84359-49-9

Upstream product

• 110-85-0 piperazine 
• 7525-23-7 4,4'-dimethoxydiphenylmethyl chloride 
• 123-11-5 4-methoxy-benzaldehyde 
• 100-66-3 methoxybenzene 
• 90-96-0 bis(p-methoxyphenyl)methanone 
• 728-87-0 4,4'-Dimethoxybenzhydrol 
• 154544-62-4 ethyl <4-(bis (4-methoxyphenyl) methyl)-1-piperazinyl> carboxylate 

Downstream Products

• 1360705-94-7 C₂₄H₂₆N₄O₆ 
• 661453-37-8 C₃₄H₃₆N₂O₃ 

Relevant academic research and scientific papers

Sequential Selective C?H and C(sp3)?+P Bond Functionalizations: An Entry to Bioactive Arylated Scaffolds

Organophosphonium salts containing C(sp3)?+P bonds are among the most utilized reagents in organic synthesis for constructing C?C double bonds. However, their use as C-selective electrophilic groups is rare. Here, we explore an efficient and general transition-metal-free method for sequential chemo- and regioselective C?H and C(sp3)?+P bond functionalizations. In the present study, C?H alkylation resulting in the synthesis of benzhydryl triarylphosphonium salts was achieved by one-pot, four-component cross-coupling reactions of simple and commercially available starting materials. The utility of the resulting phosphonium salt building blocks was demonstrated by the chemoselective post-functionalization of benzylic C(sp3)?+PPh3 groups to achieve aminations, thiolations, and arylations. In this way, benzhydrylamines, benzhydrylthioethers, and triarylmethanes, structural motifs that are present in many pharmaceuticals and agrochemicals, are readily accessed. These include the synthesis of two anticancer agents from simple materials in only two to three steps. Additionally, a protocol for late-stage functionalization of bioactive drugs has been developed using benzhydrylphosphonium salts. This new approach should provide novel transformations for application in both academic and pharmaceutical research.

Synthesis and biological evaluation of aryloxyacetamide derivatives as neuroprotective agents

A series of new aryloxyacetamide derivatives 10a-s and 14a-m are designed and synthesized. Their protective activities against the glutamate-induced cell death were investigated in differentiated rat pheochromocytoma cells (PC12 cells). Most compounds exhibited neuroprotective effects, especially for 10m, 10r, 14b and 14c, which showed potential protection of PC12 cells at three doses (0.1, 1.0, 10 μM). MTT assay, Hoechst 33342/PI double staining, and high content screening (HCS) revealed that pretreatment of the cells with 10m, 10r, 14b and 14c has significantly decreased the extent of cell apoptosis in a dose-dependent manner. The results of western blot analysis demonstrated these compounds suppressed apoptosis of glutamate-induced PC12 cells via caspase-3 pathway. These compounds can be lead compounds for further discovery of neuroprotective agents for treating cerebral ischemic stroke. Basic structure-activity relationships are also presented.

Synthesis, crystal structure and anti-ischaemic activity of (E)-1-{4-[Bis(4-methoxy-phenyl)methyl]piperazin-1-yl}-3-(4-chlorophenyl)-prop-2-en-1-one

The title compound (E)-1-{4-[bis(4-methoxyphenyl)methyl]piperazin-1-yl}-3-(4-chloro- phenyl)prop-2-en-1-one (C28H29ClN2O3, Mr = 476.98) (5) was synthesized and studied by the single crystal X-ray diffraction method. Its structure was confirmed by 1HNMR, 13CNMR, HRMSand X-ray single crystal structure determination. Compound 5 crystallized in the monoclinic system, space group P21/c with a = 10.392(2), b = 7.9180(16), c = 30.474(6) ??, ?2; =97.78(3) ?° , V = 2484.4(9)??3,Z=4, Dc = 1.275 g cm-3, F(000)= 1008, ??= 0.186mm-1, MoK?±; radiation (?? =0.71073 ??), R = 0.0692 and wR = 0.1469 for 2046 observed reflections with I 2??(I). The title compound was screened for the anti-ischaemic activity in vivo. The results showed that compound 5 significantly prolonged the survival time of mice subjected to acute cerebral ischaemia at all doses tested and exhibited potent neuroprotective activity.

Development of small-molecule probes that selectively kill cells induced to express mutant RAS

Synthetic lethal screening is a chemical biology approach to identify small molecules that selectively kill oncogene-expressing cell lines with the goal of identifying pathways that provide specific targets against cancer cells. We performed a high-throughput screen of 303,282 compounds from the National Institutes of Health-Molecular Libraries Small Molecule Repository (NIH-MLSMR) against immortalized BJ fibroblasts expressing HRASG12V followed by a counterscreen of lethal compounds in a series of isogenic cells lacking the HRASG12V oncogene. This effort led to the identification of two novel molecular probes (PubChem CID 3689413, ML162 and CID 49766530, ML210) with nanomolar potencies and 4-23-fold selectivities, which can potentially be used for identifying oncogene-specific pathways and targets in cancer cells.

Structure-activity relationships of diphenylpiperazine N-type calcium channel inhibitors

A novel series of compounds derived from the previously reported N-type calcium channel blocker NP118809 (1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one) is described. Extensive SAR studies resulted in compounds with IC50 values in the range of 10-150 nM and selectivity over the L-type channels up to nearly 1200-fold. Orally administered compounds 5 and 21 exhibited both anti-allodynic and anti-hyperalgesic activity in the spinal nerve ligation model of neuropathic pain.

Amino acid derivative having anti-CCK activity

A compound represented by the formula (1): STR1 wherein, m is an integer of 1 to 3; n is an integer 0 or 1; A represents CH or N atom, and forms together with the N atom bonded to the carbonyl group a piperidine ring or a piperazine ring; R1 independently represents a straight or branched chain alkyl group having 1 to 4 carbon atoms; a cycloalkyl group having 3 to 8 carbon atoms; a phenyl group, unsubstituted or substituted with a halogen atom or with an alkoxy group having 1 to 4 carbon atoms; or a pyridyl group; or two R1, together with the group >CH-- to which they bind, form a dibenzo cycloheptenyl group or a fluorenyl group; R2 represents a phenyl group substituted with a carboxyl or substituted carboxyl group; a pyridyl group substituted with a carboxyl or substituted carboxyl group, a pyrazyl group substituted with a carboxyl or substituted carboxyl group, an oxazolyl substituted with a carboxyl or substituted carboxyl group, a triazolyl substituted with one or two carboxyl or substituted carboxyl groups, or a phosphonopyridyl group; and R3 represents an indolyl group unsubstituted or substituted with a substituent selected from the group consisting of a halogen atom, a hydroxy group, an alkoxy group having 1 to 4 carbon atoms and methoxycarbonyl ethyl group and the pharmaceutically acceptable salts thereof.

Structure-activity relationship of newly synthesized quinoline derivatives for reversal of multidrug resistance in cancer

The effect of 24 newly synthesized quinoline derivatives on tumor cell multidrug resistance (MDR) was examined in vitro. At low concentrations, these compounds enhanced the accumulation of [3H]vincristine in K562/ADM cells and reversed tumor cell MDR. The results of the structure-activity relationship analysis indicate that in highly active compounds the two aryl rings in the hydrophobic moiety deviate from a common plane, so they are capable of interacting with hydrogen bond donors of P-170 glycoprotein (P- gp) via π-hydrogen-π interactions. Other major structural features which influence the MDR-reversing activities of these compounds are a quinoline nitrogen atom and a basic nitrogen atom in piperazine. Furthermore, in highly active compounds, the distance between the hydrophobic moiety and the basic nitrogen atom (an atom connected to 2-hydroxypropoxyquinoline) must be at least 5 A?. Several compounds were found to reverse vincristine resistance in K562/ADM cells in vitro, and compound 16 (MS-209) was selected for clinical studies.

Synthesis and pharmacological study of new calcium antagonists analogues of cinnarizine and flunarizine

Several phosphonic diethyl esters were synthesized and their calcium antagonistic activity evaluated in vitro.The diethyl phosphonate group was condensed on substituted , , , , and groups.Despite the presence of the diethyl phosphonate moiety and the benzhydrylpiperazinyl group, both present in potent calcium antagonist structures, only 1 of the 19 synthesis compounds exhibited a calcium antagonistic profile. diethyl phosphonate / benzhydryl piperazine / calcium antagonist