrast with the high heart uptake of congener non-metabolizable complexes (^99mTc-DMEOP and ^99mTc-TMEOP), which have recently emerged as potential myocardial imaging agents. The attempts made to identify the metabolites of Tc1 and Tc2 showed that the metabolization of these compounds must involve the ether functions with probable formation of carboxylic acid derivatives A comparative study with the congener fac-[^99mTc(CO)₃{[4-(MeOCH₂)pz](CH₂)₂NH(CH₂)₂NH₂}]⁺ (Tc6) led the authors to confirm the formation of such type of metabolites. In fact, Tc6 is also metabolized in mice with formation of fac-[^99mTc(CO)₃{[4-(HOCH₂)pz](CH₂)₂NH(CH₂)₂NH₂}]⁺ (Tc7) and fac-[^99mTc(CO)₃{[4-(HOOC)pz](CH₂)₂NH(CH₂)₂NH₂}]⁺ (Tc8), which were chem. identified by HPLC in comparison with the Re congeners (Re7 and Re8).

Journal of Organometallic Chemistry published new progress about 37599-34-1. 37599-34-1 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Ether, name is 4-(methoxymethyl)-1H-pyrazole, and the molecular formula is C5H8N2O, Application of 4-(methoxymethyl)-1H-pyrazole.

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

Jain, Rama published the artcileDiscovery of Potent and Selective RSK Inhibitors as Biological Probes, Related Products of pyrazoles-derivatives, the publication is Journal of Medicinal Chemistry (2015), 58(17), 6766-6783, database is CAplus and MEDLINE.

While the p90 ribosomal S6 kinase (RSK) family has been implicated in multiple tumor cell functions, the full understanding of this kinase family has been restricted by the lack of highly selective inhibitors. A bis-phenol pyrazole was identified from high-throughput screening as an inhibitor of the N-terminal kinase of RSK2. Structure-based drug design using crystallog., conformational anal., and scaffold morphing resulted in highly optimized difluorophenol pyridine inhibitors of the RSK kinase family as demonstrated cellularly by the inhibition of YB1 phosphorylation. These compounds provide for the first time in vitro tools with an improved selectivity and potency profile to examine the importance of RSK signaling in cancer cells and to fully evaluate RSK as a therapeutic target.

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, Related Products of pyrazoles-derivatives.

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

Matthews, Thomas P. published the artcileDesign and evaluation of 3,6-di(hetero)aryl imidazo[1,2-a]pyrazines as inhibitors of checkpoint and other kinases, Quality Control of 724710-02-5, the publication is Bioorganic & Medicinal Chemistry Letters (2010), 20(14), 4045-4049, database is CAplus and MEDLINE.

A range of 3,6-di(hetero)aryl imidazo[1,2-a]pyrazine ATP-competitive inhibitors, e.g. I and II, of CHK1 were developed by scaffold hopping from a weakly active screening hit. Efficient synthetic routes for parallel synthesis were developed to prepare analogs with improved potency and ligand efficiency against CHK1. Kinase profiling showed that the imidazo[1,2-a]pyrazines could inhibit other kinases, including CHK2 and ABL, with equivalent or better potency depending on the pendant substitution. These 3,6-di(hetero)aryl imidazo[1,2-a]pyrazines appear to represent a general kinase inhibitor scaffold.

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, Quality Control of 724710-02-5.

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

Matthews, Thomas P. published the artcileDesign and evaluation of 3,6-di(hetero)aryl imidazo[1,2-a]pyrazines as inhibitors of checkpoint and other kinases, SDS of cas: 763120-58-7, the publication is Bioorganic & Medicinal Chemistry Letters (2010), 20(14), 4045-4049, database is CAplus and MEDLINE.

A range of 3,6-di(hetero)aryl imidazo[1,2-a]pyrazine ATP-competitive inhibitors, e.g. I and II, of CHK1 were developed by scaffold hopping from a weakly active screening hit. Efficient synthetic routes for parallel synthesis were developed to prepare analogs with improved potency and ligand efficiency against CHK1. Kinase profiling showed that the imidazo[1,2-a]pyrazines could inhibit other kinases, including CHK2 and ABL, with equivalent or better potency depending on the pendant substitution. These 3,6-di(hetero)aryl imidazo[1,2-a]pyrazines appear to represent a general kinase inhibitor scaffold.

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, SDS of cas: 763120-58-7.

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

Sandhu, Bhupinder published the artcileAssessment of computational tools for predicting supramolecular synthons, Quality Control of 3553-12-6, the publication is Chemistry (Basel, Switzerland) (2021), 3(2), 612-629, database is CAplus.

The ability to predict the most likely supramol. synthons in a crystalline solid is a valuable starting point for subsequently predicting the full crystal structure of a mol. with multiple competing mol. recognition sites. Energy and informatics-based prediction models based on mol. electrostatic potentials (MEPs), hydrogen-bond energies (HBE), hydrogen-bond propensity (HBP), and hydrogen-bond coordination (HBC) were applied to the crystal structures of twelve pyrazole-based mols. HBE, the most successful method, correctly predicted 100% of the exptl. observed primary intermol.-interactions, followed by HBP (87.5%), and HBC = MEPs (62.5%). A further HBC anal. suggested a risk of synthon crossover and synthon polymorphism in mols. with multiple binding sites. These easy-to-use models (based on just 2-D chem. structure) can offer a valuable risk assessment of potential formulation challenges.

Chemistry (Basel, Switzerland) 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, Quality Control of 3553-12-6.

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

Sutherland, Hamish S. published the artcileSynthesis and structure-activity relationships for a new class of tetrahydronaphthalene amide inhibitors of Mycobacterium tuberculosis, Formula: C3H5BN2O2, the publication is European Journal of Medicinal Chemistry (2022), 114059, database is CAplus and MEDLINE.

Drug resistant tuberculsosis (TB) is global health crisis that demands novel treatment strategies. Bacterial ATP synthase inhibitors such as bedaquiline and next-generation analogs (such as TBAJ-876) have shown promising efficacy in patient populations and preclin. studies, resp., suggesting that selective targeting of this enzyme presents a validated therapeutic strategy for the treatment of TB. In this work, we report tetrahydronaphthalene amides (THNAs) as a new class of ATP synthase inhibitors that are effective in preventing the growth of Mycobacterium tuberculosis (M.tb) in culture. Design, synthesis and comprehensive structure-activity relationship studies for approx. 80 THNA analogs are described, with a small selection of compounds exhibiting potent (in some cases MIC90 <1 μg/mL) in vitro M.tb growth inhibition taken forward to pharmacokinetic and off-target profiling studies. Ultimately, we show that some of these THNAs possess reduced lipophilic properties, decreased hERG liability, faster mouse/human liver microsomal clearance rates and shorter plasma half-lives compared with bedaquiline, potentially addressing of the main concerns of persistence and phospholipidosis associated with bedaquiline.

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 C28H18O4, Formula: C3H5BN2O2.

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

Bao, Jianming published the artcileTetrahydroindolizinone NK₁ antagonists, COA of Formula: C3H5BN2O2, the publication is Bioorganic & Medicinal Chemistry Letters (2010), 20(7), 2354-2358, database is CAplus and MEDLINE.

A new class of potent NK₁ receptor antagonists with a tetrahydroindolizinone core has been identified. This series of compounds demonstrated improved functional activities as compared to previously identified 5,5-fused pyrrolidine lead structures. SAR at the 7-position of the tetrahydroindolizinone core is discussed in detail. A number of compounds displayed high NK₁ receptor occupancy at both 1 h and 24 h in a gerbil foot tapping model. Compound 40 has high NK₁ binding affinity, good selectivity for other NK receptors and promising in vivo properties. It also has clean P₄₅₀ inhibition and hPXR induction 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, COA of Formula: C3H5BN2O2.

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

Chen, Deheng published the artcileDiscovery, structural insight, and bioactivities of BY27 as a selective inhibitor of the second bromodomains of BET proteins, Synthetic Route of 763120-58-7, the publication is European Journal of Medicinal Chemistry (2019), 111633, database is CAplus and MEDLINE.

Recently, selective inhibition of BET BD2 is emerging as a promising strategy for drug discovery. Despite significant progress in this area, systematic studies of selective BET BD2 inhibitors are still few. In this study, we report the discovery of a potent and selective BET BD2 inhibitor BY27 (47). Our high resolution co-crystal structures of 47/BRD2 BD1 and BD2 showed that the triazole group of 47, water mols., H433 and N429 in BRD2 BD2 established a water-bridged H-bonding network, which is responsible for the observed selectivities. DNA microarray anal. of HepG2 cells treated with 47 or OTX015 demonstrated the transcriptome impact differences between a BET BD2 selective inhibitor and a pan BET inhibitor. In a MV4-11 mouse xenograft model, 47 caused 67% of tumor growth inhibition and was less toxic than a pan BET inhibitor 1 at high doses. We conclude that the improved safety profile of selective BET BD2 inhibitors warrant future studies in BET associated diseases.

European 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

Sharma, Suresh Chandra published the artcileSynthesis, reactions, and nuclear magnetic resonance spectroscopy of 4-methyl-6H-pyrazolo(3,4-b)azepin-7-ones, Quality Control of 3553-12-6, the publication is Canadian Journal of Chemistry (1979), 57(23), 3034-40, database is CAplus.

I (R = H, Me, Ph, halogenated phenyl; R¹ = H, Me) reacted with Et levulinate to give II (same R, R¹) and acetamidopyrazoles. The courses of methylation and bromination of some II were examined; conversion of one pyrazoloazepinone to 7-chloropyrazoloazepine and amination gave 7-(substituted amino)pyrazoloazepines. Structural assignments, tautomeric preferences, and through-space interactions between substituents were established through NMR (¹H and ¹³C). Some II exhibit significant antiinflammatory and analgesic effects in mice.

Canadian Journal of Chemistry 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 C10H11N3O3S, Quality Control of 3553-12-6.

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

Brzozowski, Zdzislaw published the artcileDerivatives of pyrazole-1-carboxylic acid. II. Synthesis of certain 4-[2-(1-pyrazolecarboxamido)ethyl]benzenesulfonamides, Synthetic Route of 53355-55-8, the publication is Acta Poloniae Pharmaceutica (1981), 38(4), 399-405, database is CAplus.

Fifteen title compounds (I, R = H, Me, Et; R¹ = H, Me, Et, Pr, Bu, PhCH₂, Cl; R² = H, Me) were prepared in 55-91% yields from the corresponding 1-pyrazolecarbonyl chlorides and 4-H₂NSO₂C₆H₄(CH₂)₂NH₂ in Et₃N (or NaOH in aqueous Me₂CO). Some I were also obtained in the reaction of 4-H₂NSO₂C₆H₄(CH₂)₂NHCONHNH₂ (II) with BzOCH:CR¹COR in AcOH. I (R = Me, R¹ = R² = H) was addnl. prepared also from II and MeCOCH₂CH(OEt)₂. To prepare II, I (R = R² = Me, R¹ = H) was heated with N₂H₄ in EtOH.

Acta Poloniae Pharmaceutica 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, Synthetic Route of 53355-55-8.

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