120791-13-1Relevant articles and documents
Nonsteroidal Cardiotonics. 2. The Inotropic Activity of Linear, Tricyclic 5-6-5 Fused Heterocycles
Saal, Wolfgang von der,Hoelck, Jens-Peter,Kampe, Wolfgang,Mertens, Alfred,Mueller-Beckmann, Bernd
, p. 1481 - 1491 (2007/10/02)
We previously reported the structure-activity relationships (SAR) of adibendan (1), a potent and long-acting cardiotonic.This paper describes the synthesis of a novel series of linear, tricyclic fused heterocycles of the 5-6-5 type.The compounds were evaluated for positive inotropic activity in anesthetized rats, cats, and dogs.Changes in left ventricular dP/dt were measured as an index of cardiac contractility.The increase in contractility was not mediated via stimulation of β-adrenergic receptors.The data revealed the intrinsic positive inotropic activity of the parent compound of this series, 5,7-dihydro-7,7-dimethylpyrrolobenzimidazol-6(1H)-one (2).The structural features that impart optimal inotropic activity are presented and compared with those of the 4,5-dihydro-3(2H)-pyridazinone series.The most potent compounds were evaluated orally in conscious dogs with implanted Konigsberg pressure transducers to measure ventricular pressures, and their effect on left ventricular dP/dt was compared with that of 1, pimobendan, and indolidan.After administration of 1 mg/kg, 1, 3, 7, 19, 22, 24, 31, 54, pimobendan, and indolidan were equipotent, but only with 1, 31, pimobendan, and indolidan, durations of action exceeded 6 h.
Pyrrolobenzimidazoles, pharmaceutical compositions containing them, and use of them to treat certain heart and circulatory diseases
-
, (2008/06/13)
The present invention provides new pyrrolobenzimidazoles of the general formula: STR1 wherein R1 is a hydrogen atom or an alkyl, alkenyl or cycloalkyl radical; R2 is a hydrogen atom, cyano group or alkyl or alkenyl radical or a carbonyl group substituted by hydroxyl, alkyl, alkoxy, amino, alkylamino, dialkylamino or hydrazino or together with R1 forms a cycloalkylene radical or R1 and R2 together form an alkylidene or cycloalkylidene radical; R3, R4 and R5, which can be the same or different, each represent a hydrogen atom or an alkanesulphonyloxy, trifluoromethanesulphonyloxy, alkanesulphonylamino, trifluoromethanesulphonylamino, N-alkyl-alkanesulphonylamino, N-alkyl-trifluoromethanesulphonylamino, alkylsulphenylmethyl, alkylsulphinylmethyl or alkylsulphonylmethyl radical, a carbonyl group substituted by hydroxyl, alkoxy, amino, alkylamino or dialkylamino, a sulphonyl group substituted by amino, alkylamino, dialkylamino or cyclic imino, whereby a methylene group in the 4-position can be replaced by a sulphur or oxygen atom, an alkylcarbonylamino, aminocarbonylamino or alkylaminocarbonylamino radical, an alkylthio, alkylsulphinyl or alkylsulphonyl radical, a nitro, halogen, amino, hydroxyl, alkyl, trifluoromethyl, alkoxy, alkenyloxy, alkynyloxy, cyanoalkoxy, carboxyalkoxy, alkoxycarbonylalkoxy, dialkylamino, 1-imidazolyl or cyano group; X is a valency bond, a C1 -C4 alkylene radical or a vinyl radical; and T is an oxygen or sulphur atom; the tautomers thereof and the physiologically acceptable salts thereof with inorganic and organic acids. The present invention also provides processes for the preparation of these compounds and pharmaceuticals containing them for the prophylaxis and treatment of heart and circulatory diseases.
