A series of new 1,2,4-benzothiadiazine derivatives with an arylpiperazine mojety linked at position 3 of the heterocyclic ring were synthesized and assessed for their pharmacological profiles at alpha(1)-adrenoceptor subtypes (alpha(1A), alpha(1B) and alpha(1D)) by functional experiments and by in vitro binding studies at human cloned 5-HT1A receptor. Compound I was identified as a novel (alpha(1D) antagonist (pK(b)alpha(1D) = 7.59; alpha(1D)/alpha(1A) > 389; alpha(1D)/alpha(1B) = 135) with high selectivity over 5-HT1A receptor (5-HT1A/alpha(1D) < 0.01), while compound 6, a 3,4-dihydro-derivative, was characterized as a novel 5-HT1A receptor ligand, highly selective over alpha(1D)-adrenoceptor subtype (pK(i)5-HT1A = 8.04; 5-HT1A/alpha(1D) = 1096). Further pharmacological studies demonstrated that 6 is a partial agonist at 5-HT1A receptor (E-max = 23, pD(2) = 6.92).

1,2,4-Benzothiadiazine derivatives as alpha(1) and 5-HT1A receptor ligands / Tait, Annalisa; Luppi, Amedeo; Franchini, Silvia; E., Preziosi; Parenti, Carlo; M., Buccioni; G., Marucci; A., Leonardi; E., Poggesi; Brasili, Livio. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - STAMPA. - 15:(2005), pp. 1185-1188.

1,2,4-Benzothiadiazine derivatives as alpha(1) and 5-HT1A receptor ligands

TAIT, Annalisa;LUPPI, Amedeo;FRANCHINI, Silvia;PARENTI, Carlo;BRASILI, Livio
2005

Abstract

A series of new 1,2,4-benzothiadiazine derivatives with an arylpiperazine mojety linked at position 3 of the heterocyclic ring were synthesized and assessed for their pharmacological profiles at alpha(1)-adrenoceptor subtypes (alpha(1A), alpha(1B) and alpha(1D)) by functional experiments and by in vitro binding studies at human cloned 5-HT1A receptor. Compound I was identified as a novel (alpha(1D) antagonist (pK(b)alpha(1D) = 7.59; alpha(1D)/alpha(1A) > 389; alpha(1D)/alpha(1B) = 135) with high selectivity over 5-HT1A receptor (5-HT1A/alpha(1D) < 0.01), while compound 6, a 3,4-dihydro-derivative, was characterized as a novel 5-HT1A receptor ligand, highly selective over alpha(1D)-adrenoceptor subtype (pK(i)5-HT1A = 8.04; 5-HT1A/alpha(1D) = 1096). Further pharmacological studies demonstrated that 6 is a partial agonist at 5-HT1A receptor (E-max = 23, pD(2) = 6.92).
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1,2,4-Benzothiadiazine derivatives as alpha(1) and 5-HT1A receptor ligands / Tait, Annalisa; Luppi, Amedeo; Franchini, Silvia; E., Preziosi; Parenti, Carlo; M., Buccioni; G., Marucci; A., Leonardi; E., Poggesi; Brasili, Livio. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - STAMPA. - 15:(2005), pp. 1185-1188.
Tait, Annalisa; Luppi, Amedeo; Franchini, Silvia; E., Preziosi; Parenti, Carlo; M., Buccioni; G., Marucci; A., Leonardi; E., Poggesi; Brasili, Livio
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/305855
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