EP0000306B1 - Hexahydro benzopyrano (3,2-c) pyridines substituées, leur procédé de préparation et médicament les contenant - Google Patents

Hexahydro benzopyrano (3,2-c) pyridines substituées, leur procédé de préparation et médicament les contenant Download PDF

Info

Publication number
EP0000306B1
EP0000306B1 EP78400025A EP78400025A EP0000306B1 EP 0000306 B1 EP0000306 B1 EP 0000306B1 EP 78400025 A EP78400025 A EP 78400025A EP 78400025 A EP78400025 A EP 78400025A EP 0000306 B1 EP0000306 B1 EP 0000306B1
Authority
EP
European Patent Office
Prior art keywords
benzopyrano
hexahydro
pyridine
lactam
amino
Prior art date
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
EP78400025A
Other languages
German (de)
English (en)
French (fr)
Other versions
EP0000306A1 (fr
Inventor
Philippe Briet
Jean-Jacques Berthelon
Jean-Claude Depin
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.)
Merck Sante SAS
Original Assignee
LIPHA Liyonnaise Industrielle Pharmaceutique
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.)
Filing date
Publication date
Priority claimed from FR7719360A external-priority patent/FR2395270A1/fr
Priority claimed from FR7816376A external-priority patent/FR2427336A2/fr
Application filed by LIPHA Liyonnaise Industrielle Pharmaceutique filed Critical LIPHA Liyonnaise Industrielle Pharmaceutique
Publication of EP0000306A1 publication Critical patent/EP0000306A1/fr
Application granted granted Critical
Publication of EP0000306B1 publication Critical patent/EP0000306B1/fr
Expired legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
    • C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
    • C07D311/14—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 6 and unsubstituted in position 7
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/26—Psychostimulants, e.g. nicotine, cocaine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
    • C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
    • C07D311/12—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 3 and unsubstituted in position 7
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
    • C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
    • C07D311/16—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 7

Definitions

  • the present invention relates to substituted hexahydro benzopyrano [3,2-C] pyridines.
  • R is hydrogen or a saturated or unsaturated, linear or branched lower alkyl radical, aralkyl, acyl, dialkylaminoalkyl, alkylcarbonyl, alkoxycarbonyl, haloalkoxycarbonyl, aryl, benzyloxycarbonyl, ethoxalyl and ethoxycarbonylmethyl;
  • R is hydrogen, halogen or a lower alkoxy radical;
  • R 2 is hydrogen or halogen;
  • R 3 is hydrogen, halogen, lower alkyl, alkoxy, nitro, amino or forms naphthalene with R 4 and the benzene ring;
  • R 4 is hydrogen, halogen or forms naphthalene with R 3 and the benzene ring;
  • R s is hydrogen, a lower alkyl or arylalkyl radical.
  • the polycyclic structure of the compounds suggests for a given compound the existence of several stereoisomers. Examination in thin layer chromatography of the reaction products reveals the existence of two stereoisomers A and B. Recrystallization from an adequate solvent is sufficient to isolate in the pure state the majority stereoisomer of the crude reaction product. The minority stereoisomer can be obtained by concentration of the mother liquors. It is possible to transform the minority stereoisomer by acid treatment into the majority stereoisomer.
  • Decarboxylation by heating in sodium hydrogen carbonate makes it possible to isolate the compounds belonging to the @ series.
  • the transition from the compounds of the @ series to the corresponding compounds of the @ series is achievable by treating with hot hydrochloric acid the said compound of the @ series.
  • R is hydrogen
  • R benzyl
  • halo coumarin ethyl carboxylate-3 synthetic intermediates such as fluoro-6, chloro-5 and chloro-7 ethyl coumarin carboxylate-3 are new.
  • the new substituted hexahydro benzopyrano [3,2-C] pyridines have remarkable properties which make them useful drugs in depressive states and mental disorders. This mood-modifying activity can be determined by standardized tests well known to specialists. Thus, the compounds of the invention have been found to be potent inhibitors of reserpine ptosis.
  • Table 1 lists the effective doses 50 (ED.50) obtained for some products and those obtained for standard substances well known to specialists, such as Imipramine [N- (3-dimethylaminopropyl) iminodibenzyl hydrochloride] and Amitripthyline [(dimethylamino-3) propylidene hydrochloride) -5 dibenzo (a, d) cycloheptadiene-1,4].
  • Imipramine N- (3-dimethylaminopropyl) iminodibenzyl hydrochloride
  • Amitripthyline (dimethylamino-3) propylidene hydrochloride) -5 dibenzo (a, d) cycloheptadiene-1,4].
  • LD 50 oral lethal doses 50
  • the medicament containing as active principle a compound of the invention, associated with an acceptable pharmaceutical vehicle or excipient, is presented in a form suitable for oral or parenteral administration.
  • the dosage forms are unitary such as tablets, capsules, capsules, ampoules ... These dosage forms contain from 0.05 to 100 mg of active substance and allow daily administration of 1 to 200 mg.
  • the lactam is obtained from the acid [amino-4a hexahydro-1,2,3,4,4a, 10a, [10H] (benzopyrano) (3,2-C) ( pyridine)] yl-10 acetic in the form of a white solid, melting at 212 ° C.
  • Weight obtained 20 g (Yield: 80%)
  • IR vc o : 1680 cm- 1 .
  • Mp G 206-208 ° C
  • IR ⁇ c o : 1680 cm- 1 .

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Psychiatry (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Saccharide Compounds (AREA)
EP78400025A 1977-06-24 1978-06-19 Hexahydro benzopyrano (3,2-c) pyridines substituées, leur procédé de préparation et médicament les contenant Expired EP0000306B1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
FR7719360 1977-06-24
FR7719360A FR2395270A1 (fr) 1977-06-24 1977-06-24 Hexahydro benzopyrano (3,2-c) pyridines substituees, utilisables notamment comme medicaments
FR7816376A FR2427336A2 (fr) 1978-06-01 1978-06-01 Hexahydro benzopyrano (3,2-c) pyridines substituees utilisables notamment comme medicament
FR7816376 1978-06-01

Publications (2)

Publication Number Publication Date
EP0000306A1 EP0000306A1 (fr) 1979-01-10
EP0000306B1 true EP0000306B1 (fr) 1980-05-28

Family

ID=26220098

Family Applications (1)

Application Number Title Priority Date Filing Date
EP78400025A Expired EP0000306B1 (fr) 1977-06-24 1978-06-19 Hexahydro benzopyrano (3,2-c) pyridines substituées, leur procédé de préparation et médicament les contenant

Country Status (22)

Country Link
US (1) US4201783A (enrdf_load_stackoverflow)
EP (1) EP0000306B1 (enrdf_load_stackoverflow)
JP (1) JPS5412399A (enrdf_load_stackoverflow)
AR (1) AR225732A1 (enrdf_load_stackoverflow)
AT (1) AT356662B (enrdf_load_stackoverflow)
AU (1) AU519417B2 (enrdf_load_stackoverflow)
CA (1) CA1098519A (enrdf_load_stackoverflow)
CS (1) CS207624B2 (enrdf_load_stackoverflow)
DD (1) DD137441A5 (enrdf_load_stackoverflow)
DE (1) DE2860016D1 (enrdf_load_stackoverflow)
DK (1) DK158311C (enrdf_load_stackoverflow)
ES (1) ES471060A1 (enrdf_load_stackoverflow)
HU (1) HU177341B (enrdf_load_stackoverflow)
IE (1) IE46999B1 (enrdf_load_stackoverflow)
IL (1) IL54953A (enrdf_load_stackoverflow)
IN (1) IN151192B (enrdf_load_stackoverflow)
IT (1) IT1097257B (enrdf_load_stackoverflow)
MX (1) MX5090E (enrdf_load_stackoverflow)
NO (1) NO150205C (enrdf_load_stackoverflow)
NZ (1) NZ187629A (enrdf_load_stackoverflow)
SU (1) SU931108A3 (enrdf_load_stackoverflow)
YU (1) YU40338B (enrdf_load_stackoverflow)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004091596A2 (en) * 2003-04-18 2004-10-28 Pharmacia & Upjohn Company Llc Combination therapies for chronic obstructive pulmonary disease (copd)
EP2563839B1 (de) 2010-04-30 2014-12-17 Basf Se Polyetherpolyole, verfahren zur herstellung von polyetherpolyolen, sowie deren verwendung zur herstellung von polyurethanen
EP2691383B1 (en) * 2011-03-30 2015-01-21 3M Innovative Properties Company Fluorogenic or fluorophoric compounds and uses thereof
JP7209475B2 (ja) 2018-04-09 2023-01-20 日産自動車株式会社 電池の製造方法
CN111617254B (zh) * 2020-07-02 2022-04-26 中国人民解放军军事科学院军事医学研究院 降低mysm1含量或活性的物质在治疗抑郁症中的应用

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3549641A (en) * 1966-06-28 1970-12-22 Warner Lambert Pharmaceutical Pyrano pyridines and process for their production
US3673194A (en) * 1970-05-04 1972-06-27 American Cyanamid Co DERIVATIVES OF 1,4,4a,9b-TETRAHYDRO-8,9b-DIMETHYL-2-PHENYL-1,4-ETHANOBENZOFURO {8 3,2-C{9 PYRIDINE-3(2H), 10-DIONE
US4033968A (en) * 1976-04-14 1977-07-05 Merck & Co., Inc. Diazatetracyclododecanes

Also Published As

Publication number Publication date
JPS5412399A (en) 1979-01-30
DE2860016D1 (en) 1980-10-16
IL54953A0 (en) 1978-08-31
IN151192B (enrdf_load_stackoverflow) 1983-03-05
DK158311C (da) 1990-10-08
NO150205C (no) 1984-09-05
AR225732A1 (es) 1982-04-30
CA1098519A (fr) 1981-03-31
DD137441A5 (de) 1979-09-05
IL54953A (en) 1984-06-29
DK158311B (da) 1990-04-30
YU143878A (en) 1982-10-31
IT7824705A0 (it) 1978-06-19
YU40338B (en) 1985-12-31
HU177341B (en) 1981-09-28
NO150205B (no) 1984-05-28
AU519417B2 (en) 1981-12-03
NO782184L (no) 1978-12-28
ATA464478A (de) 1979-10-15
AT356662B (de) 1980-05-12
MX5090E (es) 1983-03-15
DK281978A (da) 1978-12-25
IT1097257B (it) 1985-08-31
AU3746378A (en) 1980-01-03
IE781239L (en) 1978-12-24
IE46999B1 (en) 1983-11-30
US4201783A (en) 1980-05-06
EP0000306A1 (fr) 1979-01-10
NZ187629A (en) 1981-03-16
CS207624B2 (en) 1981-08-31
ES471060A1 (es) 1979-01-01
JPS633866B2 (enrdf_load_stackoverflow) 1988-01-26
SU931108A3 (ru) 1982-05-23

Similar Documents

Publication Publication Date Title
EP0351282B1 (fr) Dérivés de (hydroxy-1 pipéridinyl-2 alkyl)indolones-2, quinoléinones-2, benzo[b]azépinones-2, benzimidazolones-2 et quinazolinones-2, leur préparation et leur application en thérapeutique
EP0370901B1 (fr) Nouveaux dérivés du chromanne actifs sur le système nerveux central, leur procédé de préparation et les compositions pharmaceutiques en contenant
EP0307303B1 (fr) [(Pyrimidinyl-2)-aminoalkyl]-1 pipéridines, leur préparation et leur application en thérapeutique
EP0743312A1 (fr) Nouveaux composés spiro hétérocycliques, leur procédé de préparation et les compositions pharmaceutiques les contenant
EP0306375A1 (fr) Dérivés de[(pipéridinyl-4)méthyl]-2 tétrahydro-1,2,3,4 isoquinoléine, leur préparation et leur application en thérapeutique
EP0467325A2 (en) Carbostyril derivatives
US4002632A (en) Tetracyclic piperidino derivatives
EP0835254B1 (fr) Derives d'oxazolidinone, leur preparation et leur application en therapeutique
EP0000306B1 (fr) Hexahydro benzopyrano (3,2-c) pyridines substituées, leur procédé de préparation et médicament les contenant
EP0004494B1 (fr) Nouveaux dérivés de 1,3-dihydro 3-(1-(2-(2,3-dihydro 1,4-benzo-dioxin-2-yl)2-hydroxy éthyl)pipéridin-4-yl)2H-indol 2-one, leur procédé de préparation, leur application comme médicaments et les compositions pharmaceutiques les renfermant
EP0114850B1 (fr) Nouveaux derives substitues du 2,5-diamino 1,4-diazole, leurs procedes de preparation et les compositions pharmaceutiques en renfermant
EP0319412A1 (fr) Nouveaux dérivés flavonoides pipérazinyl-2 oxo-2 éthylène substitués, leurs procédés de préparation et les compositions pharmaceutiques qui les contiennent
FR2696177A1 (fr) Dérivés de pipéridine, leur préparation et leur application en thérapeutique.
FR2671350A1 (fr) Nouveaux derives de benzisoxazole et de benzisothiazole, leur procede de preparation, et les compositions pharmaceutiques les renfermant.
EP0613898A1 (fr) Nouveaux composés (aryl(alkyl)carbonyl)-hétérocycliques leurs procédés de préparation et les compositions qui les contiennent
FR2758329A1 (fr) Derives d'imidazole-4-butane boronique, leur preparation et leur utilisation en therapeutique
FR2558835A1 (fr) Derives d'hydantoine, leur procede de production et medicament les contenant
EP1828125B1 (fr) Derives d'arylpiperazine et leur utilisation comme ligands selectifs du recepteur d3 de la dopamine
EP1687312B1 (fr) Molecules duales contenant un derive peroxydique, leur synthese et leurs applications therapeutiques
EP0427606A1 (fr) Dérivés d'amidino-4 chromanne et d'amidino-4 pyranno (3,2-c) pyridine, procédé d'obtention et compositions pharmaceutiques les contenant
EP0718307A2 (fr) Dérivés de 1-oxo-2-(phénylsulfonyl-amino)pentylpipéridine, leur préparation et leur application en thérapeutique
EP0302787B1 (fr) Dérivés de (pipéridinyl-4)méthyl-2 benzofuro[2,3-c]pyridines, leur préparation et leur application en thérapeutique
EP0105881B1 (fr) Nouvelles cyanoguanidines, leur procede d'obtention et les compositions pharmaceutiques en renfermant
EP0359627A1 (fr) Nouveaux derives de dihydro-2,3 arylalcoylaminoalcoyl-3 4H-benzoxazine-1,3 ones-4 leur préparation et leur application en tant que médicaments utiles en thérapeutique
EP0406502B1 (fr) Procédé de préparation de la (-) [[(amino-2 éthoxy)-2 éthoxy]méthyl]-2 (dichloro-2,3 phényl)-4 éthoxycarbonyl-3 méthoxycarbonyl-5 méthyl-6 dihydro-1,4 pyridine, et intermédiaire pour sa préparation

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

AK Designated contracting states

Designated state(s): BE CH DE FR GB LU NL SE

17P Request for examination filed
GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Designated state(s): BE CH DE FR GB LU NL SE

REF Corresponds to:

Ref document number: 2860016

Country of ref document: DE

Date of ref document: 19801016

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: SE

Payment date: 19810531

Year of fee payment: 4

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Effective date: 19820620

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 19910513

Year of fee payment: 14

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 19910515

Year of fee payment: 14

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: CH

Payment date: 19910524

Year of fee payment: 14

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: BE

Payment date: 19910528

Year of fee payment: 14

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: LU

Payment date: 19910529

Year of fee payment: 14

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 19910530

Year of fee payment: 14

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: NL

Payment date: 19910630

Year of fee payment: 14

EPTA Lu: last paid annual fee
PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 19920619

Ref country code: GB

Effective date: 19920619

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CH

Effective date: 19920630

Ref country code: BE

Effective date: 19920630

BERE Be: lapsed

Owner name: LIPHA - LYONNAISE INDUSTRIELLE PHARMACEUTIQUE

Effective date: 19920630

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NL

Effective date: 19930101

NLV4 Nl: lapsed or anulled due to non-payment of the annual fee
GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 19920619

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: FR

Effective date: 19930226

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Effective date: 19930302

REG Reference to a national code

Ref country code: FR

Ref legal event code: ST

EUG Se: european patent has lapsed

Ref document number: 78400025.9

Effective date: 19850612

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT