123259-13-2Relevant academic research and scientific papers
Benzimidazoline-2-oxo-1-carboxylic acid compounds useful as 5-HT receptor antagonists
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, (2008/06/13)
New pharmacologically active benzimidazoline-2-oxo-1-carboxylic acid derivatives which are 5-HT receptor antagonists useful as antiemetic agents and as gastric prokinetic agents of the following formula: STR1wherein R is hydrogen, C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl; R 1 is hydrogen; R 2 is hydrogen, halogen or C 1-6 alkoxy; Y is oxygen or N--R 3 in which R 3 is hydrogen; A is a group selected from: STR2wherein p is 1; r is 0, 2 or 3: R 4 is hydrogen; R 5 is hydrogen, C 1-6 alkyl, or R 5 is a group of the formula --CR 6 =N--R 7 wherein R 6 is hydrogen, C 1-4 alkyl or amino and R 7 is hydrogen or C 1-6 alkyl; or a pharmaceutically acceptable acid addition salt thereof.The processes for the preparation of the compounds of formula (I) as well as pharmaceutical compositions contained in them are also described.
Synthesis of a New Class of 2,3-Dihydro-2-oxo-1H-benzimidazole-1-carboxylic Acid Derivatives as Highly Potent 5-HT3 Receptor Antagonists
Turconi, Marco,Nicola, Massimo,Quintero, Myrna Gil,Maiocchi, Luciano,Micheletti, Rosella,et al.
, p. 2101 - 2108 (2007/10/02)
A series of 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylic acid esters and amides containing a basic azacyclo- or azabicycloalkyl moiety has been synthesized and evaluated for 5-HT3 antagonistic activity in a radioligand binding assay (3>ICS 205930) and in the 5-HT-induced von Bezold-Jarisch reflex in the rat.It was found that endosubstituted azabicycloalkyl derivatives (e.g. 7a, 12a, 12b) were much more active than the corresponding exo analogues (e. g. 7b, 12h, 12i) or azacycloalkyl compounds.Amidic derivatives 12a, 12b, 12c, 12e, 13b, and 13c proved to be about 10 tim es more active than the corresponding ester derivatives 7a, 11a, 7d, 8a, and 8b.In particular, compound 12a (DA 6215) showed a Ki=3.8 nM in the binding test and an ED50=1 nM/kg iv in the von Bezold-Jarisch reflex assay, an activity comparable to that of the reference compound 2 (ICS 205930, Ki=2 nM, ED50=2.1 nM/kg).IR spectroscopy studies in the solid state and in CHCl3 solution revealed the existence of an intramolecular hydrogen bond in 13b, taken as a model compound for this class of substances.A molecular modeling study showed that 12a, in its internal hydrogen-bound conformation, well matches a recently proposed pharmacophoric model for 5-HT3 antagonist activity.
New benzimidazoline-2-oxo-1-carboxylic acid derivatives useful as 5-ht receptor antagonists
-
, (2008/06/13)
New pharmacologically active benzimidazoline-2-oxo-1-carboxylic acid derivatives which are 5-HT receptor antagonists useful as antiemetic agents and as gastric prokinetic agents of the following formula: wherein R represents a hydrogen atom, C1 6 alkyl, C1 6 alkenyl or C1 6 alkynil; R1 and R2 may be at the same time or not a hydrogen atom, halogen, trifluoromethyl, C1 6 alkyl, C1 6 alkoxy, C1 6 alkylthio, C1 6 acyl, carboxyl, C1 6 alkoxycarbonyl, hydroxy, nitro, amino optio-nally C1 4 alkyl N-mono or di-substituted, C1 6 acylamino, C1 6 alkoxy-carbonylamino, carbamoyl optionally C1 4 alkyl N-mono or di-substitu-ted, cyano, C1 6alkylsulphinyl, C1 6 alkylsulphonyl, amino sulphonyl optionally C1 4 alkyl N-mono or di-substituted, C1 4 alkyl N-mono or di-substituted aminosulphonylamino, aminosulphonylamino; Y is oxygen or is N - R3 in which R3 is a hydrogen, a C1 6 alkyl or optionally substituted by one or more C1 6 alkoxy benzyl; A is a group selected from: wherein p is 0, 1; r is 0, 1, 2, 3; R4 is hydrogen atom or a C1 4 alkyl; R5 is a hydrogen atom, C1 6 alkyl, C3 8 cycloalkyl, C3 8 cycloalkyl C1 4 alkyl,substituted phenyl C1 4 alkyl or R5 is a group of formula wherein R6 is hydrogen atom, C1 4 alkyl or an amino group and R7 is hydrogen atom or C1 6 alkyl, tautomers thereof and acid addition salts of the aforesaid compounds. The processes for the preparation of the compounds of formula (I) as well as pharmaceutical compositions containing them are also described.
