FR2508035A1 - Derives d'aryl-1-aminomethyl-2 cyclopropanes carboxamides (z), leur preparation et leur application en tant que medicaments utiles dans le traitement des troubles du systeme nerveux central - Google Patents
Derives d'aryl-1-aminomethyl-2 cyclopropanes carboxamides (z), leur preparation et leur application en tant que medicaments utiles dans le traitement des troubles du systeme nerveux central Download PDFInfo
- Publication number
- FR2508035A1 FR2508035A1 FR8112312A FR8112312A FR2508035A1 FR 2508035 A1 FR2508035 A1 FR 2508035A1 FR 8112312 A FR8112312 A FR 8112312A FR 8112312 A FR8112312 A FR 8112312A FR 2508035 A1 FR2508035 A1 FR 2508035A1
- Authority
- FR
- France
- Prior art keywords
- cyclopropane
- phenyl
- hydrochloride
- general formula
- dimethylaminomethyl
- 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.)
- Granted
Links
- -1 CYCLOPROPANES CARBOXAMIDE Chemical class 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title description 19
- 238000011282 treatment Methods 0.000 title description 6
- 239000003814 drug Substances 0.000 title description 3
- 208000015114 central nervous system disease Diseases 0.000 title 1
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 3
- 239000001257 hydrogen Substances 0.000 claims abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 claims abstract description 3
- 239000011707 mineral Substances 0.000 claims abstract description 3
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
- 239000001301 oxygen Substances 0.000 claims abstract description 3
- 150000002367 halogens Chemical group 0.000 claims abstract 3
- 150000007524 organic acids Chemical class 0.000 claims abstract 2
- 235000005985 organic acids Nutrition 0.000 claims abstract 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 39
- 150000001875 compounds Chemical class 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 150000004820 halides Chemical class 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- HKJBYYZWFYCKCP-UHFFFAOYSA-N 1-cyclopropyl-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.CN(C)CC1CC1 HKJBYYZWFYCKCP-UHFFFAOYSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 150000001720 carbohydrates Chemical class 0.000 claims 1
- 150000003857 carboxamides Chemical class 0.000 claims 1
- AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 150000007522 mineralic acids Chemical class 0.000 claims 1
- FMZGKCMVTMNFIH-UHFFFAOYSA-N n-(2-phenylethyl)cyclopropanecarboxamide Chemical compound C1CC1C(=O)NCCC1=CC=CC=C1 FMZGKCMVTMNFIH-UHFFFAOYSA-N 0.000 claims 1
- 239000002547 new drug Substances 0.000 claims 1
- 239000002253 acid Substances 0.000 abstract description 4
- 230000001225 therapeutic effect Effects 0.000 abstract description 3
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical compound [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 abstract 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 abstract 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical class [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 abstract 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- 239000013078 crystal Substances 0.000 description 11
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
- 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 10
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 10
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 10
- 229910052740 iodine Inorganic materials 0.000 description 10
- 239000011630 iodine Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 9
- 230000003301 hydrolyzing effect Effects 0.000 description 9
- 238000002329 infrared spectrum Methods 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- MHLMRBVCMNDOCW-UHFFFAOYSA-N acetic acid;butan-1-ol;hydrate Chemical compound O.CC(O)=O.CCCCO MHLMRBVCMNDOCW-UHFFFAOYSA-N 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- OJHAHQJRQIOCFK-UHFFFAOYSA-N azane;chloroform;methanol Chemical compound N.OC.ClC(Cl)Cl OJHAHQJRQIOCFK-UHFFFAOYSA-N 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 230000001430 anti-depressive effect Effects 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- YMVFJGSXZNNUDW-UHFFFAOYSA-N (4-chlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C=C1 YMVFJGSXZNNUDW-UHFFFAOYSA-N 0.000 description 1
- CGUNPICNMMRKHD-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-2-phenylcyclopropyl]-n,n-dimethylmethanamine Chemical compound CN(C)CC1CC1(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 CGUNPICNMMRKHD-UHFFFAOYSA-N 0.000 description 1
- PSODYUROWJSUIJ-UHFFFAOYSA-N 1-phenylethyl carbonochloridate Chemical compound ClC(=O)OC(C)C1=CC=CC=C1 PSODYUROWJSUIJ-UHFFFAOYSA-N 0.000 description 1
- PSMORJXEGALFGQ-UHFFFAOYSA-N 2-(hydroxymethyl)-1-phenylcyclopropane-1-carboxylic acid Chemical class OCC1CC1(C(O)=O)C1=CC=CC=C1 PSMORJXEGALFGQ-UHFFFAOYSA-N 0.000 description 1
- PYTANBUURZFYHD-UHFFFAOYSA-N 2-methylcyclopropan-1-amine Chemical compound CC1CC1N PYTANBUURZFYHD-UHFFFAOYSA-N 0.000 description 1
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 1
- UPWDDVVPPMNVAU-UHFFFAOYSA-N C(=O)=C1C(C1)CN Chemical compound C(=O)=C1C(C1)CN UPWDDVVPPMNVAU-UHFFFAOYSA-N 0.000 description 1
- ZSUIVGFKRHPJPP-UHFFFAOYSA-N CN(C)CC(C1)C1(CC(C=C1)=CC=C1Cl)C1=CC=CC=C1 Chemical compound CN(C)CC(C1)C1(CC(C=C1)=CC=C1Cl)C1=CC=CC=C1 ZSUIVGFKRHPJPP-UHFFFAOYSA-N 0.000 description 1
- 101100257359 Caenorhabditis elegans sox-2 gene Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 101800001195 Crustacean hyperglycemic hormone 3 Proteins 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 101100257363 Mus musculus Sox2 gene Proteins 0.000 description 1
- QIJGHPRRZMNWEQ-UHFFFAOYSA-N N,N-dimethylcyclopropanecarboxamide hydrochloride Chemical compound Cl.CN(C)C(=O)C1CC1 QIJGHPRRZMNWEQ-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical class CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 1
- 101100386054 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CYS3 gene Proteins 0.000 description 1
- BLGXFZZNTVWLAY-CCZXDCJGSA-N Yohimbine Natural products C1=CC=C2C(CCN3C[C@@H]4CC[C@@H](O)[C@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-CCZXDCJGSA-N 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- BLGXFZZNTVWLAY-UHFFFAOYSA-N beta-Yohimbin Natural products C1=CC=C2C(CCN3CC4CCC(O)C(C4CC33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- PGQRQZKSXBTFRH-UHFFFAOYSA-N chloroform ethanol Chemical compound C(C)O.C(C)O.C(C)O.C(Cl)(Cl)Cl.C(C)O PGQRQZKSXBTFRH-UHFFFAOYSA-N 0.000 description 1
- SLNPAVIBCNMVHG-UHFFFAOYSA-N cyclopropane;hydrazine Chemical class NN.C1CC1 SLNPAVIBCNMVHG-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229960003914 desipramine Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- VNXBKJFUJUWOCW-UHFFFAOYSA-N methylcyclopropane Chemical compound CC1CC1 VNXBKJFUJUWOCW-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 235000013849 propane Nutrition 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 101150035983 str1 gene Proteins 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- BLGXFZZNTVWLAY-SCYLSFHTSA-N yohimbine Chemical compound C1=CC=C2C(CCN3C[C@@H]4CC[C@H](O)[C@@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-SCYLSFHTSA-N 0.000 description 1
- 229960000317 yohimbine Drugs 0.000 description 1
- AADVZSXPNRLYLV-UHFFFAOYSA-N yohimbine carboxylic acid Natural products C1=CC=C2C(CCN3CC4CCC(C(C4CC33)C(O)=O)O)=C3NC2=C1 AADVZSXPNRLYLV-UHFFFAOYSA-N 0.000 description 1
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
- C07D295/16—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
- A61P25/24—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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Psychiatry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Priority Applications (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8112312A FR2508035A1 (fr) | 1981-06-23 | 1981-06-23 | Derives d'aryl-1-aminomethyl-2 cyclopropanes carboxamides (z), leur preparation et leur application en tant que medicaments utiles dans le traitement des troubles du systeme nerveux central |
| ES512842A ES8303293A1 (es) | 1981-06-23 | 1982-06-04 | "procedimiento de preparar derivados carboxamidicos". |
| DE8282401129T DE3263734D1 (en) | 1981-06-23 | 1982-06-21 | Derivatives of 1-aryl-2-aminomethyl-cyclopropane-carboxamides (z), their preparation and their use as medicines in the treatment of disorders of the central nervous system |
| EP82401129A EP0068999B1 (fr) | 1981-06-23 | 1982-06-21 | Dérivés d'aryl-1 aminométhyl-2 cyclopropanes carboxamides (Z), leur préparation et leur application en tant que médicaments utiles dans le traitement des troubles du système nerveux central |
| AT82401129T ATE13422T1 (de) | 1981-06-23 | 1982-06-21 | Derivate von 1-aryl-2-aminomethyl-cyclopropancarboxamiden (z), ihre herstellung und ihre verwendung fuer die behandlung von stoerungen des zentralnervensystems. |
| CA000405651A CA1202639A (fr) | 1981-06-23 | 1982-06-22 | Derives d'aryl-1 aminomethyl-2 cyclopropanes carboxamides (z) et leur preparation |
| AU85086/82A AU550774B2 (en) | 1981-06-23 | 1982-06-22 | 1-aryl-2-aminomethyl cyclopropane carboxylates |
| US06/390,810 US4478836A (en) | 1981-06-23 | 1982-06-22 | 1-Aryl 2-aminomethyl cyclopropane carboxyamide (Z) derivatives and their use as useful drugs in the treatment of disturbances of the central nervous system |
| JP57109097A JPS584752A (ja) | 1981-06-23 | 1982-06-23 | カルボキシアミド誘導体及びその製造法 |
| ZA824453A ZA824453B (en) | 1981-06-23 | 1982-06-23 | 1-aryl 2-aminomethyl cyclopropane carboxamide (z) derivatives their preparation and their use as useful drugs in the treatment of disturbances of the central nervous system |
| LU90410C LU90410I2 (fr) | 1981-06-23 | 1999-06-30 | Milnacipran (chlorhydrate) |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8112312A FR2508035A1 (fr) | 1981-06-23 | 1981-06-23 | Derives d'aryl-1-aminomethyl-2 cyclopropanes carboxamides (z), leur preparation et leur application en tant que medicaments utiles dans le traitement des troubles du systeme nerveux central |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| FR2508035A1 true FR2508035A1 (fr) | 1982-12-24 |
| FR2508035B1 FR2508035B1 (enExample) | 1984-06-29 |
Family
ID=9259785
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FR8112312A Granted FR2508035A1 (fr) | 1981-06-23 | 1981-06-23 | Derives d'aryl-1-aminomethyl-2 cyclopropanes carboxamides (z), leur preparation et leur application en tant que medicaments utiles dans le traitement des troubles du systeme nerveux central |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4478836A (enExample) |
| EP (1) | EP0068999B1 (enExample) |
| JP (1) | JPS584752A (enExample) |
| AT (1) | ATE13422T1 (enExample) |
| AU (1) | AU550774B2 (enExample) |
| CA (1) | CA1202639A (enExample) |
| DE (1) | DE3263734D1 (enExample) |
| ES (1) | ES8303293A1 (enExample) |
| FR (1) | FR2508035A1 (enExample) |
| LU (1) | LU90410I2 (enExample) |
| ZA (1) | ZA824453B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010086394A1 (en) | 2009-01-29 | 2010-08-05 | Pierre Fabre Medicament | Method for synthesis of (1s, 2r)-milnacipran |
Families Citing this family (69)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2581059B1 (fr) * | 1985-04-25 | 1988-04-22 | Pf Medicament | Procede de preparation du chlorhydrate de phenyl-1 diethyl amino carbonyl-1 aminomethyl-2 cyclopropane (z) |
| FR2581060B1 (fr) * | 1985-04-25 | 1988-07-01 | Pf Medicament | Procede industriel d'obtention du midalcipran |
| EP0747348A4 (en) * | 1994-02-22 | 1999-07-07 | Asahi Chemical Ind | AMINOALKYLCYCLOPROPAN DERIVATIVES |
| CA2134038C (en) * | 1994-06-16 | 1997-06-03 | David Taiwai Wong | Potentiation of drug response |
| EP0714663A3 (en) | 1994-11-28 | 1997-01-15 | Lilly Co Eli | Potentiation of drug responses by serotonin 1A receptor antagonists |
| PT759299E (pt) * | 1995-08-16 | 2000-09-29 | Lilly Co Eli | Potenciacao da resposta de serotonina |
| FR2752732B1 (fr) * | 1996-08-28 | 1998-11-20 | Pf Medicament | Forme galenique a liberation prolongee de milnacipran |
| CN103288815A (zh) * | 2001-10-12 | 2013-09-11 | 阿泽范药品公司 | β-内酰胺后叶加压素V1a拮抗剂 |
| US20040034101A1 (en) * | 2001-11-05 | 2004-02-19 | Cypress Bioscience, Inc. | Treatment and prevention of depression secondary to pain (DSP) |
| US6635675B2 (en) * | 2001-11-05 | 2003-10-21 | Cypress Bioscience, Inc. | Method of treating chronic fatigue syndrome |
| US6602911B2 (en) | 2001-11-05 | 2003-08-05 | Cypress Bioscience, Inc. | Methods of treating fibromyalgia |
| EP1499309A4 (en) * | 2002-04-24 | 2008-05-28 | Cypress Bioscience Inc | PREVENTION AND TREATMENT OF FUNCTIONAL SOMATIC DISEASES, INCLUDING STRESS-BASED DISEASES |
| WO2004039320A2 (en) * | 2002-10-25 | 2004-05-13 | Collegium Pharmaceutical, Inc. | STEREOISOMERS OF p-HYDROXY-MILNACIPRAN, AND METHODS OF USE THEREOF |
| FR2851163B1 (fr) * | 2003-02-14 | 2007-04-27 | Utilisation de l'enantiomere dextrogyre du milnacipran pour la preparation d'un medicament | |
| SI1601349T1 (sl) * | 2003-02-14 | 2008-10-31 | Pf Medicament | Uporaba enantiomera milnaciprana za pripravo zdravila |
| EP1620083A2 (en) * | 2003-04-18 | 2006-02-01 | Pharmacia & Upjohn Company LLC | Combination therapies |
| EP1656349B1 (en) | 2003-08-15 | 2011-10-12 | H. Lundbeck A/S | Cyclopropyl derivatives as nk3 receptor antagonists |
| JP4713474B2 (ja) * | 2003-08-15 | 2011-06-29 | ハー・ルンドベック・アクチエゼルスカベット | Ｎｋ３受容体アンタゴニストとしてのシクロプロピル誘導体 |
| DK1691811T3 (da) | 2003-12-11 | 2014-10-20 | Sunovion Pharmaceuticals Inc | Kombination af et sedativ og en neurotransmittermodulator og fremgangsmåder til forbedring af søvnkvaliteten og behandling af depression |
| WO2005102366A2 (en) * | 2004-04-19 | 2005-11-03 | Philip Maxwell Satow | Lithium combinations, and uses related thereto |
| JP4418717B2 (ja) * | 2004-06-24 | 2010-02-24 | 住友化学株式会社 | （ｚ）−１−フェニル−１−ジエチルアミノカルボニル−２−アミノメチルシクロプロパン塩酸塩の製造方法 |
| CA2601709C (en) | 2005-03-22 | 2017-02-14 | Azevan Pharmaceuticals, Inc. | Beta-lactamylalkanoic acids |
| AU2006239922A1 (en) * | 2005-04-22 | 2006-11-02 | Wyeth | Benzofuranyl alkanamine derivatives and uses thereof as 5-HT2c agonists |
| MX2007012883A (es) * | 2005-04-22 | 2007-12-10 | Wyeth Corp | Derivados de dihidrobenzofurano y usos de los mismos. |
| BRPI0610037A2 (pt) * | 2005-04-22 | 2010-05-25 | Wyeth Corp | derivados de dihidrobenzofurano e uso dos mesmos |
| WO2006132307A1 (ja) * | 2005-06-10 | 2006-12-14 | Pierre Fabre Medicament S.A. | 安定化されたミルナシプラン製剤 |
| SG163588A1 (en) * | 2005-07-08 | 2010-08-30 | Braincells Inc | Methods for identifying agents and conditions that modulate neurogenesis |
| EP1910346B1 (en) * | 2005-07-19 | 2019-02-27 | Azevan Pharmaceuticals, Inc. | Beta-lactamyl phenylalanine, cysteine, and serine vasopressin antagonist |
| WO2007025144A1 (en) * | 2005-08-24 | 2007-03-01 | University Of Illinois - Chicago | 5-ht2c receptor agonists as anorectic agents |
| US7994220B2 (en) * | 2005-09-28 | 2011-08-09 | Cypress Bioscience, Inc. | Milnacipran for the long-term treatment of fibromyalgia syndrome |
| AU2006304787A1 (en) | 2005-10-21 | 2007-04-26 | Braincells, Inc. | Modulation of neurogenesis by PDE inhibition |
| EP2314289A1 (en) | 2005-10-31 | 2011-04-27 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| AU2007208681B2 (en) * | 2006-01-27 | 2010-04-08 | Asahi Kasei Pharma Corporation | Medicine for transnasal administration |
| US20080319083A1 (en) * | 2006-01-27 | 2008-12-25 | Asahi Kasei Pharma Corporation | Medicine for transnasal administration |
| FR2912057B1 (fr) * | 2007-02-07 | 2009-04-17 | Sanofi Aventis Sa | Composition pharmaceutique contenant en association le saredutant et un inhibiteur selectif de la recapture de la serotonine ou un inhibiteur de la recapture de la serotonine/norepinephrine |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| RU2008135326A (ru) * | 2006-03-24 | 2010-04-27 | Вайет (Us) | Терапевтические композиции для лечения депрессии |
| JP2009536667A (ja) | 2006-05-09 | 2009-10-15 | ブレインセルス，インコーポレイティド | ５ｈｔ受容体介在性の神経新生 |
| US7858611B2 (en) * | 2006-05-09 | 2010-12-28 | Braincells Inc. | Neurogenesis by modulating angiotensin |
| EP2021000A2 (en) | 2006-05-09 | 2009-02-11 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| TW200817003A (en) * | 2006-07-31 | 2008-04-16 | Sanofi Aventis | Pharmaceutical composition comprising, in combination, saredutant and a selective serotonin peuptake inhibitor or a serotonin/norepinephrine reuptake inhibitor |
| MX2009002496A (es) | 2006-09-08 | 2009-07-10 | Braincells Inc | Combinaciones que contienen un derivado de 4-acilaminopiridina. |
| WO2008034032A2 (en) * | 2006-09-14 | 2008-03-20 | Azevan Pharmaceuticals, Inc. | Beta-lactam cannabinoid receptor modulators |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| US20080167363A1 (en) * | 2006-12-28 | 2008-07-10 | Braincells, Inc | Modulation of Neurogenesis By Melatoninergic Agents |
| AU2008204800A1 (en) * | 2007-01-11 | 2008-07-17 | Braincells, Inc. | Modulation of neurogenesis with use of modafinil |
| US20100145099A1 (en) * | 2007-02-28 | 2010-06-10 | Ranbaxy Laboratories Limited | Novel polymorphic forms of milnacipran hydrochloride |
| WO2009023820A1 (en) * | 2007-08-16 | 2009-02-19 | Cypress Biosciences, Inc. | Improving the tolerability of a serotonin antagonist and a nsri, a snri or a rima by using them in combination |
| US20090069431A1 (en) * | 2007-09-12 | 2009-03-12 | Protia, Llc | Deuterium-enriched milnacipran |
| WO2009128058A1 (en) | 2008-04-18 | 2009-10-22 | UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN et al | Psycho-pharmaceuticals |
| US20100092479A1 (en) * | 2008-08-18 | 2010-04-15 | Combinatorx (Singapore) Pte. Ltd. | Compositions and methods for treatment of viral diseases |
| WO2010036773A1 (en) * | 2008-09-24 | 2010-04-01 | Concert Pharmaceuticals, Inc. | Deuterated l-aryl-2 -aminomethyl cyclopropane carboxyamide derivatives |
| US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| US20100274050A1 (en) * | 2009-04-23 | 2010-10-28 | Glenmark Generics Limited | Solid milnacipran and process for the preparation of the same |
| WO2010129689A1 (en) * | 2009-05-05 | 2010-11-11 | Forest Laboratories Holdings Limited | Milnacipran formulations |
| MX2012001393A (es) | 2009-08-05 | 2012-08-03 | Lupin Ltd | Composiciones farmacéuticas de liberación controlada de milnacipran. |
| JP2013510176A (ja) | 2009-11-06 | 2013-03-21 | ピエール ファーブル メディカモン | （１ｓ，２ｒ）−２−（アミノメチル）−ｎ，ｎ−ジエチル−１−フェニルシクロプロパンカルボキサミドの新規結晶形態 |
| WO2011092065A1 (en) | 2010-01-29 | 2011-08-04 | Nicox S.A. | Nitric oxide releasing compounds for the treatment of neurophatic pain |
| EP2587919B1 (en) | 2010-07-01 | 2017-12-13 | Azevan Pharmaceuticals, Inc. | Methods for treating post traumatic stress disorder |
| JP2013536832A (ja) | 2010-08-30 | 2013-09-26 | ルピン・リミテッド | ミルナシプランの制御放出医薬組成物 |
| US20120289744A1 (en) | 2010-11-03 | 2012-11-15 | Arch Pharmalabs Limited | Process for preparing optically pure milnacipran and its pharmaceutically acceptable salts |
| US20140045936A1 (en) * | 2011-04-21 | 2014-02-13 | Wake Forest University Health Sciences | Cyclopropyl derivatives and methods of use |
| WO2014009767A1 (en) | 2012-07-07 | 2014-01-16 | Micro Labs Limited | An improved process for the preparation of 1-aryl 2-aminomethyl cyclopropane carboxyamide (z) derivatives, their isomers and salts |
| WO2014203277A2 (en) * | 2013-06-19 | 2014-12-24 | Msn Laboratories Private Limited | Process for the preparation of (1s,2r)-2-(aminomethyl)-n,n-diethyl-1-phenylcyclopropanearboxamide hydrochloride |
| IN2013MU03122A (enExample) | 2013-09-30 | 2015-07-17 | Cadila Healthcare Ltd | |
| SG11201608064WA (en) | 2014-03-28 | 2016-10-28 | Azevan Pharmaceuticals Inc | Compositions and methods for treating neurodegenerative diseases |
| US11628160B2 (en) | 2017-09-15 | 2023-04-18 | Azevan Pharmaceuticals, Inc. | Compositions and methods for treating brain injury |
| CA3145388A1 (en) | 2019-07-19 | 2021-01-28 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
| US11806334B1 (en) | 2023-01-12 | 2023-11-07 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA570688A (en) * | 1959-02-17 | E. Speeter Merrill | Antispasmodic substituted amines | |
| CA619080A (en) * | 1961-04-25 | The Upjohn Company | N-SUBSTITUTED-.alpha.-(TERTIARY-AMINOALKYL)-.alpha.-PHENYLACETAMIDES | |
| GB1415541A (en) | 1972-11-30 | 1975-11-26 | Hexachimie | 1-amino-methyl-2,2-diarylcyclopropanecarboxamide |
-
1981
- 1981-06-23 FR FR8112312A patent/FR2508035A1/fr active Granted
-
1982
- 1982-06-04 ES ES512842A patent/ES8303293A1/es not_active Expired
- 1982-06-21 EP EP82401129A patent/EP0068999B1/fr not_active Expired
- 1982-06-21 AT AT82401129T patent/ATE13422T1/de active
- 1982-06-21 DE DE8282401129T patent/DE3263734D1/de not_active Expired
- 1982-06-22 US US06/390,810 patent/US4478836A/en not_active Expired - Lifetime
- 1982-06-22 AU AU85086/82A patent/AU550774B2/en not_active Expired
- 1982-06-22 CA CA000405651A patent/CA1202639A/fr not_active Expired
- 1982-06-23 JP JP57109097A patent/JPS584752A/ja active Granted
- 1982-06-23 ZA ZA824453A patent/ZA824453B/xx unknown
-
1999
- 1999-06-30 LU LU90410C patent/LU90410I2/fr unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010086394A1 (en) | 2009-01-29 | 2010-08-05 | Pierre Fabre Medicament | Method for synthesis of (1s, 2r)-milnacipran |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS584752A (ja) | 1983-01-11 |
| AU8508682A (en) | 1983-01-06 |
| EP0068999B1 (fr) | 1985-05-22 |
| LU90410I2 (fr) | 1999-08-31 |
| DE3263734D1 (en) | 1985-06-27 |
| JPS6323186B2 (enExample) | 1988-05-16 |
| FR2508035B1 (enExample) | 1984-06-29 |
| ES512842A0 (es) | 1983-03-01 |
| AU550774B2 (en) | 1986-04-10 |
| ES8303293A1 (es) | 1983-03-01 |
| ZA824453B (en) | 1983-04-27 |
| CA1202639A (fr) | 1986-04-01 |
| EP0068999A1 (fr) | 1983-01-05 |
| ATE13422T1 (de) | 1985-06-15 |
| US4478836A (en) | 1984-10-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FR2508035A1 (fr) | Derives d'aryl-1-aminomethyl-2 cyclopropanes carboxamides (z), leur preparation et leur application en tant que medicaments utiles dans le traitement des troubles du systeme nerveux central | |
| CH647757A5 (fr) | Derives de l'acide 3-aminopropanesulfonique ayant une activite membranaire renforcee. | |
| CH639653A5 (fr) | Aminothiazoles et composition pharmaceutique les contenant. | |
| EP0046707B1 (fr) | Dérivés de l'acide amino-4 butyrique et les médicaments, actifs notamment sur le système nerveux central, en contenant | |
| DE69224861T2 (de) | Neue Phenylacetamidderivate und Verfahren zu ihrer Herstellung | |
| EP0068998B1 (fr) | Aryl-1 aminométhyl-2 cyclopropanes carboxylates (Z), leur préparation et leur application en tant que médicaments utiles dans le traitement d'algies diverses | |
| EP0007824A1 (fr) | Nouveaux dérivés de benzofuranne, leur procédé de préparation et composition thérapeutiqueles contenant. | |
| FR2534915A1 (fr) | Nouveaux derives de 2-(phenoxymethyl)-morpholine, utilisation en therapeutique et procede de preparation | |
| EP0426562B1 (fr) | Dérivés de 1-(4-aminophényl)-2-pipéridinopropanone, procédé de préparation et utilisation en thérapeutique | |
| EP0022017B1 (fr) | Nouveaux dérivés de benzoyl-2 nitro-4 anilides, leur préparation et leur application en tant que médicaments | |
| EP0001947B1 (fr) | Dérivés de l'amino-2 thiazoline, procédé de préparation et compositions pharmaceutiques les contenant | |
| EP0010030B1 (fr) | Nouveaux dérivés d'ortho chloro benzoyl-2 chloro-4 glycylanilide, leur préparation et leur application en tant que médicaments | |
| EP0406088B1 (fr) | (Alfa-tertiobutyl aminométhyl-3,4-dichlorobenzyl) thioacétamide, son procédé de préparation et ses applications | |
| FR2526793A1 (fr) | Nouveaux a-(n-pyrrolyl)-acides et leurs sels et esters, utiles comme medicaments et procede de la preparation de tels composes | |
| EP1007522B1 (fr) | 2- 4-[4-(4,5-dichloro-2-methylimidazol-1-yl)butyl]piperazin-1-yl -5-fluoropyrimidine, sa preparation et son utilisation therapeutique | |
| FR2475543A1 (fr) | Derives benzylideniques, leur preparation et leur application en therapeutique | |
| FR2584401A1 (fr) | Nouveau benzamide, son procede de preparation et son application dans le domaine therapeutique | |
| EP0174887B1 (fr) | Dérivés de 1-[N-(alpha-amino-alpha-méthylacétyl)-aminophényl]-2-amino-propanone, procédé de préparation et utilisation en thérapeutique | |
| FR2690917A1 (fr) | Aminoesters, leur procédé de préparation et leur application en thérapeutique. | |
| EP0007843A1 (fr) | Dérivés de propiophénone, leur application en thérapeutique et leur préparation | |
| CA1105053A (fr) | Sulfamido acetyleniques de benzamides utilisables en therapeutique | |
| FR2727628A1 (fr) | Application des derives de 3-cycloalkyl-propanamide a titre de medicaments analgesiques | |
| FR2525214A1 (fr) | Nouveaux derives d'halogeno benzoyl-2 nitro-4 glycylanilides, leur procede de preparation et leur application en therapeutique | |
| FR2604704A1 (fr) | Derives de 4-phenylthiazole, procede de preparation et utilisation en therapeutique | |
| FR2498449A1 (fr) | Acides halogeno biphenyl carboxyliques et leurs sels utiles en therapeutique |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| TP | Transmission of property | ||
| CP | Supplementary protection certificate (spc) filed |
Free format text: PRODUCT NAME: MILNACIPRAN HYDROCLORHYDE; NAT. REGISTRATION NO/DATE: NL21356 19961206; FIRST REGISTRATION: PT - 7528 19940225 Spc suppl protection certif: 97C0010 Filing date: 19970228 |
|
| TP | Transmission of property | ||
| CP | Supplementary protection certificate (spc) filed |
Free format text: 97C0010, 970228 |
|
| CR | Request for supplementary protection certificate laid open to the public (eec regulation of 18 june 1992) |
Free format text: 97C0010, 970228 |
|
| CP | Supplementary protection certificate (spc) filed | ||
| CY | Supplementary certificate of protection granted (eec regulation of 18 june 1992) |
Free format text: 97C0010, 19970228, EXPIRES: 20060622 |