US5348980A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Enantiomers derived from (S)-2-amino-2-(3,4-dichlorobenzyl)-1-propanol, their use and method of preparation
Assignee: Institut de Recherche Jouveinal
•
Filing: 1993-05-03
•
Granted: 1994-09-20
•
Expires: 2013-05-03
Abstract
Abstract Enantiomers of (S) configuration of formula (I) ##STR1## in which R is H or methyl, with antiallergic and in particular antihistaminic activity, useful as medicinal products.
Inventors
- 👤 Gilbert Aubard
- 👤 Jacques Bure
- 👤 Alain Calvet
- 👤 Claude J. Gouret
- 👤 Agnes Grouhel
- 👤 Jean-Louis Junien
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 22:40
CPC Classifications
C; C07; C07D; C07D213/00; C07D213/02; C07D213/04; C07D213/60; C07D213/78; C07D213/79; C07D213/80; C07C; C07C219/00; C07C219/02; C07C219/20; C07C219/22; C07C233/00; C07C233/01; C07C233/45; C07C233/53; C07C233/54; C07D295/00; C07D295/04; C07D295/08; C07D295/084; C07D295/092; C07C2601/00; C07C2601/06; C07C2601/08; C07C2601/12; C07C2601/14
Claims Analysis
Total Claims: 29
Claim 1
Independent Claim
2 words
(S)-(+)-N-allyl-2-methylamino-2-(3,4-dichlorobenzyl)-1-propanol hydrochloride.
Claim 2
Dependent Claim
2 words
(S)-(+)-N-allyl-2-methylamino-2-(3,4-dichlorobenzyl)-1-propanol hydrochloride.
Claim 3
Independent Claim
55 words
A method of treating a human suffering from allergic or histamine-mediated diseases which comprises administering an anti-allergic effective amount of an enantiomer of (S) absolute configuration defined according to the Cahn-Ingold-Prelog rule and by formula (I): ##STR7## in which R is hydrogen or a methyl radical, or one of its addition salts with non-toxic acids.
Claim 4
Independent Claim
55 words
A method of treating a human suffering from allergic or histamine-mediated diseases which comprises administering an anti-allergic effective amount of an enantiomer of (S) absolute configuration defined according to the Cahn-Ingold-Prelog rule and by formula (I): ##STR7## in which R is hydrogen or a methyl radical, or one of its addition salts with non-toxic acids.
Claim 5
Dependent Claim
19 words
The method of claim 2 which further comprises providing the enantiomer of Formula (I) in which R is hydrogen.
Claim 6
Dependent Claim
21 words
The method of claim 2 which further comprises providing the enantiomer of Formula (I) in which R is CH 3 .
Claim 7
Dependent Claim
24 words
The method of one of claim 2-4 which further comprises administering the enantiomer in a dosage of from about 50 to about 1000 mg/day.
Claim 8
Dependent Claim
47 words
The method of claim 5 which further comprises administering the enantiomer as a pharmaceutical formulation comprising between about 1 and 50 percent by weight of the enantiomer and between about 99 and 50 percent by weight of a pharmaceutically acceptable vehicle which is compatible with the enantiomer.
Claim 9
Dependent Claim
25 words
The method of claim 6 which further comprises administering the enantiomer in the form of a tablet, dragee, capsule, powder, suppository, gel, suspension or solution.
Claim 10
Dependent Claim
12 words
The method of claim 6 which further comprises administering the enantiomer orally.
Claim 11
Dependent Claim
13 words
The method of claim 6 which further comprises administering the enantiomer by injection.
Claim 12
Dependent Claim
75 words
A process for preparing (S)-(-)-2-amino-2(3,4-dichlorobenzyl)-1-propanol of formula (II) ##STR8## in which R is hydrogen, which comprises reacting 3,4-dichlorophenylacetone with a potassium cyanide and an ammonium carbonate to obtain (+/-)-5-3,4-dichlorobenzyl)-5-hydantoin; forming an addition salt by stereospecific salification of (+/-)-5-3,4-dichlorobenzyl)-5-hydantoin with (R)-(+)-α-methyl-benzylamine; treating the addition salt with acid to obtain (S)-(-)-5-(3,4-dichlorobenzyl)-5-methyl hydantoin in an alkaline aqueous solution to obtain (S)-(-)-2-amino-2-(3,4-dichlorobenzyl)alanine; and reducing the (S)-(-)-2-amino-2-(3,4-dichlorobenzyl) alanine with a borane-dimethyl sulfide complex to obtain the compound of formula (II).
Claim 13
Dependent Claim
75 words
A process for preparing (S)-(-)-2-amino-2(3,4-dichlorobenzyl)-1-propanol of formula (II) ##STR8## in which R is hydrogen, which comprises reacting 3,4-dichlorophenylacetone with a potassium cyanide and an ammonium carbonate to obtain (+/-)-5-3,4-dichlorobenzyl)-5-hydantoin; forming an addition salt by stereospecific salification of (+/-)-5-3,4-dichlorobenzyl)-5-hydantoin with (R)-(+)-α-methyl-benzylamine; treating the addition salt with acid to obtain (S)-(-)-5-(3,4-dichlorobenzyl)-5-methyl hydantoin in an alkaline aqueous solution to obtain (S)-(-)-2-amino-2-(3,4-dichlorobenzyl)alanine; and reducing the (S)-(-)-2-amino-2-(3,4-dichlorobenzyl) alanine with a borane-dimethyl sulfide complex to obtain the compound of formula (II).
Claim 14
Dependent Claim
32 words
The process of claim 10 which further comprises conducting the reaction between the 3,4-dichlorophenylacetone, the potassium cyanide and the ammonium carbonate in ethanol at a temperature of at least about 40° C.
Claim 15
Dependent Claim
42 words
The process of claim 10 which further comprises mixing the (+/-)-5-3,4-dichlorobenzyl)-5-hydantoin with water and a base to form a solution; adding (R)-(+)-α-methylbenzylamine to the solution; heating the solution to dissolve the reactants; and thereafter cooling the solution to form the addition salt.
Claim 16
Dependent Claim
41 words
The process of claim 10 which further comprises mixing the (S)-(-)-5-(3,4-dichlorobenzyl)-5-methyl hydantoin with a solution of sodium hydroxide with stirring and at a temperature of at least about 140° C. and at elevated pressure for a sufficient time to obtain (S)-(-)-2-amino-2-(3,4-dichlorobenzyl)alanine.
Claim 17
Dependent Claim
46 words
The process of claim 10 which further comprises reducing the (S)-(-)-2-amino-2-(3,4-dichlorobenzyl)alanine by adding it with the borane-dimethyl sulfide complex to tetrahydrofuran in the absence of moisture with stirring to form a solution; and gradually adding methanol and sodium hydroxide to form the compound of formula (II).
Claim 18
Dependent Claim
45 words
The process of claim 10 which further comprises conducting an N-allylation of the compound of formula (II) with an allyl halide to obtain an enantiomer of (S) absolute configuration defined according to the Cahn-Ingold-Prelog rule and by formula (I) ##STR9## in which R is hydrogen.
Claim 19
Dependent Claim
17 words
The process of claim 15 which further comprises conducting the N-allylation of (S)-(-)-2-amino-2-(3,4-dichlorobenzyl)-1-propanol in an inert solvent.
Claim 20
Dependent Claim
17 words
The process of claim 16 which further comprises selecting the inert solvent to be toluene or acetonitrile.
Claim 21
Dependent Claim
21 words
The process of claim 16 which further comprises adding a basic agent to the inert solvent to promote the N-allylation reaction.
Claim 22
Dependent Claim
21 words
The process of claim 15 which further comprises selecting the allyl halide to be allyl chloride, allyl bromide or allyl iodide.
Claim 23
Dependent Claim
42 words
The process of claim 19 which further comprises utilizing about 0.5 to 1.5 mol of allyl halide per mole of amino alcohol and conducting the N-allylation reaction for about 1 to 24 hours at a temperature of about 20° to 110° C.
Claim 24
Dependent Claim
41 words
The process of claim 15 which further comprises utilizing about 0.5 to 1.5 mol of allyl bromide per mole of amino alcohol and conducting the N-allylation reaction for about 2 to 5 hours at a temperature about 40° to 100° C.
Claim 25
Dependent Claim
36 words
The process of claim 15 which further comprises conducting an N-methylation of the compound of formula (II) by reaction of formaldehyde and formic acid to obtain the enantiomer of formula (I) in which R is methyl.
Claim 26
Dependent Claim
40 words
The process of claim 22 which further comprises conducting the reductive methylation reaction in an aqueous formaldehyde solution which contains formic acid and provides about 1.2 to 3.5 mol of formaldehyde and about 2 and 5 mol of formic acid.
Claim 27
Dependent Claim
52 words
The process of claim 22 which further comprises initially reacting the formaldehyde exothermically with the compound of formula (I) to form a reaction product; adding the formic acid to the reaction product to form a mixture and heating the mixture for about 1 to 2 hours at about 90° to 100° C.
Claim 28
Dependent Claim
18 words
The process of claim 22 which further comprises purifying the enantiomer of formula (I) by a chromatographic method.
Claim 29
Dependent Claim
18 words
The process of claim 15 which further comprises purifying the enantiomer of formula (I) by a chromatographic method.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1997-09-19 | 1998-03-21 | 1998-09-20 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2001-09-19 | 2002-03-21 | 2002-09-20 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2005-09-19 | 2006-03-21 | 2006-09-20 | $7700.00 | Window Closed / Lapsed |