1352050-79-3

Upstream product

• 110-85-0 piperazine 
• 105919-36-6 trans-4-(trifluoromethyl)cinnamoyl chloride 
• 120681-07-4 3-(4-trifluoromethyl-phenyl)-acryloyl chloride 
• 16642-92-5 4-(trifluoromethyl)cinnamic acid 
• 455-19-6 4-Trifluoromethylbenzaldehyde 

Downstream Products

• 1352051-00-3 (E)-3-(4-fluorophenyl)-1-(4-((E)-3-[4-(trifluoromethyl)phenyl]-2-propenoyl)piperazino)-2-propen-1-one 
• 1352051-01-4 (E)-3-(4-chlorophenyl)-1-(4-((E)-3-[4-(trifluoromethyl)phenyl]-2-propenoyl)piperazino)-2-propen-1-one 
• 1352051-02-5 (E)-3-(4-bromophenyl)-1-(4-((E)-3-[4-(trifluoromethyl)phenyl]-2-propenoyl)piperazino)-2-propen-1-one 
• 1352050-98-6 (E)-3-[4-(trifluoromethyl)phenyl]-1-(4-((E)-3-[4-(trifluoromethyl)phenyl]-2-propenoyl)piperazino)-2-propen-1-one 
• 1352051-04-7 (E)-3-(3,4-dichlorophenyl)-1-(4-((E)-3-[4-(trifluoromethyl)phenyl]-2-propenoyl)piperazino)-2-propen-1-one 
• 1352051-05-8 (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-((E)-3-[4-(trifluoromethyl)phenyl]-2-propenoyl)piperazino)-2-propen-1-one 
• 1352050-99-7 (E)-3-[3-(trifluoromethoxy)phenyl]-1-(4-((E)-3-[4-(trifluoromethyl)phenyl]-2-propenoyl)piperazino)-2-propen-1-one 
• 1352051-03-6 (E)-3-(3,4-difluorophenyl)-1-(4-((E)-3-[4-(trifluoromethyl)phenyl]-2-propenoyl)piperazino)-2-propen-1-one 

Relevant academic research and scientific papers

Synthesis and discovery of 18β-glycyrrhetinic acid derivatives inhibiting cancer stem cell properties in ovarian cancer cells

Despite advances in ovarian cancer treatment, the five-year overall survival rate is less than 30% with the presence of cancer stem cells (CSCs). To develop CSC-targeting therapy, a series of 18β-glycyrrhetinic acid (GA) derivatives containing cinnamamide moiety have been designed, synthesized, and screened for their antiproliferative activity in SKOV3 and OVCAR3 cells. Most of the compounds exhibited stronger antiproliferative activity than GA, and compound 7c was the most active one. Further biological studies showed that compound 7c could induce apoptosis and suppress migration. In addition, compound 7c could not only observably decrease the colony formation and sphere formation ability, but also significantly reduce the CD44+, CD133+, and ALDH+ subpopulation in SKOV3 and OVCAR3 cells. In conclusion, these results indicate that compound 7c is a promising anti-CSC agent for further anti-ovarian cancer studies.

Synthesis and biological evaluation of celastrol derivatives as anti-ovarian cancer stem cell agents

Ovarian cancer is associated with a high percentage of recurrence of tumors and resistance to chemotherapy. Cancer stem cells (CSCs) are responsible for cancer progression, tumor recurrence, metastasis, and chemoresistance. Thus, developing CSC-targeting therapy is an urgent need in cancer research and clinical application. In an attempt to achieve potent and selective anti-CSC agents, a series of celastrol derivatives with cinnamamide chains were synthesized and evaluated for their anti-ovarian cancer activities. Most of the compounds exhibited stronger antiproliferative activity than celastrol, and celastrol derivative 7g with a 3,4,5-trimethoxycinnamamide side chain was found to be the most potent antiproliferative agent against ovarian cancer cells with an IC50 value of 0.6 μM. Additionally, compound 7g significantly inhibited the colony formation ability and reduced the number of tumor spheres. Furthermore, compound 7g decreased the percentage of CD44+, CD133+ and ALDH+ cells. Thus, compound 7g is a promising anti-CSC agent and could serve as a candidate for the development of new anti-ovarian cancer drugs.

Synthesis, preliminarily biological evaluation and molecular docking study of new Olaparib analogues as multifunctional PARP-1 and cholinesterase inhibitors

A series of new Olaparib derivatives was designed and synthesized, and their inhibitory activities against poly (ADP-ribose) polymerases-1 (PARP-1) enzyme and cancer cell line MDA-MB-436 in vitro were evaluated. The results showed that compound 5l exhibited the most potent inhibitory effects on PARP-1 enzyme (16.10 ± 1.25 nM) and MDA-MB-436 cancer cell (11.62 ± 2.15 μM), which was close to that of Olaparib. As a PARP-1 inhibitor had been reported to be viable to neuroprotection, in order to search for new multitarget-directed ligands (MTDLs) for the treatment of Alzheimer’s disease (AD), the inhibitory activities of the synthesized compounds against the enzymes AChE (from electric eel) and BChE (from equine serum) were also tested. Compound 5l displayed moderate BChE inhibitory activity (9.16 ± 0.91 μM) which was stronger than neostigmine (12.01 ± 0.45 μM) and exhibited selectivity for BChE over AChE to some degree. Molecular docking studies indicated that 5l could bind simultaneously to the catalytic active of PARP-1, but it could not interact well with huBChE. For pursuit of PARP-1 and BChE dual-targeted inhibitors against AD, small and flexible non-polar groups introduced to the compound seemed to be conducive to improving its inhibitory potency on huBChE, while keeping phthalazine-1-one moiety unchanged which was mainly responsible for PARP-1 inhibitory activity. Our research gave a clue to search for new agents based on AChE and PARP-1 dual-inhibited activities to treat Alzheimer’s disease.

Pyridazinone derivative, and preparation method and medical application thereof

The invention provides a pyridazinone derivative, and a preparation method and a medical application thereof. O-formylbenzoic acid used as a raw material reacts with dimethyl phosphite to obtain dimethyl (3-oxo-1,3-dihydroisobenzofuran-1-yl)phosphonate, the dimethyl (3-oxo-1,3-dihydroisobenzofuran-1-yl)phosphonate reacts with 3-cyano-4-fluorobenzaldehyde in the presence of triethylamine to prepare (Z,E)-2-fluoro-5-[(3-oxoisobenzofuran-1(3H)-ylidene)methyl]benzonitrile, and the (Z,E)-2-fluoro-5-[(3-oxoisobenzofuran-1(3H)-ylidene)methyl]benzonitrile is reduced by hydrazine hydrate to prepare 2-fluoro-5-[(4-oxo-3,4-dihydropyridazin-1-yl)methyl]benzoic acid; and benzaldehyde or substituted aromatic formaldehyde or furfural used as a raw material and malonic acid undergo a Knoevenagel reaction to obtain cinnamic acid or substituted cinnamic acid or furan-2-acrylic acid, the cinnamic acid or substituted cinnamic acid or furan-2-acrylic acid and 1-tert-butoxycarbonylpiperazine undergo an amidation reaction, a tert-butoxycarbonyl group is removed from the obtained amidation product in the presence of trifluoroacetic acid, and the obtained product and the 2-fluoro-5-[(4-oxo-3,4-dihydropyridazin-1-yl)methyl]benzoic acid undergo the amidation reaction to obtain a series of (E)-4-{3-[4-[(3-substituted aryl)acryloyl]piperazin-1-carbonyl]-4-fluorobenzyl}-2H-pyridazin-1-one derivatives. Results of preliminary pharmacological activity screening show that the compound represented by a general formula shown in the present invention has a certain in-vitro PARP-1 inhibition ability and a certain in-vitro tumor cell proliferation resisting activity. The structural general formula of compound is shown in the description; and in the general formula, Ar is selected from two formulas also shown in the description, and R1, R2, R3, R3, R4 and R5 can be the hydrogen atom, the fluorine atom, the chlorine atom, the bromine atom, a methyl group, a methoxy group, a tetrafluoromethyl group and a nitro group.

Synthesis of cinnamide dimers as potential antibacterial and antifungal agents

A series of new cinnamide dimers was synthesized (5a-6a) and evaluated for th e i r antimicrobial and antifungal activity. All the compounds investigated have shown significant antimicrobial a c t iv i ty against gram-positive and gram-negative bacterial