US 4,732,898 AGranted

2-(2-aryl-2-oxoalkylidene) analogs of-3,5-pyridinedicarboxylic acid dialkyl esters useful for treatment of cardiovascular disorders

AssigneeWarner-Lambert Company

InventorsEdward W. Badger, Michael D. Taylor

Life of this patent

Estimating the term…

Abstract

The present invention are 2-(2-aryl-2-oxo-alkylidene) analogs of 1,2,3,4-tetrahydropyridine-3,5-pyridinecarboxylic acids and particularly esters thereof having valuable calcium antagonist and positive inotropic activity useful in the treatment of cardiovascular disorders, pharmaceutical compositions and methods of use therefor.

Claims20

Dependent claims

A compound of the formula (I) ##STR5## and pharmaceutically acceptable base or acid addition salts thereof;

wherein
(2) R.sup.1 is
(i) cyano,
(ii) nitro,
(iii) ##STR6## wherein R.sup.2 is (i) OR.sup.7 wherein R.sup.7 is hydrogen or (ii) ZR.sup.8 wherein Z is alkylenyl of from one to six carbons, inclusive, and R.sup.8 is hydrogen, optionally substituted phenyl which may have one or two substituents the same or different wherein the substituents are alkyl of from one to six carbons, inclusive, NO.sub.2, halogen, alkoxy, amino, monoalkylamino wherein the alkyl is of from one to six carbons, inclusive, or dialkylamino wherein the alkyl is of from one to six carbons, inclusive;
thienyl, furyl, pyryl, pyridyl, quinolyl, isoquinolyl, pyrimidyl, pyridazinyl, quinazolyl, quinoxalyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, triazolyl, pyrazinyl, oxazinyl, thiazinyl, indolizinyl, indolyl, benzofuranyl, indazolyl, benzothienyl, benzimidazolyl, benzoxazolyl, cinnolinyl, phthalazinyl, naphthyridinyl or benzothiazinyl, amino, monoalkylamino wherein the alkyl is of from one to six carbons, inclusive, or dialkylamino wherein alkyl is of from one to six carbons, inclusive;
or
(iv) A-(CH.sub.2).sub.q wherein q is an integer of two, three, or four and A is ##STR7## when taken together with R.sup.5;
( 3) R.sup.3 is
(i) ZR.sup.8 wherein Z and R.sup.8 are each independently as defined above,
(ii) OR.sup.7 wherein R.sup.7 is independently as defined above, or
(iii) phenyl unsubstituted or substituted by from one to five, wherein the substituents are the same or different and are (i) hydrogen, (ii) alkyl of from one to six carbons, inclusive, (iii) nitro, (iv) alkoxy of from one to six carbons, inclusive, (v) cyano, (vi) amino, (vii) monoalkylamino wherein the alkyl is of from one to six carbons, inclusive, (viii) dialkylamino wherein the alkyl is of from one to six carbons, inclusive (ix) halogen or (x) trifluoromethyl;
(4) R.sup.4 is hydrogen or alkyl of from one to six carbons, inclusive
(5) R.sup.5 is (i) hydrogen,
(ii) alkyl of from one to six carbons, inclusive, or
(iii) taken together with R.sup.1 as defined above;
(6) R.sup.6 is
(i) hydrogen,
(ii) alkyl of from one to six carbons, inclusive, or
(iii) (CH.sub.2).sub.q, when taken together with X.sup.2 when X.sup.2 is on the carbon having the ---- and q' is 1, 2, or 3;
(7) n is an integer of zero through five;
(8) X.sup.1 may each be the same or different and is
(i) alkyl of from one to six carbons, inclusive,
(ii) nitro,
(iii) halogen,
(iv) alkoxy of from one to six carbons, inclusive,
(v) cyano,
(vi) amino,
(vii) monalkylamino wherein the alkyl is of from one to six carbons, inclusive,
(viii) dialkylamino wherein the alkyl is of from one to six carbons, inclusive, or
(ix) trifluoromethyl;
and
(9) X.sup.2 may each be the same or different and is
(i) alkyl of from one to six atom carbons, inclusive,
(ii) nitro,
(iii) halogen,
(iv) alkoxy of from one to six carbons, inclusive,
(v) cyano,
(vi) amino,
(vii) monoalkylamino wherein the alkyl is of from one to six carbons, inclusive,
(viii) dialkylamino wherein the alkyl is of from one to six, inclusive, or
(ix) trifluoromethyl;
(10) n' is an integer of from zero through five;
(11) L is CH;
or N with the proviso that then n' is 0 and --- is nothing.

42 more elements

Dependencies are inferred from the claim text.

Facts

Application: 07/016,896Filed 3 Mar 1987 · continuation in part
Priority: 29 Apr 1986
Granted: 22 Mar 1988
Term ends: Not estimatedThe source records don’t support an estimate.

Classification5 codes

C07D 401/06
Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms
C07D 211/82
Having two double bonds between ring members or between ring members and non-ring members: with only hydrogen atoms, hydrocarbon or substituted…
C07D 211/90
With hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon…
C07D 215/48
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…

Family

Serial857,012Parent of this continuation-in-part · filed 29 Apr 1986
US 4,732,898 AThis patent

From the US filing history. Foreign family members aren’t listed.

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

Abstract

A compound of the formula (I) ##STR5## and pharmaceutically acceptable base or acid addition salts thereof;

wherein
(2) R.sup.1 is
(i) cyano,
(ii) nitro,
(iii) ##STR6## wherein R.sup.2 is (i) OR.sup.7 wherein R.sup.7 is hydrogen or (ii) ZR.sup.8 wherein Z is alkylenyl of from one to six carbons, inclusive, and R.sup.8 is hydrogen, optionally substituted phenyl which may have one or two substituents the same or different wherein the substituents are alkyl of from one to six carbons, inclusive, NO.sub.2, halogen, alkoxy, amino, monoalkylamino wherein the alkyl is of from one to six carbons, inclusive, or dialkylamino wherein the alkyl is of from one to six carbons, inclusive;
thienyl, furyl, pyryl, pyridyl, quinolyl, isoquinolyl, pyrimidyl, pyridazinyl, quinazolyl, quinoxalyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, triazolyl, pyrazinyl, oxazinyl, thiazinyl, indolizinyl, indolyl, benzofuranyl, indazolyl, benzothienyl, benzimidazolyl, benzoxazolyl, cinnolinyl, phthalazinyl, naphthyridinyl or benzothiazinyl, amino, monoalkylamino wherein the alkyl is of from one to six carbons, inclusive, or dialkylamino wherein alkyl is of from one to six carbons, inclusive;
or
(iv) A-(CH.sub.2).sub.q wherein q is an integer of two, three, or four and A is ##STR7## when taken together with R.sup.5;
( 3) R.sup.3 is
(i) ZR.sup.8 wherein Z and R.sup.8 are each independently as defined above,
(ii) OR.sup.7 wherein R.sup.7 is independently as defined above, or
(iii) phenyl unsubstituted or substituted by from one to five, wherein the substituents are the same or different and are (i) hydrogen, (ii) alkyl of from one to six carbons, inclusive, (iii) nitro, (iv) alkoxy of from one to six carbons, inclusive, (v) cyano, (vi) amino, (vii) monoalkylamino wherein the alkyl is of from one to six carbons, inclusive, (viii) dialkylamino wherein the alkyl is of from one to six carbons, inclusive (ix) halogen or (x) trifluoromethyl;
(4) R.sup.4 is hydrogen or alkyl of from one to six carbons, inclusive
(5) R.sup.5 is (i) hydrogen,
(ii) alkyl of from one to six carbons, inclusive, or
(iii) taken together with R.sup.1 as defined above;
(6) R.sup.6 is
(i) hydrogen,
(ii) alkyl of from one to six carbons, inclusive, or
(iii) (CH.sub.2).sub.q, when taken together with X.sup.2 when X.sup.2 is on the carbon having the ---- and q' is 1, 2, or 3;
(7) n is an integer of zero through five;
(8) X.sup.1 may each be the same or different and is
(i) alkyl of from one to six carbons, inclusive,
(ii) nitro,
(iii) halogen,
(iv) alkoxy of from one to six carbons, inclusive,
(v) cyano,
(vi) amino,
(vii) monalkylamino wherein the alkyl is of from one to six carbons, inclusive,
(viii) dialkylamino wherein the alkyl is of from one to six carbons, inclusive, or
(ix) trifluoromethyl;
and
(9) X.sup.2 may each be the same or different and is
(i) alkyl of from one to six atom carbons, inclusive,
(ii) nitro,
(iii) halogen,
(iv) alkoxy of from one to six carbons, inclusive,
(v) cyano,
(vi) amino,
(vii) monoalkylamino wherein the alkyl is of from one to six carbons, inclusive,
(viii) dialkylamino wherein the alkyl is of from one to six, inclusive, or
(ix) trifluoromethyl;
(10) n' is an integer of from zero through five;
(11) L is CH;
or N with the proviso that then n' is 0 and --- is nothing.

42 more elements

Facts

Application

07/016,896Filed 3 Mar 1987 · continuation in part

Priority

29 Apr 1986

Granted

22 Mar 1988

Term ends

Not estimatedThe source records don’t support an estimate.

Classification5 codes

C07D 401/06
Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms
C07D 211/82
Having two double bonds between ring members or between ring members and non-ring members: with only hydrogen atoms, hydrocarbon or substituted…
C07D 211/90
With hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon…
C07D 215/48
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…