EP0322184A2
Expired / Lapsed
EP
⏱️ 0.0 years remaining
N-(2-Alkyl-3-mercapto-1,5-di-oxoalkyl)glycinamide derivatives and their use as collagenase inhibitors
Assignee: Beecham Group PLC
•
Filing: 1988-12-19
•
Granted: —
•
Expires: 2008-12-19
Abstract
Abstract Novel compounds of the formula (I), a process for their preparation and their use as collagenase inhibitors are described: in which,R 1 is hydrogen, alkyl, or optionally substituted aryl; R 2 is hydrogen, or acyl such as where Z is optionally substituted aryl; R 3 is C 3 - 6 alkyl; R 4 is hydrogen, alkyl, -CH 2 -R 10 where R 10 is optionally substituted phenyl or heteroaryl, or a group where R 11 is hydrogen, alkyl, or -CH 2 -Ph where Ph is optionally substituted phenyl, and R 12 is hydrogen or alkyl; and Rs is hydrogen, alkyl, or a group where R 13 is hydrogen, or alkyl, and R 14 is hydroxy, alkoxy, or -NR 6 R 7 , where each of R 6 and R 7 is hydrogen or alkyl, or R 6 and R 7 together with the nitrogen atom to which they are bonded form a 5-, 6- or 7-membered ring with an optional oxygen or sulphur atom in the ring or an optional further nitrogen atom optionally substituted by alkyl.
Inventors
- 👤 Roger Edward Beecham Research Centre Markwell
- 👤 Stephen Allan Beecham Research Centre Smith
- 👤 Laramie Mary Beecham Research Centre Gaster
- 👤 Ian Dr. Smithkline Beecham Pharmaceuticals Hughes
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-08 13:14
CPC Classifications
C; C07; C07C; C07C323/00; C07C323/23; C07C323/24; C07C323/25; C07C323/50; C07C323/51; C07C323/60; A; A61; A61P; A61P1/00; A61P1/02; A61P17/00; A61P29/00; A61P35/00; A61P43/00; C07C327/00; C07C327/20; C07C327/32; C07D; C07D317/00; C07D317/08; C07D317/10; C07D317/14; C07D317/18; C07D317/22; C07D317/30
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
168 words
A compound of formula (I) or a salt, solvate or hydrate thereof: in which, R, is hydrogen, alkyl, or optionally substituted aryl; R 2 is hvdroaen, or acvl such as where Z is optionally substituted aryl; R 3 is C 3-6 alkyl; R 4 is hydrogen, alkyl, -CH 2 -R 10 where R 10 is optionally substituted phenyl or heteroaryl, or a group where R 11 is hydrogen, alkyl, or -CH 2 -Ph where Ph is optionally substituted phenyl, and R 12 is hydrogen or alkyl; and R s is hydrogen, alkyl, or a group where R 13 is hydrogen, or alkyl, and R 14 is hydroxy, alkoxy, or -NR 6 R 7 , where each of Rs and R 7 is hydrogen or alkyl, or R 6 and R 7 together with the nitrogen atom to which they are bonded form a 5-, 6- or 7-membered ring with an optional oxygen or sulphur atom in the ring or an optional further nitrogen atom optionally substituted by alkyl.
Claim 2
Dependent Claim
168 words
A compound of formula (I) or a salt, solvate or hydrate thereof: in which, R, is hydrogen, alkyl, or optionally substituted aryl; R 2 is hvdroaen, or acvl such as where Z is optionally substituted aryl; R 3 is C 3-6 alkyl; R 4 is hydrogen, alkyl, -CH 2 -R 10 where R 10 is optionally substituted phenyl or heteroaryl, or a group where R 11 is hydrogen, alkyl, or -CH 2 -Ph where Ph is optionally substituted phenyl, and R 12 is hydrogen or alkyl; and R s is hydrogen, alkyl, or a group where R 13 is hydrogen, or alkyl, and R 14 is hydroxy, alkoxy, or -NR 6 R 7 , where each of Rs and R 7 is hydrogen or alkyl, or R 6 and R 7 together with the nitrogen atom to which they are bonded form a 5-, 6- or 7-membered ring with an optional oxygen or sulphur atom in the ring or an optional further nitrogen atom optionally substituted by alkyl.
Claim 3
Dependent Claim
14 words
A compound according to claim 1, in which R 1 is C 1-4 alkyl.
Claim 4
Dependent Claim
15 words
A compound according to claim 1 or 2, in which R 2 is hydrogen, or
Claim 5
Dependent Claim
20 words
A compound according to any one of claims 1 to 3, in which R 3 is n-butyl, iso-butyl or sec-butyl.
Claim 6
Dependent Claim
21 words
A compound according to any one of claims 1 to 4, in which R 4 is benzyl, 4-hydroxybenzyl, 4-methoxybenzyl or 3-indolylmethyl.
Claim 7
Dependent Claim
23 words
A compound according to any one of claims 1 to 5, in which Rs is hydrogen, C 1-4 alkyl or 1-(C 1-4 alkoxycarbonyl)ethyl.
Claim 8
Dependent Claim
35 words
A compound according to any one of claims 1 to 6, in which R, is methyl; R 2 is hydrogen or acetyl; R 3 is iso-butyl; R 4 is 4-methoxybenzyl; and R s is methyl.
Claim 9
Dependent Claim
26 words
A compound according to any one of claims 1 to 7, in which the chiral centre marked with an asterisk in formula (I) has the S-configuration.
Claim 10
Dependent Claim
9 words
A compound selected from: 3-acetylmercapto-N-[2-(4-methoxyphenyl)-1-S- 5methylaminocarbonyl)ethyl]-2-(2-methylpropyl)-5-oxohex- anamide, or 3-mercapto-N-[2-(4-methoxyphenyl)-1-S-(methylaminocarbonyl)ethyl]-2-(2-methylpropyl)-5-oxohexanamide.
Claim 11
Dependent Claim
9 words
A compound selected from: 3-acetylmercapto-N-[2-(4-methoxyphenyl)-1-S- 5methylaminocarbonyl)ethyl]-2-(2-methylpropyl)-5-oxohex- anamide, or 3-mercapto-N-[2-(4-methoxyphenyl)-1-S-(methylaminocarbonyl)ethyl]-2-(2-methylpropyl)-5-oxohexanamide.
Claim 12
Dependent Claim
19 words
A pharmaceutically acceptable salt, solvate or hydrate of a compound according to any one of claims 1 to 9.
Claim 13
Dependent Claim
292 words
A process for the preparation of a compound of formula (I) as defined in claim 1, which process comprises: (a) the reaction of a compound of formula (III): in which Ri, R 3 , R 4 and Rs are as defined for formula (I) in claim 1, X is a carbonyl group or a protected carbonyl group, and the dotted line represents a double bond in a position either alpha or beta to variable R 3 , with a compound of formula (IV): in which L is a conventional sulphur protecting group; or (b) the reaction of a compound of formula (V): in which Ri, R 3 , R 4 . and R 5 are as defined for formula (I) in claim 1, X is a carbonyl group or a protected carbonyl group, and Y is a labile leaving group, with a compound of formula (IV) or a sodium salt thereof: in which L is an acyl group; the product of process variant (a) being a compound of formula (II): in which R 1 , R 3 , R 4 . and Rs are as defined for formula (I) in claim 1, X is a carbonyl group or a protected carbonyl group, and L is a conventional sulphur protecting group; and the product of process variant (b) being a compound of formula (II) in which R,, R 3 , R 4 . and Rs are as defined for formula (I) in claim 1, X is a carbonyl group or a protected carbonyl group, and L is an acyl group; and thereafter cleaving a group L when other than an acyl group, optionally cleaving a group L when an acyl group, and, where X is a protected carbonyl group, removing the protecting group.
Claim 14
Dependent Claim
26 words
A process according to claim 11 in which L is acetyl, X is a carbonyl group or 1,3-dioxolan-2-yl, and where applicable Y is tosyloxy or trifluoromethanesulphonyloxy.
Claim 15
Dependent Claim
57 words
A compound of formula (II): in which Ri, R 3 , R 4 and Rs are as defined for formula (I) in claim 1, X is a carbonyl group and L is a conventional sulphur protecting group other than an acyl group, or X is a protected carbonyl group and L is a conventional sulphur protecting group.
Claim 16
Dependent Claim
33 words
A pharmaceutical composition comprising a compound of formula (I) as defined in any one of claims 1 to 10, or a pharmaceutically acceptable salt, solvate or hydrate thereof, and a pharmaceutically acceptable carrier.
Claim 17
Dependent Claim
31 words
A compound of formula (I) as defined in any one of claims 1 to 10, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for use as an active therapeutic substance.
Claim 18
Dependent Claim
34 words
A compound of formula (I) as defined in any one of claims 1 to 10, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for use in the treatment of collagenolytic conditions in mammals.
Claim 19
Dependent Claim
41 words
The use of a compound of formula (I) as defined in any one of claims 1 to 10, or a pharmaceutically acceptable salt, solvate or hydrate thereof, in the manufacture of a medicament for the treatment of collagenolytic conditions in mammals.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
Maintenance schedule is calculated for granted US utility patents.