A class of rigid, dibasic, non-imidazole H3 antagonists was developed, starting from a series of previously described flexible compounds. The original polymethylene chain between two tertiary amine groups was replaced by a rigid scaffold, composed by a phenyl ring or a biphenyl fragment. Modulation of the distance between the two amine groups, and of their alkyl substituents, was driven by superposition of molecular models and docking into a receptor model, resulting in the identification of 1,10-[biphenyl-4,40- diylbis(methylene)]bis-piperidine (5) as a subtype-selective H3 antagonist with high binding affinity (pKi = 9.47) at human H3 histamine receptor.

Dibasic non-imidazole histamine H3 receptor antagonists with a rigid byphenyl scaffold / Morini, Giovanni; Comini, Mara; Rivara, Mirko; Rivara, Silvia; Lorenzi, Simone; Bordi, Fabrizio; Mor, Marco; Flammini, Lisa; Bertoni, Simona; Ballabeni, Vigilio; Barocelli, Elisabetta; Plazzi, Pier Vincenzo. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 16:(2006), pp. 4063-4067. [10.1016/j.bmcl.2006.04.092]

Dibasic non-imidazole histamine H3 receptor antagonists with a rigid byphenyl scaffold.

MORINI, Giovanni;COMINI, Mara;RIVARA, Mirko;RIVARA, Silvia;LORENZI, Simone;BORDI, Fabrizio;MOR, Marco;FLAMMINI, Lisa;BERTONI, Simona;BALLABENI, Vigilio;BAROCELLI, Elisabetta;PLAZZI, Pier Vincenzo
2006-01-01

Abstract

A class of rigid, dibasic, non-imidazole H3 antagonists was developed, starting from a series of previously described flexible compounds. The original polymethylene chain between two tertiary amine groups was replaced by a rigid scaffold, composed by a phenyl ring or a biphenyl fragment. Modulation of the distance between the two amine groups, and of their alkyl substituents, was driven by superposition of molecular models and docking into a receptor model, resulting in the identification of 1,10-[biphenyl-4,40- diylbis(methylene)]bis-piperidine (5) as a subtype-selective H3 antagonist with high binding affinity (pKi = 9.47) at human H3 histamine receptor.
2006
Dibasic non-imidazole histamine H3 receptor antagonists with a rigid byphenyl scaffold / Morini, Giovanni; Comini, Mara; Rivara, Mirko; Rivara, Silvia; Lorenzi, Simone; Bordi, Fabrizio; Mor, Marco; Flammini, Lisa; Bertoni, Simona; Ballabeni, Vigilio; Barocelli, Elisabetta; Plazzi, Pier Vincenzo. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 16:(2006), pp. 4063-4067. [10.1016/j.bmcl.2006.04.092]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/1493262
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