EP0000299B1 - Neue substituierte 2-Benzoyl-4-chloro-glycinanilidederivate, Verfahren zu ihrer Herstellung und deren Verwendung als Heilmittel. - Google Patents

Neue substituierte 2-Benzoyl-4-chloro-glycinanilidederivate, Verfahren zu ihrer Herstellung und deren Verwendung als Heilmittel. Download PDF

Info

Publication number
EP0000299B1
EP0000299B1 EP78400009A EP78400009A EP0000299B1 EP 0000299 B1 EP0000299 B1 EP 0000299B1 EP 78400009 A EP78400009 A EP 78400009A EP 78400009 A EP78400009 A EP 78400009A EP 0000299 B1 EP0000299 B1 EP 0000299B1
Authority
EP
European Patent Office
Prior art keywords
chloro
benzoyl
general formula
methyl
compound
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
EP78400009A
Other languages
English (en)
French (fr)
Other versions
EP0000299A1 (de
Inventor
Gilbert Mouzin
Henri Cousse
Antoine Stenger
Sylvano Casadio
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.)
Pierre Fabre SA
Original Assignee
Pierre Fabre 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.)
Filing date
Publication date
Application filed by Pierre Fabre SA filed Critical Pierre Fabre SA
Publication of EP0000299A1 publication Critical patent/EP0000299A1/de
Application granted granted Critical
Publication of EP0000299B1 publication Critical patent/EP0000299B1/de
Expired legal-status Critical Current

Links

Classifications

    • 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
    • C07D295/14—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/145—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/15—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • 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
    • 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
    • A61P25/20—Hypnotics; Sedatives

Definitions

  • the present invention carried out at the PIERRE FABRE Research Center relates to new derivatives of substituted 2-benzoyl-4-chloro-glycinanilides, their preparation process and their application as medicaments.
  • the present invention however relates to derivatives which differ from those of the aforementioned prior art by a substitution on the first nitrogen atom in the glycynanilide series, corresponding to the formula:
  • Alkyl groups denote straight or branched chain alkyl groups, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec.butyl, tert.-butyl, pentyl, isopentyl, neopentyl, tert.pentyl, hexyl, isohexyl, heptyle, etc.
  • the alkoxy substituents can for example be chosen from methoxy, ethoxy, propoxy, isopropoxy, etc. groups.
  • the aralkyl groups can be chosen from benzyl, phenethyl, phenylpropyl, etc.
  • the alkenyl groups can be chosen from allyl, butenyl, pentadienyl groups, etc.
  • the alkynyl groups can be chosen from ethynyl, propargyl, etc.
  • saturated or unsaturated heterocycles are chosen for example from pyrrolyl, imidazolyl, pyrazolyl, isoxazolyl, pyridyl, pyrazinyl, pyrinidinyl, pyridazinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidyl, piperazinyl, morpholinyl, etc.
  • the present invention also applies to the salts of the compounds of formula 1 obtained with therapeutically acceptable acids.
  • therapeutically or physiologically acceptable addition salts mention may be made of the salts of mineral acids, such as hydrochloric, phosphoric and sulfuric acids, and the salts of organic acids, such as succinic acids. , tartaric, etc.
  • the present invention finally relates to the application of the compounds of general formula I as medicaments with activity on the central nervous system and in particular as anxiolytic, sedative, anticonvulsant, hypnotic agents or as muscle relaxant.
  • the crystals are recovered by filtration, then these crystals are dissolved in two liters of ethyl acetate, the aqueous phase formed is decanted, the organic phase is dried over sodium sulfate and discolored by addition of animal black. After filtration, the organic phase is evaporated. A crude crystallized residue is recovered which is triturated in petroleum ether. The coloration partly disappears and 330 g of pale yellow crystals are obtained after filtration and drying. Yield 95%.
  • the mixture is stirred at ambient temperature for 6 hours and left to stand overnight, then the mixture is brought to 50 ° C. for 2 hours and to 70 ° C. for 3 hours.
  • the free base is poured into 6 liters of ice water, released and crystallized.
  • the crystals are recovered by filtration. These crystals are dissolved in 1.5 liters of ethyl acetate, the aqueous phase is decanted and the organic phase is dried over sodium sulfate. After filtration and concentration, 124.5 g of yellow crystals are recovered. 85% yield.
  • 2-methyl-5-chloro-benzophenone can also be prepared by direct methylation of 2-amino-5-chloro-benzophenone according to the following procedure:
  • the organic phase is dried over sodium sulfate.
  • the mixture After addition of the brominated derivative, the mixture is heated for 6 hours at 45 ° C., then left to stand overnight and evaporated to dryness under reduced pressure. The residue is taken up in a bicarbonate solution and extracted with ethyl acetate. Washed with water, dried over sodium sulfate and discolored in animal black. After filtration, evaporated to dryness. The residual oil is treated with an ethanolic solution saturated with hydrochloric acid.
  • Solubility soluble in water at 1%.
  • Solubility soluble in water at 1%.
  • the compounds of the present invention endowed with remarkable activity on the central nervous system, are therefore capable of being administered to humans or to animals: orally or by injection, in the form of a base. free or one of its therapeutically acceptable salts.
  • the compounds of the present invention have been subjected to toxicity controls.
  • the toxicity of certain compounds determined by the lethal dose 50 is reported in the following table. It was tested on batches of 10 mice by oral, intraperitoneal and intravenous route in certain cases, and calculated according to the method of MILLER and TAINTER (Proc. Soc. Exper. Biol. Méd., 1944, 57,261) .
  • mice have tonic convulsions whose outcome is fatal.
  • the compound is administered orally 60 minutes before the injection of pentamethylenetetrazole.
  • the animals are observed for 2 hours after administration of pentamethylenetetrazole. In certain specific cases the tests have been confirmed intraperitoneally.
  • the results are expressed by the effective dose of DE 50 (Goodman and Col. ⁇ J. Pharmacol. 108, 1953).
  • mice This test is carried out on male Swiss strain mice.
  • the mouse is placed on a wooden rod with a diameter of 3 cm, rotating at the rate of 5 revolutions / minute. Mice are chosen which can remain on the rod for at least 3 minutes during successive tests and they are grouped together in groups of 10 for the test of each dose. If the mouse falls from the stem in less than 2 minutes, the compound tested is considered to be effective.
  • the results are expressed by the effective dose DE 50 according to NW DUNHAN and TS MIVA-J. bitter. pharm. Ass., 1957, 46, 208.
  • the compounds of the invention and more particularly the compounds of Examples 2, 10, 11, 14, 19 and 20 can be used therapeutically in the treatment of anxiety and neuroses.
  • These compounds and their therapeutically compatible acid addition salts can be used as medicaments, for example in the form of pharmaceutical preparations suitable for enteral or parenteral administration, with for example water, lactose, gelatin, starches , magnesium stearate, talc, vegetable oils, gums, polyalkylene glycols, petroleum jelly, etc.
  • preparations can be in solid form, for example tablets, dragees, capsules, etc. or in liquid form, for example solutions, suspensions or emulsions.
  • compositions in a form suitable for injection are preferred. These preparations can be subjected to conventional pharmaceutical operations such as sterilization and / or can contain adjuvants, for example preservatives, wetting or emulsification stabilizers, buffer compounds, etc.
  • the dosages, to which the active compounds and their therapeutically compatible acid addition salts can be administered can vary in large proportions depending on the condition of the patient.
  • a daily dosage of about 0.01 mg to 1 mg per kg of body weight is preferred, however.
  • compositions according to the invention can be used in internal medicine, for example in the treatment of organic pathological conditions, such as high blood pressure and coronary artery, accompanied and aggravated by an anxious state; in psychosomatic medicine, for example for the treatment of asthma, peptic ulcers, colopathies and other functional digestive disorders; as well as in psychiatry, for example for the treatment of anxious states of agitation in psychotic subjects.
  • organic pathological conditions such as high blood pressure and coronary artery
  • psychosomatic medicine for example for the treatment of asthma, peptic ulcers, colopathies and other functional digestive disorders
  • psychiatry for example for the treatment of anxious states of agitation in psychotic subjects.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biomedical Technology (AREA)
  • Public Health (AREA)
  • Anesthesiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Furan Compounds (AREA)

Claims (27)

1. Neue Derivate von 2 - Benzoyl - 4 - chlor - glycinaniliden der allgemeinen Formel I.
Figure imgb0050
worin
R eine lineare oder verzweigte Alkylgruppe, vorzugsweise eine niedere Alkylgruppe darstellt;
R1 und R2 identisch oder verschieden sein können und ausgewählt werden aus Wasserstoff, Alkyl-, Alkenyl-, Alkinyl-, Hydroxyalkyl-, Alkoxyalkyl-, Aralkyl-Gruppen, wobei diese verschiedenen Gruppen linear oder verzweigt sein können, und 3- bis 6-gliedrigen Cycloalkyl-Gruppen, die an dem Kohlenstoffatom in a-Stellung gegebenenfalls durch einen Alkinylrest substituert sein können;
wobei die Gruppen R, und R2 außerdem zusammen mit dem Stickstoffatom, an das sie gebunden sind, einen gesättigten oder ungesättigten, 5-oder 6-gliedrigen, stickstoffhaltigen Heterocyclus bilden können, der gegebenenfalls ein zweites Heteroatom, ausgewählt aus Sauerstoff und Stickstoff, enthält und gegebenenfalls, vorzugsweise an dem zweiten Stickstoffatom, durch einen niederen Alkylrest substituiert ist;
sowie ihre Salze, die mit therapeutisch akzeptablen Mineralsäuren oder organischen Säuren erhalten werden.
2. Verbindungen der allgemeinen Formel I nach Anspruch 1, dadurch gekennzeichnet, daß R den Methylrest bedeutet.
3. Verbindung der allgemeinen Formel I nach Anspruch 2, dadurch gekennzeichnet, daß es sich dabei handelt um das Hydrochlorid von N - Methyl - N' - 1,1 - dimethyl - propargyl - (2 - benzoyl - 4 - chlor)glycinanilid.
4. Verbindung der allgemeinen Formel I nach Anspruch 2, dadurch gekennzeichnet, daß es sich dabei handelt um das Hydrochlorid von N - Methyl - N' - (2' - methoxy - äthyl) - (2 - benzoyl - 4 - chlor)glycinanilid.
5. Verbindung der allgemeinen Formel I nach Anspruch 2, dadurch gekennzeichnet, daß es sich dabei handelt um das Hydrochlorid von N - Methyl - N' - allyl - (2 - benzoyl - 4 - chlor)glycinanilid.
6. Verbindung der allgemeinen Formel I nach Anspruch 2, dadurch gekennzeichnet, daß es sich dabei handelt um das Hydrochlorid von N - Methyl - N' - (1',1' - diäthyl - propargyl) - (2 - benzoyl - 4 - chlor)glycinanilid.
7. Verbindung der allgemeinen Formel I nach Anspruch 2, dadurch gekennzeichnet, daß es sich dabei handelt um das Hydrochlorid von N - Methyl - N' - (1' - äthinyl - cyclohexyl) - (2 - benzoyl - 4 - chlor)glycinanilid.
8. Verbindung der allgemeinen Formel nach Anspruch 2, dadurch gekennzeichnet, daß es sich dabei handelt um das Hydrochlorid von N - Methyl - N' - cyclopropyl - (2 benzoyl - 4 - chlor)glycinanilid.
9. Verbindung der allgemeinen Formel I nach Anspruch 2, dadurch gekennzeichnet, daß es sich dabei handelt um das Hydrochlorid von N - Methyl - N' - cyclohexyl - (2 - benzoyl - 4 - chlor)glyci- nanilid.
10. Verbindung der allgemeinen Formel I nach Anspruch 2, dadurch gekennzeichnet, daß es sich dabei handelt um N,N' - Dimethyl - N' - (2' - hydroxy - äthyl) - (2 - benzoyl - 4 - chlor)glycina- nilid.
11. Verbindung der allgemeinen Formel I nach Anspruch 2, dadurch gekennzeichnet, daß es sich dabei handelt um N - Methyl - N' - äthyl - N' - (2' - hydroxy - äthyl) - (2 - benzoyl - 4 - chlor)-glycinanilid.
12. Verbindung der allgemeinen Formel I nach Anspruch 2, dadurch gekennzeichnet, daß es sich dabei handelt um das Hydrochlorid von N-Methyl-N'-bis-(2'-hydroxy-äthyl)-(2-benzoyl-4-chlor)glycin- anilid.
13. Verbindung der allgemeinen Formel I nach Anspruch 2, dadurch gekennzeichnet, daß es sich dabei handelt um das Hydrochlorid von N - Methyl - 2 - piperidino - (2' - benzoyl - 4' - chlor)acetanilid.
14. Verbindung der allgemeinen Formel nach Anspruch 2, dadurch gekennzeichnet, daß es sich dabei handelt um das Hydrochlorid von N - Methyl - 2 - morpholino - (2' - benzoyl - 4' - chlor)acetanilid.
15. Verbindung der allgemeinen Formel I nach Anspruch 2, dadurch gekennzeichnet, daß es sich dabei handelt um das Hydrochlorid von N - Methyl - N' - (2' - methyl - allyl) - (2 - benzoyl - 4 - chlor)glycinanilid.
16. Verbindung der allgemeinen Formel nach Anspruch 2, dadurch gekennzeichnet, daß es sich dabei handelt um das Hydrochlorid von N,N' - Dimethyl - N' - cyclohexyl - (2 - benzoyl - 4 - chlor)-glycinanilid.
17. Verbindung der allgemeinen Formel 1 nach Anspruch 2, dadurch gekennzeichnet, daß es sich dabei handelt um das Hydrochlorid von N - Methyl - N' - isopropyl - N' - cyclohexyl - (2 - benzoyl - 4 - chlor)glycinanilid.
18. Verbindung der allgemeinen Formel 1 nach Anspruch 2, dadurch gekennzeichnet, daß es sich dabei handelt um N - Methyl - 4' - methyl - 2 - piperazino - (2' - benzoyl - 4' - chlor)acetanilid.
19. Verbindung der allgemeinen Formel 1 nach Anspruch 2, dadurch gekennzeichnet, daß es sich dabei handelt um N - Methyl - 2 - imidazolyl - (2' - benzoyl - 4' - chlor)acetanilid.
20. Verfahren zur Herstellung der Verbindungen der allgemeinen Formel I nach einem der Ansprüche 1 bis 19, dadurch gekennzeichnet, daß man.
ein Halogenacetamid der allgemeinen Formel II
Figure imgb0051
worin
R die in Anspruch 1 angegebene Bedeutung hat und
X ein Halogenatom darstellt,

mit einem Amin der Formel III
Figure imgb0052
worin R1 und R2 die in Anspruch 1 angegebenen Bedeutungen haben, reagieren läßt.
21 Verfahren nach Anspruch 20, dadurch gekennzeichnet, daß das Halogenacetamid der Formel II hergestellt wurde durch Umsetzung eines Halogenacetylhalogenids der Formel IV
Figure imgb0053
mit einem N-substituierten Derivat von 2 - Amino - 5 - chlor - benzophenon der Formel V
Figure imgb0054
worin R und X die in Anspruch .20 angegebenen Bedeutungen haben.
22. Verfahren nach Anspruch 21, dadurch gekennzeichnet, daß das N-substituierte Derivat des 2-Amino-5-chlor-benzophenons der Formel V hergestellt wurde durch Hydrolyse einer N-substituierten Verbindung von 2-Tosylamido-5-chlor-benzophenon der Formel VI
Figure imgb0055
worin R die in Anspruch 20 angegeben Bedeutungen hat.
23. Verfahren nach Anspruch 22, dadurch gekennzeichnet, daß die N-substituierte Verbindung des 2-Tosylamido-5-chlor-benzophenons der Formel VI hergestellt wurde durch Umsetzung eines Halogenids der Formel VII
Figure imgb0056
mit 2-Tosylamidop-5-chlor-benzophenon,
wobei R und X die in Anspruch 20 angegebenen Bedeutungen haben.
24. Verfahren nach Anspruch 23, dadurch gekennzeichnet, daß das 2-Tosylamido-5-chlorbenzophenon hergestellt wurde durch Umsetzung eines Tosylhalogenids mit 2-Amino-5-chlorbenzophenon.
25. Verfahren nach Anspruch 21, dadurch gekennzeichnet, daß das N-substituierte Derivat des 2-Amino-5-chlor-benzophenons der Formel V hergestellt wurde durch Umsetzung eines Sulfats der Formel VIII
Figure imgb0057
worin R die in Anspruch 20 angegebene Bedeutung hat, mit 2-Amino-5-chlor-benzophenon in Gegenwart von Essigsäure.
26. Als neue Medikamente die Verbindungen der allgemeinen Formel nach einem der Ansprüche 1 bis 19 sowie ihre Additionssalze mit physiologisch akzeptablen Säuren.
27. Pharmazeutische Mittel, dadurch gekennzeichnet, daß sie als aktive Substanze mindestens eine Verbindung der allgemeinen Formel I nach einem der Ansprüche 1 bis 19 oder eines ihrer Additionssalze mit physiologisch akzeptablen Säuren enthalten.
EP78400009A 1977-06-16 1978-06-01 Neue substituierte 2-Benzoyl-4-chloro-glycinanilidederivate, Verfahren zu ihrer Herstellung und deren Verwendung als Heilmittel. Expired EP0000299B1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR7718511 1977-06-16
FR7718511A FR2403330A1 (fr) 1977-06-16 1977-06-16 Nouveaux derives de benzoyl-2-chloro-4-glycinanilides substitues, leur procede de preparation et leur application en tant que medicaments

Publications (2)

Publication Number Publication Date
EP0000299A1 EP0000299A1 (de) 1979-01-10
EP0000299B1 true EP0000299B1 (de) 1980-11-12

Family

ID=9192181

Family Applications (1)

Application Number Title Priority Date Filing Date
EP78400009A Expired EP0000299B1 (de) 1977-06-16 1978-06-01 Neue substituierte 2-Benzoyl-4-chloro-glycinanilidederivate, Verfahren zu ihrer Herstellung und deren Verwendung als Heilmittel.

Country Status (9)

Country Link
US (1) US4372975A (de)
EP (1) EP0000299B1 (de)
JP (1) JPS5436238A (de)
CA (1) CA1124256A (de)
DE (1) DE2860270D1 (de)
ES (1) ES470861A1 (de)
FR (1) FR2403330A1 (de)
IT (1) IT1156820B (de)
ZA (1) ZA783410B (de)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2436776A1 (fr) * 1978-09-25 1980-04-18 Fabre Sa Pierre Nouveaux derives d'ortho chloro benzoyl-2 chloro-4 glycylanilide, leur preparation et leur application en tant que medicaments
FR2449677B1 (fr) * 1979-02-26 1986-03-28 Fabre Sa Pierre Nouveaux derives de benzoyl-2 glycylanilides substitues, leur preparation et leur application en tant que medicaments anxiolytiques
FR2459793A1 (fr) * 1979-06-25 1981-01-16 Fabre Sa Pierre Nouveaux derives de benzoyl-2 nitro-4 anilides, leur preparation et leur application en tant que medicaments
FR2492818B1 (fr) * 1980-10-28 1988-03-04 Fabre Sa Pierre Ortho halogeno benzoyl-2 halogeno-4 glycylanilides substitues, leur preparation et leur application comme medicaments
FR2552083B1 (fr) * 1983-09-15 1986-05-09 Cerm Cent Europ Rech Mauvernay Derives de (alkynyloxy-3 hydroxy-2-propyl)-4 piperazinyl-1 n-phenyl acetamide, leur preparation et leur application en therapeutique
DE4312778C3 (de) * 1993-04-20 2001-10-25 Vossloh Schwabe Gmbh Elektrische Anschlußklemmeinrichtung
US6900228B1 (en) * 1998-03-10 2005-05-31 Research Triangle Institute Opiate compounds, methods of making and methods of use
EP1507756B1 (de) * 2002-05-24 2015-07-22 Millennium Pharmaceuticals, Inc. Ccr9-inhibitoren und verfahren zu deren verwendung
DK1798223T4 (da) * 2002-11-18 2014-09-22 Chemocentryx Inc Arylsulfonamider
US7741519B2 (en) * 2007-04-23 2010-06-22 Chemocentryx, Inc. Bis-aryl sulfonamides
US7420055B2 (en) 2002-11-18 2008-09-02 Chemocentryx, Inc. Aryl sulfonamides
US20070021466A1 (en) * 2002-11-18 2007-01-25 Solomon Ungashe CCR2 inhibitors and methods of use thereof
US20060111351A1 (en) * 2002-11-18 2006-05-25 Solomon Ungashe Aryl sulfonamides
US7227035B2 (en) * 2002-11-18 2007-06-05 Chemocentryx Bis-aryl sulfonamides
CN105001105A (zh) * 2015-06-26 2015-10-28 华中药业股份有限公司 一种2-甲氨基-5-氯二苯甲酮的制备方法

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK104746C (da) * 1960-06-27 1966-06-27 Hoffmann La Roche Fremgangsmåde til fremstilling af 2-α-aminoalkanoylamido-benzophenon-forbindelser eller syreadditionssalte eller kvaternære ammoniumforbindelser deraf.
US3202699A (en) * 1961-07-11 1965-08-24 Hoffmann La Roche Carbobenzoxyglycylamino-benzophenones
US3914215A (en) * 1967-11-27 1975-10-21 Sankyo Co Benzodiazepine derivatives and process for preparing the same
BG19177A3 (bg) * 1968-07-01 1975-04-30 Sankyo Co Ltd Бензодиазепинни деривати и процес за приготовлението им
CA1041498A (en) * 1968-10-18 1978-10-31 Hoffmann-La Roche Limited Benzodiazepine derivatives
US3927010A (en) * 1969-10-17 1975-12-16 Hoffmann La Roche Diarylmethane derivatives and processes for their preparation
SE410732B (sv) * 1971-12-13 1979-10-29 Sumitomo Chemical Co Analogiforfarande for framstellning av anilidderivat med terapeutisk verkan
US3928415A (en) * 1973-05-08 1975-12-23 Cassella Farbwerke Mainkur Ag Benzophenone derivatives and process for their production II
AU471999B2 (en) 1973-08-10 1976-05-13 Sankyo Company Limited Substituted amino-acetylamino-benzophenone compounds
DE2356239A1 (de) * 1973-11-10 1975-05-15 Cassella Farbwerke Mainkur Ag Benzophenon-derivate und verfahren zu ihrer herstellung
JPS5139654A (ja) * 1974-09-27 1976-04-02 Sumitomo Chemical Co Aminoasetoaniridojudotai no shinkinaseizoho

Also Published As

Publication number Publication date
FR2403330B1 (de) 1982-11-05
IT1156820B (it) 1987-02-04
DE2860270D1 (en) 1981-02-05
IT7849859A0 (it) 1978-06-14
US4372975A (en) 1983-02-08
EP0000299A1 (de) 1979-01-10
ZA783410B (en) 1979-06-27
JPS5436238A (en) 1979-03-16
CA1124256A (fr) 1982-05-25
ES470861A1 (es) 1979-02-01
FR2403330A1 (fr) 1979-04-13

Similar Documents

Publication Publication Date Title
CA1202639A (fr) Derives d'aryl-1 aminomethyl-2 cyclopropanes carboxamides (z) et leur preparation
EP0000299B1 (de) Neue substituierte 2-Benzoyl-4-chloro-glycinanilidederivate, Verfahren zu ihrer Herstellung und deren Verwendung als Heilmittel.
EP0487408A1 (de) Oxazolopyridinderivate, Verfahren zu ihrer Herstellung und die sie enthaltenden pharmazeutischen Zusammensetzungen
EP0094271B1 (de) Aren- und Heteroarencarboxamid-Derivate, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel
FR2656609A1 (fr) Derives de 2-aminopyrimidine-4-carboxamide, leur preparation et leur application en therapeutique.
FR2468601A1 (fr) Nouveaux derives de flavanne utiles notamment comme anticonvulsivants
EP0076199B1 (de) Triazoloquinazolone und deren Salze, Verfahren und Zwischenprodukte zu ihrer Herstellung, ihre Verwendung als Arzneimittel und diese enthaltende Zusammensetzungen
EP0068998B1 (de) (Z)-1-Aryl-2-aminomethyl-cyclopropan-carboxylate, ihre Herstellung und ihre Verwendung als Arzneimittel für die Behandlung von verschiedenen Schmerzen
EP0205362A1 (de) Chinolylglycinamidderivate, Verfahren zu ihrer Herstellung und therapeutische Verwendung als Psychotrope
EP0239461A1 (de) N-¬¬(Hydroxy-2-phenyl)(phenyl)methylen amino-2 äthylacetamid-Derivate, Verfahren zu ihrer Herstellung und ihre Anwendung als Heilmittel
EP0015214B1 (de) Substituierte 2-(Benzoyl)-glycinanilid-Derivate, ihre Herstellung und ihre Verwendung in anxiolytischen Arzneimitteln
EP0002978B1 (de) Thiazolidindion-2,4 Derivate, deren Herstellung und Verwendung als Arzneimittel
EP0077720B1 (de) Derivate von Biphenyl-Alkyl-Carboxylaten, deren Herstellungsverfahren und deren Verwendung als Arzneimittel
EP0301936B1 (de) Piperidin-Derivate, deren Herstellung und deren Verwendung als Heilmittel
FR2643634A1 (fr) Nouveaux derives benzoxazolinoniques, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent
EP0022017B1 (de) Derivate von 2-Benzoyl-4-nitro-aniliden, deren Herstellung und deren Verwendung als Heilmittel
EP0087337B1 (de) 2-Piperazinyl-4-phenyl-quinazolin-Derivate mit antidepressiven Eigenschaften, Verfahren zu deren Herstellung und diese enthaltende Arzneimitteln
EP0010030B1 (de) 2'-(Ortho-chlor-benzoyl),4'-chlor-glycinanilid-Derivate, ihre Herstellung und ihre Verwendung als Arzneimittel
CA2045849A1 (fr) Derives d'oxazolo pyridines, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
EP0161143B1 (de) 1,2,4-Thiadiazine und ihre Salze, Verfahren und Zwischenprodukte zu ihrer Herstellung, ihre Verwendung als Arzneimittel und sie enthaltende Arzneimittel
EP0035619B1 (de) 3-Amino-(1H,3H)-2,4-chinazolindionderivate
EP0067094A1 (de) Heterocyclische Derivate von Amidoxinen, ihre Herstellung und therapeutische Verwendung
CH618171A5 (en) Process for the preparation of new imidazolobenzodiazepines and of their salts
FR2539414A1 (fr) Derives de la pyrimidine, leur procede de preparation et les medicaments ayant une activite sur le systeme nerveux central qui en contiennent
FR2492818A1 (fr) Ortho halogeno benzoyl-2 halogeno-4 glycylanilides substitues, leur preparation et leur application comme medicaments

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 NL

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 NL

REF Corresponds to:

Ref document number: 2860270

Country of ref document: DE

Date of ref document: 19810205

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

Ref country code: GB

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: CH

Payment date: 19910610

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: 19910620

Year of fee payment: 14

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

Ref country code: FR

Payment date: 19910626

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

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

Ref country code: BE

Payment date: 19910715

Year of fee payment: 14

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

Ref country code: GB

Effective date: 19920601

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: PIERRE FABRE S.A.

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

GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 19920601

NLV4 Nl: lapsed or anulled due to non-payment of the annual fee
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

Ref country code: CH

Ref legal event code: AUV

Free format text: LE BREVET CI-DESSUS EST TOMBE EN DECHEANCE FAUTE DE PAIEMENT, DE LA 15E ANNUITE.

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

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