Patent EP0446699A1 successfully refreshed from Google Patents.
EP0446699A1
Expired / Lapsed
EP
⏱️ 0.0 years remaining
Inhibitors of nitric oxide biosynthesis
Assignee: Aventis Pharmaceuticals Inc
•
Filing: 1991-02-26
•
Granted: —
•
Expires: 2011-02-26
Abstract
Abstract The present invention is directed to a new class of compound which are useful as inhibitors of the biosynthesis of nitric oxide.
Inventors
- 👤 Jeffrey P. Whitten
- 👤 Laurie E. Lambert
- 👤 Ian A. Mcdonald
- 👤 Niall S. Doherty
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-24 23:53
CPC Classifications
C; C07; C07K; C07K5/00; C07K5/04; C07K5/06; C07K5/06086; C07C; C07C235/00; C07C235/02; C07C235/04; C07C235/16; A; A61; A61K; A61K31/00; A61K31/13; A61K31/155; A61P; A61P25/00; A61P3/00; A61P3/08; A61P9/00; A61P9/08; A61P9/10; C07C243/00; C07C243/24; C07C243/36; C07C271/00; C07C271/06; C07C271/08; C07C271/10; C07C271/24; C07C279/00; C07C279/04; C07C279/14; C07C281/00; C07C281/02; C07C281/06; C07C281/16; A61K38/00; C07C2601/00; C07C2601/02
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
172 words
Compounds of the formulae Ia, Ib or Ic in which A is represented by -(CH₂)₂-, -(CH₂)3- or -CH=CH-; X is represented by cyano, cyclopropyl, 2-propyne, 2,3-butadiene or NHR₂, in which R₂ is represented by H, -CF₃, -CH₂CF₃, or C₁₋₆ alkyl; R is represented by an amino acid or OM in which M is represented by H, C₁₋₆ alkyl, benzyl, phenyl, pivoyl methyl ether, Z is represented by O or NR₁, in which R₁ is represented by H, -CF₃, -CH₂CF₃, or C₁₋₆ alkyl; and W is represented by a substituent selected from the group consisting of -CH₂-NH-, -(CH₂)₂-NH-, -NH-NH-, -CH₂-NH-NH-, -CH₂-O-NH- and -O-NH-; and the pharmaceutically acceptable salts thereof, with the following provisos: 1) that when W is -NH-NH or -(CH₂)₂-NH- then Z must be represented by O, and 2) when Z is represented by O and X is represented by NR₁, then W must be -CH₂-NH- or -(CH₂)₂-NH- and; 3) that when W is represented by CH₂-NH, Z is represented NH₂, and X is NHR₂, then R₂ is not represented by H.
Claim 2
Dependent Claim
14 words
A compound according to claim 1 in which W is -CH₂-NH-, -NH-NH-, or -O-NH-.
Claim 3
Dependent Claim
14 words
A compound according to claim 1 in which W is -(CH₂)₂-NH-, -CH₂-NH-NH-, or -CH₂-O-NH-.
Claim 4
Dependent Claim
160 words
A process for producing compounds of the formula Ia as defined in claim 1, comprising: a) carrying out a displacement reaction between phosgene (2, Y = Cl) or triphosgene (2, Y = OCCl₃) and a functionalized amino acid as described by structure (1) in which A is as defined in claim 1 and Pr is a t-butyloxycarbonyl group, while Pr' is a t-butyl group thereby producing a chloroformate or a trichloromethylurethane as described by structure (3) in which Pr, Pr' and A are as defined above, b) subjecting the chloroformate (3, Y = Cl) or the trichloromethylurethane (3, Y = OCCl₃) to an amidation reaction with an amino-derivative as described by structure (4) in which X is as defined in claim 1, thereby producing the protected compound of formula Ia', and c) deprotecting compound Ia' to produce a compound of formula Ia which is d) optionally functionalized to introduce the substituent R as defined in claim 1 into the molecule.
Claim 5
Dependent Claim
109 words
A process for producing compounds of formula Ib in which Z is represented by NR₁, comprising : a) carrying out a displacement reaction between a functionalized amino acid as described by structure (5) in which Pr and Pr' are either hydrogen or protecting groups and an amidino derivative as described by structure (6) in which Alk is represented by a C₁₋₄ alkyl, and R₁ and X are as defined in claim 1, thereby producing the optionally protected compound which has been depicted as Ib', b) subjecting this product to a deprotection reaction, and c) optionally functionalizing to introduce the substituent R as defined in claim 1 into the molecule.
Claim 6
Dependent Claim
110 words
A process for producing compounds of formula Ic in which Z is represented by NR₁, comprising: a) carrying out a displacement reaction between a functionalized amino acid as described by structure (7) in which W' is -CH₂-NH₂, NH₂-NH, -CH₂-O-NH₂, -CH₂-NH-NH₂, -(CH₂)₂-NH₂ or -O-NH₂ and in which Pr and Pr' are hydrogen or protecting groups and an amidino derivative as described by structure (6) in which Alk, R₁, and X are as defined in claim 5, thereby producing the compound of formula Ic', b) removing the protecting groups, if present, via an acidic hydrolysis, and c) optionally functionalizing to introduce the substituent R as defined in claim 1 into the molecule.
Claim 7
Dependent Claim
91 words
A process for producing compounds of formula Ic in which Z is represented by O, comprising: a) carrying out an addition reaction between a functionalized amino acid as described by structure (7) as defined in claim 6, and an isocyanate derivative as described by structure (8) in which X is as defined in claim 1 wherein Z is O, thereby producing the protected compound of formula Ic'', b) deprotecting the compound of formula Ic'', and c) optionally functionalizing to introduce the substituent R as defined in claim 1 into the molecule.
Claim 8
Dependent Claim
45 words
A process for producing compounds of formula Ib in which Z is O, comprising: a) carrying out the reaction as shown in claim 7, but substituting the following compound (5) for the amino acid of structure (7) in which Pr and Pr' are as above.
Claim 9
Dependent Claim
19 words
Use of a compound according to any of claims 1 to 3 for the preparation of a pharmaceutical composition.
Claim 10
Dependent Claim
17 words
Use according to claim 9 wherein the composition is useful for inhibiting the biosynthesis of nitric oxide.
Claim 11
Dependent Claim
16 words
Use according to claim 9 wherein the composition is useful for the treatment of hypotensive conditions.
Claim 12
Dependent Claim
16 words
Use according to claim 9 wherein the composition is useful for the treatment of inflammatory diseases.
Claim 13
Dependent Claim
15 words
Use according to claim 9 wherein the composition is useful for the treatment of epilepsy.
Claim 14
Dependent Claim
23 words
Use according to claim 9 wherein the composition is useful for the treatment of neurotoxicity associated with ischemic, hypoxic, traumatic or hypoglysemic conditions.
Claim 15
Dependent Claim
16 words
Use according to claim 9 wherein the composition is useful for the treatment of neurodegenerative diseases.
Claim 16
Dependent Claim
22 words
A pharmaceutical composition containing a compound according to any of claims 1 to 3 and optionally a pharmaceutically acceptable carrier and/or diluent.
Claim 17
Dependent Claim
13 words
The composition according to claim 16 for inhibiting the biosynthesis of nitric oxide.
Claim 18
Dependent Claim
12 words
The composition according to claim 16 for the treatment of hypotensive conditions.
Claim 19
Dependent Claim
12 words
The composition according to claim 16 for the treatment of inflammatory diseases.
Claim 20
Dependent Claim
11 words
The composition according to claim 16 for the treatment of epilepsy.
Claim 21
Dependent Claim
19 words
The composition according to claim 16 for the treatment of neurotoxicity associated with ischemic, hypoxic, traumatic or hypoglycemic conditions.
Claim 22
Dependent Claim
12 words
The composition according to claim 16 for the treatment of neurodegenerative diseases.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
Maintenance schedule is calculated for granted US utility patents.