Month: December 2022

Frosini, Maria published the artcileEffects of taurine and some structurally related analogues on the central mechanism of thermoregulation: A structure-activity relationship study, Product Details of C5H5NO3S, the publication is Advances in Experimental Medicine and Biology (2000), 273-282, database is CAplus and MEDLINE.

There is large body of evidences on the role of taurine in the central mechanisms of thermoregulation in mammals, but it is not clear, whether the hypothermic effect of taurine depends on its interaction with GABA receptors or with a specific receptor. In order to answer this question, the authors have performed a structure-activity relationship study by using both in vitro and in vivo preparations μM amounts of taurine or each of 20 analogs were injected intracerebroventricularly in conscious, restrained rabbits while rectal temperature was recorded. Receptor-binding studies, with synaptic membrane preparations from rabbit brain were used to determine the affinities of these compounds for GABA_A and GABA_B receptors. Furthermore, the interaction with presynaptic GABA and taurine uptake systems was studied using crude synaptosomal preparations from rabbit brain. Among the compounds tested, (±)-cis-2-aminocyclohexane sulfonic acid, induced hypothermia, but did not interact with GABA_A and GABA_B receptors neither did it affect GABA and taurine uptake, thus suggesting that its effect on body temperature is not mediated by the central GABA-ergic system. Interestingly, the trans-isomer was devoid of effects either in vivo or in vitro. In order to explain (±)-cis-2-aminocyclohexane sulfonic acid-induced hypothermia, a stereoscopic model was produced showing its possible interactions with a putative taurine brain receptor.

Advances in Experimental Medicine and Biology published new progress about 636-73-7. 636-73-7 belongs to pyridine-derivatives, auxiliary class Pyridine,Sulfonic acid, name is Pyridine-3-sulfonic acid, and the molecular formula is C5H5NO3S, Product Details of C5H5NO3S.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Frosini, Maria published the artcileInteractions of taurine and structurally related analogues with the GABAergic system and taurine binding sites of rabbit brain, Quality Control of 636-73-7, the publication is British Journal of Pharmacology (2003), 138(6), 1163-1171, database is CAplus and MEDLINE.

The aim of this study was to find taurinergic compounds that do not interact with brain GABAergic systems. Washed synaptic membranes (SM) from whole rabbit brain were able to bind [³H]muscimol. Saturation experiments of the binding of [³H]GABA to GABA_B receptors showed that SM possess two binding components; twice Triton X-100-treated SM contained 0.048 mmol endogenous taurine/kg protein and bound [³H]taurine in a saturable manner (K_d = 249.0 nM and B_max = 3.4 pmol mg^-1 prot). Among the 19 structural analogs of taurine, 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide (TAG), 2-aminoethylarsonic (AEA), 2-hydroxyethanesulfonic (ISE) and (±)cis-2-aminocyclohexane sulfonic acids (CAHS) displaced [³H]taurine binding (K_i = 0.13, 0.13, 13.5 and 4.0 μM, resp.). These analogs did not interact with GABA_A and GABA_B receptors and did not affect taurine- and GABA-uptake systems and GABA-transaminase activity. 3-Aminopropanesulfonic acid (OMO), β-alanine, pyridine-3-sulfonic acid, N,N,N-trimethyltaurine (TMT), 2-(guanidino)ethanesulfonic acid (GES), ethanolamine-O-sulfate, N,N-dimethyltaurine (DMT), taurine and (±)piperidine-3-sulfonic acid (PSA) inhibited [³H]muscimol binding to GABA_A receptors with different affinities (K_i = 0.013, 7.9, 24.6, 47.5, 52.0, 91.0, 47.5, 118.1 and 166.3 μM, resp.). Taurine, 2-aminoethylphosphonic acid, DMT, TMT and OMO inhibited the binding of [³H]GABA to GABA_B receptors with K_i‘s in the μM range (0.8, 3.5, 4.4, 11.3 and 5.0, resp.). GES inhibited taurine uptake (IC₅₀ = 3.72 μM) and PSA GABA transaminase activity (IC₅₀ = 103.0 μM). In conclusion, AEA, TAG, ISE and CAHS fulfill the criteria for taurinergic agents.

British Journal of Pharmacology published new progress about 636-73-7. 636-73-7 belongs to pyridine-derivatives, auxiliary class Pyridine,Sulfonic acid, name is Pyridine-3-sulfonic acid, and the molecular formula is C5H5NO3S, Quality Control of 636-73-7.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Mahajan, Dinesh published the artcileDiscovery and Development of SPR519 as a Potent, Selective, and Orally Bioavailable Inhibitor of PI3Kα and mTOR Kinases for the Treatment of Solid Tumors, Recommanded Product: (6-Amino-5-methylpyridin-3-yl)boronic acid, the publication is Journal of Medicinal Chemistry (2020), 63(19), 11121-11130, database is CAplus and MEDLINE.

Herein, we report the identification and preclin. profile of a lead compound 10, (SPR519) as an equally potent dual inhibitor of PI3Kα and mTOR kinases. SPR519 exhibits an EC₅₀ of low sub-micromolar range among various tested cancer cell lines such as A2780 (0.23μM), PC3 (0.48μM), and SKOV3 (0.50μM). When administrated orally, it shows a considerably high plasma exposure (area under curve: 26,858 nM/h at 1 mg/kg) in mice. Moreover, it is found to be safe in animals with a dose of 30 mg/kg BID for 12 days in the dose tolerance study. SPR519 did not show any CYP or hERG liability. The identified lead compound demonstrates significant efficacy and bioavailability in ovarian and colon cancer xenograft models when evaluated for dose-ranging efficacy studies, at a dose as low as 2.5 mg/kg.

Journal of Medicinal Chemistry published new progress about 1032759-01-5. 1032759-01-5 belongs to pyridine-derivatives, auxiliary class Boronic acid and ester,Boronic acid and ester, name is (6-Amino-5-methylpyridin-3-yl)boronic acid, and the molecular formula is C6H9BN2O2, Recommanded Product: (6-Amino-5-methylpyridin-3-yl)boronic acid.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Joshi, Abhisek published the artcileRu-Catalyzed Selective C-H Functionalization of Pyridotriazoles with Acrylates, Quality Control of 91-02-1, the publication is SynOpen (2021), 5(4), 294-300, database is CAplus.

Ruthenium-catalyzed efficient and selective C-H alkenylation of pyridotriazoles with acrylates is described. The combination of metals (Ru and Fe) plays a crucial role in achieving quant. yields of the desired products. The reaction is proposed to involve the formation of a ruthenium cyclometalated intermediate.

SynOpen published new progress about 91-02-1. 91-02-1 belongs to pyridine-derivatives, auxiliary class Pyridine,Benzene,Ketone, name is Phenyl(pyridin-2-yl)methanone, and the molecular formula is C12H9NO, Quality Control of 91-02-1.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Fujiwara, Tomoya published the artcileUseful procedures for fluorocyclization of tryptamine and tryptophol derivatives to 3a-fluoropyrrolo[2,3-b]indoles and 3a-fluorofuro[2,3-b]indoles, Safety of 1-Fluoropyridiniumtriflate, the publication is Journal of Fluorine Chemistry (2014), 7-13, database is CAplus.

Versatile procedures for fluorocyclization of various tryptamine and tryptophol derivatives to obtain the corresponding 3a-fluoropyrrolo[2.3-b]indoles and 3a-fluorofuro[2.3-b]indoles, resp. were developed employing N-fluoro-2,4,6-trimethylpyridinium triflate (FP-T300) or Selectfluor as the electrophilic fluorinating agent. The use of NaHCO₃ for fluorocyclization was effective in improving the yield of acid-labile fluoropyrrolo(furo)indoles. Our procedures are especially useful for the synthesis of fluoropyrrolo(furo)indoles bearing a free NH indole group.

Journal of Fluorine Chemistry published new progress about 107263-95-6. 107263-95-6 belongs to pyridine-derivatives, auxiliary class Fluorination reagent, name is 1-Fluoropyridiniumtriflate, and the molecular formula is C6H5F4NO3S, Safety of 1-Fluoropyridiniumtriflate.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Yoshida, Hiroto published the artcileDirect Suzuki-Miyaura Coupling with Naphthalene-1,8-diaminato (dan)-Substituted Organoborons, Safety of 5-Methyl-2-(p-tolyl)pyridine, the publication is ACS Catalysis (2020), 10(1), 346-351, database is CAplus.

The direct Suzuki-Miyaura coupling with “protected” R-B(dan) (dan = naphthalene-1,8-diaminato) (R = Ph, 4-MeOC₆H₄, 2-pyridyl) was demonstrated to smoothly occur without in situ deprotection of the B(dan) moiety. The use of KOt-Bu (Ba(OH)₂ in some cases) as a base under anhydrous conditions is the key to the successful cross-coupling, where R-B(dan) is readily converted into a transmetalation-active borate-form, regardless of the well-accepted diminished boron-Lewis acidity.

ACS Catalysis published new progress about 85237-71-4. 85237-71-4 belongs to pyridine-derivatives, auxiliary class Pyridine,Benzene, name is 5-Methyl-2-(p-tolyl)pyridine, and the molecular formula is C10H12BF3KNO2, Safety of 5-Methyl-2-(p-tolyl)pyridine.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Terashima, Masanao published the artcilePhotoinduced reactions. XXVII. Photochemistry of the phthalimide system. XIV. Photochemical synthesis of a pyridopyrrolo[2,1-a]isoindole system by cyclization of N-methylpyridylphthalimides, HPLC of Formula: 18437-58-6, the publication is Chemical & Pharmaceutical Bulletin (1977), 25(7), 1591-5, database is CAplus.

Photochem. reactions of N-(3-methyl-2-pyridyl)-(I), N-(4-methyl-3-pyridyl)-(II), and N-(3-methyl-4-pyridyl)phthalimide (III) were investigated. Although irradiation of II in an acetone solution gave only the dihydro product, 3-hydroxy-2-(3-methyl-2-pyridyl)phthalimidine, III afforded the expected cyclized product, 10b,11-dihydro-10b-hydroxy-6H-pyrido[4′,3′:4,5]pyrrolo[2,1-a]isoindol-6-one (IV) and dihydro product, 3-hydroxy-2-(4-methyl-3-pyridyl)phthalimidine. Under similar conditions, the cyclized product, 10b,11-dihydro-10b-hydroxy-6H-pyrido[3′,4′:4,5]pyrrolo[2,1-a]isoindol-6-one was obtained from the photolysis of III and none of the reduced product was isolated.

Chemical & Pharmaceutical Bulletin published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C15H14O3, HPLC of Formula: 18437-58-6.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Jayakumar, K. published the artcileSpectral, thermal and DFT studies of novel nickel(II) complexes of 2-benzoylpyridine-N⁴-methyl-3- thiosemicarbazone: Crystal structure of a square planar azido-nickel(II) complex, COA of Formula: C12H9NO, the publication is Journal of Molecular Structure (2022), 132257, database is CAplus.

Novel six Ni(II) complexes of an NNS donor 2-benzoylpyridine-N⁴-methyl-3- thiosemicarbazone(HL) were synthesized and characterized. Various physicochem. techniques are applied for the study of the coordination behavior of the thiosemicarbazone to the nickel center. In all the complexes, thiosemicarbazone is coordinated in the thiolate form. A four coordinated Ni(II) complex [NiLN₃] is crystallized and its mol. and crystal structures are determined by single-crystal x-ray crystallog. Single-crystal XRD reveals that the complex got crystallized in the monoclinic space group P2₁/n and nickel(II) has a square planar environment. Intramol. hydrogen bonding interactions make the complex more rigid and in the crystal lattice, the intermol. hydrogen bonding interactions generate a supramol. 1 D chain. The chem. reactivity behavior of the HL and six Ni(II) complexes was evaluated with the CAM-B3LYP quantum chem. calculations The validity of electronic structure principles like Maximum Hardness, Min. Polarizability, and Min. Electrophilicity Principle in the study is discussed.

Journal of Molecular Structure published new progress about 91-02-1. 91-02-1 belongs to pyridine-derivatives, auxiliary class Pyridine,Benzene,Ketone, name is Phenyl(pyridin-2-yl)methanone, and the molecular formula is C12H9NO, COA of Formula: C12H9NO.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Mayer, Nicole published the artcileStructure-activity relationship studies for the development of inhibitors of murine adipose triglyceride lipase (ATGL), COA of Formula: C7H10BNO3, the publication is Bioorganic & Medicinal Chemistry (2020), 28(16), 115610, database is CAplus and MEDLINE.

High serum fatty acid (FA) levels are causally linked to the development of insulin resistance, which eventually progresses to type 2 diabetes and non-alc. fatty liver disease (NAFLD) generalized in the term metabolic syndrome. Adipose triglyceride lipase (ATGL) is the initial enzyme in the hydrolysis of intracellular triacylglycerol (TG) stores, liberating fatty acids that are released from adipocytes into the circulation. Hence, ATGL-specific inhibitors have the potential to lower circulating FA concentrations, and counteract the development of insulin resistance and NAFLD. In this article, we report about structure-activity relationship (SAR) studies of small mol. inhibitors of murine ATGL which led to the development of Atglistatin. Atglistatin is a specific inhibitor of murine ATGL, which has proven useful for the validation of ATGL as a potential drug target.

Bioorganic & Medicinal Chemistry published new progress about 612845-44-0. 612845-44-0 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester,Ether,Boronic Acids,Boronic acid and ester, name is (6-Ethoxypyridin-3-yl)boronic acid, and the molecular formula is C7H10BNO3, COA of Formula: C7H10BNO3.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Cirek, Zdenek published the artcileEfficacy and tolerability of a fixed combination of cinnarizine and dimenhydrinate versus betahistine in the treatment of otogenic vertigo: A double-blind, randomised clinical study, HPLC of Formula: 54856-23-4, the publication is Clinical Drug Investigation (2005), 25(6), 377-389, database is CAplus and MEDLINE.

Introduction: Peripheral vestibular disorders frequently lead to the manifestation of symptoms of vertigo. The objective of this study was to compare the efficacy and tolerability of a fixed combination of cinnarizine 20mg and dimenhydrinate 40mg per tablet with betahistine (betahistine dimesylate) 12mg per tablet in the treatment of patients with otogenic vertigo. Patients and methods: Sixty-one patients with vertigo due to peripheral vestibular disorders (otogenic vertigo) participated in this prospective, double-blind, comparative, single-center study. Patients were randomly allocated to treatment with betahistine 12mg or the fixed combination of cinnarizine 20mg and dimenhydrinate 40mg, both treatments given three times daily for 4 wk. Efficacy was determined by patients’ assessments of vertigo symptoms after 1 and 4 wk of treatment using a visual analog scale to determine a ‘mean vertigo score’. Results: Treatment with the fixed combination led to significantly greater improvements in mean vertigo scores compared with the reference therapy betahistine. This was evident as early as 1 wk after the onset of treatment (p = 0.002). Over 4 wk of therapy, the fixed combination decreased the intensity of vertigo symptoms about 2-fold compared with betahistine (p = 0.001). Furthermore, reductions in symptoms typically associated with vertigo were more pronounced (p = 0.009) in the fixed-combination group compared with the betahistine group after 4 wk of treatment. No serious adverse events were reported in either treatment group. Tolerability of the fixed combination was judged as ‘very good’ by 97% (betahistine 90%) and as ‘good’ by 3% (betahistine 10%) of patients. Conclusion: The fixed combination of cinnarizine and dimenhydrinate was shown to be an effective and very well tolerated treatment option for patients with otogenic vertigo. It proved to be statistically more efficient in reducing vertigo than the widely used betahistine. Therefore, the fixed combination of cinnarizine and dimenhydrinate may be considered a first-line treatment option for the treatment of otogenic vertigo.

Clinical Drug Investigation published new progress about 54856-23-4. 54856-23-4 belongs to pyridine-derivatives, auxiliary class Pyridine,Salt,Amine,Inhibitor,Inhibitor, name is N-Methyl-2-(pyridin-2-yl)ethan-1-amine dimethanesulfonate, and the molecular formula is C10H20N2O6S2, HPLC of Formula: 54856-23-4.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem