Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-08-23
1999-08-17
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
544247, 544251, C07D48714, C07D48720, C07D49122, A61K 31505
Patent
active
059394196
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND
The present invention relates to 2-benzyl-polycyclic guanine derivatives useful for treating cardiovascular and pulmonary disorders, as well as to their pharmaceutical compositions, methods for using the same and a process for preparing them. Most compounds of this invention were generically but not specifically disclosed in PCT publication WO91/19717, published Dec. 26, 1991. We have found that the compounds of the present invention show unexpectedly superior cardiovascular and pulmonary activity compared to the compounds of the prior publication.
SUMMARY OF THE INVENTION
The present invention is directed to novel 2-benzyl-polycyclic guanine derivatives of the formula: ##STR1## or a pharmaceutically acceptable salt thereof, wherein: R.sub.1, R.sub.2 and R.sub.3 are independently selected from the group consisting of hydrogen, lower alkyl, lower alkoxy, halogeno, hydroxy, (di-lower alkyl)amino, 4-morpholinyl, 1-pyrrolidinyl, 1-pyrrolyl, --CF.sub.3, --OCF.sub.3, phenyl and methoxyphenyl; or R.sub.1 and R.sub.2 together are methylenedioxy; or R.sub.1 and R.sub.2 together with the carbon atoms to which they are attached form a benzene ring; and to which they are attached, form a saturated ring of 5 carbons; or R.sup.a is lower alkyl, R.sup.b is hydrogen or lower alkyl, and R.sup.c is hydrogen; or R.sup.a, R.sup.b and the carbon atom to which they are attached form a saturated ring of 5-7 carbons, and R.sup.c is hydrogen; or R.sup.a is hydrogen, and R.sup.b, R.sup.c and the carbon atoms to which they are attached form a tetrahydrofuran ring; or R.sup.a and R.sup.b, together with the carbon atom to which they are attached, and R.sup.b and R.sup.c, together with the carbon atoms to which they are attached, each form a saturated ring of 5-7 carbons.
Preferred compounds are those wherein R.sub.1 and R.sub.3 are hydrogen. More preferred are compounds wherein R.sub.1 and R.sub.3 are hydrogen and R.sub.2 is hydrogen, --OCF.sub.3, methyl, methoxy, fluoro, phenyl, methoxyphenyl, dimethylamino, 1-pyrrolidinyl or 1-pyrrolyl, and compounds wherein R.sub.1 and R.sub.2 together are methylenedioxy and R.sub.3 is hydrogen.
Also preferred are compounds wherein R.sup.a is hydrogen and R.sup.b and R.sup.c, together with the carbon atoms to which they are attached, form a saturated ring of 5 carbons; compounds wherein R.sup.a is lower alkyl, R.sup.b is hydrogen or lower alkyl, and R.sup.c is hydrogen; compounds wherein R.sup.a and R.sup.b and the carbon atom to which they are attached form a saturated ring of 5 carbons and R.sup.c is hydrogen; compounds wherein R.sup.a is hydrogen and R.sup.b, R.sup.c and the carbon atoms to which they are attached form a tetrahydrofuran ring; and compounds wherein R.sup.a and R.sup.b, together with the carbon atoms to which they are attached, and R.sup.b and R.sup.c, together with the carbon atoms to which they are attached, each form a saturated ring of 5 carbons. More preferred are compounds wherein R.sup.a is hydrogen and R.sup.b and R.sup.c, together with the carbon atoms to which they are attached, form a saturated ring of 5 carbons; compounds wherein R.sup.a and R.sup.b and the carbon atom to which they are attached form a saturated ring of 5 carbons and R.sup.c is hydrogen; and compounds wherein R.sup.a is lower alkyl, R.sup.b is hydrogen or lower alkyl, and R.sup.c is hydrogen.
Of compounds of formula I wherein R.sup.a is hydrogen and R.sup.b and R.sup.c, together with the carbon atoms to which they are attached, form a saturated ring of 5 carbons, most preferred are compounds wherein R.sub.1, R.sub.2 and R.sub.3 are as listed in the following table:
______________________________________ R.sub.1 R.sub.2 R.sub.3
______________________________________
H H H
H F H
H --OCH.sub.3 H
H --CH.sub.3 H
H (CH.sub.3).sub.2 N--
H
H C.sub.6 H.sub.5 --
H
H --OCF.sub.3 H
1 #STR2## H
H
2 #STR3## H
3,4-OCH.sub.2 O-- H
H --C.sub.6 H.sub.4 OCH.sub.3
H
______________________________________
The compounds of formula I are useful as antihypertensive, bronchodilating and blood
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Chackalamannil Samuel
McKittrick Brian A.
Tulshian Deen
Xia Yan
Magatti Anita W.
Rao Deepak R.
Schering-Plough Corporation
Shah Mukund J.
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