Month: October 2022

Ma, Junlong; Chen, Heng; Yang, Jie; Yu, Zutao; Huang, Pan; Yang, Haofeng; Zheng, Bifeng; Liu, Rangru; Li, Qianbin; Hu, Gaoyun; Chen, Zhuo published the artcile< Binding pocket-based design, synthesis and biological evaluation of novel selective BRD4-BD1 inhibitors>, Safety of 3-(3-Chlorophenyl)-3-oxopropanenitrile, the main research area is neoplasm antitumor BRD4 BD1; BD1 inhibitor; BRD4; Cancer; Computer-aided drug design; Fibrosis; Structure-activity relationship.

Bromodomain-containing protein 4 (BRD4), consisting of two tandem bromodomains (BD1 and BD2), is key epigenetic regulator in fibrosis and cancer, which has been reported that BD1 and BD2 have distinct roles in post-translational modification. But there are few selective inhibitors toward those two domains. Herein, this study designed and synthesized a series of novel selective BRD4-BD1 inhibitors, using computer-aided drug design (CADD) approach focused on exploring the difference of the binding pockets of BD1 and BD2, and finding the His437 a crucial way to achieve BRD4-BD1 selectivity. Our results revealed that the compound 3u(I) is a potent selective BRD4-BD1 inhibitor with IC50 values of 0.56 μM for BD1 but >100 μM for BD2. I exhibited a broad spectrum of anti-proliferative activity against several human cancer and fibroblastic cell lines, which might be related to its capability of reducing the expression of c-Myc and collagen I. Furthermore, I could induce apoptosis in A375 cells. To the contrary, the selective BD2 inhibitor, RVX-208, did not indicate any of these activities. Our findings highlight that the function of BRD4-BD1 might be predominant in fibrosis and cancer. And it is rational to further develop novel selective BRD4-BD1 inhibitors.

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 21667-62-9 belongs to class nitriles-buliding-blocks, and the molecular formula is C9H6ClNO, Safety of 3-(3-Chlorophenyl)-3-oxopropanenitrile.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Val, Cristina; Rodriguez-Garcia, Carlos; Prieto-Diaz, Ruben; Crespo, Abel; Azuaje, Jhonny; Carbajales, Carlos; Majellaro, Maria; Diaz-Holguin, Alejandro; Brea, Jose M.; Loza, Maria Isabel; Gioe-Gallo, Claudia; Contino, Marialessandra; Stefanachi, Angela; Garcia-Mera, Xerardo; Estevez, Juan C.; Gutierrez-de-Teran, Hugo; Sotelo, Eddy published the artcile< Optimization of 2-Amino-4,6-diarylpyrimidine-5-carbonitriles as Potent and Selective A1 Antagonists>, Recommanded Product: 3-(3-Chlorophenyl)-3-oxopropanenitrile, the main research area is amino diarylpyrimidin carbonitrile preparation adenosine receptor SAR docking.

Herein, document of a large collection of 108 2-amino-4,6-disubstituted-pyrimidine derivatives as potent, structurally simple, and highly selective A1AR ligands. The most attractive ligands were confirmed as antagonists of the canonical cyclic adenosine monophosphate pathway, and some pharmacokinetic parameters were preliminarilly evaluated. The library, built through a reliable and efficient three-component reaction, comprehensively explored the chem. space allowing the identification of the most prominent features of the structure-activity and structure-selectivity relationships around this scaffold. These included the influence on the selectivity profile of the aromatic residues at positions R4 and R6 of the pyrimidine core but most importantly the prominent role to the unprecedented A1AR selectivity profile exerted by the Me group introduced at the exocyclic amino group. The structure-activity relationship trends on both A1 and A2AARs were conveniently interpreted with rigorous free energy perturbation simulations, which started from the receptor-driven docking model that guided the design of these series.

Journal of Medicinal Chemistry published new progress about Adenosine A1 receptor antagonists. 21667-62-9 belongs to class nitriles-buliding-blocks, and the molecular formula is C9H6ClNO, Recommanded Product: 3-(3-Chlorophenyl)-3-oxopropanenitrile.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Jia, Qianfa; Lan, Yunfei; Ye, Xin; Lin, Yinhe; Ren, Qiao published the artcile< Direct access to multi-functionalized benzenes via [4 + 2] annulation of α-cyano-β-methylenones and α,β-unsaturated aldehydes>, Recommanded Product: 3-(3-Chlorophenyl)-3-oxopropanenitrile, the main research area is cyano butanone propenal metal free regioselective cycloaddition reaction; benzene preparation.

An efficient [4 + 2] benzannulation of α-cyano-β-methylenones and α,β-unsaturated aldehydes was achieved under metal-free reaction conditions selectively delivering a wide range of polyfunctional benzenes in high yields resp. (up to 94% yield).

RSC Advances published new progress about [4+2] Cycloaddition reaction (regioselective). 21667-62-9 belongs to class nitriles-buliding-blocks, and the molecular formula is C9H6ClNO, Recommanded Product: 3-(3-Chlorophenyl)-3-oxopropanenitrile.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Liu, Hao; Sun, Zhenliang; Xu, Kai; Zheng, Yan; Liu, Delong; Zhang, Wanbin published the artcile< Pd-Catalyzed Asymmetric Allylic Substitution Cascade of But-2-ene-1,4-diyl Dimethyl Dicarbonate for the Synthesis of Chiral 2,3-Dihydrofurans>, Reference of 21667-62-9, the main research area is dihydrofuran preparation asym allylic substitution cascade butene dicarbonate cyanoketone.

Herein an efficient Pd-catalyzed asym. allylic substitution cascade of both (E)- and (Z)-but-2-ene-1,4-diyl di-Me dicarbonates with α-substituted cyano ketones is described for the preparation of chiral 2,3-dihydrofurans in up to 97% yield with 98% ee. A suggested steric control process has been proposed to illustrate the differences in enantioselectivity between the reactions of (E)- and (Z)-allyl substrates. The cascade reaction could be conducted on a gram-scale, and the resulting product allows for several transformations.

Organic Letters published new progress about Alkenes Role: RCT (Reactant), RACT (Reactant or Reagent) (dicarbonates). 21667-62-9 belongs to class nitriles-buliding-blocks, and the molecular formula is C9H6ClNO, Reference of 21667-62-9.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Sato, Nagaaki; Ando, Makoto; Ishikawa, Shiho; Jitsuoka, Makoto; Nagai, Keita; Takahashi, Hirobumi; Sakuraba, Aya; Tsuge, Hiroyasu; Kitazawa, Hidefumi; Iwaasa, Hisashi; Mashiko, Satoshi; Gomori, Akira; Moriya, Ryuichi; Fujino, Naoko; Ohe, Tomoyuki; Ishihara, Akane; Kanatani, Akio; Fukami, Takehiro published the artcile< Discovery of Tetrasubstituted Imidazolines as Potent and Selective Neuropeptide Y Y5 Receptor Antagonists: Reduced Human Ether-a-go-go Related Gene Potassium Channel Binding Affinity and Potent Antiobesity Effect>, COA of Formula: C6H11NO2, the main research area is aminoester fluorophenylmagnesium bromide bromofluoropyridine coupling ring opening closure reduction; imidazoline asym preparation; neuropeptide Y5 receptor antagonist antiobesity structure activity human.

A series of novel imidazoline derivatives was synthesized and evaluated as neuropeptide Y (NPY) Y5 receptor antagonists. Optimization of previously reported imidazoline leads, I and II, was attempted by introduction of substituents at the 5-position on the imidazoline ring and modification of the bis(4-fluorophenyl) moiety. A number of potent derivatives without human ether-a-go-go related gene potassium channel (hERG) activity were identified. Selected compounds, including III, were shown to have excellent brain and CSF permeability. Compound III displayed a suitable pharmacokinetic profile for chronic in vivo studies and potently inhibited D-Trp34NPY-induced acute food intake in rats. Oral administration of III resulted in a potent reduction of body weight in a diet-induced obese mouse model.

Journal of Medicinal Chemistry published new progress about Amino acid esters Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 6136-93-2 belongs to class nitriles-buliding-blocks, and the molecular formula is C6H11NO2, COA of Formula: C6H11NO2.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Park, Yunjeong; Bae, Song Yi; Hah, Jung-Mi; Lee, Sang Kook; Ryu, Jae-Sang published the artcile< Synthesis of stereochemically diverse cyclic analogs of tubulysins>, Recommanded Product: 2,2-Diethoxyacetonitrile, the main research area is tubulysin cyclic analog peptide peptidomimetic enantioselective synthesis thiazole; Diels Alder reaction stereoselective Danishefsky diene type peptide coupling; antitumor agent tubulin polymerization inhibiting structure activity; Antitumor agents; Asymmetric catalysis; Hetero Diels–Alder reaction; Peptides; Tubulysin.

The synthesis of tubulysin analogs containing stereochem. diverse cyclic Tuv moieties is described. A tetrahydropyranyl moiety was incorporated into the Tuv unit by enantioselective hetero Diels-Alder reactions of Danishefsky’s diene and thiazole aldehyde. Four different stereoisomers of cyclic Tuv units were used as surrogates for the Tuv moiety. The synthesized stereochem. diverse simplified cyclic analogs were evaluated for the inhibition of tubulin polymerization

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 6136-93-2 belongs to class nitriles-buliding-blocks, and the molecular formula is C6H11NO2, Recommanded Product: 2,2-Diethoxyacetonitrile.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Wang, Yu-Hao; Zhang, De-Hua; Cao, Ze-Hun; Li, Wang-Lai; Huang, Yi-Yong published the artcile< A formal [3 + 3] cycloaddition of allenyl imide and activated ketones for the synthesis of tetrasubstituted 2-pyrones>, Related Products of 21667-62-9 , the main research area is pyrone preparation; allenyl imide ketoester cycloaddition; diketone allenyl imide cycloaddition; ketonitrile allenyl imide cycloaddition.

CsOH.H2O-catalyzed formal [3 + 3] cycloadditions of allenyl imide with β-ketoesters RC(O)CH2C(O)OR1 (R = Ph, cyclohexyl, 2-thienyl, Me, etc.; R1 = Me, Et), 1,3-diketones R2C(O)CH2R3 [R2 = Ph, 3-fluorophenyl, 2-iodophenyl, etc; R3 = C(O)C6H5, C(O)(3-CH3C6H4), C(O)(3-(CH3O)C6H4), C(O)(3-(CF3)C6H4)] or β-ketonitriles R2C(O)CH2R3 (R3 = CN) for the synthesis of tetrasubstituted 2-pyrone derivatives I, II have been demonstrated. The allenyl imide was utilized as a C3-synthon, and a ketenyl intermediate was proposed via the process of 1,4-addition of carbon anion to allene followed by elimination of the 2-oxazolidinyl group.

RSC Advances published new progress about [3+3] Cycloaddition reaction. 21667-62-9 belongs to class nitriles-buliding-blocks, and the molecular formula is C9H6ClNO, Related Products of 21667-62-9 .

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Brooks, Allen F.; Garcia, George A.; Showalter, Hollis D. published the artcile< Synthesis of azide congeners of preQ1 as potential substrates for tRNA guanine transglycosylase>, Reference of 69205-79-4, the main research area is tRNA guanine transglycosylase preQ azide congener.

PreQ1 (2) is a precursor of queuine (1) that in eubacteria is incorporated into tRNA (tRNA) by tRNA guanine transglycosylase (TGT) before being further elaborated into queuine. The queuine modification is unusual and occurs across all eukaryotes and eubacteria with few exceptions, but its function remains unclear. As the modified nucleotide occurs through incorporation of a specially synthesized nucleotide instead of via modification of a genetically encoded base, a study of the sites of modification by prepared probes is possible. We report the synthesis of two novel azide congeners (3,4) of preQ1 for this purpose. The evaluation of their interaction with TGT shows that both probes act as weak competitive inhibitors of guanine exchange of guanine(34) tRNATyr with a Ki of ∼70 μM. However, we could not show that these are substrates for TGT-catalyzed incorporation into tRNA. We believe the reason for this is a marked loss of binding due to the azide functionality of 3 and 4 abrogating the possibility of two hydrogen bonds to the carbonyl group of Leu231 and Met260 of TGT, previously observed for the terminal methylene amine of preQ1 by x-ray crystallog.

Journal of Heterocyclic Chemistry published new progress about Enzyme functional sites, substrate-binding. 69205-79-4 belongs to class nitriles-buliding-blocks, and the molecular formula is C7H5N5O, Reference of 69205-79-4.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Alhatem, Aamer A. published the artcile< Tautomeric equilibria of substituted 2-pyridone/2-hydroxypyridine in the gas and aqueous phases>, Application of C6H4N2O, the main research area is pyridone hydroxypyridine tautomer substituent effects formation enthalpy free energy.

Heats of formation, entropies and Gibbs free energies for the twenty structures of substituted 2-pyridone and 2-hydroxypyridine were studied using semiempirical Austin Model (AM1) and Parametric Method 3 (PM3) calculations at the SCF level, both in the gas and liquid phases, with full geometry optimization. It was revealed from the study that 2-hydroxypyridine is predominant in gas phase, while 2-pyridone in the liquid phase which agrees with the exptl. and theor. predictions. All substituents such as F, Cl, OH, CH3, NH2, NO2, CHO, CN, CF3 stabilize the 2-pyridone in the gas and liquid phases except F, Cl and NH2 in PM3 calculations in the gas phase. The substituents stabilization is more effective in liquid phase. This was also confirmed by thermodn. calculations and isodesmic reactions.

Chemical Science International Journal published new progress about Entropy. 89324-17-4 belongs to class nitriles-buliding-blocks, and the molecular formula is C6H4N2O, Application of C6H4N2O.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Jia, Qianfa; Yin, Guoliang; Lan, Yunfei; Lin, Yinhe; Ren, Qiao published the artcile< Base-mediated Benzannulation Reactions for the Synthesis of Densely Functionalized Aryl α-Keto Esters>, Computed Properties of 21667-62-9 , the main research area is phenyl keto ester preparation; cyano phenyl methanone ynedione regioselective cycloaddition.

A novel and straightforward strategy for the construction of versatile densely functionalized aryl α-keto esters were disclosed through a one-pot and efficient [4+2] benzannulation reaction of α-cyano-β-methylenones and ynediones, which were synthesized easily from the corresponding starting materials. This protocol featured high yield, mild metal-free reaction condition, high atom economy, high functional-group tolerance, easy handing and gram-scale synthesis.

Asian Journal of Organic Chemistry published new progress about [4+2] Cycloaddition reaction (regioselective). 21667-62-9 belongs to class nitriles-buliding-blocks, and the molecular formula is C9H6ClNO, Computed Properties of 21667-62-9 .

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts