Piperdine derivatives and hypotensives containing the same

Abstract

A piperidine compound of the formula (I): wherein A is a fused aromatic ring; R is hydrogen, chloro or methoxy; X is (CH 2 ) n , which may be substituted, in which n is 0 or an integer of 1 to 10, —CH≡CH—, —C≡C—, —O—, —S—, —NH—, —N(COCH 3 )—, —N(COOC 2 H 5 )—, —N(CHO)—, —N(CH 3 )—, —CO—, —SO—, or —SO 2 —; Y is —CH≡CH—, —CH 2 CH 2 —, —CH 2 CO—, —O—, —S—, —NH—, —OCH 2 —, —SCH 2 —, —NHCH 2 —, —CH(OH)CH 2 — or —CH(OH)CH(OH)—; and Q is substituted or unsubstituted n-hexyl, carboxypropyl, ethoxycarbonylpropyl, cyanopropyl, cyclohexyl, phenyl, indanyl, naphthyl, tetrahydronaphthyl, benzocycloheptyl, piperidinyl, tetrahydroisoquinolinyl, indolyl, pyrolyl, furyl, thienyl, thiazolyl, oxazolyl or N-methylpyrolyl, wherein any one or more of the —(CH 2 )-groups of the hexyl, carboxypropyl, ethoxycarbonylpropyl and cyanopropyl groups may be replaced by —CH≡CH—, —C≡C—, —O—, —S—, —NH—, —N(COCH 3 ), —N(COC 2 H 5 )—, —N(CHO)—, —N(CH 3 ), —CO—, —SO— or —SO 2 —, and wherein one or more of the —(CH 2 )-groups in X and Q may be substituted by —(CH 2 ) 4 — or —(CH 2 ) 5 — thereby forming a ring structure.

What is claimed as new and is intended to be secured by Letters Patent of the United States is:  
     
       1. A piperidine compound of the formula (I)                    
       wherein: 
       A is pyridine;  
       R is —H, —Cl or —OCH 3 ;  
       X is —(CH 2 ) n —, —CO—(CH 2 ) 3 , —CONH—(CH 2 ) 2 , —NHCO—(CH 2 ) 2 , or —CH≡CH—(CH 2 ) 2 —; and  
       n is an integer of from 3 to 5;  
       Y is —CH≡CH—, —(CH 2 ) 2 , —OCH 2 —, —SCH 2 —, or —O—; and  
       Q is —CN, substituted or unsubstituted cyclohexyl, substituted or unsubstituted piperidinyl, substituted or unsubstituted piperazinyl, substituted or unsubstituted phenyl, substituted or unsubstituted furyl, substituted or unsubstituted thienyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted pyridyl, substituted or unsubstituted morpholinyl, or substituted or unsubstituted thiomorpholinyl, wherein when Q is substituted, the substituent(s) is/are selected from the group consisting of HCH 2  n  wherein n is an integer of 1 to 10, ClCH 2  3 , allyl, phenyl, isopropyl, hydroxy, methoxy, ethoxy, fluoro, chloro, acetoxy, 2-methoxyacetoxy, ethoxycarboxyl, carboxyl, methoxycarbonyl, ethoxycarbonyl, cyano, imidazolylmethyl, trifluoromethyl, benzoyl, 2-hydroxybenzyl, nitro, amino, acetylamino, propanoylamino, butanoylamino, pivaloylamino, trifluoromethylamino, methoxycarbonylamino, ethoxycarbonylamino, cinnamoylamino, methanesulfonylamino, N,N-bis(methanesulfonyl)amino, aminocarbonyl, aminosulfonyl, hydroxymethyl and acetoxymethyl, and wherein when X and/or Q contain CH 2  groups, one or more of the CH 2  groups in X and/or Q may be substituted by CH 2  4  CH 2  5 , thereby forming a ring structure.  
     
     
       2. The piperidine compound of  claim 1 , wherein the hydrogen atoms of one or more of the —CH 2 — groups in X and Q are substituted by CH 2  4  or CH 2  5 , thereby forming a ring structure. 
     
     
       3. The piperidine compound of  claim 1 , wherein Q is substituted by at least one substituent selected from the group consisting of HCH 2  n  wherein n is an integer of 1 to 10, ClCH 2  3 , allyl, phenyl, isopropyl; hydroxy, methoxy, ethoxy, fluoro, chloro, acetoxy, 2-methoxyacetoxy, ethoxycarboxyl, carboxyl, methoxycarbonyl, ethoxycarbonyl, cyano, imidazolylmethyl, trifluoromethyl, benzoyl, 2-hydroxybenzyl, nitro, amino, acetylamino, propanoylamino, butanoylamino, pivaloylamino, trifluoromethylamino, methoxycarbonylamino, ethoxycarbonylamino, cinnamoylamino, methanesulfonylamino, N,N-bis(methanesulfonyl)amino, aminocarbonyl, aminosulfonyl, hydroxymethyl and acetoxymethyl. 
     
     
       4. The piperidine compound of  claim 1 , wherein X is —CONH—(CH 2 ) 2 . 
     
     
       5. The piperidine compound of  claim 1 , wherein Y is —CH≡CH—. 
     
     
       6. The piperidine compound of  claim 1 , wherein Y is —(CH 2 ) 2 —. 
     
     
       7. The piperidine compound of  claim 1 , wherein Q is substituted or unsubstituted piperidinyl. 
     
     
       8. The piperidine compound of  claim 1 , wherein X is —CONH—(CH 2 ) 2 , and Q is substituted or unsubstituted piperidinyl. 
     
     
       9. A piperidine compound of the formula                    
       wherein: 
       R is —H, —Cl or —OCH 3 ;  
       X is —(CH 2 ) n —, —CO—(CH 2 ) 3 , —CONH—(CH 2 ) 2 , —NHCO—(CH 2 ) 2 , or —CH≡CH—(CH 2 ) 2 —; and  
       n is an integer of from 3 to 5;  
       Y is —CH≡CH—, —(CH 2 ) 2 —, —OCH 2 —, —SCH 2 —; and  
       Q is —CN, substituted or unsubstituted piperidinyl, substituted or unsubstituted piperazinyl, substituted or unsubstituted thienyl, substituted or unsubstituted morpholinyl, or substituted or unsubstituted thiomorpholinyl, wherein when Q is substituted, the substituent(s) is/are selected from the group consisting of HCH 2  n  wherein n is an integer of 1 to 10, ClCH 2  3 , allyl, formyl, phenyl, isopropyl, hydroxy, methoxy, ethoxy, fluoro, chloro, acetoxy, 2-methoxyacetoxy, carboxyl, methoxycarbonyl, ethoxycarbonyl, cyano, imidazolylmethyl, trifluoromethyl, benzoyl, 2-hdyroxybenzyl, nitro, amino, acetylamino, propanoylamino, butanoylamino, pivaloylamino, trifluoromethylamino, methoxycarbonylamino, ethoxycarbonylamino, cinnamoylamino, methanesulfonylamino, N,N-bis(methanesulfonyl)amino, aminocarbonyl, aminosulfonyl, hydroxymethyl and acetoxymethyl, and wherein when X and/or Q contain CH 2 groups, one or more of the CH 2  groups in X and/or Q may be substituted by CH 2  4  or CH 2  5 , thereby forming a ring structure.  
     
     
       10. The piperidine compound of  claim 9 , wherein X is —CONH—(CH 2 ) 2 , Y is —CH≡CH—, and Q is N-formylpiperidinyl. 
     
     
       11. A piperidine compound of the formula                    
       wherein: 
       R is —H, —Cl or —OCH 3 ;  
       X is —CO—(CH 2 ) 3 , —CONH—(CH 2 ) 2 , —NHCO—(CH 2 ) 2 , or —CH≡CH— (CH 2 ) 2 —; and  
       Q is —CN, substituted or unsubstituted cyclohexyl, substituted or unsubstituted piperidinyl, substituted or unsubstituted piperazinyl, substituted or unsubstituted phenyl, substituted or unsubstituted furyl, substituted or unsubstituted thienyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted pyridyl, substituted or unsubstituted morpholinyl, or substituted or unsubstituted thiomorpholinyl, wherein when Q is substituted, the substituent(s) is/are selected from the group consisting of HCH 2  n  wherein n is an integer of 1 to 10, ClCH 2  3 , allyl, phenyl, isopropyl, hydroxy, methoxy, ethoxy, fluoro, chloro, acetoxy, 2-methoxyacetoxy, ethoxycarboxyl, carboxyl, methoxycarbonyl, ethoxycarbonyl, cyano, imidazolylmethyl, trifluoromethyl, benzoyl, 2-hydroxybenzyl, nitro, amino, acetylamino, propanoylamino, butanoylamino, pivaloylamino, trifluoromethylamino, methoxycarbonylamino, ethoxycarbonylamino, cinnamoylamino, methanesulfonylamino, N,N-bis(methanesulfonyl)amino, aminocarbonyl, aminosulfonyl, hydroxymethyl and acetoxymethyl, and wherein when X and/or Q contain CH 2  groups, one or more of the CH 2  groups in X and/or Q may be substituted by CH 2  4  or CH 2  5  thereby forming a ring structure.  
     
     
       12. A piperidine compound of the formula                    
       wherein: 
       R is —H, —Cl or —OCH 3 ;  
       X is —(CH 2 ) n —;  
       n is an integer of from 3 to 5; and  
       Q is —CN, substituted or unsubstituted phenyl, substituted or unsubstituted furyl, substituted or unsubstituted thienyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted pyridyl, wherein when Q is substituted, the substituent(s) is/are selected from the group consisting of HCH 2  n  wherein n is an integer of 1 to 10, ClCH 2  3 , allyl, phenyl, isopropyl, hydroxy, methoxy, ethoxy, fluoro, chloro, acetoxy, 2-methoxyacetoxy, ethoxycarboxyl, carboxyl, methoxycarbonyl, ethoxycarbonyl, cyano, imidazolylmethyl, trifluoromethyl, benzoyl, 2-hydroxybenzyl, nitro, amino, acetylamino, propanoylamino, butanoylamino, pivaloylamino, trifluoromethylamino, methoxycarbonylamino, ethoxycarbonylamino, cinnamoylamino, methanesulfonylamino, N,N-bis(methanesulfonyl)amino, aminocarbonyl, aminosulfonyl, hydroxymethyl and acetoxymethyl, and wherein one or more of the CH 2  groups in X may be substituted by CH 2  4  or CH 2  5  thereby forming a ring structure.  
     
     
       13. The piperidine compounds of  claim 10 , wherein R is —H.