Tricyclic and tetracyclic systems acting upon the vascular and central nervous systems

Abstract

Tricyclic and tetracyclic derivatives of benzodiazepine, pyridodiazepine, and pyrimidodiazepine fused with 1,4-dihydropyridine derivatives are disclosed. The present derivatives can be obtained from derivatives containing a dihydropyrldine ring reacting with compounds of the ortho-phenyldiamine, ortho-diaminopyridine, and ortho-diaminopyrimidine type, as well as some subsequent transformations and, tricyclic and tetracyclic derivatives can be obtained with a diazepine or diazepinone nucleus fused to a 1,4-dihydropyridine nucleus, having a substituted or unsubstituted ring of benzene, pyridine or pyrimidine. The present derivatives exhibit vascular and central nervous system therapeutic activity.

1 - 17 . (canceled) 
     
     
         18 . A pharmaceutical composition comprising a compound of Formula I 
       
         
           
           
               
               
           
         
         wherein: 
         R represents H, an alkyl, a cyclic alkyl, a vinyl, an aryl, phenyl, or heteroaryl; 
         R 1  represents H, alkyl, alicyclics, —OR′, —NHR″, —NHR′″, —NH—(CH 2 ) n —NH(C=O)-R 3 , —NH—CH(R 4 )—COOH, —NH—OH, —NH—NH 2 , —NH—NH—(C=O)-NH 2 , —NH—NH—(C=S)—NH 2 , or —NHR 5 ; 
         R′ represents H, Nat*, K*, straight or branched alkyl groups having 1 to 24 carbon atoms, or lipid chains derived from mono or polyunsaturated fatty acids having up to 24 carbon atoms, 
         R″ represents H, straight or branched alkyl groups having 1 to 24 carbon, or lipid chains derived from mono or polyunsaturated fatty acids having up to 24 carbon atoms; 
         R′″ represents —(CH 2 ) n —NH 2 ; 
         n=1-10 
         R 2  represents an alkyl or a cycloalkyl; 
         A represents benzene; and 
         R 3  represents an alkyl; 
         R 4  represents amino acid remnants; 
         R 5  represents a thiazole, 4-phenylthiazole, or phenyl; wherein: 
         alkyl groups, unless specified otherwise, are straight or branched having up to 8 carbon atoms and may be unsubstituted or substituted with a halogen; 
         alicyclics have 1 to 16 carbon atoms; 
         vinyl groups may be unsubstituted or substituted with a halogen; 
         phenyl groups may be unsubstituted or substituted with one or more of —NO 2 , —NH 2 , —OH, F, Cl, Br, I, —CN, —OCH 3 , —N(CH 3 ) 2 , —CH 3 , —OCOCH 3 , —COOCH 3 , —OCF 3 , —SH,  13  NH(C=O)—CH 3 , —CHO, —C=NH, —C=NH—NH 2 , or —C=NH—OH; and 
         benzene may be unsubstituted or substituted with one or more of OH, COOH, CH 3 , NO 2 , NH 2 , CHO, or halogens. 
       
     
     
         19 . The pharmaceutical composition according to  claim 18  wherein R is an unsubstituted or substituted phenyl group. 
     
     
         20 . The pharmaceutical composition according to  claim 18  wherein R 1  is —OR 3 . 
     
     
         21 . The pharmaceutical composition according to  claim 18  wherein R′ is a straight or branched alkyl group having 1 to 24 carbon atoms. 
     
     
         22 . The pharmaceutical composition according to  claim 18  wherein R 2  represents an alkyl. 
     
     
         23 . The pharmaceutical composition according to  claim 18  wherein A is a benezene substituted with NO 2 . 
     
     
         24 . A pharmaceutical composition comprising a compound of Formula I 
       
         
           
           
               
               
           
         
         wherein: 
         R represents H, an alkyl, a cyclic alkyl, a vinyl, phenyl, or heteroaryl; 
         R 1  represents H, alkyl, —OR′, —NHR″, —NHR′″, or —NHR 5 ; 
         R′ represents H, Na*, K*, or straight or branched alkyl groups having 1 to 24 carbon atoms, 
         R″ represents H or straight or branched alkyl groups having 1 to 24 carbon; 
         R′″ represents —(CH 2 ) n —NH 2 ; 
         n=1-10 
         R 2  represents an alkyl; 
         A represents benzene; and 
         R 5  represents a thiazole, 4-phenylthiazole, or phenyl; wherein: 
         alkyl groups, unless specified otherwise, are straight or branched having up to 8 carbon atoms and may be unsubstituted or substituted with a halogen; 
         vinyl groups may be unsubstituted or substituted with a halogen; 
         phenyl groups may be unsubstituted or substituted with one or more of —NO 2 , —NH 2 , —OH, F, Cl, Br, I, —CN, —OCH 3 , —N(CH 3 ) 2 , —CH 3, —OCOCH 3 , —COOCH 3 , —OCF 3 , —SH, —NH(C=O)—CH 3 , —CHO, —C=NH, —C=NH—NH 2 , or —C=NH—OH; and 
         benzene may be unsubstituted or substituted with one or more of OH, COOH, CH 3 , NO 2 , NH 2 , CHO, or halogens. 
       
     
     
         25 . A pharmaceutical composition comprising