Abstract: Novel compounds comprising chemically reactive intermediates which can react with available reactive functionalities on blood components to form covalent linkages, where the resulting covalently-bound conjugates are found to have thrombin inhibition activity are provided. Specifically, the thrombin inhibitor compounds of the present invention are derivatives of the known thrombin inhibitor argatroban, which can be covalently linked to chemically reactive functionalities on various blood components. The conjugated thrombin inhibitors thereby have extended lifetimes in the bloodstream, as compared to the unconjugated parent drug, and are, therefore, capable of maintaining thrombin inhibitory activity for extended periods of time as compared to the unconjugated parent drug. Also provided herein are methods for inhibiting thrombin activity in vivo comprising administering to the bloodstream of a mammalian host the novel compounds of the present invention.

Abstract: Novel compounds comprising chemically reactive intermediates which can react with available reactive functionalities on blood components to form covalent linkages, where the resulting covalently-bound conjugates are found to have thrombin inhibition activity are provided. Specifically, the thrombin inhibitor compounds of the present invention are derivatives of the known thrombin inhibitor argatroban, which can be covalently linked to chemically reactive functionalities on various blood components. The conjugated thrombin inhibitors thereby have extended lifetimes in the bloodstream, as compared to the unconjugated parent drug, and are, therefore, capable of maintaining thrombin inhibitory activity for extended periods of time as compared to the unconjugated parent drug. Also provided herein are methods for inhibiting thrombin activity in vivo comprising administering to the bloodstream of a mammalian host the novel compounds of the present invention.

Abstract: Novel compounds comprising chemically reactive intermediates which can react with available reactive functionalities on blood components to form covalent linkages, where the resulting covalently-bound conjugates are found to have thrombin inhibition activity are provided. Specifically, the thrombin inhibitor compounds of the present invention are derivatives of the known thrombin inhibitor argatroban, which can be covalently linked to chemically reactive functionalities on various blood components. The conjugated thrombin inhibitors thereby have extended lifetimes in the bloodstream, as compared to the unconjugated parent drug, and are, therefore, capable of maintaining thrombin inhibitory activity for extended periods of time as compared to the unconjugated parent drug. Also provided herein are methods for inhibiting thrombin activity in vivo comprising administering to the bloodstream of a mammalian host the novel compounds of the present invention.

Abstract: Aryl-fused- and hetaryl-fused-2,4-diazepines of formula XXXVI, benzodiazocines of formula XXX, benzodiazepines of formula II ##STR1## .delta.-aminoamides of formula III and aryldimethanamines of formula XXXVII ##STR2## wherein A is an aryl or hetaryl ring;R.sup.1 is hydrogen, alkyl, aryl or hetaryl;R.sup.2 is hydrogen, alkyl, substituted alkyl, or aryl;R.sup.3 is alkyl, aryl, aralkyl or heteroatom substituted alkyl or aralkyl;R.sup.4 is hydrogen or alkyl;R.sup.5 is hydrogen, alkyl, aryl or hetaryl;R.sup.6 is hydrogen, alkyl, alkoxy, halogen or a fused benzene ring;R.sup.9 is hydrogen, alkyl, or substituted alkyl; andR.sup.10 is hydrogen, alkyl, or substituted alkyl the invention further relates to processes for the preparation of, pharmaceutical compositions containing, and methods of treating cardiac arrhythmia with the compounds of formulas XXXVI, XXX, II, III, and XXXVII.

Abstract: Aryl-fused- and hetaryl-fused-2,4-diazepines of formula XXXVI, benzodiazocines of formula XXX, benzodiazepines of formula II ##STR1## .delta.-aminoamides of formula III and aryldimethanamines of formula XXXVII ##STR2## wherein A is an aryl or hetaryl ring;R.sup.1 is hydrogen, alkyl, aryl or hetaryl;R.sup.2 is hydrogen, alkyl, substituted alkyl, or aryl;R.sup.3 is alkyl, aryl, aralkyl or heteroatom substituted alkyl or aralkyl;R.sup.4 is hydrogen or alkyl;R.sup.5 is hydrogen, alkyl, aryl or hetaryl;R.sup.6 is hydrogen, alkyl, alkoxy, halogen or a fused benzene ring;R.sup.9 is hydrogen, alkyl, or substituted alkyl; andR.sup.10 is hydrogen, alkyl, or substituted alkyl.The invention further relates to processes for the preparation of, pharmaceutical compositions containing, and methods of treating cardiac arrhythmia with the compounds of formulas XXXVI, XXX, II, III, and XXXVII.

Abstract: N-[(alkylamino)alkyl]-4,5-diaryl-1H-pyrazole-1-acetamides, wherein at least one of the aryl substituents is a pyridine, useful for treating cardiac arrhythmias in mammals, are prepared by reacting a lower-alkyl ester of pyrazole-1-acetic acid with an appropriate diamine.