1000051-65-9

Upstream product

• 777-37-7 4-chloro-3-(trifluoromethyl)nitrobenzene 
• 73874-95-0 (piperidin-4-yl)carbamic acid tert-butyl ester 
• 400-74-8 2-Fluoro-5-nitrobenzotrifluoride 

Downstream Products

• 1291141-92-8 1-benzo[b]thiophen-3-yl-3-[-1-(4-nitro-2-trifluoromethylphenyl)piperidin-4-ylamino]propan-1-one 
• 1179605-04-9 1-[4-nitro-2-(trifluoromethyl)phenyl]piperidin-4-amine 
• 1291057-82-3 1-benzo[b]thiophen-3-yl-3-[1-(4-nitro-2-trifluoromethylphenyl)piperdin-4-ylamino]propan-1-one hydrochloride 
• 1000053-80-4 tert-butyl N-{1-[4-amino-2-(trifluoromethyl)phenyl]piperidin-4-yl}carbamate 

Relevant academic research and scientific papers

Design, synthesis, and anticancer properties of isocorydine derivatives

Isocorydine (ICD), an aporphine alkaloid, is widely distributed in nature. Its ability to target side population (SP) cells found in human hepatocellular carcinoma (HCC) makes it and its derivative 8-amino-isocorydine (NICD) promising chemotherapeutic agents for the treatment of HCC. To improve the anticancer activity of isocorydine derivatives, twenty derivatives of NICD were designed and synthesized through chemical structure modifications of the aromatic amino group at C-8. The anti-proliferative activities of all synthesized compounds against human hepatocellular (HepG2), cervical (HeLa), and gastric (MGC-803) cancer cell lines were evaluated using an MTT assay. The results showed that all the synthetic compounds had some tumor cell growth inhibitory activity. The compound COM33 (24) was the most active with IC50 values under 10 μM (IC50 for HepG2 = 7.51 μM; IC50 for HeLa = 6.32 μM). FICD (12) and COM33 (24) were selected for further investigation of their in vitro and in vivo activities due to their relatively good antiproliferative properties. These two compounds significantly downregulated the expression of four key proteins (C-Myc, β-Catenin, CylinD1, and Ki67) in HepG2 cells. The tumor inhibition rate of COM33 (24) in vivo was 73.8% after a dose 100 mg/kg via intraperitoneal injection and the combined inhibition rate of COM33 (24) (50 mg/kg) with sorafenib (50 mg/kg) was 66.5%. The results indicated that these isocorydine derivatives could potentially be used as targeted chemotherapy agents or could be further developed in combination with conventional chemotherapy drugs to target cancer stem cells (CSCs) and epithelial-to-mesenchymal transition (EMT), the main therapeutic targets in HCC.

Alsinol, an arylamino alcohol derivative active against Plasmodium, Babesia, Trypanosoma, and Leishmania: past and new outcomes

Malaria, babesiosis, trypanosomosis, and leishmaniasis are some of the most life-threatening parasites, but the range of drugs to treat them is limited. An effective, safe, and low-cost drug with a large activity spectrum is urgently needed. For this purpose, an aryl amino alcohol derivative called Alsinol was resynthesized, screened in silico, and tested against Plasmodium, Babesia, Trypanosoma, and Leishmania. In silico Alsinol follows the Lipinski and Ghose rules. In vitro it had schizontocidal activity against Plasmodium falciparum and was able to inhibit gametocytogenesis; it was particularly active against late gametocytes. In malaria-infected mice, it showed a dose-dependent activity similar to chloroquine. It demonstrated a similar level of activity to reference compounds against Babesia divergens, and against promastigotes, and amastigotes stages of Leishmania in vitro. It inhibited the in vitro growth of two African animal strains of Trypanosoma but was ineffective in vivo in our experimental conditions. It showed moderate toxicity in J774A1 and Vero cell models. The study demonstrated that Alsinol has a large spectrum of activity and is potentially affordable to produce. Nevertheless, challenges remain in the process of scaling up synthesis, creating a suitable clinical formulation, and determining the safety margin in preclinical models.

Structure-activity relationship of new antimalarial 1-aryl-3-susbtituted propanol derivatives: Synthesis, preliminary toxicity profiling, parasite life cycle stage studies, target exploration, and targeted delivery

Design, synthesis, structure-activity relationship, cytotoxicity studies, in silico drug-likeness, genotoxicity screening, and in vivo studies of new 1-aryl-3-substituted propanol derivatives led to the identification of nine compounds with promising in vitro (55, 56, 61, 64, 66, and 70–73) and in vivo (66 and 72) antimalarial profiles against Plasmodium falciparum and Plasmodium berghei. Compounds 55, 56, 61, 64, 66 and 70–73 exhibited potent antiplasmodial activity against chloroquine-resistant strain FCR-3 (IC50s 50s 0.7 μM for 3D7, D6, FCR-3 and C235). All of these compounds share appropriate drug-likeness profiles and adequate selectivity indexes (77 SI 184) as well as lack genotoxicity. In vivo efficacy tests in a mouse model showed compounds 66 and 72 to be promising candidates as they exhibited significant parasitemia reductions of 96.4% and 80.4%, respectively. Additional studies such as liver stage and sporogony inhibition, target exploration of heat shock protein 90 of P. falciparum, targeted delivery by immunoliposomes, and enantiomer characterization were performed and strongly reinforce the hypothesis of 1-aryl-3-substituted propanol derivatives as promising antimalarial compounds.

Isocorydine derivative, preparation method and applications thereof

The present invention discloses a chemical structure derivative of isocorydine (represented by a formula I), wherein the amino of NICD and the carbonyl of aryl isocyanate, carboxylic acid and acyl chloride are subjected to an amidation condensation reaction or NICD and aromatic amino are subjected to a symmetric amidation condensation reaction through solid phosgene to obtain the chemical structure derivative, wherein the compound has a certain in vitro and in vivo anticancer activity, and can be used as cancer prevention and treatment drug. The formula I is defined in the specification.

Novel FLT3 kinase inhibitor and application thereof

The invention provides a novel FLT3 kinase inhibitor. The novel FLT3 kinase inhibitor comprises a compound shown in the formula (I) or pharmacy acceptable salt or solvate or isomer or ester or acid or metabolin or prodrug. The invention also provides a pharmaceutical composition of the compound shown in the formula (I) and an application and method of the pharmaceutical composition for preventing or treating cell proliferation disease and/or FLT3 and c-Kit related disease and disease responding to FLT3 kinase ( particularly, responding to FLT3/ITD mutant kinase) inhibition.

Discovery of N-((1-(4-(3-(3-((6,7-Dimethoxyquinolin-3-yl)oxy)phenyl)ureido)-2-(trifluoromethyl)phenyl)piperidin-4-yl)methyl)propionamide (CHMFL-KIT-8140) as a Highly Potent Type II Inhibitor Capable of Inhibiting the T670I gatekeeper Mutant of cKIT Kinase

cKIT kinase inhibitors, e.g., imatinib, could induce drug-acquired mutations such as cKIT T670I that rendered drug resistance after chronic treatment. Through a type II kinase inhibitor design approach we discovered a highly potent type II cKIT kinase inhibitor compound 35 (CHMFL-KIT-8140), which potently inhibited both cKIT wt (IC50 = 33 nM) and cKIT gatekeeper T670I mutant (IC50 = 99 nM). Compound 35 displayed strong antiproliferative effect against GISTs cancer cell lines GIST-T1 (cKIT wt, GI50 = 4 nM) and GIST-5R (cKIT T670I, GI50 = 26 nM). In the cellular context it strongly inhibited c-KIT mediated signaling pathways and induced apoptosis. In the BaF3-TEL-cKIT-T670I isogenic cell inoculated xenograft mouse model, 35 exhibited dose dependent tumor growth suppression efficacy and 100 mg/kg dosage provided 47.7% tumor growth inhibition (TGI) without obvious toxicity. We believe compound 35 would be a good pharmacological tool for exploration of the cKIT-T670I mutant mediated pathology in GISTs.

Novel benzo[ b ]thiophene derivatives as new potential antidepressants with rapid onset of action

We report benzo[b]thiophene derivatives synthesized according to a dual strategy. 8j, 9c, and 9e with affinity values toward 5-HT7R and 5-HTT were selected to probe their antidepressant activity in vivo using the forced swimming text (FST). The results showed significant antidepressant activity after chronic treatment. 9c was effective in reducing the immobility time in FST even after acute treatment. These findings identify these compounds as a new class of antidepressants with a rapid onset of action.

N-(3,4-disubstituted phenyl) salicylamide derivatives

A compound represented by the following formula (I) or a salt thereof: wherein R1, R2, R3 and R4 represent hydrogen atom, a halogen atom, cyano group, nitro group, a C1-4 alkyl group, a halogenated C