66021-71-4

Upstream product

• 827-52-1 1-phenyl-1-cyclohexane 
• 771-98-2 1-Phenylcyclohexene 
• 591-50-4 iodobenzene 
• 108-94-1 cyclohexanone 
• 1589-60-2 1-phenylcyclohexanol 

Downstream Products

• 1072895-10-3 (1-phenylcyclohexyl)glycine 

Relevant academic research and scientific papers

Spiro [benzo [c] aza-1, 1 '-cyclohexyl]-3-ketone compound

The invention belongs to the technical field of medicines, relates to a compound with anti-tumor activity and a specific chemical structure, and particularly relates to a 4, 5-dihydrospiro [benzo [c] aza-1, 1 '-cyclohexyl]-3 (2H)-ketone compound as well as a preparation method and application of the 4, 5-dihydrospiro [benzo [c] aza-1, 1'-cyclohexyl]-3 (2H)-ketone compound. The structural general formula of the compound is shown in the specification, wherein an R group on an a benzene ring is substituted by a 2-position, 3-position or 4-position monosubstituted fluorine atom, methyl, chlorine atom, methoxyl, bromine atom or hydrogen atom. Pharmacological studies show that the compound provided by the invention has certain inhibitory activity on human colon cancer HCT-116 cells, can be used for preparing antitumor drugs, and opens up a new way for deep research and development of tumor drugs in the future. The preparation method provided by the invention is simple and feasible, relatively high in yield and easy for large-scale production.

Novel 4,5-dihydrospiro[benzo[c]azepine-1,1′-cyclohexan]-3(2H)-one derivatives as PARP-1 inhibitors: Design, synthesis and biological evaluation

To further explore the research of novel PARP-1 inhibitors, we designed and synthesized a series of novel amide PARP-1 inhibitors based on our previous research. Most compounds displayed certain antitumor activities against four tumor cell lines (A549, HepG2, HCT-116, and MCF-7). Specifically, the candidate compound R8e possessed strong anti-proliferative potency toward A549 cells with the IC50 value of 2.01 μM. Compound R8e had low toxicity to lung cancer cell line. And the in vitro enzyme inhibitory activity of compound R8e was better than rucaparib. Molecular docking studies provided a rational binding model of compound R8e in complex with rucaparib. The following cell cycle and apoptosis assays revealed that compound R8e could arrest cell cycle in the S phase and induce cell apoptosis. Western blot analysis further showed that compound R8e could effectively inhibit the PAR's biosynthesis and was more effective than rucaparib. Overall, based on the biological activity evaluation, compound R8e could be a potential lead compound for further developing novel amide PARP-1 inhibitors.

Mangana(iii/iv)electro-catalyzed C(sp3)-H azidation

Manganaelectro-catalyzed azidation of otherwise inert C(sp3)-H bonds was accomplished using most user-friendly sodium azide as the nitrogen-source. The operationally simple, resource-economic C-H azidation strategy was characterized by mild reaction conditions, no directing group, traceless electrons as the sole redox-reagent, Earth-abundant manganese as the catalyst, high functional-group compatibility and high chemoselectivity, setting the stage for late-stage azidation of bioactive compounds. Detailed mechanistic studies by experiment, spectrophotometry and cyclic voltammetry provided strong support for metal-catalyzed aliphatic radical formation, along with subsequent azidyl radical transfer within a manganese(iii/iv) manifold.

1-azaspiro[5.5]undecyl-3-one and 1-azaspiro[5.5]undecyl-3-alcohol compounds

The invention belongs to the technical field of medicines, and particularly relates to 1-azaspiro[5.5]undecyl-3-one and 1-azaspiro[5.5]undecyl-3-alcohol compounds and a preparation method and application thereof. The general formulas of the 1-azaspiro[5.5]undecyl-3-one compound and the 1-azaspiro[5.5]undecyl-3-alcohol compounds are shown in a formula I and a formula II in the specification. A six-membered spiro structure is synthesized for the first time, a brand-new compound with a better anti-tumor effect is obtained, and pharmacological research shows that the compound has certain inhibitory activity on human colon cancer HCT-116 cells. The preparation method of the 1-azaspiro[5.5]undecyl-3-one compound and the 1-azaspiro[5.5]undecyl-3-alcohol compound is simple and feasible, the yieldis relatively good, and the method is suitable for industrial production.

Design, synthesis and biological evaluation of homoerythrina alkaloid derivatives bearing a triazole moiety as PARP-1 inhibitors and as potential antitumor drugs

A series of homoerythrina alkaloid derivatives containing a 1,2,3-triazole moiety as PARP-1 inhibitors were designed and synthesized. And their anti-proliferative activity was further evaluated. Compound 10n had excellent activity to inhibit proliferation of A549 cells (IC50 = 1.89 μM), which was higher than harringtonine (IC50 = 10.55 μM), pemetrexed (IC50 = 3.39 μM), and rucaparib (IC50 = 4.91 μM). Furthermore, the selectivity index of compound 10n was higher than rucaparib and pemetrexed for lung cancer cells. Flow cytometry analysis showed that compound 10n significantly arrested the cell cycle in the S phase, then induced apoptosis of A549 cells (apoptosis rate is 46%), which effectively inhibited cell proliferation. Simultaneously, western blot analysis revealed that compound 10n could prevent the biosynthesis of PAR. Further analysis results revealed that compound 10n could inhibit the expression of cyclin A, down-regulate the expression of bcl-2/bax, activate caspase-3, and ultimately induce apoptosis of A549 cells. All the results indicated that compound 10n had potential research value as a novel PARP-1 inhibitor in antitumor, and it provided a new reference for further development of PARP-1 inhibitors.

Design, synthesis and biological evaluation of erythrina derivatives bearing a 1,2,3-triazole moiety as PARP-1 inhibitors

Inhibitors of poly (ADP-ribose) polymerase-1 (PARP-1) have shown to be promising in clinical trials against cancer, and many researchers are interested in the development of new PARP-1 inhibitors. Herein, we designed and synthesized 44 novel erythrina derivatives bearing a 1,2,3-triazole moiety as PARP-1 inhibitors. MTT assay results indicated that compound 10b had the most potent anti-proliferative activity against A549 cells among five cancer cells. The enzyme inhibitory activity in vitro of compound 10b was also significantly better than rucaparib. Furthermore, the selectivity index of compound 10b was higher than rucaparib for lung cancer cells. Flow cytometry analysis showed that compound 10b induced apoptosis of A549 cells by the mitochondrial pathway. Western blot analysis indicated that compound 10b was able to inhibit the biosynthesis of PAR effectively, and it was more potent than rucaparib. Also, compound 10b was able to up-regulate the ratio of bax/bcl-2, activate caspase-3, and ultimately induced apoptosis of A549 cells. The combined results revealed that the discovery of novel non-amide based PARP-1 inhibitors have great research significance and provide a better choice for the future development of drugs.

Manganese-Catalyzed Oxidative Azidation of C(sp3)-H Bonds under Electrophotocatalytic Conditions

The selective installation of azide groups into C(sp3)-H bonds is a priority research topic in organic synthesis, particularly in pharmaceutical discovery and late-stage diversification. Herein, we demonstrate a generalized manganese-catalyzed oxidative azidation methodology of C(sp3)-H bonds using nucleophilic NaN3 as an azide source under electrophotocatalytic conditions. This approach allows us to perform the reaction without the necessity of adding an excess of the substrate and successfully avoiding the use of stoichiometric chemical oxidants such as iodine(III) reagent or NFSI. A series of tertiary and secondary benzylic C(sp3)-H, aliphatic C(sp3)-H, and drug-molecule-based C(sp3)-H bonds in substrates are well tolerated under our protocol. The simultaneous gram-scale synthesis and the ease of transformation of azide to amine collectively advocate for the potential application in the preparative synthesis. Good reactivity of the tertiary benzylic C(sp3)-H bond and selectivity of the tertiary aliphatic C(sp3)-H bond in substrates to incorporate nitrogen-based functionality at the tertiary alkyl group also provide opportunities to manipulate numerous potential medicinal candidates. We anticipate our synthetic protocol, consisting of metal catalysis, electrochemistry, and photochemistry, would provide a new sustainable option to execute challenging organic synthetic transformations.

7-azaspiro[5.6]dodecane-10-ketone compound as well as preparation method and application thereof

The invention belongs to the field of medicine, and specifically relates to 7-azaspiro[5.6]dodecane-10-ketone compound as well as a preparation method and application thereof. According to the invention, a seven-membered ring structure is synthesized for the first time to obtain a novel compound with a better anti-tumor effect; reports of related structures have not been found; pharmacological studies show that the compound provided by the invention has certain inhibitory activity for human lung cancer A549 cells and human ovarian cancer OVCAR-3 cells, and provides a basis for subsequent preparation of anti-tumor drugs.

Syntheses and N-methyl-D-aspartate receptor antagonist pharmacology of fluorinated arylcycloheptylamines

Selective uncompetitive antagonists of the phencyclidine (PCP) binding site of the N-methyl-D-aspartate receptor (NMDAR) are known to have therapeutic potential as anticonvulsants and neuroprotective agents. Several fluorinated molecules with each containing a cycloheptane ring were designed to probe the PCP pharmacophore and test the influence of fluorine substitution on NMDAR binding and in vivo efficacy. Syntheses and analyses of six novel compounds, 1-(4-fluorophenyl)cycloheptanamine (3), 1-(1-(4-fluorophenyl)cycloheptyl)piperidine (4), 1-(1-(4-fluorophenyl)cycloheptyl) pyrrolidine (5), 1-(3-fluorophenyl)cycloheptanamine (6), 1-(1-(3-fluorophenyl)cycloheptyl)piperidine (7), 1-(1-(3-fluorophenyl)cycloheptyl)pyrrolidine (8) and several related reference arylcyloalkylamines are described. Receptor binding was performed at the PCP site of NMDAR for each compound using [3H]-(+)-MK-801 displacement. Unexpectedly, the 3-fluoro-primary amine 6 had the greatest affinity of the series and these binding results support a different structure activity relationship (SAR) profile for arylcycloheptylamines when compared to arylcyclohexylamines like PCP. Five of the novel compounds have affinity (Ki) in the hundred nM (10-7) range. In addition, compounds 3, 5, 6, 7 and 8 were evaluated and found to exhibit neuroprotective effects from NMDA induced toxicity in vitro and compounds 6, 7 and 8 exhibited anticonvulsant activities in rats. An ED50 of 13.84 mg/kg was found for compound 6 in rat maximal electroshock (MES) test with a protective index (PI) of 3.66 against ataxia. These results support further investigation of the arylcycloheptylamine class.

Structure-guided design and synthesis of P1′ position 1-phenylcycloalkylamine-derived pentapeptidic BACE1 inhibitors

Previously, we reported potent pentapeptidic BACE1 inhibitors with the hydroxymethylcarbonyl isostere as a substrate transition-state mimic. To improve the in vitro potency, we further reported pentapeptidic inhibitors with carboxylic acid bioisosteres at the P4 and P1′ positions. In the current study, we screened new P1′ position 1-phenylcycloalkylamine analogs to find non-acidic inhibitors that possess double-digit nanomolar range IC50 values. An extensive structure-activity relationship study was performed with various amine derivatives at the P1′ position. The most potent inhibitor of this pentapeptide series, KMI-1830, possessing 1-phenylcyclopentylamine at the P 1′ position had an IC50 value of 11.6 nM against BACE1 in vitro enzymatic assay.