US 4,910,190 AGranted

Peptide derivatives

AssigneeICI Americas Inc.

InventorsScott H. Bergeson, Philip D. Edwards, John A. Schwartz, Andrew Shaw, Mark M. Stein, Diane A. Trainor, Richard A. Wildonger, Donald J. Wolanin

Life of this patent

Estimating the term…

Abstract

The invention concerns pharmaceutically useful trifluoromethyl ketone substituted di-, tri- and tetra-peptide derivatives of the formulae Ia, Ib, Ic set out hereinafter, and salts thereof, which are inhibitors of human leukocyte elastase. Also described herein are pharmaceutical compositions containing a peptide derivative and processes and intermediates for use in the manufacture of the peptide derivatives.

Claims9

Dependent claims

A compound of formula Ia, Ib or Ic:

##STR5## wherein R.sup.1 is an alkyl group containing from 1 to 5 carbon atoms;
R.sup.2 and R.sup.5 are each selected independently from the group consisting of:
(I) an alkyl group containing from 1 to 10 carbons;
and
(II) an alkyl group containing from 1 to 6 carbon atoms substituted by at least one member selected from the group consisting of:
(a) hydroxy;
(b) amino;
(c) alkylamino containing from 1 to 6 carbons;
(d) dialkylamino wherein each alkyl group contains from 1 to 6 carbons;
(e) alkanoyl containing from 1 to 6 carbons;
(f) arylcarbonyl wherein the aryl contains 6, 10 or 12 carbons;
(g) aralkanoyl containing 8 to 13 carbons;
(h) amido which may be attached to the alkyl group via either a nitrogen or carbon of said amido;
(i) alkylcarbonylamino wherein the alkyl group contains from 1 to 6 carbons;
(j) alkylaminocarbonyl wherein the alkyl group contains from 1 to 6 carbons;
(k) arylcarbonylamino wherein the aryl group contains 6, 10 or 12 carbons;
(l) aralkylcarbonylamino wherein the aralkyl group contains from 7 to 13 carbons;
(m) arylaminocarbonyl wherein the aryl group contains 6, 10 or 12 carbons;
(n) aralkylaminocarbonyl wherein the aralkyl group contains from 7 to 13 carbons;
(o) carboxy;
(p) aryloxycarbonyl wherein the aryl group contains 6, 10 or 12 carbons;
(q) aralkoxycarbonyl wherein the aralkoxy group contains from 7 to 13 carbons;
(r) alkanoyloxy containing from 1 to 6 carbons;
(s) aroyloxy wherein the aryl portion contains 6, 10 or 12 carbons;
(t) aralkanoyloxy containing from 8 to 14 carbons;
(u) alkylsulfonamido wherein the alkyl group contains from 1 to 6 carbons;
(v) aralkylsulfonamido wherein the aralkyl group contains from 7 to 13 carbons;
(w) arylsulfonamido wherein the aryl group contains 6, 10 or 12 carbons;
(x) acylsulfonamido (i.e. acylaminosulfonyl and sulfonylaminocarbonyl) including acylsulfonamido wherein the acyl group contains 1 to 7 carbons when it is the terminal portion of the acylsulfonamide and provided that when the acylsulfonamido contains an aryl the aryl may be further substituted by a member selected from fluoro, chloro, bromo, iodo and nitro;
(y) alkoxycarbonyl wherein the alkoxy group contains from 1 to 6 carbons;
(z) aralkoxycarbonylamino wherein the aralkoxy group contains from 8 to 13 carbons;
(aa) aryloxycarbonylamino wherein the aryloxy group contains 6, 10 or 12 carbons;
(bb) alkoxycarbonylamino wherein the alkyloxy group contains from 1 to 6 carbons;
(cc) aryl containing 6, 10 or 12 carbons;
(dd) aryl containing 6, 10 or 12 carbons and substituted by 1 to 3 members selected from the group consisting of chloro, bromo, iodo, fluoro, trifluoromethyl, hydroxy, alkyl (1 to 6 carbons), alkoxy (1 to 6 carbons), alkoxycarbonyl (1 to 6 carbons), carboxy, 5-tetrazolo, and acylsufonamido (i.e. acylaminosulfonyl and sulfonylaminocarbonyl) (1 to 15 carbons) and provided that when the acylsulfonamido contains an aryl the aryl may be further substituted by a member selected from fluoro, chloro, bromo, iodo and nitro;
(ee) cycloalkyl containing from 3 to 15 carbons;
(ff) alkylureido wherein the alkyl group contains from 1 to 6 carbons;
(gg) aralkylureido wherein the aralkyl group contains from 8 to 13 carbons;
(hh) arylureido wherein the aryl group contains 6, 10 or 12 carbons;
R.sup.3 is an aryl group containing 6, 10 or 12 carbons suitably substituted by acylsulfonamido (i.e. acylaminosulfonyl and sulfonylaminocarbonyl) containing from 1 to 15 carbons, and provided that when the acylsulfonamido contains an aryl the aryl may be further substituted by fluoro, chloro, bromo, iodo or nitro;
R.sup.4 and R.sup.6 are independently hydrogen or methyl;
n is 0, 1 or 2;
and
A is selected from the group consisting of ##STR6## and where appropriate, the acid- and base-addition salts thereof and provided that:
(1) alkyls may be straight or branched chain;
(2) no carbon of an alkyl may be directly bonded to two heteroatoms;
and
(3) no heteroatom may be directly bonded to a sulfur, nitrogen or oxygen.

45 more elements

Dependencies are inferred from the claim text.

Facts

Application: 07/005,538Filed 20 Jan 1987 · continuation in part
Priority: GB 850152222 Jan 1985
Granted: 20 Mar 1990
Term ends: Not estimatedThe source records don’t support an estimate.

Classification15 codes

C07C 205/26
The carbon skeleton being further substituted by hydroxy groups: and being further substituted by halogen atoms
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…
A61P 11/00
Drugs for disorders of the respiratory system
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents

Family

Serial821,150Parent of this continuation-in-part · filed 21 Jan 1986
US 4,910,190 AThis patent

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

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Abstract

A compound of formula Ia, Ib or Ic:

##STR5## wherein R.sup.1 is an alkyl group containing from 1 to 5 carbon atoms;
R.sup.2 and R.sup.5 are each selected independently from the group consisting of:
(I) an alkyl group containing from 1 to 10 carbons;
and
(II) an alkyl group containing from 1 to 6 carbon atoms substituted by at least one member selected from the group consisting of:
(a) hydroxy;
(b) amino;
(c) alkylamino containing from 1 to 6 carbons;
(d) dialkylamino wherein each alkyl group contains from 1 to 6 carbons;
(e) alkanoyl containing from 1 to 6 carbons;
(f) arylcarbonyl wherein the aryl contains 6, 10 or 12 carbons;
(g) aralkanoyl containing 8 to 13 carbons;
(h) amido which may be attached to the alkyl group via either a nitrogen or carbon of said amido;
(i) alkylcarbonylamino wherein the alkyl group contains from 1 to 6 carbons;
(j) alkylaminocarbonyl wherein the alkyl group contains from 1 to 6 carbons;
(k) arylcarbonylamino wherein the aryl group contains 6, 10 or 12 carbons;
(l) aralkylcarbonylamino wherein the aralkyl group contains from 7 to 13 carbons;
(m) arylaminocarbonyl wherein the aryl group contains 6, 10 or 12 carbons;
(n) aralkylaminocarbonyl wherein the aralkyl group contains from 7 to 13 carbons;
(o) carboxy;
(p) aryloxycarbonyl wherein the aryl group contains 6, 10 or 12 carbons;
(q) aralkoxycarbonyl wherein the aralkoxy group contains from 7 to 13 carbons;
(r) alkanoyloxy containing from 1 to 6 carbons;
(s) aroyloxy wherein the aryl portion contains 6, 10 or 12 carbons;
(t) aralkanoyloxy containing from 8 to 14 carbons;
(u) alkylsulfonamido wherein the alkyl group contains from 1 to 6 carbons;
(v) aralkylsulfonamido wherein the aralkyl group contains from 7 to 13 carbons;
(w) arylsulfonamido wherein the aryl group contains 6, 10 or 12 carbons;
(x) acylsulfonamido (i.e. acylaminosulfonyl and sulfonylaminocarbonyl) including acylsulfonamido wherein the acyl group contains 1 to 7 carbons when it is the terminal portion of the acylsulfonamide and provided that when the acylsulfonamido contains an aryl the aryl may be further substituted by a member selected from fluoro, chloro, bromo, iodo and nitro;
(y) alkoxycarbonyl wherein the alkoxy group contains from 1 to 6 carbons;
(z) aralkoxycarbonylamino wherein the aralkoxy group contains from 8 to 13 carbons;
(aa) aryloxycarbonylamino wherein the aryloxy group contains 6, 10 or 12 carbons;
(bb) alkoxycarbonylamino wherein the alkyloxy group contains from 1 to 6 carbons;
(cc) aryl containing 6, 10 or 12 carbons;
(dd) aryl containing 6, 10 or 12 carbons and substituted by 1 to 3 members selected from the group consisting of chloro, bromo, iodo, fluoro, trifluoromethyl, hydroxy, alkyl (1 to 6 carbons), alkoxy (1 to 6 carbons), alkoxycarbonyl (1 to 6 carbons), carboxy, 5-tetrazolo, and acylsufonamido (i.e. acylaminosulfonyl and sulfonylaminocarbonyl) (1 to 15 carbons) and provided that when the acylsulfonamido contains an aryl the aryl may be further substituted by a member selected from fluoro, chloro, bromo, iodo and nitro;
(ee) cycloalkyl containing from 3 to 15 carbons;
(ff) alkylureido wherein the alkyl group contains from 1 to 6 carbons;
(gg) aralkylureido wherein the aralkyl group contains from 8 to 13 carbons;
(hh) arylureido wherein the aryl group contains 6, 10 or 12 carbons;
R.sup.3 is an aryl group containing 6, 10 or 12 carbons suitably substituted by acylsulfonamido (i.e. acylaminosulfonyl and sulfonylaminocarbonyl) containing from 1 to 15 carbons, and provided that when the acylsulfonamido contains an aryl the aryl may be further substituted by fluoro, chloro, bromo, iodo or nitro;
R.sup.4 and R.sup.6 are independently hydrogen or methyl;
n is 0, 1 or 2;
and
A is selected from the group consisting of ##STR6## and where appropriate, the acid- and base-addition salts thereof and provided that:
(1) alkyls may be straight or branched chain;
(2) no carbon of an alkyl may be directly bonded to two heteroatoms;
and
(3) no heteroatom may be directly bonded to a sulfur, nitrogen or oxygen.

45 more elements

Facts

Application

07/005,538Filed 20 Jan 1987 · continuation in part

Priority

GB 850152222 Jan 1985

Granted

20 Mar 1990

Term ends

Not estimatedThe source records don’t support an estimate.

Classification15 codes

C07C 205/26
The carbon skeleton being further substituted by hydroxy groups: and being further substituted by halogen atoms
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…
A61P 11/00
Drugs for disorders of the respiratory system
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents