Day: December 5, 2022

Gunaga, Prashantha published the artcileSelective I_Kur Inhibitors for the Potential Treatment of Atrial Fibrillation: Optimization of the Phenyl Quinazoline Series Leading to Clinical Candidate 5-[5-Phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide, HPLC of Formula: 636-73-7, the publication is Journal of Medicinal Chemistry (2017), 60(9), 3795-3803, database is CAplus and MEDLINE.

We have recently disclosed 5-phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine (I) as a potent I_Kur current blocker with selectivity vs. hERG, Na and Ca channels and an acceptable preclin. PK profile. On further characterization in vivo, Compound I demonstrated an unacceptable level of brain penetration. In an effort to reduce the level of brain penetration while maintaining the overall profile, SAR was developed at the C2′ position for a series of close analogs by employing hydrogen bond donors. As a result, 5-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)pyridine-3-sulfonamide (II) was identified as the lead compound in this series. Compound II showed robust effects in rabbit and canine pharmacodynamic models and an acceptable cross-species pharmacokinetic profile and was advanced as the clin. candidate. Further optimization of II to mitigate pH dependent absorption resulted in identification of the corresponding phosphoramide prodrug (29) with an improved solubility and pharmacokinetic profile.

Journal of Medicinal Chemistry 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, HPLC of Formula: 636-73-7.

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

Tang, Luning published the artcileSelective single C-F bond arylation of trifluoromethylalkene derivatives, Application of (1-(tert-Butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)boronic acid, the publication is Chemical Science (2019), 10(37), 8701-8705, database is CAplus and MEDLINE.

A strategically novel single C-F bond functionalization of CF₃-derived mols., which shows a prominent advantage for the expedient construction of difluoromethylene-bridged organic scaffolds, is disclosed. The reported protocol consists of S_N2′ amination, N-alkylation and palladium-catalyzed allylic substitution reactions, which enables straightforward arylation and alkenylation of vinyltrifluoromethane derivatives Furthermore, this strategy is characterized by its broad substrate scope with respect to both CF₃-alkene and arylboronic acid derivatives

Chemical Science published new progress about 844501-00-4. 844501-00-4 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester,Amide,Boronic Acids,Boronic acid and ester, name is (1-(tert-Butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)boronic acid, and the molecular formula is C12H9N3O4, Application of (1-(tert-Butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)boronic acid.

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

Wang, Chao-Yu published the artcilePalladium(II) complexes containing a bulky pyridinyl N-heterocyclic carbene ligand: Preparation and reactivity, HPLC of Formula: 89076-64-2, the publication is Journal of Organometallic Chemistry (2007), 692(18), 3976-3983, database is CAplus.

Coordination chem. of a pyridine imidazole-2-ylidene ligand (pyN-C) with sterically hindered substituents toward Pd(II) metal ions was studied. The Pd carbene complex [(C-pyN-C)Pd(η³-allyl)Cl] (3) was prepared via transmetalation from the corresponding Ag carbene complexes with [ClPd(η³-allyl)]₂. Upon the abstraction of chloride, coordination of pyridinyl N becomes feasible to form [C,N-(pyN-C)Pd(η³-allyl)](BF₄) (4). Ligand substitution reaction of 4 with PPh₃ gave [(C-pyN-C)Pd(PPh₃)(η³-allyl)](BF₄), in which the pyridinyl N donor is substituted by the phosphine. This Pd complex appears to be base sensitive. Treatment of 4 with KOCMe₃ causes decomposition to yield metal nanoparticles. Also, decomplexation of 4 takes place under H atm. to generate the carbene precursor, 1-(6-mesityl-2-picolyl)-3-mesitylimidazolium salt. Nevertheless, the Pd complex 4 shows good catalytic activity on the Suzuki-Miyaura and Mizoroki-Heck reactions.

Journal of Organometallic Chemistry published new progress about 89076-64-2. 89076-64-2 belongs to pyridine-derivatives, auxiliary class Pyridine,Nitro Compound,Benzene, name is 5-Nitro-2-phenylpyridine, and the molecular formula is C7H4ClIO2, HPLC of Formula: 89076-64-2.

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

Fang, Zhen published the artcileDiscovery of a potent and selective inhibitor of histone lysine demethylase KDM4D, Quality Control of 197958-29-5, the publication is European Journal of Medicinal Chemistry (2021), 113662, database is CAplus and MEDLINE.

Histone lysine demethylase 4D (KDM4D) plays an important role in the regulation of tumorigenesis, progression and drug resistance and has been considered a potential target for cancer treatment. However, there is still a lack of potent and selective KDM4D inhibitors. In this investigation, we report a new class of KDM4D inhibitors containing the 2-(aryl(pyrrolidine-1-yl)methyl)phenol scaffold, identified through AlphaLisa-based screening, structural optimization, and structure-activity relationship analyses. Among these inhibitors, 24s (I) was the most potent, with an IC₅₀ value of 0.023 ± 0.004μM. This compound exhibited more than 1500-fold selectivity towards KDM4D vs. KDM4A as well as other JMJD subfamily members, indicating good selectivity for KDM4D. Kinetic anal. indicated that 24s did not occupy the 2-oxoglutarate binding pocket. In an in vitro assay, 24s significantly suppressed the proliferation and migration of colorectal cancer (CRC) cells. Overall, this study has identified a good tool compound to explore the biol. function of KDM4D and a good lead compound for drug discovery targeting KDM4D.

European 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 C5H6BNO2, Quality Control of 197958-29-5.

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

Zhu, Shan-Shan published the artcilePolymerization-Enhanced Photocatalysis for the Functionalization of C(sp³)-H Bonds, Safety of Phenyl(pyridin-2-yl)methanone, the publication is ACS Catalysis (2022), 12(1), 126-134, database is CAplus.

A series of conjugated polymeric photocatalysts (CPPs) based on 1,2,3,5-tetrakis(carbazol-9-yl)4,6-dicyanobenzene (4CzIPN) were synthesized via nucleophilic substitution reaction and Sonogashira-Hagihara coupling. Among the as-prepared CPPs (CPP1-CPP6), CPP3 [the copolymer of a tetrakis(dibromocarbazolyl)isophthalonitrile with 1,3,5-triethynylbenzene] was selected as the optimized heterogeneous photocatalyst for visible-light-driven functionalization of C(sp³)-H bonds to synthesize 87 final products with yields up to 99%. The heterogeneous photocatalyst CPP3 is easily recovered from the reaction with excellent retention of photocatalytic activity, which can be reused at least for five times. Time-dependent d. functional theory (TD-DFT) calculations demonstrate that the photocatalysis performance of CPP3 is superior to the corresponding monomer 4CzIPN because of the enhanced intersystem crossing (ISC) process. Spin-orbit coupling calculations prove that the rate constant of ISC outcompetes that of reverse intersystem crossing (RISC). The rapidly generated and long-lived triplet state T₁ is considered to be a more accessible excited state than the singlet-state S₁ generated from either direct excitation or RISC. The successful application of this polymerization-enhanced photocatalysis strategy should guide a metal-free approach to the rational design of CPP-type heterogeneous photocatalysts to address the dilemma of homogeneous photocatalysts in sustainability, stability, and recyclability.

ACS Catalysis 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 C19H34ClN, Safety of Phenyl(pyridin-2-yl)methanone.

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

Wei, Feng published the artcileStructural and photophysical study of copper iodide complex with PN̂ or PN̂P̂ ligand, Application of 2,6-Bis((di-tert-butylphosphino)methyl)pyridine, the publication is CrystEngComm (2014), 16(24), 5338-5344, database is CAplus.

Two PN̂-type ligands, 8-(diphenylphosphino)quinoline (L₁) and 2-[2-(diphenylphosphino)ethyl]pyridine (L₂), and two PN̂P̂-type ligands, 2,6-bis((diphenylphosphino)methyl)pyridine (L₃) and 2,6-bis((di-tert-butylphosphino)methyl)pyridine (L₄), were synthesized to coordinate with copper iodide (CuI). As a result, CuI complexes with rich structures, such as discrete complexes with formulas of [Cu₂I₂(L₁)₂] (5), [Cu₃I₃(L₂)₂] (6), and [CuI(L₃)] (7), and polymeric complexes with repeating units of [Cu₂I₂(L₄)] (8), and [Cu₃I₃(L₄)] (9) were synthesized and characterized by single crystal X-ray diffraction. Besides the intriguing structures, these complexes showed rich photoluminescent properties, with emission color that varied from blue to red and a photoluminescence quantum yield (PLQY) from 1.6 to 29.9% in the solid state. MO calculation and exptl. study showed that the emissions involve halide to ligand charge transfer (XLCT), metal to ligand charge transfer (MLCT), and/or cluster-centered (CC) excited states.

CrystEngComm 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 C8H6ClF3, Application of 2,6-Bis((di-tert-butylphosphino)methyl)pyridine.

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

Yuan, Yu-Chang published the artcileMetal-Free Catalyzed Synthesis of Fluorescent Indolizine Derivatives, Computed Properties of 91-02-1, the publication is Journal of Organic Chemistry (2021), 86(18), 12737-12744, database is CAplus and MEDLINE.

A mild and high efficient method to prepare indolizines such as I [R = H, Me; R¹ = Me, Ph, CH₂CH₂CO₂Et; R² = H, Me, OEt; R³ = Me, Ph, 4-ClC₆H₄; R¹R² = (CH₂)₃] by two-component reaction with the acid as the catalyst was developed. In this reaction, a new ring efficiently formed in one-step reaction. A wide range of substrates could be applied and the desired products were obtained in 8-95% yields under metal-free conditions. Different indolizine derivatives I were synthesized by general conditions and microwave irradiation conditions, and compound I [R = H, R¹ = Me, R² = H, R³ = Ph] gave the best results with an isolated yield of 95% and 82%, resp. The structures of synthesized compounds I were characterized by spectral anal., and compound I [R = H, R¹R² = (CH₂)₃, R³ = 4-ClC₆H₄] was confirmed by single crystal X-ray anal. UV-vis absorption and fluorescence properties of these compounds I were correlated with substituent groups on indolizine rings.

Journal of Organic Chemistry 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 C8H14O2, Computed Properties of 91-02-1.

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

Chen, Jian Jeffrey published the artcileDevelopment of 2-aminooxazoline 3-azaxanthenes as orally efficacious β-secretase inhibitors for the potential treatment of Alzheimer’s disease, Computed Properties of 197958-29-5, the publication is Bioorganic & Medicinal Chemistry Letters (2015), 25(4), 767-774, database is CAplus and MEDLINE.

The β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is one of the most hotly pursued targets for the treatment of Alzheimer’s disease. We used a structure- and property-based drug design approach to identify 2-aminooxazoline 3-azaxanthenes as potent BACE1 inhibitors which significantly reduced CSF and brain Aβ levels in a rat pharmacodynamic model. Compared to the initial lead 2, compound 28 exhibited reduced potential for QTc prolongation in a non-human primate cardiovascular safety model.

Bioorganic & Medicinal Chemistry Letters 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, Computed Properties of 197958-29-5.

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

Kopf, Sara published the artcileBase-Mediated Remote Deuteration of N-Heteroarenes – Broad Scope and Mechanism, Application In Synthesis of 39856-58-1, the publication is European Journal of Organic Chemistry (2022), 2022(19), e202200204, database is CAplus.

Using KOtBu as base and DMSO-d₆ as deuterium source, a general and applicable method was presented for the selective deuteration of a set of nitrogen-containing heterocycles (pyridines, azines and bioactive mols.). Exptl. and DFT mechanistic studies indicated that this reaction proceeded via deprotonation of the substrates by the dimsyl anion. The relative thermodn. stability of the heterocycle anions determines the distribution and degree of deuteration.

European Journal of Organic Chemistry 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, Application In Synthesis of 39856-58-1.

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

Ma, Junjie published the artcileNi-Catalyzed C-H Cyanation of (Hetero)arenes with 2-Cyanoisothiazolidine 1,1-Dioxide as a Cyanation Reagent, Name: 5-Nitro-2-phenylpyridine, the publication is Organic Letters (2021), 23(8), 2868-2872, database is CAplus and MEDLINE.

A nickel-catalyzed C-H cyanation reaction of arenes has been developed using 2-cyanoisothiazolidine 1,1-dioxide as an electrophilic cyanation reagent. Many different directing groups can be used in this cyanation to obtain a series of cyanation products with good yields. Adopting this strategy to introduce a cyano group, natural alkaloid menisporphine was successfully synthesized through cyano group conversion that further proved the practicality of this cyanation method.

Organic Letters published new progress about 89076-64-2. 89076-64-2 belongs to pyridine-derivatives, auxiliary class Pyridine,Nitro Compound,Benzene, name is 5-Nitro-2-phenylpyridine, and the molecular formula is C11H8N2O2, Name: 5-Nitro-2-phenylpyridine.

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