US 4,791,138 AGranted

Method for treating or preventing deep vein thrombosis using lipoxygenase inhibitors

AssigneeThe Upjohn Company

InventorRobert G. Schaub

Life of this patent

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Abstract

The present invention provides a novel methoda for preventing deep vein thrombosis comprising the administration of lipoxygenase inhibitors of Formula I ##STR1##

Claims5

Dependent claims

A method for preventing deep vein thrombosis (DVT) in a mammal susceptible to said DVT comprising administering to said mammal an amount effective to prevent said DVT of a lipoxygenase inhibitor, wherein the lipoxygenase inhibitor is a compound of the Formula I

wherein R.sub.1 and R.sub.2 are the same or different and are
(a) hydrogen,
(b) (C.sub.1 -C.sub.10)alkyl,
(c) (C.sub.2 -C.sub.10)alkenyl, or
(d) PhX;
wherein (PhX) is phenyl substituted by zero to 3 of the following:
(a) (C.sub.1 -C.sub.4)alkyl,
(b) chloro,
(c) fluoro,
(d) bromo,
(e) nitro,
(f) trifluoromethyl;
or
(g) OR.sub.4 ;
wherein D is
(a) --CH.dbd.CH--,
wherein R.sub.3 is
(a) CH.sub.3 --C(O)--,
(b) hydrogen;
(c) --C(O)--(CR.sub.17 R.sub.18).sub.m --(CH.sub.2).sub.n --NR.sub.14 R.sub.15,
(d) --C(O)--AA, or
(e) --C(O)--PhX--NH.sub.2 ;
wherein m is 1, 2, 3, or 4;
wherein n is 0, 1, 2, 3, 4, or 5;
wherein --C(O)AA is the acyl portion derived from any naturally occurring alpha-amino acid,
wherein R.sub.14 and R.sub.15 are the same or different and are:
(a) hydrogen,
(b) (C.sub.1 -C.sub.10)alkyl,
(c) --C(O)R.sub.16,
(d) --C(O)--PhX, or
(e) --PhX;
with the proviso that R.sub.14 and R.sub.15 are other than hydrogen when n is zero;
wherein R.sub.16 is (C.sub.1 -C.sub.4)alkyl;
wherein R.sub.17 and R.sub.18 are the same or different and are:
(a) hydrogen,
(b) (C.sub.1 -C.sub.10)alkyl,
(c) --CH.sub.2 --PhX, or
(d) --PhX;
with the proviso that each occurrence of R.sub.17 and R.sub.18 may be the same or different;
wherein PhX--NH.sub.2 is an amino-substituted phenyl group additionally substituted by zero to 3 of the following:
(a) (C.sub.1 -C.sub.4)alkyl,
(b) chloro,
(c) fluoro,
(d) bromo,
(e) nitro,
(f) trifluoromethyl, or
(g) OR.sub.4 ;
wherein R.sub.4 is
(a) hydrogen, or
(b) (C.sub.1 -C.sub.4)alkyl;
with the following provisos
(1) R.sub.3 is not hydrogen;
(2) and one of R.sub.2 and R.sub.1 is hydrogen or methyl, the other is not hydrogen or methyl;
(3) when R.sub.2 is phenyl, R.sub.1 is other than hydrogen;
or a pharmacologically acceptable acid addition salt thereof,
when R.sub.3 is
(c) --C(O)--(CR.sub.17 R.sub.18).sub.m --(CH.sub.2).sub.n --NR.sub.14 R.sub.15,
(d) --C(O)--AA, or
(e) --C(O)--PhX--NH.sub.2.

56 more elements

Dependencies are inferred from the claim text.

Facts

Application: 06/878,116Filed 25 Jun 1986 · continuation in part
Priority: 14 Dec 1983
Granted: 13 Dec 1988
Term ends: Not estimatedThe source records don’t support an estimate.

Classification8 codes

A61K 31/40
Having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins: having five-membered rings with one nitrogen as the only ring hetero atom,…
A61K 31/085
Ethers or acetals: having an ether linkage to aromatic ring nuclear carbon
A61K 31/195
Carboxylic acids, e.g. valproic acid: having an amino group
A61K 31/215
Esters, e.g. nitroglycerine, selenocyanates: of carboxylic acids

Family

Serial561,602Parent of this continuation-in-part · filed 14 Dec 1983
US 4,791,138 AThis patent

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

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Abstract

The present invention provides a novel methoda for preventing deep vein thrombosis comprising the administration of lipoxygenase inhibitors of Formula I ##STR1##

wherein R.sub.1 and R.sub.2 are the same or different and are
(a) hydrogen,
(b) (C.sub.1 -C.sub.10)alkyl,
(c) (C.sub.2 -C.sub.10)alkenyl, or
(d) PhX;
wherein (PhX) is phenyl substituted by zero to 3 of the following:
(a) (C.sub.1 -C.sub.4)alkyl,
(b) chloro,
(c) fluoro,
(d) bromo,
(e) nitro,
(f) trifluoromethyl;
or
(g) OR.sub.4 ;
wherein D is
(a) --CH.dbd.CH--,
wherein R.sub.3 is
(a) CH.sub.3 --C(O)--,
(b) hydrogen;
(c) --C(O)--(CR.sub.17 R.sub.18).sub.m --(CH.sub.2).sub.n --NR.sub.14 R.sub.15,
(d) --C(O)--AA, or
(e) --C(O)--PhX--NH.sub.2 ;
wherein m is 1, 2, 3, or 4;
wherein n is 0, 1, 2, 3, 4, or 5;
wherein --C(O)AA is the acyl portion derived from any naturally occurring alpha-amino acid,
wherein R.sub.14 and R.sub.15 are the same or different and are:
(a) hydrogen,
(b) (C.sub.1 -C.sub.10)alkyl,
(c) --C(O)R.sub.16,
(d) --C(O)--PhX, or
(e) --PhX;
with the proviso that R.sub.14 and R.sub.15 are other than hydrogen when n is zero;
wherein R.sub.16 is (C.sub.1 -C.sub.4)alkyl;
wherein R.sub.17 and R.sub.18 are the same or different and are:
(a) hydrogen,
(b) (C.sub.1 -C.sub.10)alkyl,
(c) --CH.sub.2 --PhX, or
(d) --PhX;
with the proviso that each occurrence of R.sub.17 and R.sub.18 may be the same or different;
wherein PhX--NH.sub.2 is an amino-substituted phenyl group additionally substituted by zero to 3 of the following:
(a) (C.sub.1 -C.sub.4)alkyl,
(b) chloro,
(c) fluoro,
(d) bromo,
(e) nitro,
(f) trifluoromethyl, or
(g) OR.sub.4 ;
wherein R.sub.4 is
(a) hydrogen, or
(b) (C.sub.1 -C.sub.4)alkyl;
with the following provisos
(1) R.sub.3 is not hydrogen;
(2) and one of R.sub.2 and R.sub.1 is hydrogen or methyl, the other is not hydrogen or methyl;
(3) when R.sub.2 is phenyl, R.sub.1 is other than hydrogen;
or a pharmacologically acceptable acid addition salt thereof,
when R.sub.3 is
(c) --C(O)--(CR.sub.17 R.sub.18).sub.m --(CH.sub.2).sub.n --NR.sub.14 R.sub.15,
(d) --C(O)--AA, or
(e) --C(O)--PhX--NH.sub.2.

56 more elements

Facts

Application

06/878,116Filed 25 Jun 1986 · continuation in part

Priority

14 Dec 1983

Granted

13 Dec 1988

Term ends

Not estimatedThe source records don’t support an estimate.

Classification8 codes

A61K 31/40
Having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins: having five-membered rings with one nitrogen as the only ring hetero atom,…
A61K 31/085
Ethers or acetals: having an ether linkage to aromatic ring nuclear carbon
A61K 31/195
Carboxylic acids, e.g. valproic acid: having an amino group
A61K 31/215
Esters, e.g. nitroglycerine, selenocyanates: of carboxylic acids