EP0072286A1
Expired / Lapsed
EP
⏱️ 0.0 years remaining
Organic amide compounds derived from nitrogenous lipids
Assignee: Fidia SpA
•
Filing: 1982-07-27
•
Granted: —
•
Expires: 2002-07-27
Abstract
Abstract Organic amide compounds of the formula: wherein: R 1 -CO is a residue of a carboxylic acid with the proviso that the carboxylic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids, R 1 is a hydrogen atom, a C 1-7 alkyl group, or a C 4-7 cycloalkyl group, and R 3-N is a residue of a nitrogenous lipid. The compounds are useful in increasing or stimulating the in vivo biological activity of in vitro biologically active carboxylic acids.
Inventors
- 👤 Francesco Della Valle
- 👤 Aurelio Romeo
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-06 01:00
CPC Classifications
C; C07; C07D; C07D213/00; C07D213/02; C07D213/04; C07D213/60; C07D213/78; C07D213/81; A; A61; A61P; A61P25/00; A61P25/08; A61P25/20; A61P25/24; A61P25/26; A61P43/00; C07D213/82; C07D457/00; C07D457/04; C07D457/06; C07D473/00; C07D473/02; C07D473/04; C07D473/06; C07D473/08; C07F; C07F9/00; C07F9/02; C07F9/06; C07F9/08; C07F9/09; C07F9/091; C07F9/10; C07F9/113; C07F9/547; C07F9/553; C07F9/576; C07F9/58; C07H; C07H15/00; C07H15/02; C07H15/04; C07H15/10; C07H15/18; C07H15/26
Claims Analysis
Total Claims: 58
Claim 1
Independent Claim
72 words
- Organic amide compounds of the formula: wherein: R 1 -CO is a residue of a carboxylic acid with the proviso that the carboxilic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids; R2 is a hydrogen atom, a saturated C 1-7 alkyl group or a saturated C 4-7 cycloalkyl group, and R 3 -N is a residue of a nitrogenous lipid, or pharmaceutically acceptable salts thereof
Claim 2
Dependent Claim
72 words
- Organic amide compounds of the formula: wherein: R 1 -CO is a residue of a carboxylic acid with the proviso that the carboxilic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids; R2 is a hydrogen atom, a saturated C 1-7 alkyl group or a saturated C 4-7 cycloalkyl group, and R 3 -N is a residue of a nitrogenous lipid, or pharmaceutically acceptable salts thereof
Claim 3
Dependent Claim
36 words
- Compounds according to claim 1, wherein said carboxylic acid is selected from the group consisting of lysergic, isolysergic, dihydrolysergic, 2-bromolysergic, 2-bromo-dihydrolysergic, I-methyllysergic, 1-methyl- dihydrolysergic, 1-methyl-2-bromo-Tysergic, 1-methyl-2-bromo-dihydrolysergic, gamma-aminobutyric, valproic, trimethoxybenzoic, nicotinic, isonicotinic, picolinic and theophyllineacetic acids.
Claim 4
Dependent Claim
13 words
- Compounds according to claim 2, wherein: R 2 represents a hydrogen atom.
Claim 5
Dependent Claim
15 words
- Compounds according to claim 1 or 2, wherein said nitrogenous lipid is a phospholipid.
Claim 6
Dependent Claim
15 words
- Compounds according to claim 1 or 2, wherein said nitrogenous lipid is a sphingolipid.
Claim 7
Dependent Claim
15 words
- Compounds according to claim 4, wherein said phospholipid is a phosphatidylethanolamine or a phosphatidylserine.
Claim 8
Dependent Claim
32 words
- Compounds according to claim 5, wherein said sphingolipid is a sphingolipid having a free amine (NH 2 ) group and a residue of sphingosine having from 12 to 22 carbon atoms.
Claim 9
Dependent Claim
23 words
- Compounds according to claim 5,wherein said sphingolipid is selected from the group consisting of sphingosine, dihydrosphingosine, psychosine, dihydropsychosine, sphingosinephosphorylcholine, dihydrosphingosinephosphorylcholine and phytosphingosine.
Claim 10
Dependent Claim
46 words
- Compounds according to claim 1, wherein: R 2 is hydrogen, said lipid is sphingosine, and said carboxylic acid is selected from the group consisting of gamma-amino- butyric acid, lysergic acid, isolysergic acid, dihydrolysergic acid, valproic acid, trimethoxybenzoic acid, theophyllineacetic acid, nicotinic acid and isonicotinic acid.
Claim 11
Dependent Claim
36 words
- Compounds according to claim 1, wherein: R 2 is hydrogen, said lipid is psychosine, and said carboxylic acid is selected from the group consisting of trimethoxybenzoic, nicotinic acid, dihydrolysergic acid, lysergic acid and isolysergic acid.
Claim 12
Dependent Claim
22 words
- Compounds according to claim 1, wherein: R 2 is hydrogen, said lipid is sphingosinephosphorylcholine, and said carboxylic acid is trimethoxybenzoic acid.
Claim 13
Dependent Claim
22 words
- Compounds according to claim 1, wherein: R 2 is hydrogen, said lipid is dihydrosphingosine, and said carboxylic acid is dihydrolysergic acid.
Claim 14
Dependent Claim
23 words
- Compounds according to claim 1, which are trimethoxybenzoyl-phosphatidylserine amides of the formula: wherein: R and R' are saturated or unsaturated fatty acids.
Claim 15
Dependent Claim
23 words
- Compounds according to claim 1, which are nicotinylphosphatidylserine amides of the formula: wherein: R and R' are saturated or unsaturated fatty acids.
Claim 16
Dependent Claim
26 words
- Compounds according to claim 13 or 14, wherein: said R' is selected from the group consisting of stearic, palmitic, oleic, linolenic, linoleic and arachidonic acids.
Claim 17
Dependent Claim
23 words
- Compounds according to claim 1, which are trimethoxybenzoyl-iso- phosphatidylserine amides of the formula: wherein: R is a saturated or unsaturated fatty acid.
Claim 18
Dependent Claim
14 words
- A compound according to claim 16, wherein: R is stearic or oleic acid.
Claim 19
Dependent Claim
23 words
- Compounds according to claim 1, which are trimethoxybenzoylphosphatidylethanolamine amides of the formula: wherein: R and R' are saturated or unsaturated fatty acids.
Claim 20
Dependent Claim
25 words
- Compounds according to claim 18, wherein: R and R ' are selected from the group consisting of oleic, stearic, palmitic, linoleic and arachidonic acids.
Claim 21
Dependent Claim
92 words
- A pharmaceutical composition containing as an active ingredient an organic amide compound of the formula: wherein: R i -CO is a residue of a carboxylic acid with the proviso that the carboxylic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids, R 2 is a hydrogen atom, a saturated C 1-7 alkyl group or a saturated C 4 - 7 cycloalkyl group, and R 3 -N is a residue of a nitrogenous lipid, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier ou diluent.
Claim 22
Dependent Claim
92 words
- A pharmaceutical composition containing as an active ingredient an organic amide compound of the formula: wherein: R i -CO is a residue of a carboxylic acid with the proviso that the carboxylic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids, R 2 is a hydrogen atom, a saturated C 1-7 alkyl group or a saturated C 4 - 7 cycloalkyl group, and R 3 -N is a residue of a nitrogenous lipid, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier ou diluent.
Claim 23
Dependent Claim
38 words
- A pharmaceutical composition according to claim 20, wherein: said carboxylic acid is selected from the group consisting of lysergic, isolysergic, dihydrolysergic, 2-bromo-lysergic, 3-bromo-dihydrolysergic, 1-methyl-lysergic, 1-methyl-dihydrolysergic, 1-methyl-2-bromo-lysergic, 1-methyl-2-bromo-dihydrolysergic, gamma-amino-butyric, valprioc, trimethoxybenzoic, nicotinic, isonicotinic, picolinic and theophylline- acetic acids.
Claim 24
Dependent Claim
15 words
- A pharmaceutical composition according to claim 20, wherein: R 2 represents a hydrogen atom.
Claim 25
Dependent Claim
15 words
- A pharmaceutical composition according to claim 20, wherein: said nitrogenous lipid is a phospholipid.
Claim 26
Dependent Claim
15 words
- A pharmaceutical composition according to claim 20, wherein: said nitrogenous lipid is a sphingolipid.
Claim 27
Dependent Claim
17 words
- A pharmaceutical composition according to claim 23, wherein: said phospholipid is a phosphatidyl-ethanolamine or a phosphatidylserine.
Claim 28
Dependent Claim
33 words
- A pharmaceutical composition according to claim 24, wherein: said sphingolipid is a sphingolipid having a free amine (NH z ) group and a residue of sphingosine from 12 to 22 carbon atoms.
Claim 29
Dependent Claim
27 words
- A pharmaceutical composition according to claim 20, wherein: said sphingolipid is selected from the group consisting of sphingosine, dihydrosphingosine, psychosine, dihydropsychosine, sphingosinephosphorylcholine, dihydrosphingosine, phosphorylcholine and phytosphingosine.
Claim 30
Dependent Claim
86 words
- A pharmaceutical composition according to claim 20, wherein: R z is hydrogen, said lipid is sphingosine, and said carboxylic acid is selected from the group consisting of gamma-amino- butyric acid, lysergic acid, isolysergic acid, dihydrolysergic acid, valproic acid, trimethoxybenzoic acid, theophylline-acetic acid, nicotinic acid and isonicotinic acid. 29.- A pharmaceutical composition according to claim 20, wherein: Rz is hydrogen, said lipid is psychosine, and said carboxylic acid is selected from the group consisting of trimethoxybenzoic acid, nicotinic acid, dihydrolysergic acid, lysergic acid and isolysergic acid.
Claim 31
Dependent Claim
24 words
- A pharmaceutical composition according to claim 20, wherein: R 2 is hydrogen, said lipid is sphingosinephosphorylcholine, and said carboxylic acid is trimethoxybenzoic acid.
Claim 32
Dependent Claim
24 words
- A pharmaceutical composition according to claim 20, wherein: R 2 is hydrogen, said lipid is dihydrosphingosine, and said carboxylic acid is dihydrolysergic acid.
Claim 33
Dependent Claim
107 words
- A process for preparing organic amide compounds of the formula: wherein: R 1 -CO is a residue of a carboxylic acid with the proviso that the carboxylic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids, R 2 is a hydrogen atom, a saturated C 1-7 alkyl group or a saturated C 4 - 7 cycloalkyl group, and R 3 -N is a residue of a nitrogenous lipid, the process comprising the steps of: a) reacting a carboxylic acid of the formula R 1 COOH with a phenol to form an ester; and b) reacting said ester with said nitrogenous lipid.
Claim 34
Dependent Claim
107 words
- A process for preparing organic amide compounds of the formula: wherein: R 1 -CO is a residue of a carboxylic acid with the proviso that the carboxylic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids, R 2 is a hydrogen atom, a saturated C 1-7 alkyl group or a saturated C 4 - 7 cycloalkyl group, and R 3 -N is a residue of a nitrogenous lipid, the process comprising the steps of: a) reacting a carboxylic acid of the formula R 1 COOH with a phenol to form an ester; and b) reacting said ester with said nitrogenous lipid.
Claim 35
Dependent Claim
12 words
- The process according to claim 32, wherein: said phenol is para-nitrophenol.
Claim 36
Dependent Claim
106 words
- A process for preparing organic amide compounds of the formula: wherein: R 1 -CO is a residue of a carboxylic acid with the proviso that the carboxylic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids, R2 is a hydrogen atom, a saturated C 1-7 alkyl group or a saturated C 4-7 cycloalkyl group, and R 3 -N is a residue of a nitrogenous lipid, the process comprising the steps of: a) reacting a carboxylic acid of the formula R 1 -COOH with trifluoroacetic acid to form a mixed anhydride; and b) reacting said mixed anhydride with said nitrogenous lipid.
Claim 37
Dependent Claim
106 words
- A process for preparing organic amide compounds of the formula: wherein: R 1 -CO is a residue of a carboxylic acid with the proviso that the carboxylic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids, R2 is a hydrogen atom, a saturated C 1-7 alkyl group or a saturated C 4-7 cycloalkyl group, and R 3 -N is a residue of a nitrogenous lipid, the process comprising the steps of: a) reacting a carboxylic acid of the formula R 1 -COOH with trifluoroacetic acid to form a mixed anhydride; and b) reacting said mixed anhydride with said nitrogenous lipid.
Claim 38
Dependent Claim
106 words
- A process for preparing organic amide compounds of the formula: wherein: R 1 -CO is a residue of a carboxylic acid with the proviso that the carboxylic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids, R2 is a hydrogen atom, a saturated C 1-7 alkyl group or a saturated C 4-7 cycloalkyl group, and R 3 -N is a residue of a nitrogenous lipid, the process comprising reacting a carboxylic acid of the formula R 1 -COOH with said nitrogenous lipid in the presence of at least one member selected from the group consisting of a carbociimide and 1-hydrobenzotriazol.
Claim 39
Dependent Claim
106 words
- A process for preparing organic amide compounds of the formula: wherein: R 1 -CO is a residue of a carboxylic acid with the proviso that the carboxylic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids, R2 is a hydrogen atom, a saturated C 1-7 alkyl group or a saturated C 4-7 cycloalkyl group, and R 3 -N is a residue of a nitrogenous lipid, the process comprising reacting a carboxylic acid of the formula R 1 -COOH with said nitrogenous lipid in the presence of at least one member selected from the group consisting of a carbociimide and 1-hydrobenzotriazol.
Claim 40
Dependent Claim
15 words
- The process according to claim 35, wherein: said carbodiimide is dicyclohexylcarbodiimide, benzylisopropylcarbodiimide or benzylethylcarbodiimide.
Claim 41
Dependent Claim
101 words
- A process for preparing organic amide compounds of the formula: wherein: R 1 -CO is a residue of a carboxylic acid with the proviso that the carboxylic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids, R 2 is a hydrogen atom, a saturated C 1 - 7 alkyl group or a saturated C 4-7 cycloalkyl group, and R3-N is a residue of a nitrogenous lipid, the process comprising the steps of: a) preparing the chloride of a carboxylic acid of the formula R 1 -COOH; and b) reacting said chloride with said nitrogenous lipid.
Claim 42
Dependent Claim
101 words
- A process for preparing organic amide compounds of the formula: wherein: R 1 -CO is a residue of a carboxylic acid with the proviso that the carboxylic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids, R 2 is a hydrogen atom, a saturated C 1 - 7 alkyl group or a saturated C 4-7 cycloalkyl group, and R3-N is a residue of a nitrogenous lipid, the process comprising the steps of: a) preparing the chloride of a carboxylic acid of the formula R 1 -COOH; and b) reacting said chloride with said nitrogenous lipid.
Claim 43
Dependent Claim
106 words
- A process for preparing organic amide compounds of the formula: wherein: R1 - CO is a residue of a carboxylic acid with the proviso that the carboxylic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids, R is a hydrogen atom, a saturated C 1-7 alkyl group or a saturated C 4-7 cycloalkyl group, and - R 3 -N is a residue of a nitrogenous lipid, the process comprising the steps of: a) reacting a carboxylic acid of the formula R 1 -COOH with N,N'-carbo- nyldiimidazol to form an acylimidazol thereof; and b) reacting said acylimidazol with said nitrogenous lipid.
Claim 44
Dependent Claim
106 words
- A process for preparing organic amide compounds of the formula: wherein: R1 - CO is a residue of a carboxylic acid with the proviso that the carboxylic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids, R is a hydrogen atom, a saturated C 1-7 alkyl group or a saturated C 4-7 cycloalkyl group, and - R 3 -N is a residue of a nitrogenous lipid, the process comprising the steps of: a) reacting a carboxylic acid of the formula R 1 -COOH with N,N'-carbo- nyldiimidazol to form an acylimidazol thereof; and b) reacting said acylimidazol with said nitrogenous lipid.
Claim 45
Dependent Claim
116 words
- A process for preparing organic amide compounds of the formula: wherein: R 1 -CO is a residue of a carboxylic acid with the ' proviso that the carboxylic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids, R2 is a hydrogen atom, a saturated C 1-7 alkyl group or a saturated C 4-7 cycloalkyl group, and R 3 -N is a residue of a nitrogenous lipid, the process comprising the steps of: a) reacting gamma-aminobutyric acid with a protecting group to thereby protect the amine group thereof; b) reacting said protected gamma-aminobutyric acid with said nitrotenous lipid according to anyone of claims 32-38; and c) subsequently removing said protecting group.
Claim 46
Dependent Claim
17 words
- The process according to claim 39, wherein: said protecting group is a phthaloyl or benzyloxy carbonyl.
Claim 47
Dependent Claim
104 words
- A method for increasing or stimulating the in vivo biological activity of in vitro biologically active carboxylic acids which comprises preparing an amide of said carboxylic acid with a nitrogenous lipid to forme a compound of the formula: wherein: R 1 -CO is a residue of a carboxylic acid with the proviso that the carboxylic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids, R2 is a hydrogen atom, a saturated C 1-7 alkyl group or a saturated C 4-7 cycloalkyl group, and R 3 -N is a residue of a nitrogenous lipid, or pharmaceutically acceptable salts thereof.
Claim 48
Dependent Claim
104 words
- A method for increasing or stimulating the in vivo biological activity of in vitro biologically active carboxylic acids which comprises preparing an amide of said carboxylic acid with a nitrogenous lipid to forme a compound of the formula: wherein: R 1 -CO is a residue of a carboxylic acid with the proviso that the carboxylic acid is not a natural fatty acid normally bound to nitrogen of nitrogenous lipids, R2 is a hydrogen atom, a saturated C 1-7 alkyl group or a saturated C 4-7 cycloalkyl group, and R 3 -N is a residue of a nitrogenous lipid, or pharmaceutically acceptable salts thereof.
Claim 49
Dependent Claim
37 words
- A method according to claim 41, wherein: said carboxylic acid is selected from the group consisting of lysergic, isolysergic, dihydrolysergic, 2-bromolysergic, 2-bromo-dihydrolysergic, 1-methyllysergic, 1-methyl-dihydrolysergic, I-methyl-2-bromo-lysergic, I-methyl-2-bromo-dihydrolysergic, gamma-aminobutyric, valproic, trimethoxybenzoic, nicotinic, isonicotinic, picolinic and theophylline- acetic acids.
Claim 50
Dependent Claim
14 words
- A method according to claim 41, wherein: R 2 represents a hydrogen atom.
Claim 51
Dependent Claim
16 words
- A method according to claim 41 or 42, wherein: said nitrogenous lipid is a phospholipid.
Claim 52
Dependent Claim
16 words
- A method according to claim 41 or 42, wherein: said nitrogenous lipid is a sphingolipid.
Claim 53
Dependent Claim
16 words
- A method according to claim 44, wherein: said phospholipid is a phosphatidylethanolamine or a phosphatidylserine.
Claim 54
Dependent Claim
25 words
- A method according to claim 45, wherein: said sphingolipid is selected from the group consisting of sphingosine, dihydrosphingosine, psychosine, dihydropsychosine, sphingosinephosphorylcholine, dihydrosphingosinephosphorylcholine and phytosphingosine.
Claim 55
Dependent Claim
47 words
- A method according to claim 41, wherein: R 2 is hydrogen, said lipid is sphingosine, and said carboxylic acid is selected from the group consisting of gamma-amino- butyric acid, lysergic acid, isolysergic acid, dihydrolysergic acid, valproic acid, trimethoxybenzoic acid, theophyllineacetic acid, nicotinic acid and isonicotinic acid.
Claim 56
Dependent Claim
38 words
- A method according to claim 41, wherein: R 2 is hydrogen, said lipid is psychosine, and said carboxylic acid is selected from the group consisting of trimethoxybenzoic acid, nicotinic acid, dihydrolysergic acid, lysergic acid and isolysergic acid.
Claim 57
Dependent Claim
22 words
- A method according to claim 41, wherein: Rz is hydrogen, said lipid is sphingosinephosphorylcholine, and said carboxylic acid is trimethoxybenzoic acid.
Claim 58
Dependent Claim
22 words
- A method according to claim 41, wherein: Rz is hydrogen, said lipid is dihydrosphingosine, and said carboxylic acid is dihydrolysergic acid.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
Maintenance schedule is calculated for granted US utility patents.