85663-24-7

Upstream product

• 74-87-3 methylene chloride 
• 104887-11-8 trans-1-<3-(4-fluorophenyl)indan-1-yl>piperazine 
• 50737-52-5 ethyl 2-cyano-3-(4-fluorophenyl)acrylate 
• 111448-52-3 ethyl 2-cyano-3,3-bis(4-fluorophenyl)propionate 
• 80272-65-7 cis-6-fluoro-3-(4-fluorophenyl)indan-1-ol 
• 80272-24-8 3-(4'-fluorophenyl)-6-fluoro-1-indanone 
• 459-57-4 4-fluorobenzaldehyde 
• 342-75-6 3,3-bis(4-fluorophenyl)-propanoic acid 
• 104087-10-7 1-chloro-4-(4-flurophenyl)indan 
• 109-01-3 1-methyl-piperazine 
• 344755-05-1 1-chloro-3-(4-fluorophenyl)-6-fluoroindan 

Relevant academic research and scientific papers

Antihypertensive Activity in a Series of 1-Piperazino-3-phenylindans with Potent 5-HT2-Antagonistic Activity

A series of trans-1-piperazino-3-phenylindans were synthesized with the goal of replacing their established neuroleptic profile with that of peripheral 5-hydroxytryptamine (5-HT2) antagonism.Compounds with an unsubstituted or fluoro-substituted 6-position in the indan ring, and wich had a five- or six-membered heterocyclic ring attached by an ethylene chain to the piperazine ring, satisfied this objective.Some of the compounds had potent antihypertensive activity in conscious, spontaneously hypertensive rats (SHR).In pithed rats they antagonized the pressor effect induced by 5-HT in doses 100-1000 times lower than doses needed to antagonize the pressor effect of phenylephrine.The effect was stereoselective and associated with enatiomers with 1R,3S absolute configuration. 1S,3R enantiomers inhibited the uptake of dopamine and norepinephrine in vitro.The compound with the best antihypertensive activity was (+)-(1R,3S)-1-1-piperazinyl>-2-imidazolidinone (Lu 21-098, irindalone).Its pharmacological profile resembled that of the standard compound ketanserin.There was a close structural correspondence between ketanserin and irindalone in a conformation that we recently identified as a D-2 receptor-relevant configuration of its neuroleptic "parent" tefludazine.This suggests that the dopaminergic (D-2) and the serotonergic (5-HT2) pharmacophores are structurally closely related.

Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans

A series of 1-piperazino-3-phenylindans was synthesized and tested for neuroleptic and thymoleptic activity. Neuroleptic activity was found only in trans racemates and was associated with one of the enantiomers only. The potent and long-acting neuroleptic compound trans-4-[3-(4-fluorophenyl)-6-(trifluoromethyl)indan-1-yl]-1-piperazineeth anol (Lu 18-012, tefludazine) was developed by systematic variation of structural components. Thymoleptic activity was optimized, especially with respect to dopamine-uptake inhibition. No geometrical stereoselectivity was found with regard to dopamine-uptake inhibition, but a high enantioselectivity could be demonstrated for both cis and trans racemates. The most potent compounds were 1-piperazino-3-(3,4-dichlorophenyl)indans with IC50 values of about 2 nM for inhibition of dopamine uptake.