Wyniki wyszukiwania - BazTech

Ograniczanie wyników

Powiadomienia systemowe

Sesja wygasła!

Znaleziono wyników: 2

Liczba wyników na stronie

Wyniki wyszukiwania

Sortuj według:

Ogranicz wyniki do:

Synthesis, Pharmacological Properties and SAR of New 1,4-Disubstituted Pierazine Derivatives with Hypnotic-Sedative Activity

Chilmonczyk Z., Mazgajska M., Chojnacka-Wójcik E., Tatarczyńska E., Kłodzińska A., Ulman M.

Polish Journal of Chemistry

2004

Vol. 78 / nr 8

1027-1037

Synthesis, chromatographic behaviour, pharmacological data and structure activity relationship (SAR) studies of some 1-(pyrimidin-2-yl)piperazine derivatives 1-13 are reported. The hydrophobic indices and chromatographic retention factors of the compounds exhibited statistically significant linear correlation with the calculated lipophilicities. The highest hypnotic-sedative activity as measured in loss of the righting reflex, rota-rod and spontaneous locomotor activity tests exhibited compound6 possessing n-hexyl R substituent. The hypnotic activity of compounds 1-13 measured in loss of the righting reflex test could be described with the aid of hydrophobic indices in terms of Hansch parabolic relationship for structurally related group of compounds (separately for compounds withR= alkyl orR= cycloalkyl). The necessity to describe the pharmacological activity for aliphatic and alicyclic series with 2 different equations corresponded well to the observed difference in the pharmacological properties between the both

Arilopiperazynowe ligandy receptorów serotoninowych (5-HT)1A/5-HT2A

Chojnacka-Wójcik E.

Wiadomości Chemiczne

2001

[Z] 55, 7-8

751--761

Recently some interest has focused on compounds which - through interaction with both 5-HT1A and 5-HT2A receptors - may act as potential psychotropic agents. Compounds with a dual activity at these receptor systems have been predicted to be more efficacious than those acting at only one of these systems. Some such compounds are arylpiperazine derivatives. This is the case with flibanserin and adatanserin, regarded as 5-HT1A agonists and 5-HT2A antagonists, which show an robust activity in a number of animal models of anxiety and depression; at present they are studied in the clinic as potential anxiolytics/antidepressants. Another arylopiperazine, ziprazidon, binds with a high affinity to 5-HT1A, 5-HT2A and D2 receptors; being an antagonist at the latter receptors, it behaves like a 5-HT1A agonist. Ziprasidon is a novel antipsychotic drug. In our own studies, a number of new arylpiperazines with high 5-HT1A / 5-HT2A and D2 affinity were obtained. In fact, 1-{3-[4-(3-chlorophenyl)-1-piperazinyl]propyl}-6-fluoroindolin-2(1H)-one (1) and 1-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl}-6-fluoroindolin-2(1H)-one (2) demonstrated a high 5-HT1A / 5-HT2A affinity and an in vivo antagonistic activity towards both the receptor subtypes, a phenomenon which is probably connected with the presence of a tree-membered spacer beetween terminal molecule fragments. Also 1-{3-[4-(3-chlorophenyl)-1-piperazynyl]propyl}-2,4-benzoxazin-3(4H)-one (3) showed the same pharmacolo-gical profile of action. It has been suggested that the oxygen atom in position 2 in the amide fragment, as well as the 3-[4-(3-chlorophenyl)-1-piperazinyl]propyl fragment are a prerequisite for its pharmacological properties. The new 1-(3-chlorophenyl) piperazine derivative of 1,3-benzoxazolin-2,4-dione with n-butyl chain may be qualified as a 5-HT1A partial agonist and 5-HT2A antagonist; its 5-HT1A functional activity is likely to be connected with the character of the amide fragment, whereas the 1-arylphenyl fragment is important to the binding to both receptors. The connection of the 1,2,3,4-tetrahydro-b-carbolin-1-one moiety - through the 2-4 membered alkyl spacer - with 1-(2-methoxyphenyl)-piperazine permitted us to obtain compounds (5-7) with a high and an equal affinity for 5-HT1A / 5-HT2A receptors and with the expected functional properties, i.e. a distinct antagonistic activity at 5-HT1A receptors and an antagonistic one at 5-HT2A ones. These findings corroborate hypothesis that the presence of the 1-arylpiperazine fragment is crucial to the 5-HT1A / 5-HT2A affinity. It has also been shown that 3-chloro and 2-methoxy derivatives of 1-[4-(4-aryl-1-piperazinyl]-3,4-dihydro-2(1H)quinolinones are potent antagonists of 5-HT1A / 5-HT2A/D2 receptors and resemble some atypical antipsychotics. Summing up, some of the new investigated arylpiperazines may be considered as novel agents with psychotropic (i.e. anxiolytic/andidepressant/antipsychotic) properties.