Month: December 2022

Liu, Gang published the artcileDiscovery of Novel Macrocyclic Hedgehog Pathway Inhibitors Acting by Suppressing the Gli-Mediated Transcription, Computed Properties of 21286-54-4, the publication is Journal of Medicinal Chemistry (2017), 60(19), 8218-8245, database is CAplus and MEDLINE.

A systemic medicinal chem. campaign was conducted based on a literature hit compound I bearing the 4,5-dihydro-2H-benzo[b][1,5]oxazocin-6(3H)-one core through cyclization of two side substituents of the bicyclic skeleton combined with N-atom walking or ring walking and the central ring expansion or extraction approaches, leading to several series of structurally unique tricyclic compounds Among these, compound II was identified as the most potent against the Hedgehog (Hh) signaling pathway showing an IC₅₀ value of 23 nM. Mechanism studies indicated that compound II inhibited the Hh signaling pathway by suppressing the expression of the transcriptional factors Gli rather than by interrupting the binding of Gli with DNA. We further observed that II was equally potent against both Smo wild type and the two major resistant mutants (Smo D473H and Smo W535L). It potently inhibited the proliferation of medulloblastoma cells and showed significant tumor growth inhibition in the ptch± ;p53-/- medulloblastoma allograft mice model. Though more studies are needed to clarify the precise interaction pattern of II with Gli, its promising in vitro and in vivo properties encourage further profiling as a new-generation Hh signaling inhibitor to treat tumors primarily or secondarily resistant to current Smo inhibitors.

Journal of Medicinal Chemistry published new progress about 21286-54-4. 21286-54-4 belongs to chlorides-buliding-blocks, auxiliary class Chiral,Chloride,Sulfonyl chlorides,Aliphatic cyclic hydrocarbon,Ketone, name is ((1S,4R)-7,7-Dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonyl chloride, and the molecular formula is C10H15ClO3S, Computed Properties of 21286-54-4.

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

Kimura, Tatsuo published the artcileProperties of metal species in square-shape mesopores of KSW-2-based silica, Application In Synthesis of 14799-93-0, the publication is Journal of Materials Chemistry (2009), 19(23), 3859-3866, database is CAplus.

Properties arising from 2-D orthorhombic mesoporous silica (KSW-2) were investigated for each structural feature: (1) periodicity in silicate framework and (2) square-shape mesopore. Titanium species were grafted onto the periodic silica walls of KSW-2-based mesoporous silica through silylation with octylmethyldichlorosilane in the presence of organotitanium compounds with cyclopentadienyl ligands. The surface TiO₄ units formed after calcination at 550 °C showed a higher activity in the oxidation of cyclohexene with peroxides than those onto FSM-16 and MCM-41 grafted in the same manner, indicating that (1) the periodicity in the framework influenced the catalytic activity due to the heteroatoms fixed at the silicate surfaces. The synthesis of metallic Pt species inside square-shape mesopores of KSW-2-based silica was conducted by reduction of impregnated H₂PtCl₆. Considering the morphol. of metallic Pt species formed through wet H₂ and UV reduction, it is considered that (2) the square-shape mesopore is useful for suppressing the sintering of metallic Pt species.

Journal of Materials Chemistry published new progress about 14799-93-0. 14799-93-0 belongs to chlorides-buliding-blocks, auxiliary class Aliphatic Chain, name is Dichloro(methyl)(octyl)silane, and the molecular formula is C9H20Cl2Si, Application In Synthesis of 14799-93-0.

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

Song, Zhendong published the artcileSynthesis and biological evaluation of morpholine-substituted diphenylpyrimidine derivatives (Mor-DPPYs) as potent EGFR T790M inhibitors with improved activity toward the gefitinib-resistant non-small cell lung cancers (NSCLC), Formula: C6H3ClFNO2, the publication is European Journal of Medicinal Chemistry (2017), 329-339, database is CAplus and MEDLINE.

Potential new EGFR^T790M inhibitors comprising of structurally modified diphenylpyrimidine derivatives bearing a morpholine functionality (Mor-DPPYs), e.g., I were synthesized and used to improve the activity and selectivity of gefitinib-resistant non-small cell lung cancer (NSCLC) treatment. This led to the identification of inhibitor I, which displayed high activity against EGFR^T790M/L858R kinase (IC₅₀ = 0.71 nM) and repressed H1975 cell replication harboring EGFR^T790M mutations at a concentration of 0.037 μM. Inhibitor I demonstrated high selectivity (SI = 631.9) for T790M-containing EGFR mutants over wild type EGFR and suggested that it will cause few side effects. Moreover, this compound also shows promising antitumor efficacy in a murine EGFR^T790M/L858R-driven H1975 xenograft model without affecting body weight This study provides new potential lead compounds for further development of anti-NSCLC drugs.

European Journal of Medicinal Chemistry published new progress about 350-30-1. 350-30-1 belongs to chlorides-buliding-blocks, auxiliary class Fluoride,Chloride,Nitro Compound,Benzene, name is 3-Chloro-4-fluoronitrobenzene, and the molecular formula is C10H10O2, Formula: C6H3ClFNO2.

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

Xia, Zhenqiang published the artcileThe synthesis and bioactivity of pyrrolo[2,3-d]pyrimidine derivatives as tyrosine kinase inhibitors for NSCLC cells with EGFR mutations, Recommanded Product: 3-Chloro-4-fluoronitrobenzene, the publication is European Journal of Medicinal Chemistry (2021), 113711, database is CAplus and MEDLINE.

A series of pyrrolo[2,3-d]pyrimidine derivatives able to block mutant EGFR activity in a covalent manner were synthesized, through optimized Buchwald-Hartwig C-N cross coupling reactions. Their preliminary bioactivity and corresponding inhibitory mechanistic pathways were investigated at mol. and cellular levels. Several compounds exhibited increased biol. activity and enhanced selectivity compared to the control compound Notably, N-(3-((2-((3-amino-4-(4-methylpiperazin-1-yl)phenyl)amino)-7H-cyclopenta[d]pyrimidin-4-yl)oxy)phenyl)acrylamide selectively inhibits HCC827 cells harboring the EGFR activating mutation with up to 493-fold increased efficacy compared to in normal HBE cells. Augmented selectivity was also confirmed by kinase enzymic assay, with the test compound selectively inhibiting the T790 M activating mutant EGFRs (IC₅₀ values of 0.21 nM) with up to 104-fold potency compared to the wild-type EGFR (IC₅₀ values of 22 nM). Theor. simulations provided structural evidence of selective kinase inhibitory activity. Thus, this series of pyrrolo[2,3-d]pyrimidine derivatives could serve as a starting point for the development of new EGFR-TKIs.

European Journal of Medicinal Chemistry published new progress about 350-30-1. 350-30-1 belongs to chlorides-buliding-blocks, auxiliary class Fluoride,Chloride,Nitro Compound,Benzene, name is 3-Chloro-4-fluoronitrobenzene, and the molecular formula is C12H21NO7, Recommanded Product: 3-Chloro-4-fluoronitrobenzene.

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

Liao, Li-min published the artcileStructural characterization and acute toxicity simulation for nitroaromatic compounds, Name: 3-Chloro-4-fluoronitrobenzene, the publication is Chinese Journal of Structural Chemistry (2016), 35(3), 449-456, database is CAplus.

Three-dimensional holog. vector of at. interaction field (3D-HoVAIF) is used to characterize mol. structures of 45 nitroarom. compounds Two quant. structure-toxicity relationship (QSAR) models are built up by stepwise regression (SMR), multiple linear regression (MLR) and partial least-squares regression (PLS). The correlation coefficients (R) of the models are 0.960 and 0.961, resp. Then the models are evaluated by performing the cross-validation with the leave-one-out (LOO) procedure, and the correlation coefficients (R_CV) are 0.949 and 0.941, resp. The results show that the descriptors can successfully describe the structures of organic compounds The stability and predictability of the model are satisfactory.

Chinese Journal of Structural Chemistry published new progress about 350-30-1. 350-30-1 belongs to chlorides-buliding-blocks, auxiliary class Fluoride,Chloride,Nitro Compound,Benzene, name is 3-Chloro-4-fluoronitrobenzene, and the molecular formula is C6H3ClFNO2, Name: 3-Chloro-4-fluoronitrobenzene.

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

Wilson, G. Edwin Jr. published the artcileHalosulfonium salts. IX. Halogen-induced ring cleavages of 1,3-oxathiolanes, Formula: C4H8Cl2S2, the publication is Journal of Organic Chemistry (1976), 41(6), 966-8, database is CAplus.

Halogenation of the 2,2-disubstituted 1,3-oxathiolanes derived from benzophenone, diisopropyl ketone, and cycloheptanone provides a route to regenerate the ketone in good yield. For diisopropyl ketone addnl. products, Me2CHCOCMe2S(CH2)2R (R = Cl, Br), are obtained.

Journal of Organic Chemistry published new progress about 1002-41-1. 1002-41-1 belongs to chlorides-buliding-blocks, auxiliary class Aliphatic Chain, name is 1,2-Bis(2-chloroethyl)disulfane, and the molecular formula is C7H7BF2O3, Formula: C4H8Cl2S2.

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

Johnson, Joshua L. published the artcileOptimal pH 8.5 to 9 for the hydrolysis of vixotrigine and other basic substrates of carboxylesterase-1 in human liver microsomes, Quality Control of 637-07-0, the publication is Xenobiotica (2022), 52(2), 105-112, database is CAplus and MEDLINE.

Vixotrigine is a voltage- and use-dependent sodium channel blocker under investigation for the potential treatment of neuropathic pain. One of the major in vivo metabolic pathways of vixotrigine in humans is the hydrolysis of the carboxamide to form the carboxylic acid metabolite M14. The in vitro formation of M14 in human hepatocytes was inhibited by the carboxylesterase (CES) inhibitor Bis(4-nitrophenyl) phosphate in a concentration-dependent manner. The hydrolysis reaction was identified to be catalyzed by recombinant human CES1b. Initial observation of only trace level formation of M14 in human liver microsomes at pH 7.4 caused us to doubt the involvement of CES1, an enzyme localised at the endoplasmic reticulum and the dominant carboxylesterase in human liver. Further investigation has revealed that optimal pH for the hydrolysis of vixotrigine and two other basic substrates of CES1, methylphenidate and oseltamivir, in human liver microsomes was pH 8.5-9 which is higher than their resp. pKa(base), suggesting that neutral form of basic substrates is probably preferred for CES1 catalysis in liver microsomes.

Xenobiotica published new progress about 637-07-0. 637-07-0 belongs to chlorides-buliding-blocks, auxiliary class Inhibitor,Cell Cycle,PPAR, name is Ethyl 2-(4-chlorophenoxy)-2-methylpropanoate, and the molecular formula is C12H15ClO3, Quality Control of 637-07-0.

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

Dong, Jinyun published the artcileDiscovery of heterocycle-containing α-naphthoflavone derivatives as water-soluble, highly potent and selective CYP1B1 inhibitors, COA of Formula: C6H4ClNO2, the publication is European Journal of Medicinal Chemistry (2021), 112895, database is CAplus and MEDLINE.

A set of forty-six 6,7,10-trimethoxy-α-naphthoflavone derivatives I [R = 2-furyl, 2-chloro-4-pyridyl, 5-bromo-2-pyridyl, etc.] was synthesized and screened against CYP1 enzymes, leading to the identification of fluorine-containing compound I [R = 5-bromo-2-pyridyl] as the most potent and selective CYP1B1 inhibitor (IC₅₀ value of 0.07 nM), being 84-fold more potent than that of the template mol. ANF. Alternatively, the amino-substituted derivative I [R = 4-amino-3-pyridyl] not only possessed a potent inhibitory effect on CYP1B1 (IC₅₀ value of 0.98 nM), but also had a substantially increased water solubility as compared with the lead ANF. The current study expanded the structural diversity of CYP1B1 inhibitors and compound I [R = 4-amino-3-pyridyl] could be considered as a promising starting point with great potential for further studies.

European Journal of Medicinal Chemistry published new progress about 6313-54-8. 6313-54-8 belongs to chlorides-buliding-blocks, auxiliary class Pyridine,Chloride,Carboxylic acid, name is 2-Chloroisonicotinic acid, and the molecular formula is C6H4ClNO2, COA of Formula: C6H4ClNO2.

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

Liu, Qiufeng published the artcileStructure-Guided Discovery of Novel, Potent, and Orally Bioavailable Inhibitors of Lipoprotein-Associated Phospholipase A2, Application of 3-Chloro-4-fluoronitrobenzene, the publication is Journal of Medicinal Chemistry (2017), 60(24), 10231-10244, database is CAplus and MEDLINE.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a promising therapeutic target for atherosclerosis, Alzheimer’s disease, and diabetic macular edema. Here the authors report the identification of novel sulfonamide scaffold Lp-PLA2 inhibitors derived from a relatively weak fragment. Similarity searching on this fragment followed by mol. docking leads to the discovery of a micromolar inhibitor with a 300-fold potency improvement. Subsequently, by the application of a structure-guided design strategy, a successful hit-to-lead optimization was achieved and a number of Lp-PLA2 inhibitors with single-digit nanomolar potency were obtained. After preliminary evaluation of the properties of drug-likeness in vitro and in vivo, compound 37 (4-amino-N-(4-(4-chloro-3-(trifluoromethyl)phenoxy)-3-cyanophenyl)benzenesulfonamide) stands out from this congeneric series of inhibitors for good inhibitory activity and favorable oral bioavailability in male Sprague-Dawley rats, providing a quality candidate for further development. The present study thus clearly demonstrates the power and advantage of integrally employing fragment screening, crystal structures determination, virtual screening, and medicinal chem. in an efficient lead discovery project, providing a good example for structure-based drug design.

Journal of Medicinal Chemistry published new progress about 350-30-1. 350-30-1 belongs to chlorides-buliding-blocks, auxiliary class Fluoride,Chloride,Nitro Compound,Benzene, name is 3-Chloro-4-fluoronitrobenzene, and the molecular formula is C6H3ClFNO2, Application of 3-Chloro-4-fluoronitrobenzene.

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

Li, Jun published the artcileIndium-promoted preparation of α-methylene-γ-trifluoromethyl-γ-lactams via one-pot reaction, Category: chlorides-buliding-blocks, the publication is Youji Huaxue (2017), 37(11), 2985-2992, database is CAplus.

An one-pot reaction of trifluoroacetaldehyde Me hemiacetal or trifluoroketones, acylhydrazines and Et 2-(bromomethyl)acrylate promoted by indium powder was investigated, and a series of α-methylene-γ-trifluoromethyl-γ-lactams were obtained with high yields. The features of this process included readily available starting materials as trifluoromethyl source, mild conditions and easy operation. The reaction provided a new method for the synthesis of trifluoromethylated α-methylene-γ-lactams.

Youji Huaxue published new progress about 5860-95-7. 5860-95-7 belongs to chlorides-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Chloride,Benzene,Ketone, name is 1-(2-Chlorophenyl)-2,2,2-trifluoroethanone, and the molecular formula is C8H4ClF3O, Category: chlorides-buliding-blocks.

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