138197-91-8

Upstream product

• 6651-36-1 1-(Trimethylsilyloxy)cyclohexene 
• 2929-92-2 m-chlorobenzylidene diacetate 
• 108-94-1 cyclohexanone 
• 587-04-2 m-Chlorobenzaldehyde 

Downstream Products

• 1428653-78-4 (E)-7-(3-chlorobenzylidene)-3-(3-chlorophenyl)-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-indazole 

Relevant academic research and scientific papers

Synthesis of diarylidenecyclohexanone derivatives as potential anti-inflammatory leads against COX-2/mPGES1 and 5-LOX

Inflammation is a pathophysiological condition which progresses through the prostaglandin (PG) and leukotriene (LT) pathways channelized by the enzymes COX/mPGES1 and 5-LOX respectively. Diarylidenecyclohexanone (DAC) derivatives (Ia-j, IIa-c, IIIa and IVa) were synthesized, characterized and screened for their in vitro anti-inflammatory activity via inhibition of 5-LOX and COX-2/mPGES1 enzymes. Compound Ic inhibited PGE2 production exhibiting an IC50 of 6.7 ± 0.19 μM, comparable to the standard inhibitor, licofelone (IC50 of 5.4 ± 0.02 μM). Compounds Ie and Ig showed maximum in vitro inhibitory activity against 5-LOX, exhibiting an IC50 of 1.4 ± 0.1 μM and 1.5 ± 0.13 μM, respectively, and these are comparable to that of the standard drug, zileuton (IC50 = 1.2 ± 0.11 μM). Ie and Ig do not possess radical scavenging properties and may not be disrupting the redox cycle of the enzyme. Hence they may be inhibiting the enzyme by a competitive mode. One of the compounds in the DAC series (IIc) containing a heterocyclic thienyl ring inhibited all the three enzymes. It inhibited 5-LOX and COX-2/mPGES1 with an IC50 of 1.8 ± 0.12 μM and 7.5 ± 0.4 μM respectively. An RT-PCR based mRNA expression study highlighted that Ic predominantly inhibited the expression of COX-2 rather than mPGES1. No toxicity towards the HeLa cell line indicated that the DACs could serve as structural templates towards lead optimization of compounds for discovery of novel, potent, safe and affordable drugs as anti-inflammatory agents.

Synthesis, characterization, crystal structure of novel bis-thiomethylcyclohexanone derivatives and their inhibitory properties against some metabolic enzymes

In this study, a series of novel bis-thiomethylcyclohexanone compounds (3a–3j) were synthesized by the addition of thio-Michael to the bis-chalcones under mild reaction conditions. The bis-thiomethylcyclohexanone derivatives (bis-sulfides) were characterized by 1H NMR, 13C NMR, FTIR and elemental analysis techniques. Furthermore, the molecular and crystal structures of 3h, 3i and 3j compounds were determined by single crystal X-ray diffraction studies. In this study, X-ray crystallography provided an alternative and often-complementary means for elucidating functional groups at the enzyme inhibitory site. Acetylcholinesterase (AChE) is a member of the hydrolase protein super family and has a significant role in acetylcholine-mediated neurotransmission. Here, we report the synthesis and determining of novel bis-thiomethylcyclohexanone compounds based hybrid scaffold of AChE inhibitors. The newly synthesized bis-thiomethylcyclohexanone compounds showed Ki values of in range of 39.14–183.23 nM against human carbonic anhydrase I isoenzyme (hCA I), 46.03–194.02 nM against human carbonic anhydrase II isoenzyme (hCA II), 4.55–32.64 nM against AChE and 12.77–37.38 nM against butyrylcholinesterase (BChE). As a result, novel bis-thiomethylcyclohexanone compounds can have promising anti Alzheimer drug potential and record novel hCA I, and hCA II enzymes inhibitor.

Synthesis, mechanistic and synergy studies of diarylidenecyclohexanone derivatives as new antiplasmodial pharmacophores

Diarylidenecyclohexanone (DAC) derivatives (Ia-i, IIa-c and IIIa-b) were synthesized, characterized and screened for their invitro antiplasmodial activities against erythrocytic stages of chloroquine (CQ) sensitive and resistant strains of P. falciparum by using SYBR green I fluorescence assay. SAR studies of DAC derivatives showed antiplasmodial activity in the order of 3-NO2 (Ib, IC50 0.95 μM) > 3-chloro (Id, IC50 3 μM) > 4-chloro (Ie, IC50 8.5 μM) > 2-chloro (Ic, IC50 13 μM). Further Ib and Id exhibited nearly equal potencies against CQ-resistant strains P. falciparum Dd2, {IC50 1 μM (Ib) and 2.7 μM (Id)} and PfINDO {IC50 1.1 μM (Ib) and 2.5 μM (Id)}. Drug exposure followed by drug withdrawal-based stage-specific kill kinetic studies showed that Ib is shizonticidal within 3 h while the earliest killing actions against Trophozoites and Rings were seen at >3 h and >6 h, respectively. Combination studies of the most potent leads viz. Ib and Id showed strong to moderate synergistic effects with Artemisinin (?FIC50: 0.34 to 0.63) whereas no interaction (?FIC50: 0.65 to 2.36) was observed with Chloroquine. The DACs showed significant insilico binding affinity with β-haematin and P. falciparum lactate dehydrogenase (PfLDH) suggesting these to be the targets of their antiplasmodial action. High compliance with Lipinski rule of 5 and high selectivity index of Ib (105.3) and Id (8.3) against HeLa cell line indicated that Diarylidenecyclohexanones could serve as structural templates towards lead optimization of compounds for discovery of novel, potent, safe and affordable drugs against malaria.

Design, characterization, and use of N,N-diethyl-N-sulfoethanaminium hydrogen sulfate {[Et3N-SO3H]HSO4} as a novel and highly efficient catalyst for preparation of α,α′-bis(arylidene)cycloalkanones

Abstract: The aim of this work is to introduce a novel and attractive protic acidic ionic liquid as catalyst for organic synthesis. To achieve this aim, N,N-diethyl-N-sulfoethanaminium hydrogen sulfate {[Et3N-SO3H]HSO4} was prepared by reaction of NEt3 with ClSO3H and then with H2SO4. The novel acidic ionic liquid was identified by Fourier-transform infrared (FT-IR), 1H nuclear magnetic resonance (NMR), 13C NMR, and mass spectroscopies. Its catalytic activity was then examined in the cross-aldol condensation reaction of arylaldehydes with cycloalkanones under solvent-free conditions, obtaining α,α′-bis(arylidene)cycloalkanones in high yield after short reaction time. Graphical Abstract: [Figure not available: see fulltext.]

Study of in situ generation of carbocationic system from trityl chloride (Ph3CCl) which efficiently catalyzed cross-aldol condensation reaction

Organocatalyst trityl chloride (Ph3CCl), by in situ formation of trityl carbocation with inherent instability, efficiently promotes the cross-aldol condensation reaction between cycloalkanones and arylaldehydes in solvent-free and homogeneous media to afford α,α′- bis(arylidene)cycloalkanones in high yields. Moreover, an attractive and plausible mechanism based on observations and the literature is proposed for the reaction.

Synthesis, molecular docking and in vitro antimicrobial studies of new hexahydroindazole derivatives of curcumin

A series of hexahydroindazole analogues of curcumin were synthesized and investigated for in vitro and in silico antimicrobial activity. The structures of synthesized compounds were identified on the basis of satisfactory analytical and spectral data (1H NMR, 13C NMR, EI-MASS techniques and elemental analysis). Synthesized compounds showed moderate to high activity against both bacterial and fungal strains. All compounds were docked computationally to the active site of enzyme L-glutamine: D-fructose-6-phosphate amido-transferase [GlcN-6-P] (EC 2.6.1.16). The autodock programme 4.0 was employed to perform automated molecular docking. (E)-1-(7-(3-methoxybenzylidene) -3-(3- methoxyphenyl)-3,3a,4,5,6,7-hexahydro-2H-indazol-2-yl)ethanone (A7) turned out to be the most potent analogue of the series, showing best activity against bacterial and fungal strains. Compound A7 showed minimum binding and docking energy and may be considered as good inhibitor of GlcN-6-P synthase. Further investigation and optimization of this lead could provide new antimicrobial molecules.

Effects of diarylpentanoid analogues of curcumin on chemiluminescence and chemotactic activities of phagocytes

Objectives A series of 43 curcumin diarylpentanoid analogues were synthesized and evaluated for their inhibitory effects on the chemiluminescence and chemotactic activity of phagocytes in vitro. Methods The effects of the compounds on the respiratory burst of human whole blood and isolated human polymorphonuclear leukocytes (PMNs) were evaluated using a luminol-based chemiluminescence assay and their effect on chemotactic migration of PMNs was investigated using the Boyden chamber technique. Key findings Compounds 6, 17, 25 and 30 exhibited significant inhibitory activity on the oxidative burst of PMNs. The presence of methoxy groups at positions 2 and 5, and methoxylation and fluorination at positions 4 and 2 of both phenyl rings, respectively, may contribute significantly to their reactive oxygen species inhibition activity. Compounds 7, 17, 18, 24 and 32 showed strong inhibition of the chemotaxis migration of PMNs. Chlorination at various positions of both phenyl rings of cyclohexanone diarylpentanoid resulted in compounds with potent inhibitory effects on PMN migration. Conclusions The results suggest that some of these diarylpentanoid analogues are able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as a source of new immunomodulatory agents.

Highly selective claisen-schmidt condensation catalyzed by silica chloride under solvent-free reaction conditions

Silica chloride serves as a useful catalyst in the cross-aldol condensation, leading to the synthesis of a wide variety of bisarylidene cycloalkanones and chalcones. The catalyst showed high selectivity; self-condensation of ketones was not observed.

Solvent-free, cross-aldol condensation reaction using silica-supported, phosphorus-containing reagents leading to α,α′-Bis(arylidene) cycloalkanones

This article describes an efficient, simple, and clean method for the synthesis of α,α′-bis(arylidene, furylidene and cinnamylidene)cycloalkanones under solvent-free conditions. The cross-aldol condensation of cycloalkanones with aldehydes in the presence of silica-supported phosphorus pentoxide (P2O5/SiO 2) or silicaphosphinoxide (silphox, [POCl3-n(SiO 2)n]) as heterogeneous reagents produces the title compounds in good to excellent yields. Copyright Taylor & Francis Group, LLC.

Chemistry of acylals, part IV: BF3-catalyzed formation of substituted α,α′-bis(arylmethylidene)cycloalkanones from acylals and 1-cycloalkenyl trimethylsilyl ethers

When mixtures of an aromatic aldehyde acylal and a I-cycloalkenyl trimethylsilyl ether in dichloromethane were treated with boron trifluoride at room temperature, the corresponding α,α′-bis(arylmethylidene) cycloalkanones were formed. The yield was sensitive to both the acetal/ether ratio and the structure of the acylal. The best results, up to 97% yield, were obtained when acylals containing a diacetoxy moiety were reacted with 1-cyclohexenyl trimethylsilyl ether with an acetal-to-ether ratio of 2:1. Georg Thieme Verlag Stuttgart.