CA1164012A - Procede de preparation de nouveaux derives du glycerol ayant des proprietes pharmacologiques et derives ainsi obtenus - Google Patents

Procede de preparation de nouveaux derives du glycerol ayant des proprietes pharmacologiques et derives ainsi obtenus

Info

Publication number: CA1164012A
Authority: CA; Canada
Prior art keywords: propylacetate; glyceryl; bis; mixture; acid
Prior art date: 1979-03-06
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

CA000415623A

Other languages

English (en)

Inventor

Michel Chignac

Fernand Jammot

Pierre Eymard

Claude Grain

Charles Pigerol

Bernard Ferrandes

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Sanofi Aventis France

Original Assignee

Sanofi SA

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1979-03-06

Filing date

1982-11-15

Publication date

1984-03-20

1980-03-05 Priority claimed from CA000347041A external-priority patent/CA1162928A/fr

1982-11-15 Application filed by Sanofi SA filed Critical Sanofi SA

1982-11-15 Priority to CA000415623A priority Critical patent/CA1164012A/fr

1984-03-20 Application granted granted Critical

1984-03-20 Publication of CA1164012A publication Critical patent/CA1164012A/fr

Status Expired legal-status Critical Current

Links

238000004519 manufacturing process Methods 0.000 title claims abstract description 7
150000002314 glycerols Chemical class 0.000 title claims description 7
230000000144 pharmacologic effect Effects 0.000 title abstract description 8
NIJJYAXOARWZEE-UHFFFAOYSA-N Valproic acid Chemical compound CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 claims abstract description 90
239000000203 mixture Substances 0.000 claims abstract description 70
125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 claims abstract description 64
-1 alkali metal salt Chemical class 0.000 claims abstract description 29
150000002148 esters Chemical class 0.000 claims abstract description 27
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 25
229910052783 alkali metal Inorganic materials 0.000 claims abstract description 12
239000002904 solvent Substances 0.000 claims abstract description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims abstract 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 52
238000000034 method Methods 0.000 claims description 27
150000005690 diesters Chemical class 0.000 claims description 12
KTHXOYWHJBTQNC-UHFFFAOYSA-N 2-methyl-2-propylpentanoic acid Chemical compound CCCC(C)(C(O)=O)CCC KTHXOYWHJBTQNC-UHFFFAOYSA-N 0.000 claims description 9
RUANPKDCXUEVST-UHFFFAOYSA-N 2-methoxy-2-propylpentanoic acid Chemical compound CCCC(C(O)=O)(OC)CCC RUANPKDCXUEVST-UHFFFAOYSA-N 0.000 claims description 7
229940051269 1,3-dichloro-2-propanol Drugs 0.000 claims description 6
DEWLEGDTCGBNGU-UHFFFAOYSA-N 1,3-dichloropropan-2-ol Chemical compound ClCC(O)CCl DEWLEGDTCGBNGU-UHFFFAOYSA-N 0.000 claims description 6
159000000000 sodium salts Chemical class 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
230000032050 esterification Effects 0.000 claims description 3
238000005886 esterification reaction Methods 0.000 claims description 3
238000000926 separation method Methods 0.000 claims description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
210000003169 central nervous system Anatomy 0.000 abstract description 3
230000001575 pathological effect Effects 0.000 abstract 1
230000036765 blood level Effects 0.000 description 22
150000001875 compounds Chemical class 0.000 description 21
AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 17
239000002253 acid Substances 0.000 description 12
241000700159 Rattus Species 0.000 description 10
230000001225 therapeutic effect Effects 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
241001465754 Metazoa Species 0.000 description 8
239000003814 drug Substances 0.000 description 5
238000002329 infrared spectrum Methods 0.000 description 5
238000007912 intraperitoneal administration Methods 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
150000005691 triesters Chemical class 0.000 description 5
241000282412 Homo Species 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
238000005119 centrifugation Methods 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
235000014113 dietary fatty acids Nutrition 0.000 description 4
238000004821 distillation Methods 0.000 description 4
239000012153 distilled water Substances 0.000 description 4
229940079593 drug Drugs 0.000 description 4
239000000194 fatty acid Substances 0.000 description 4
229930195729 fatty acid Natural products 0.000 description 4
150000004665 fatty acids Chemical class 0.000 description 4
239000007792 gaseous phase Substances 0.000 description 4
230000004060 metabolic process Effects 0.000 description 4
230000000926 neurological effect Effects 0.000 description 4
239000000047 product Substances 0.000 description 4
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
239000001961 anticonvulsive agent Substances 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
230000000694 effects Effects 0.000 description 3
206010015037 epilepsy Diseases 0.000 description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
206010010904 Convulsion Diseases 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
230000001773 anti-convulsant effect Effects 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
239000008280 blood Substances 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
230000002276 neurotropic effect Effects 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
229920005862 polyol Polymers 0.000 description 2
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011734 sodium Substances 0.000 description 2
239000000243 solution Substances 0.000 description 2
150000003626 triacylglycerols Chemical class 0.000 description 2
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
208000023105 Huntington disease Diseases 0.000 description 1
206010029333 Neurosis Diseases 0.000 description 1
208000028017 Psychotic disease Diseases 0.000 description 1
102000003929 Transaminases Human genes 0.000 description 1
108090000340 Transaminases Proteins 0.000 description 1
231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
238000011047 acute toxicity test Methods 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
239000003708 ampul Substances 0.000 description 1
230000000496 anti-anoxic effect Effects 0.000 description 1
230000000561 anti-psychotic effect Effects 0.000 description 1
229960003965 antiepileptics Drugs 0.000 description 1
239000002249 anxiolytic agent Substances 0.000 description 1
230000000949 anxiolytic effect Effects 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
230000037396 body weight Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
239000003874 central nervous system depressant Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
229910017052 cobalt Inorganic materials 0.000 description 1
239000010941 cobalt Substances 0.000 description 1
GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
239000000470 constituent Substances 0.000 description 1
230000002920 convulsive effect Effects 0.000 description 1
239000012043 crude product Substances 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
208000002173 dizziness Diseases 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 1
NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
238000007701 flash-distillation Methods 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000007788 liquid Substances 0.000 description 1
230000005923 long-lasting effect Effects 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
239000003094 microcapsule Substances 0.000 description 1
YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
208000015238 neurotic disease Diseases 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
150000003077 polyols Chemical class 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
ONQDRCKUHDTWRA-UHFFFAOYSA-N propane-1,2,3-triol;2-propylpentanoic acid Chemical class OCC(O)CO.CCCC(C(O)=O)CCC ONQDRCKUHDTWRA-UHFFFAOYSA-N 0.000 description 1
229940090181 propyl acetate Drugs 0.000 description 1
230000000506 psychotropic effect Effects 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
WOYKYKKUVAMRIT-UHFFFAOYSA-M sodium 2-methoxy-2-propylpentanoate Chemical compound C(CC)C(C(=O)[O-])(OC)CCC.[Na+] WOYKYKKUVAMRIT-UHFFFAOYSA-M 0.000 description 1
WEOHWZGKYWAGSK-UHFFFAOYSA-M sodium 2-methyl-2-propylpentanoate Chemical compound C(CC)C(C(=O)[O-])(C)CCC.[Na+] WEOHWZGKYWAGSK-UHFFFAOYSA-M 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
229940084026 sodium valproate Drugs 0.000 description 1
239000007787 solid Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
229960000604 valproic acid Drugs 0.000 description 1
239000003981 vehicle Substances 0.000 description 1

Landscapes

Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

CA000415623A 1979-03-06 1982-11-15 Procede de preparation de nouveaux derives du glycerol ayant des proprietes pharmacologiques et derives ainsi obtenus Expired CA1164012A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000415623A CA1164012A (fr)	1979-03-06	1982-11-15	Procede de preparation de nouveaux derives du glycerol ayant des proprietes pharmacologiques et derives ainsi obtenus

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
GB7907932		1979-03-06
GB7907932		1979-03-06
CA000347041A CA1162928A (fr)	1979-03-06	1980-03-05	Derives de polyols, methodes de preparation et usages therapeutiques
CA000415623A CA1164012A (fr)	1979-03-06	1982-11-15	Procede de preparation de nouveaux derives du glycerol ayant des proprietes pharmacologiques et derives ainsi obtenus

Publications (1)

Publication Number	Publication Date
CA1164012A true CA1164012A (fr)	1984-03-20

Family

ID=27166611

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000415623A Expired CA1164012A (fr)	1979-03-06	1982-11-15	Procede de preparation de nouveaux derives du glycerol ayant des proprietes pharmacologiques et derives ainsi obtenus

Country Status (1)

Country	Link
CA (1)	CA1164012A (fr)

1982
- 1982-11-15 CA CA000415623A patent/CA1164012A/fr not_active Expired

Legal Events

Date	Code	Title	Description
2001-03-20	MKEX	Expiry

Publication	Publication Date	Title
FI69449C (fi)	1986-02-10	Foerfarande foer framstaellning av farmakologiskt verksamma glseroldiestrar
US4654370A (en)	1987-03-31	Glyceryl valproates
SU1138024A3 (ru)	1985-01-30	Способ получени аминопроизводных пиридазина
FR2460919A1 (fr)	1981-01-30	Amino-ethers oxydes, leur procede de preparation et leur application en therapeutique
EP0184905B1 (fr)	1989-03-01	Dérivés d'acétoacétyl-2 glycérol, leur production et utilisation
EP0797564B1 (fr)	2001-06-27	Lignanes, procede de production de ceux-ci, compositions pharmaceutiques les contenant, et leurs utilisations
US4599355A (en)	1986-07-08	Treatment of sleep disorders
CA1164012A (fr)	1984-03-20	Procede de preparation de nouveaux derives du glycerol ayant des proprietes pharmacologiques et derives ainsi obtenus
EP0586518B1 (fr)	1997-03-12	Produits analogues aux tocopherols abaissant le taux de cholesterol
US3002978A (en)	1961-10-03	Glyceryl pyrrolidone carboxylates
KR840001917B1 (ko)	1984-10-25	글리세릴 1,2-비스-(디-n-프로필아세테이트)와 글리세릴 1,3-비스-(디-n-프로필아세테이트) 혼합물의 제조방법
US5532380A (en)	1996-07-02	R,R,S,S-2-nitroimidazole derivatives
IE52289B1 (en)	1987-09-02	2-amino-3(halobenzoyl)-methylphenylacetic acids,esters and salts thereof
NL8102537A (nl)	1981-12-16	Esters van alkoxy-acylderivaten van carnitine, werkwijze ter bereiding ervan en farmaceutische preparaten, die deze derivaten bevatten.
US5438047A (en)	1995-08-01	Diphosphates of catecholamines and pharmaceutical compositions containing them
US3066167A (en)	1962-11-27	4-amino-3, 5-dichloro-benzamides
US4483999A (en)	1984-11-20	Phenoxy alkanoic acid derivatives having the ability to lower the level of fatty substances in the blood
EP0209239B1 (fr)	1989-03-01	Dérivés d'alcanoyloxy-2 propane, leur production et leur utilisation
US4133890A (en)	1979-01-09	Hypolipidemic compositions and method employing derivatives of 4-(((1,3-benzodioxol-5-yl)methyl)amino)benzoic acid
KR810001320B1 (ko)	1981-10-14	신규한 이소부티라미드류의 제조방법
US4124706A (en)	1978-11-07	Esters of bis-(hydroxyalkylthio)-alkanes
US3422141A (en)	1969-01-14	3,4-dihydroxyphenylalkanamides
US4358441A (en)	1982-11-09	Nicotinic derivatives of glucosamine and related pharmaceutical compositions
KR810001697B1 (ko)	1981-10-27	이소부티라미드 유도체의 신규한 제조방법
JPH02292213A (ja)	1990-12-03	制癌剤