- 1H-1,2,4-thiadiazolo(3,4-b)quinazolin-5-one-2,2-dioxides, and a method for increasing the cardiac output of a mammal with them
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1H-1,2,4-thiadiazolo[3,4-b]quinazolin-5-one-2,2-dioxides are disclosed. These compounds are useful as caridotonic agents. A preferred compound is 7-(n-cyclohexyl-N-methyl-4-amino-4-oxobutyloxy)-1H-1,2,4-thiadiazolo[3,4-b]quinazolin-5-one-2,2-dioxide.
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- Inhibitors of cyclic AMP phosphodiesterase. 1. Analogues of cilostamide and anagrelide
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Evaluation of a series of lactam heterocyclic analogues of cilostamide as inhibitors of cyclic AMP phosphodiesterase derived from both human platelets and rat heart in comparison with their corresponding methoxy-substituted heterocycles has revealed that the N-cyclohexyl-N-methyl-4-oxybutyramide side chain of 2 is an important lipophilic and/or steric pharmacophore. Attachment of this side chain to the parent heterocycle of the potent cyclic AMP phosphodiesterase inhibitor anagrelide afforded the hybrid structure RS-82856, shown to be more potent than either of its progenitors as an inhibitor of cyclic AMP phosphodiesterase or of ADP-induced platelet aggregation. The available in vitro data suggest that 1 possesses potentially useful antithrombotic and cardiotonic properties.
- Jones,Venuti,Alvarez,Bruno,Berks,Prince
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p. 295 - 303
(2007/10/02)
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- Method of treating heart failure using (2-oxo-1,2,3,5-tetrahydroimidazo-[2,1-b]quinazolinyl)oxyalkylamides
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Compounds according to the formula STR1 and the pharmaceutically acceptable acid addition salts thereof wherein: n is an integer of 1 to 6; R1 is hydrogen or alkyl of 1 to 4 carbon; R2 is hydrogen or R1 and R2 combined are oxo; R3 is hydrogen, alkyl of 1 to 6 carbons, phenyl, benzyl, hydroxy lower alkyl and its acylates, carbamoyl alkyl, carboxyalkyl, alkoxycarbonylalkyl or amino acid side chains; R4 is hydrogen, alkyl of 1 to 6 carbons, benzyl, or hydroxy lower alkyl; Y is hydrogen, alkyl of 1 to 4 carbon atoms, halo or lower alkoxy; A is an amide forming group wherein the nitrogen substituents are: hydrogen; alkyl of 1 to 6 carbon atoms; hydroxyalkyl of 1 to 6 carbon atoms and its aliphatic acylates of 1 to 6 carbon atoms or aryl acylates of 7 to 12 carbon atoms; cycloalkyl of 3 to 8 carbon atoms or cycloalkyl lower alkyl of 4 to 12 carbon atoms wherein the cycloalkyl ring is unsubstituted or substituted with a lower alkyl, lower alkoxy, --OH, --OCOR5, halo, --NH2, --N(R5)2, --NHCOR5, --COOH, or --COO(R5) group wherein R5 is lower alkyl; phenyl or phenyl lower alkyl wherein phenyl is unsubstituted or substituted with 1 or more lower alkyl, halo or lower alkoxy groups or an --NH2, --N(R5)2, --NHCOR5, --COOH, or --COOR5 group wherein R5 is lower alkyl; morpholinyl; piperidinyl; perhexylenyl; N-loweralkylpiperazinyl; pyrrolidinyl; tetrahydroquinolinyl; tetrahydroisoquinolinyl; (±)-decahydroquinolinyl or indolinyl. These compounds have inotropic activity.
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- N,N-Disubstituted-(2-oxo-1,2,3,5-tetrahydroimidazo-[2,1-B]quinazolinyl)oxyalkylamides
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Compounds according to the formula STR1 and the pharmaceutically acceptable acid addition salts thereof wherein: n is an integer of 1 to 6; R1 is hydrogen or alkyl of 1 to 4 carbons; R2 is hydrogen or R1 and R2
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