854892-34-5

Usage

InChI:InChI=1/C13H14Cl2O/c14-11-7-6-10(8-12(11)15)13(16)9-4-2-1-3-5-9/h6-9H,1-5H2

Upstream product

• 151169-75-4 3,4-dichlophenylboronic acid 
• 2719-27-9 cyclohexanylcarbonyl chloride 
• 1025918-21-1 Cyclohexyl-(3,4-dichloro-phenyl)-methanol 
• 6287-38-3 3,4-dichlorobenzaldehyde 
• 931-51-1 cyclohexylmagnesiumchloride 

Downstream Products

• 868396-39-8 3-cyclohexyl-3-(3,4-dichloro-phenyl)-3-hydroxy-1-piperidin-1-yl-propan-1-one 
• 847448-21-9 {[cyclohexyl-(3,4-dichloro-phenyl)-methyl]-formyl-amino}-acetic acid methyl ester 

Relevant academic research and scientific papers

Discovery of potent thiosemicarbazone inhibitors of rhodesain and cruzain

Herein we report the synthesis and evaluation of a series of thiosemicarbazones as potential inhibitors of cysteine proteases relevant to parasitic diseases. Derivatives of thiosemicarbazone 1 were discovered to be potent inhibitors of cruzain and rhodesain, crucial proteases in the life cycles of Trypanosoma cruzi and T. brucei rhodesiense, the organisms causing Chagas' disease and sleeping sickness. However, the entire series had only modest potency against falcipain-2, an essential protease for Plasmodium falciparum, the organism causing malaria. Among the active inhibitors, several potently inhibited proliferation of cultures of T. brucei. However, only modest activity was observed in inhibition of proliferation of T. cruzi or P. falciparum. Herein we report the synthesis and evaluation of a series of thiosemicarbazones as potential inhibitors of cysteine proteases relevant to parasitic diseases. Derivatives of thiosemicarbazone 1 were discovered to be potent inhibitors of cruzain and rhodesain, crucial proteases in the life cycles of Trypanosoma cruzi and T. brucei rhodesiense, the organisms causing Chagas' disease and sleeping sickness. However, the entire series had only modest potency against falcipain-2, an essential protease for Plasmodium falciparum, the organism causing malaria. Among the active inhibitors, several potently inhibited proliferation of cultures of T. brucei. However, only modest activity was observed in inhibition of proliferation of T. cruzi or P. falciparum.

Structure-activity relationship of trihexyphenidyl analogs with respect to the dopamine transporter in the on going search for a cocaine inhibitor

A series of trihexyphenidyl (THP) analogs were used to search for a derivative that could serve as a cocaine inhibitor. A compound that blocks binding of the cocaine analog carboxyfluorotropane (CFT), allows dopamine uptake and exhibits low side effects could serve as a good candidate for that purpose. All analogs were tested for the extent to which they inhibit CFT binding, dopamine uptake and n-methyl scopolamine (NMS) binding. Several structure-function relationships emerged. Methylation/halogenation of THP's benzene ring enhanced the compound's ability to block CFT binding in comparison to its ability to block dopamine uptake (5a-e). Replacement of the cyclohexyl ring with a benzene ring tended to create compounds that had lower affinities to the dopamine transporter (7b compared to THP, 7d compared to 5h, 7c compared to 8c) and modification of THP's piperidine ring tended to enhance affinity to the dopamine transporter (5f-h, 8a, 8c). One analog (5f) that showed little muscarinic activity indicating that it would probably have few side effects was investigated for its effects as an in vivo cocaine inhibitor. However, it showed few antagonistic effects in vivo. Nevertheless, this work greatly elucidates the structure-function relationships required for potential cocaine inhibitors and so lays out promising directions for future research.