Day: December 1, 2022

Thomas, Michael published the artcileScaffold-Hopping Strategy on a Series of Proteasome Inhibitors Led to a Preclinical Candidate for the Treatment of Visceral Leishmaniasis, Product Details of C5H6BNO2, the publication is Journal of Medicinal Chemistry (2021), 64(9), 5905-5930, database is CAplus and MEDLINE.

There is an urgent need for new treatments for visceral leishmaniasis (VL), a parasitic infection which impacts heavily large areas of East Africa, Asia, and South America. We previously reported on the discovery of GSK3494245/DDD01305143 (1) as a preclin. candidate for VL and, herein, we report on the medicinal chem. program that led to its identification. A hit from a phenotypic screen was optimized to give a compound with in vivo efficacy, which was hampered by poor solubility and genotoxicity. The work on the original scaffold failed to lead to developable compounds, so an extensive scaffold-hopping exercise involving medicinal chem. design, in silico profiling, and subsequent synthesis was utilized, leading to the preclin. candidate. The compound was shown to act via proteasome inhibition, and we report on the modeling of different scaffolds into a cryo-EM structure and the impact this has on our understanding of the series’ structure-activity relationships.

Journal of Medicinal Chemistry published new progress about 197958-29-5. 197958-29-5 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester, name is 2-Pyridinylboronic acid, and the molecular formula is C12H10O4S, Product Details of C5H6BNO2.

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

Lim, Xin Rui published the artcileFast voltage-dependent sodium (Na_v) currents are functionally expressed in mouse corpus cavernosum smooth muscle cells, Synthetic Route of 21829-25-4, the publication is British Journal of Pharmacology (2022), 179(5), 1082-1101, database is CAplus and MEDLINE.

Corpus cavernosum smooth muscle (CCSM) exhibits phasic contractions that are coordinated by ion channels. Mouse models are commonly used to study erectile dysfunction, but there are few published electrophysiol. studies of mouse CCSM. We describe the voltage-dependent sodium (NaV) currents in mouse CCSM and investigate their function. We used electrophysiol., pharmacol. and immunocytochem. methods to study the NaV currents in isolated CCSM cells from C57BL/6 mice. Tension measurements were carried out using crural sections of the corpus cavernosum in whole tissue. Fast, voltage-dependent, sodium currents in mouse CCSM were induced by depolarising steps. Steady-state activation and inactivation curves revealed a window current between -60 and -30 mV. Two populations of NaV currents, ′TTX-sensitiveâ€?and ′TTX-insensitiveâ€? were identified. TTX-sensitive currents showed 48% block with the NaV channel subtype-specific blockers ICA-121431 (NaV1.1-1.3), PF-05089771 (NaV1.7) and 4,9-anhydro-TTX (NaV1.6). TTX-insensitive currents were resistant to blockade by A803467, specific for NaV1.8 channels. Immunocytochem. confirmed expression of NaV1.5 and NaV1.4 in freshly dispersed CCSM cells. Veratridine, a NaV channel activator, reduced time-dependent inactivation of NaV currents and increased duration of evoked action potentials. Veratridine induced phasic contractions in CCSM strips, reversible with TTX and nifedipine but not KB-R7943. There are fast, voltage-dependent, sodium currents in mouse CCSM. Stimulation of these currents increased contractility of CCSM in vitro, suggesting an involvement in detumescence and potentially providing a clin. relevant target in erectile dysfunction. Further work will be necessary to define its role.

British Journal of Pharmacology published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Synthetic Route of 21829-25-4.

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

Besmer, Manuel Luca published the artcileExploring the Coordination Chemistry of N₂ with Technetium PNP Pincer-Type Complexes, COA of Formula: C23H43NP2, the publication is Inorganic Chemistry (2021), 60(9), 6696-6701, database is CAplus and MEDLINE.

Dinitrogen (N₂) complexes of technetium (⁹⁹Tc) are rare, and only two examples have been reported. To complement this important class of complexes also for ⁹⁹Tc, two different pincer-type complexes of ⁹⁹Tc were studied to assess their abilities for coordinating dinitrogen. The reactions of the ⁹⁹Tc^III complex [⁹⁹TcCl₃(PPh₃)₂(NCCH₃)] with the pincer ligands PNP^tBu and ^PyrPNP^tBu resp. gave [⁹⁹Tc(PNP^tBu)Cl₂] and [⁹⁹Tc(^PyrPNP^tBu)Cl₃], the first structurally characterized ⁹⁹Tc complexes with mer-coordinated pincer ligands. Reductions with [Co(Cp*)₂] under N₂ gave the mononuclear bis-dinitrogen complex [⁹⁹Tc^I(PNP^tBu)(N₂)₂] and the dinuclear complex [⁹⁹Tc^I(^PyrPNP^tBu)(N₂)Cl]₂(μ-N₂) with both a bridging and a terminal N₂ ligand. Spectroscopy and crystal structures confirm their identities. The complexes are stable under a dinitrogen atm., and the N₂ ligands are tightly bound. The results for the complexes with the PNP^tBu pincer allow a comparison to its rhenium homolog, which has recently been shown to split the N₂ ligand with the formation of a nitrido complex.

Inorganic Chemistry published new progress about 338800-13-8. 338800-13-8 belongs to pyridine-derivatives, auxiliary class Bis-phosphine Ligands, name is 2,6-Bis((di-tert-butylphosphino)methyl)pyridine, and the molecular formula is C23H43NP2, COA of Formula: C23H43NP2.

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

Shimeno, Hiroshi published the artcileInhibition of rat liver tryptophan pyrrolase activity and elevation of brain tryptophan concentration by administration of DL-α-amino-β-pyridinepropanoic acid (pyridylalanine) analogs, Computed Properties of 18437-58-6, the publication is Journal of Enzyme Inhibition (1987), 2(1), 57-66, database is CAplus and MEDLINE.

Single doses of DL-α-amino-β-(2-pyridine)propanoic acid (2-PA, 100 mg/kg) decreased the holoenzyme and apoenzyme activities of rat liver tryptophan pyrrolase (TP) and increased brain tryptophan, serotonin (5-HT) and 5-hydroxyindole-3-ylacetic acid concentrations 2-PA had no inhibitory effect on either of the enzyme activities in vitro, but its expected metabolites were effective. Single doses of DL-α-amino-β-(3-pyridine)propanoic acid (3-PA, 100 mg/kg) decreased only the holoenzyme activity and elevated brain tryptophan and its metabolites levels in rats. 3-PA and its metabolite, 3-pyridylpyruvate, inhibited only the holoenzyme activity in vitro. DL-α-Amino-β-(4-pyridine)propanoic acid (4-PA) caused changes in liver TP (holo- and apoenzyme forms) activity and brain tryptophan concentration only after repeated administration (100 mg/kg/day). 4-PA was a weak inhibitor of the holoenzyme, but its metabolites apparently inhibited the holo- and apoenzyme activities in vitro. These findings suggest that PA analogs (and(or) their metabolites) increased brain tryptophan (and hence 5-HT synthesis) by directly inhibiting liver TP activity.

Journal of Enzyme Inhibition 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 C8H11NO, Computed Properties of 18437-58-6.

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

Largeau, Berenger published the artcileGabapentinoid-induced peripheral edema and acute heart failure: A translational study combining pharmacovigilance data and in vitro animal experiments, Category: pyridine-derivatives, the publication is Biomedicine & Pharmacotherapy (2022), 112807, database is CAplus and MEDLINE.

Gabapentinoids are ligands of the α2-δ subunit of voltage-gated calcium channels (Cav) that have been associated with a risk of peripheral edema and acute heart failure in connection with a potentially dual mechanism, vascular and cardiac. All cases of peripheral edema or heart failure involving gabapentin or pregabalin reported to the French Pharmacovigilance Centers between Jan. 1, 1994 and Apr. 30, 2020 were included to describe their onset patterns (e.g., time to onset). Based on these data, we investigated the impact of gabapentinoids on the myogenic tone of rat third-order mesenteric arteries and on the electrophysiol. properties of rat ventricular cardiomyocytes. A total of 58 reports were included (gabapentin n = 5, pregabalin n = 53). The female-to-male ratio was 4:1 and the median age was 77 years (IQR 57-85, range 32-95). The median time to onset were 23 days (IQR 10-54) and 17 days (IQR 3-30) for non-cardiogenic edema and acute heart failure, resp. Cardiogenic and non-cardiogenic peripheral edema occurred frequently after a dose escalation (27/45, 60%), and the course was rapidly favorable after discontinuation of gabapentinoid (median 7 days, IQR 5-13). On rat mesenteric arteries, gabapentinoids significantly decreased the myogenic tone to the same extent as verapamil and nifedipine. Acute application of gabapentinoids had no significant effect on Cav1.2 currents of ventricular cardiomyocytes. Gabapentinoids can cause concentration-dependent peripheral edema of early onset. The primary mechanism of non-cardiogenic peripheral edema is vasodilatory edema secondary to altered myogenic tone, independent of Cav1.2 blockade under the exptl. conditions tested.

Biomedicine & Pharmacotherapy published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Category: pyridine-derivatives.

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

Zhang, Xian Man published the artcileEquilibrium acidities and homolytic bond dissociation energies of the acidic carbon-hydrogen bonds in N-substituted trimethylammonium and pyridinium cations, Related Products of pyridine-derivatives, the publication is Journal of Organic Chemistry (1993), 58(11), 3060-6, database is CAplus.

Equilibrium acidities (pK_HA) of the cations in 16 N-substituted trimethylammonium salts, one N-phenacylquinuclidinium salt, 8 N-substituted pyridinium salts, and N-(ethoxycarbonyl)isoquinolinium bromide, together with the oxidation potentials of their conjugate bases, have been determined in Me₂SO. The acidifying effects of the α-trimethylammonium groups (α-Me₃N⁺) and the α-pyridinium groups (α-PyN⁺) on the adjacent acidic C-H bonds in these cations were found to average about 10 and 18 pK_HA units, resp. The homolytic bond dissociation energies of the acidic C-H bonds in these cations, estimated by the combination of the equilibrium acidities with the oxidation potentials of their corresponding conjugate bases (ylides), show that the α-trimethylammonium groups destabilize adjacent radicals by 2-6 kcal/mol, whereas α-pyridinium groups stabilize adjacent radicals by 3-6 kcal/mol. The effects of α-pyridinium groups on the stabilization energies of the radicals derived from these cations were ca. 4-10 kcal/mol smaller than those of the corresponding Ph groups, whereas their effects on the equilibrium acidities of the cations were 5.4-13.1 pK_HA units larger. The pK_HA value of tetramethylammonium cation (Me₄N⁺) was estimated by extrapolation to be about 42 in Me₂SO.

Journal of Organic Chemistry published new progress about 17281-59-3. 17281-59-3 belongs to pyridine-derivatives, auxiliary class Pyridine,Nitrile,Salt, name is 1-(Cyanomethyl)pyridin-1-ium chloride, and the molecular formula is C8H11BO3, Related Products of pyridine-derivatives.

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

Biot, Nicolas published the artcileProgramming Recognition Arrays through Double Chalcogen-Bonding Interactions, Safety of 2-Bromopyridin-3-amine, the publication is Chemistry – A European Journal (2018), 24(21), 5439-5443, database is CAplus and MEDLINE.

In this work, we have programmed and synthesized a recognition motif constructed around a chalcogenazolo-pyridine scaffold (CGP) that, through the formation of frontal double chalcogen-bonding interactions, associates into dimeric EX-type complexes. The reliability of the double chalcogen-bonding interaction has been shown at the solid-state by X-ray anal., depicting the strongest recognition persistence for a Te-congener. The high recognition fidelity, chem. and thermal stability and easy derivatization at the 2-position makes CGP a convenient motif for constructing supramol. architectures through programmed chalcogen-bonding interactions.

Chemistry – A European Journal published new progress about 39856-58-1. 39856-58-1 belongs to pyridine-derivatives, auxiliary class Pyridine,Bromide,Amine, name is 2-Bromopyridin-3-amine, and the molecular formula is C5H5BrN2, Safety of 2-Bromopyridin-3-amine.

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

Biot, Nicolas published the artcileConcurring Chalcogen- and Halogen-Bonding Interactions in Supramolecular Polymers for Crystal Engineering Applications, Related Products of pyridine-derivatives, the publication is Chemistry – A European Journal (2020), 26(13), 2904-2913, database is CAplus and MEDLINE.

The engineering of crystalline mol. solids through the simultaneous combination of distinctive non-covalent interactions is an important field of research, as it could allow chemist to prepare materials depicting multi-responsive properties. It is in this context that, pushed by a will to expand the chem. space of chalcogen-bonding interactions, a concept is put forward for which chalcogen- and halogen-bonding interactions can be used simultaneously to engineer multicomponent co-crystals. Through the rational design of crystallizable mols., chalcogenazolo pyridine scaffold (CGP) modules were prepared that, bearing either a halogen-bond acceptor or donor at the 2-position, can interact with suitable complementary mol. modules undergoing formation of supramol. polymers at the solid state. The recognition reliability of the CGP moiety to form chalcogen-bonded dimers allows the formation of heteromol. supramol. polymers through halogen-bonding interactions, as confirmed by single-crystal X-ray diffraction anal.

Chemistry – A European Journal published new progress about 39856-58-1. 39856-58-1 belongs to pyridine-derivatives, auxiliary class Pyridine,Bromide,Amine, name is 2-Bromopyridin-3-amine, and the molecular formula is C5H5BrN2, Related Products of pyridine-derivatives.

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

Calugi, Lorenzo published the artcileSuzuki and Heck Processes for the Synthesis of New Anthraquinone-Based Glycoconjugated Dyes, Safety of 2-Pyridinylboronic acid, the publication is ChemistrySelect (2018), 3(8), 2235-2239, database is CAplus.

Starting from a bromo-anthraquinone dye, different aryl- and styril- derivates are obtained following Suzuki and Heck procedures. Bathochromic shifts are displayed for the products, if compared to the starting anthraquinone dye. Two of these dyes, coming from either the Suzuki and the Heck processes, have been glycosylated with a piperazinyl-lactose derivative, so that two naturalized species are finally obtained. Therefore, the disperse chromophores were transformed in water soluble direct species. These kinds of dyes allow to avoid azo- structures, that are object of growing criticism in the European Union due to their environmental impact.

ChemistrySelect published new progress about 197958-29-5. 197958-29-5 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester, name is 2-Pyridinylboronic acid, and the molecular formula is C5H6BNO2, Safety of 2-Pyridinylboronic acid.

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

Lamers, Philip published the artcileTetrahydrobenzo[c]thieno[2,1-e]isothiazole 4-Oxides: Three-Dimensional Heterocycles as Cross-Coupling Building Blocks, Related Products of pyridine-derivatives, the publication is Organic Letters (2018), 20(1), 116-118, database is CAplus and MEDLINE.

Tetrahydrobenzothienoisothiazole oxides such as I (R = H, I, Br, F, Cl, NC, MeO₂C, O₂N, F₅S, F₃C), cyclic sulfoximines, were prepared as novel heterocycles amenable to cross-coupling reactions and automated parallel synthesis. Reaction of tetrahydrothiophene with anilines such as 4-RC₆H₄NH₂ (R = H, I, Br, F, Cl, NC, MeO₂C, O₂N, F₅S, F₃C) mediated by N-chlorosuccinimide (NCS) and Et₃N in CH₂Cl₂ yielded (tetrahydrothienyl)anilines such as II (R = H, I, Br, F, Cl, NC, MeO₂C, O₂N, F₅S, F₃C) in 29-89% yields; tetrahydrothiopyran, N-Boc thiomorpholine, and 1,4-thioxane yielded thioether-substituted anilines, but the products did not undergo oxidative cyclocondensation. Further oxidation of (tetrahydrothienyl)anilines with N-chlorosuccinimide, treatment with aqueous NaOH, and oxidation with meta-chloroperbenzoic acid (mCPBA) yielded such as I (R = H, I, Br, F, Cl, NC, MeO₂C, O₂N, F₅S, F₃C). I (R = I, Br) and related tetrahydrobenzothienoisothiazole oxides underwent borylation, Sonogashira, and Suzuki coupling reactions.

Organic Letters published new progress about 39856-58-1. 39856-58-1 belongs to pyridine-derivatives, auxiliary class Pyridine,Bromide,Amine, name is 2-Bromopyridin-3-amine, and the molecular formula is C5H5BrN2, Related Products of pyridine-derivatives.

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