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WO1987002035A1 - Aminoalcools cycloaliphatiques fusionnes - Google Patents

Aminoalcools cycloaliphatiques fusionnes Download PDF

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Publication number
WO1987002035A1
WO1987002035A1 PCT/EP1986/000606 EP8600606W WO8702035A1 WO 1987002035 A1 WO1987002035 A1 WO 1987002035A1 EP 8600606 W EP8600606 W EP 8600606W WO 8702035 A1 WO8702035 A1 WO 8702035A1
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WO
WIPO (PCT)
Prior art keywords
cis
formula
trans
compound
piperidinyl
Prior art date
Application number
PCT/EP1986/000606
Other languages
English (en)
Inventor
Giampaolo Picciola
Mario Riva
Franco Ravenna
Piergiorgio Gentili
Original Assignee
Maggioni-Winthrop S.P.A.
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 GB858524491A external-priority patent/GB8524491D0/en
Priority claimed from GB868615560A external-priority patent/GB8615560D0/en
Application filed by Maggioni-Winthrop S.P.A. filed Critical Maggioni-Winthrop S.P.A.
Publication of WO1987002035A1 publication Critical patent/WO1987002035A1/fr
Priority to DK281187A priority Critical patent/DK281187D0/da
Priority to KR870700473A priority patent/KR870700595A/ko
Priority to NO872362A priority patent/NO872362L/no

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
    • C07C217/60—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/182—Radicals derived from carboxylic acids
    • C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
    • 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
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • This invention is concerned with new pharmacologically active compounds. More particularly, the compounds with which this invention is concerned are fused cycloaliphatic aminoalcohols of the formula:
  • n represents an integer selected from 1 and 2;
  • R, R 1 and R 2 represent hydrogen or a lower alkoxy group, with the proviso that at least two alkoxy groups are present, or two adjacent radicals selected' from R+R 1 and R 1 +R 2 represent an alkylenedioxy group,
  • R 3 represents hydrogen and R 4 represents an alkyl group; or alternatively R 3 and R 4 taken together represent a divalent group selected from a)
  • A is a group selected from
  • R 4 represents a lower alkyl group ; c )
  • W represents hydrogen, phenyl, alkoxyphenyl, methylphenyl, 2-furoyl, nicotinoyl radical or a radical
  • -CO-CH CH-Z in which Z represents 2-thienyl or phenyl optionally substituted with 1-3 halogen or alkoxy groups: and their salts with inorganic acids, organic acids, cationic exchange resins and complexes with cyclodextrins.
  • the compounds having two structural asymmetry centers, may exist both in the cis and trans configuration.
  • the chemical process for the preparation of the invention compounds consists in contacting a bromo ketone of the partial formula IV with a secondary amine to give the amino ketone of the partial formula V.
  • the amino ketone V may be isolated from the reaction mixture before it is hydrogenated.
  • the intermediate V show a low degree of stability, it Is preferable to hydrogenate it directly in the reaction mixture in which it is formed by reaction of the bromo ketone with the secondary amine.
  • the first step of the process is carried out in the presence of a proton acceptor, such as an alkali metal or earth alkali carbonate or bicarbonate or a tertiary amine.
  • a proton acceptor such as an alkali metal or earth alkali carbonate or bicarbonate or a tertiary amine.
  • this first step is carried out in an inert solvent such as a lower alkanol, for instance methanol or ethanol, or a ketone, such as a di-lower alkyl ketone, for instance acetone or methyl ethyl ketone. It is immaterial whether the amine is added to the bromo ketone, both or only one of them being dissolved in the solvent, or vice versa the bromo ketone is added to the amine, still both in solution or only one of them.
  • the appropriate way of conducting the first step will be selected considering the properties of the reactants and their reactivity.
  • the reaction temperature is also adjusted depending of the reactivity of the two reactants, although normally the boiling temperature of the solvent is generally preferred.
  • the second step of the process i.e. the hydrogenation
  • a metal hydride preferably a double hydride, such as NaBH 4 , LiAlH 4 etc.
  • a solvent inert to the hydrogenation reaction which in the case of NaBH 4 may be water, or a lower alkanol, such as methanol or ethanol, both in the presence of various amounts of water or under anhydrous condition; or alternatively, when for instance LiAlH 4 in used, the solvent may be diethyl ether, tetrahydrofuran and the like, at a temperature which may range from 0-5°C to the boiling temperature of the selected solvent.
  • the intermediate When the intermediate is not isolated from the reaction mixture of the first reaction step, and depending on the nature of the selected hydrogenating agent, this may added directly to the intermediate reaction mixture either in the form of a solution in an appropriate solvent not interfering with the hydrogenation, and the solution of the hydrogenating agent is added while mantaining the mixture at the reflux temperature or at a lower temperature which may be found more convenient depending on the observed reaction rate; or the hydrogenating agent may be added at portions or by dropping its solution in an appropriate solvent while maintaining the reaction mixture at 0-5°C until the addition is complete, then heating the mixture to reflux until the reaction is complete.
  • An alternative process for preparing the invention compounds consists in reacting an amino alcohol of the partial formula VI with an aldehyde of the partial formula VII at a temperature between about 0°C and 20°C in a solvent, preferably in a lower alkanol such
  • a hydrogenating agent preferably selected from metal hydrides or double hydrides or double cyano hydrides, such as sodium boron cyano hydride or lithium boron cyano hydride, these latter hydrogenating agents being preferred.
  • the mixture is allowed to arrive slowly to the room temperature in order to complete the reaction.
  • the hydrogenation may be carried out by using conventional procedures such as hydrogen in the presence of a catalyst.
  • the compounds of this invention show anti-hypertensive, platelet aggregation inhibiting, hypolipemic, antianoxic, spasmolytic, antithrombotic and Ca++ antagonizing activity.
  • the anti-hypertensive activity was tested on groups of 5 SH rats (spontaneously hypertensive rats) and 5 DOCA rats (deoxycorticosterone acetate and sodium chloride loaded rats) weighing 200+10g, fasting from 18 hrs and treated orally with the invention compounds suspended in 0.5% gum arabic.
  • the heart rate was also tested (BP Recorder No. 8006 supplied by Basile, Comerio, Italy).
  • the arterial pressure before the treatment was 210 ⁇ 10 mmHg in SHR and 200 ⁇ 10 in DOCA rats.
  • Table 1 shows that the tested compounds are endowed with good anti-hypertensive activity.
  • PHE was administered cumulatively and dose-response curves were obtained (controls). Dose-response curves were similarly obtained after administration of the test drugs (1 mg/kg i.v.). From the two curves the PHE dosis causing a 50 mm Hg increase of the arterial pressure was calculated. The PHE dosis was about 3 times, in comparison with the controls, after administration of MG 28401 and MG 28427, and about 9 times after MG 38007, MG 38060 and 38041.
  • mice CrI:CD 1(CR) BR were treated orally with carrier (controls) and with various doses of the compounds. After 2 hrs 14.5 mg/kg of 1-adrenaline was administered intraperitoneally and mortality was recorded after 24 hrs; in controls mortality was 100%. From log-dose-% protection curves the 50% protective doses were calculated ( Litchfield et al., J. Pharmacol. Exp. Ther. 96, 99, 1949).
  • Table 2 gives the results obtained with some of the compounds as compared with known drugs.
  • the receptor binding assay for the inhibition of 3 H-Prazosin, 3 H-clonidine and 3 H-spiperone binding to rat brain membrane was carried out according to Greenberg et al., Life Sci. 19, 69, 1976, and U'Prichard et al., Molec. Pharmacol. 13, 454, 1977.
  • a moderate affinity toward serotoninergic 2 (5-HT 2 ) receptors is diplayed by MG 38007 MG 28401.
  • Platelet aggregation was stimulated with collagen (2-4-mcg/ml) added simultaneously to PRP of control and treated rats. The results were assessed photometrically. Each test was replicated 4 times in groups of 3 animals. Aggregation curves were evaluated in terms of two parameters namely maximum optical density variation (maximum aggregation) and aggregation rate.
  • Table 4 gives the effects recorded after treatment with some of the tested compounds. They show an activity comparable to Ticlopidine and Suloctidil and only slightly lower than Dipiridamol.
  • Sprague Dawley Nos male rats (180-200 g) were treated orally for 4 consecutive days with vehicle (0.5 ml/100 g gum arable 2.5%, controls) and with 1-2 doses of the tested compounds, and were sacrificed at the 5th day after 18 hrs. fasting.
  • Total cholesterol (CHOL), triglycerides (TG), HDL cholesterol (CHOL-HDL) were assayed in serum and the liver was weighed.
  • Table 5 gives the obtained results.
  • MG 38112 and MG 38107 cause a marked decrease both of CHOL and TG while MG 38041, MG 38128 and MG 38131 decrease TG and increase CHOL-HDL.
  • the liver weight is not affected.
  • the effect of MG 38112 and MG 38107 is higher than with Clofibrate which, as known, causes a signicative liver increase,
  • the Probucol activity is moderate and is noted only after prolonged treatment (8 days).
  • the anti-hypoxic activity was determined according to Yasuda et al., Arch. Int. Pharmacodyn. 233, 136, 1978.
  • mice Groups of 10 male mice (21-23 g) were treated orally with vehicle (controls) and the invention compounds. After 45 or 90 minutes the animals were decapitated and the gasping time was determined. Table 6 gives the results obtained after administration of some of the invention compounds which display an activity higher than Suloctidil.
  • the oral acute toxicity in male mice of the invention compound is very low.
  • the LD 50 is higher than 500 mg/kg for
  • MG 38041, MG 28400 and MG 38100 higher than 1,000 mg/kg for MG 38019, MG 38006, MG 38112 and MG 38107; and higher than 2,000 mg/kg for MG 38005, MG 28401, MG-28414 and MG 28427.
  • the formed salts are filtered off and the solution is concentrated under reduced pressure.
  • the obtained crude product is purified by flash chromatography through a column filled with silicagel 60
  • the mixture is then cooled causing separation of a precipitate which is collected and washed with water.
  • the filtered mother liquor from the reaction mixture is made acidic with aqueous 15% HCl and concentrated under reduced pressure.
  • the residue is made alkaline by addition of an aqueous 5% sodium carbonate solution and extracted with methylene dichloride.
  • the organic phase is washed with water until neutral and dried over sodium sulfate.
  • the residue which is obtained by evaporation of the solvent under reduced pressure is crystallized from acetone. 1.22 g of trans-isomer are obtained (yield 30%); m.p. 168-170°C.
  • EXAMPLE 4 cis and trans 2-[4-(1-Oxo-3-phenyl-2-propenyl)-1-piperazinyl]-4,5,6-trimethoxy-1-indanol (MG 38004 and MG 38015).
  • the above obtained amino ketone hydrochloride is dissolved in 50 ml of methanol, then 2 g of NaBH 4 are added in small portions at 5°C under continuous stirring, the mixture is then allowed to stand at room temperature for 1 hour, then it is diluted with water, extracted with chloroform and the organic solution is dried over magnesium sulfate. After concentration under reduced pressure the residue is cristallized from chloroform/hexane.
  • the product is dissolved in methanol and treated with HCl in ethanol giving 1.09 g of trans-2-amino-4,5,6-trimethoxy-1-indanol hydrochloride on addition of diethyl ether, as a precipitate having m.p. 167°C (dec); yield 54%.
  • EXAMPLE 12 cis and trans-2-[4-(2-Oxo-5-chloro-1-benzimidazolinyl)-1-piperidinyl]-5,6-dimethoxy-1-indanol.
  • EXAMPLE 19 cis and trans-2-[4(2-Oxo-5-chloro-1-benzimidazolinyl)-1-piperidinyl]-5,6,7- trimethoxy-1-tetralol.
  • cis (MG 16489) 10%; 124-126°C (CHCl 3 /petroleum ether) trans (MG 16456) 40%; 222-224°C (isopropanol)

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Catalysts (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Hydrogenated Pyridines (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Un composé possédant une activité pharmacologique sous forme d'activité anti-hypertensive, d'inhibition d'aggrégation de plaquettes, hypolipémique, antianoxique et spasmolytique. Ces composés ont la formule générique (I) dans laquelle le symbole n est un entier sélectionné parmi 1 et 2, et ils appartiennent par conséquent aux séries indanoles et tétraloles.
PCT/EP1986/000606 1985-10-04 1986-09-29 Aminoalcools cycloaliphatiques fusionnes WO1987002035A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
DK281187A DK281187D0 (da) 1985-10-04 1987-06-02 Kondenserede cycloaliphatiske aminoalkoholer
KR870700473A KR870700595A (ko) 1985-10-04 1987-06-03 융합지환족 아미노알코올
NO872362A NO872362L (no) 1985-10-04 1987-06-04 Kondenserte cykloalifatiske aminoalkoholer.

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB8524491 1985-10-04
GB858524491A GB8524491D0 (en) 1985-10-04 1985-10-04 Fused cycloaliphatic aminoalcohols
GB8615560 1986-06-25
GB868615560A GB8615560D0 (en) 1986-06-25 1986-06-25 Aminoalcohols

Publications (1)

Publication Number Publication Date
WO1987002035A1 true WO1987002035A1 (fr) 1987-04-09

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Application Number Title Priority Date Filing Date
PCT/EP1986/000606 WO1987002035A1 (fr) 1985-10-04 1986-09-29 Aminoalcools cycloaliphatiques fusionnes

Country Status (6)

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JP (1) JPH01503777A (fr)
KR (1) KR870700595A (fr)
AU (1) AU6548286A (fr)
DK (1) DK281187D0 (fr)
GR (1) GR862492B (fr)
WO (1) WO1987002035A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5457121A (en) * 1994-09-02 1995-10-10 Eli Lilly And Company Cis-hexahydro-5-(1,2,3,4-tetrahydro-2-naphthalenyl)pyrrolo<3,4-c>pyrroles as inhibitors of serotonin reuptake
US5637624A (en) * 1989-02-27 1997-06-10 Eli Lilly And Company Ring-substituted 2-amino-1,2,3,4-tetrahydronaphthalenes and 3-aminochromanes
EP0906912A1 (fr) * 1997-10-03 1999-04-07 Adir Et Compagnie Nouveaux composés de l'indanol, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent
WO2003020263A1 (fr) * 2001-08-31 2003-03-13 Aventis Pharma Deutschland Gmbh Utilisation de systemes d'indane-1-ol substitues en c2 pour produire des medicaments permettant de prevenir ou traiter l'obesite
WO2006061193A1 (fr) * 2004-12-07 2006-06-15 Glaxo Group Limited Derives d'indenyle et leur utilisation dans le traitement de troubles neurologiques

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1331191C (fr) * 1988-03-25 1994-08-02 Bengt Ronny Andersson Derives de la tetraline utiles comme medicaments

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2549685A (en) * 1948-09-30 1951-04-17 Upjohn Co Dioxy substituted 2-aminoindanols
FR1360532A (fr) * 1962-06-13 1964-05-08 Res Lab Dr C Janssen Nv Procédé de production de dérivés de la benzimidazolone et de leurs sels d'addition avec des acides
JPS50151853A (fr) * 1974-05-20 1975-12-06
GB1429028A (en) * 1972-12-18 1976-03-24 Takeda Chemical Industries Ltd Bicyclic compounds
FR2323388A1 (fr) * 1975-09-15 1977-04-08 Squibb & Sons Inc Nouveaux phenylpiperazinotetrahydronaphtols, leur preparation et leur utilisation therapeutique comme hypotenseurs
EP0000395A1 (fr) * 1977-07-18 1979-01-24 Sandoz Ag Dérivés de 2-pipérazinotétraline, leur préparation et leur utilisation comme médicament
GB2008106A (en) * 1977-11-08 1979-05-31 Mitsubishi Yuka Pharma Quinazoline derivatives process for preparing the same and anthypertensive drugs containing the same
US4533745A (en) * 1980-12-08 1985-08-06 Merck & Co., Inc. Amino ketones and their preparation

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2549685A (en) * 1948-09-30 1951-04-17 Upjohn Co Dioxy substituted 2-aminoindanols
FR1360532A (fr) * 1962-06-13 1964-05-08 Res Lab Dr C Janssen Nv Procédé de production de dérivés de la benzimidazolone et de leurs sels d'addition avec des acides
GB1429028A (en) * 1972-12-18 1976-03-24 Takeda Chemical Industries Ltd Bicyclic compounds
JPS50151853A (fr) * 1974-05-20 1975-12-06
FR2323388A1 (fr) * 1975-09-15 1977-04-08 Squibb & Sons Inc Nouveaux phenylpiperazinotetrahydronaphtols, leur preparation et leur utilisation therapeutique comme hypotenseurs
EP0000395A1 (fr) * 1977-07-18 1979-01-24 Sandoz Ag Dérivés de 2-pipérazinotétraline, leur préparation et leur utilisation comme médicament
GB2008106A (en) * 1977-11-08 1979-05-31 Mitsubishi Yuka Pharma Quinazoline derivatives process for preparing the same and anthypertensive drugs containing the same
US4533745A (en) * 1980-12-08 1985-08-06 Merck & Co., Inc. Amino ketones and their preparation

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Volume 85, No. 9, 30 August 1976, Columbus, Ohio (US) see page 542, Abstract 62844s & JP, A, 75151853 (Takeda Chemical Industries, Ltd) 6 December 1975 *
European Journal of Medicinal Chemistry, Volume 18, No, 3, 1983 Chatenay-Malabry (FR) J.G. CANNON: "Demi-Rigid Ketone Congeners of Catechiolemines", pages 291-292, see page 291 *
Journal of Chemical Society C, 1967 (US) R.I. THRIFT: "Derivatives of 2-Aminotetralin", pages 288-293, see pages 289,290,292 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5637624A (en) * 1989-02-27 1997-06-10 Eli Lilly And Company Ring-substituted 2-amino-1,2,3,4-tetrahydronaphthalenes and 3-aminochromanes
US5457121A (en) * 1994-09-02 1995-10-10 Eli Lilly And Company Cis-hexahydro-5-(1,2,3,4-tetrahydro-2-naphthalenyl)pyrrolo<3,4-c>pyrroles as inhibitors of serotonin reuptake
EP0906912A1 (fr) * 1997-10-03 1999-04-07 Adir Et Compagnie Nouveaux composés de l'indanol, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent
FR2769312A1 (fr) * 1997-10-03 1999-04-09 Adir Nouveaux composes de l'indanol, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
US5958927A (en) * 1997-10-03 1999-09-28 Adir Et Compagnie Indanol compounds
US6060487A (en) * 1997-10-03 2000-05-09 Adir Et Compagnie Indanol compounds
WO2003020263A1 (fr) * 2001-08-31 2003-03-13 Aventis Pharma Deutschland Gmbh Utilisation de systemes d'indane-1-ol substitues en c2 pour produire des medicaments permettant de prevenir ou traiter l'obesite
US7763662B2 (en) 2001-08-31 2010-07-27 Sanofi-Aventis Deutschland Gmbh Use of C2-substituted indan-1-ol systems for preparing medicaments for the prophylaxis or treatment of obesity
WO2006061193A1 (fr) * 2004-12-07 2006-06-15 Glaxo Group Limited Derives d'indenyle et leur utilisation dans le traitement de troubles neurologiques

Also Published As

Publication number Publication date
GR862492B (en) 1987-02-03
AU6548286A (en) 1987-04-24
KR870700595A (ko) 1987-12-30
DK281187A (da) 1987-06-02
DK281187D0 (da) 1987-06-02
JPH01503777A (ja) 1989-12-21

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