NO310683B1 - 3-pyrazol-karboksamid-derivater med cannabinoid reseptor- affinitet, anvendelse derav, farmasöytisk preparat, samtfremgangsmåte for fremstilling - Google Patents
3-pyrazol-karboksamid-derivater med cannabinoid reseptor- affinitet, anvendelse derav, farmasöytisk preparat, samtfremgangsmåte for fremstilling Download PDFInfo
- Publication number
- NO310683B1 NO310683B1 NO19982589A NO982589A NO310683B1 NO 310683 B1 NO310683 B1 NO 310683B1 NO 19982589 A NO19982589 A NO 19982589A NO 982589 A NO982589 A NO 982589A NO 310683 B1 NO310683 B1 NO 310683B1
- Authority
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- Norway
- Prior art keywords
- formula
- compound
- compounds
- hydrogen
- pyrazole
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 137
- 238000002360 preparation method Methods 0.000 title claims description 20
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 8
- BNYCHCAYYYRJSH-UHFFFAOYSA-N 1h-pyrazole-5-carboxamide Chemical class NC(=O)C1=CC=NN1 BNYCHCAYYYRJSH-UHFFFAOYSA-N 0.000 title description 27
- 102000018208 Cannabinoid Receptor Human genes 0.000 title description 9
- 108050007331 Cannabinoid receptor Proteins 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims description 485
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 243
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 111
- 239000002904 solvent Substances 0.000 claims description 95
- 229910052739 hydrogen Inorganic materials 0.000 claims description 63
- 239000001257 hydrogen Substances 0.000 claims description 63
- 150000003839 salts Chemical class 0.000 claims description 51
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
- -1 1,3,3-trimethylbicyclo-[2,2,1]hept- 2-yl residue Chemical group 0.000 claims description 30
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical class OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 claims description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 27
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 22
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 21
- 239000004480 active ingredient Substances 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 15
- 238000010992 reflux Methods 0.000 claims description 14
- 102000009135 CB2 Cannabinoid Receptor Human genes 0.000 claims description 12
- 108010073376 CB2 Cannabinoid Receptor Proteins 0.000 claims description 12
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 150000001450 anions Chemical class 0.000 claims description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 2
- 239000005977 Ethylene Substances 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 2
- 239000000243 solution Substances 0.000 description 208
- 239000000543 intermediate Substances 0.000 description 195
- 239000000047 product Substances 0.000 description 186
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 150
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 147
- 239000000203 mixture Substances 0.000 description 138
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 117
- 239000011541 reaction mixture Substances 0.000 description 102
- 229910001868 water Inorganic materials 0.000 description 100
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 93
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 86
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 85
- 239000012074 organic phase Substances 0.000 description 63
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 55
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 50
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 47
- 239000003480 eluent Substances 0.000 description 47
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- 239000002244 precipitate Substances 0.000 description 45
- 239000000377 silicon dioxide Substances 0.000 description 45
- 239000011734 sodium Substances 0.000 description 44
- 229910000104 sodium hydride Inorganic materials 0.000 description 38
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 36
- 239000012312 sodium hydride Substances 0.000 description 36
- 238000005481 NMR spectroscopy Methods 0.000 description 35
- 239000006185 dispersion Substances 0.000 description 34
- 229920006395 saturated elastomer Polymers 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 32
- 238000001816 cooling Methods 0.000 description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 239000000706 filtrate Substances 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- 239000000725 suspension Substances 0.000 description 23
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 18
- 239000002198 insoluble material Substances 0.000 description 17
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 16
- 239000007853 buffer solution Substances 0.000 description 16
- 239000000460 chlorine Substances 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 13
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 239000005457 ice water Substances 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 229910052708 sodium Inorganic materials 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 159000000000 sodium salts Chemical class 0.000 description 9
- XLWSBDFQAJXCQX-UHFFFAOYSA-N 4-(bromomethyl)-1,2-dichlorobenzene Chemical compound ClC1=CC=C(CBr)C=C1Cl XLWSBDFQAJXCQX-UHFFFAOYSA-N 0.000 description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 8
- 150000008064 anhydrides Chemical class 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 8
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- 230000007062 hydrolysis Effects 0.000 description 8
- 238000006460 hydrolysis reaction Methods 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 7
- 229940121376 cannabinoid receptor agonist Drugs 0.000 description 7
- 239000003537 cannabinoid receptor agonist Substances 0.000 description 7
- 238000010908 decantation Methods 0.000 description 7
- 150000003217 pyrazoles Chemical class 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- PXEODPDCEHMCKE-UHFFFAOYSA-N 2-chloro-4-(iodomethyl)-1-methylbenzene Chemical compound CC1=CC=C(CI)C=C1Cl PXEODPDCEHMCKE-UHFFFAOYSA-N 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
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- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 239000012442 inert solvent Substances 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
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- IRSVDHPYXFLLDS-UHFFFAOYSA-N 2,4-dichloro-1-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1Cl IRSVDHPYXFLLDS-UHFFFAOYSA-N 0.000 description 5
- YNZFFALZMRAPHQ-SYYKKAFVSA-N 2-[(1r,2r,5r)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol Chemical compound OC1=CC(C(C)(C)CCCCCC)=CC=C1[C@H]1[C@H](CCCO)CC[C@@H](O)C1 YNZFFALZMRAPHQ-SYYKKAFVSA-N 0.000 description 5
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- 238000007796 conventional method Methods 0.000 description 3
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- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9514547A FR2742148B1 (fr) | 1995-12-08 | 1995-12-08 | Nouveaux derives du pyrazole-3-carboxamide, procede pour leur preparation et compositions pharmaceutiques les contenant |
PCT/FR1996/001953 WO1997021682A1 (fr) | 1995-12-08 | 1996-12-06 | Derives de 3-pyrazolecarboxamide avec une affinite pour le recepteur des cannabinoides |
Publications (3)
Publication Number | Publication Date |
---|---|
NO982589D0 NO982589D0 (no) | 1998-06-05 |
NO982589L NO982589L (no) | 1998-08-03 |
NO310683B1 true NO310683B1 (no) | 2001-08-13 |
Family
ID=9485291
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19982589A NO310683B1 (no) | 1995-12-08 | 1998-06-05 | 3-pyrazol-karboksamid-derivater med cannabinoid reseptor- affinitet, anvendelse derav, farmasöytisk preparat, samtfremgangsmåte for fremstilling |
Country Status (34)
Country | Link |
---|---|
US (1) | US5925768A (xx) |
EP (2) | EP0868420B1 (xx) |
JP (1) | JP3510270B2 (xx) |
KR (1) | KR100488610B1 (xx) |
CN (1) | CN1101813C (xx) |
AR (1) | AR004364A1 (xx) |
AT (1) | ATE191211T1 (xx) |
AU (1) | AU718763B2 (xx) |
BR (1) | BR9611986A (xx) |
CA (1) | CA2239489C (xx) |
CZ (1) | CZ294307B6 (xx) |
DE (1) | DE69607484T2 (xx) |
DK (1) | DK0868420T3 (xx) |
EE (1) | EE04674B1 (xx) |
ES (1) | ES2148820T3 (xx) |
FR (1) | FR2742148B1 (xx) |
GR (1) | GR3033626T3 (xx) |
HU (1) | HUP9901244A3 (xx) |
IL (1) | IL124801A (xx) |
IS (1) | IS4765A (xx) |
MX (1) | MX9804565A (xx) |
MY (1) | MY115228A (xx) |
NO (1) | NO310683B1 (xx) |
NZ (1) | NZ323962A (xx) |
PL (1) | PL186466B1 (xx) |
PT (1) | PT868420E (xx) |
RU (1) | RU2170230C2 (xx) |
SI (1) | SI0868420T1 (xx) |
SK (1) | SK283706B6 (xx) |
TR (1) | TR199801041T2 (xx) |
TW (1) | TW402594B (xx) |
UA (1) | UA44913C2 (xx) |
WO (1) | WO1997021682A1 (xx) |
ZA (1) | ZA9610299B (xx) |
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US7589220B2 (en) * | 1998-06-09 | 2009-09-15 | University Of Connecticut | Inhibitors of the anandamide transporter |
US7897598B2 (en) * | 1998-06-09 | 2011-03-01 | Alexandros Makriyannis | Inhibitors of the anandamide transporter |
US7161016B1 (en) | 1998-11-24 | 2007-01-09 | University Of Connecticut | Cannabimimetic lipid amides as useful medications |
US7276613B1 (en) | 1998-11-24 | 2007-10-02 | University Of Connecticut | Retro-anandamides, high affinity and stability cannabinoid receptor ligands |
HUP0203437A3 (en) | 1999-03-22 | 2003-07-28 | Immugen Pharmaceuticals Inc So | Use of resorcinol derivatives for producing pharmaceutical compositions for treatment of immune diseases |
US6566560B2 (en) | 1999-03-22 | 2003-05-20 | Immugen Pharmaceuticals, Inc. | Resorcinolic compounds |
US6900236B1 (en) | 1999-10-18 | 2005-05-31 | University Of Connecticut | Cannabimimetic indole derivatives |
US8084467B2 (en) * | 1999-10-18 | 2011-12-27 | University Of Connecticut | Pyrazole derivatives as cannabinoid receptor antagonists |
JP2003511469A (ja) | 1999-10-18 | 2003-03-25 | ユニバーシティ オブ コネチカット | 抹消カンナビノイド受容体(cb2)選択的配位子 |
US6943266B1 (en) | 1999-10-18 | 2005-09-13 | University Of Connecticut | Bicyclic cannabinoid agonists for the cannabinoid receptor |
US7119108B1 (en) | 1999-10-18 | 2006-10-10 | University Of Connecticut | Pyrazole derivatives as cannabinoid receptor antagonists |
US7393842B2 (en) * | 2001-08-31 | 2008-07-01 | University Of Connecticut | Pyrazole analogs acting on cannabinoid receptors |
US7741365B2 (en) * | 1999-10-18 | 2010-06-22 | University Of Connecticut | Peripheral cannabinoid receptor (CB2) selective ligands |
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FR2800372B1 (fr) * | 1999-11-03 | 2001-12-07 | Sanofi Synthelabo | Derives tricycliques d'acide 1-benzylpyrazole-3- carboxylique, leur preparation, les medicaments en contenant |
AU2001296402A1 (en) * | 2000-09-28 | 2002-04-08 | Immugen Pharmaceuticals, Inc. | Methods and compounds for inhibiting eicosanoid metabolism and platelet aggregation |
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EP1361876A4 (en) * | 2001-01-26 | 2004-03-31 | Univ Connecticut | NEW CANNABIMIMETIC LIGANDS |
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CA2452881C (en) * | 2001-07-13 | 2012-03-06 | University Of Connecticut | Novel bicyclic and tricyclic cannabinoids |
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US10053444B2 (en) | 2009-02-19 | 2018-08-21 | University Of Connecticut | Cannabinergic nitrate esters and related analogs |
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CN102329192A (zh) * | 2011-09-30 | 2012-01-25 | 山东天一化学股份有限公司 | 溴化苄的合成方法 |
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US5015651A (en) * | 1988-01-07 | 1991-05-14 | E. I. Du Pont De Nemours And Company | Treatment of hypertension with 1,2,4-angiotensin II antagonists |
FR2665898B1 (fr) * | 1990-08-20 | 1994-03-11 | Sanofi | Derives d'amido-3 pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant. |
FR2692575B1 (fr) * | 1992-06-23 | 1995-06-30 | Sanofi Elf | Nouveaux derives du pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant. |
FR2713225B1 (fr) * | 1993-12-02 | 1996-03-01 | Sanofi Sa | N-pipéridino-3-pyrazolecarboxamide substitué. |
FR2714057B1 (fr) * | 1993-12-17 | 1996-03-08 | Sanofi Elf | Nouveaux dérivés du 3-pyrazolecarboxamide, procédé pour leur préparation et compositions pharmaceutiques les contenant. |
-
1995
- 1995-12-08 FR FR9514547A patent/FR2742148B1/fr not_active Expired - Fee Related
-
1996
- 1996-12-06 EP EP96941716A patent/EP0868420B1/fr not_active Expired - Lifetime
- 1996-12-06 AT AT96941716T patent/ATE191211T1/de not_active IP Right Cessation
- 1996-12-06 EP EP98401565A patent/EP0885889A3/fr not_active Withdrawn
- 1996-12-06 NZ NZ323962A patent/NZ323962A/xx not_active IP Right Cessation
- 1996-12-06 DK DK96941716T patent/DK0868420T3/da active
- 1996-12-06 DE DE69607484T patent/DE69607484T2/de not_active Expired - Lifetime
- 1996-12-06 ZA ZA9610299A patent/ZA9610299B/xx unknown
- 1996-12-06 RU RU98112606/04A patent/RU2170230C2/ru not_active IP Right Cessation
- 1996-12-06 AU AU11010/97A patent/AU718763B2/en not_active Ceased
- 1996-12-06 IL IL12480196A patent/IL124801A/en not_active IP Right Cessation
- 1996-12-06 CZ CZ19981775A patent/CZ294307B6/cs not_active IP Right Cessation
- 1996-12-06 CA CA002239489A patent/CA2239489C/en not_active Expired - Fee Related
- 1996-12-06 PL PL96327177A patent/PL186466B1/pl not_active IP Right Cessation
- 1996-12-06 KR KR10-1998-0704296A patent/KR100488610B1/ko not_active IP Right Cessation
- 1996-12-06 US US09/077,767 patent/US5925768A/en not_active Expired - Lifetime
- 1996-12-06 UA UA98062944A patent/UA44913C2/uk unknown
- 1996-12-06 CN CN96199643A patent/CN1101813C/zh not_active Expired - Fee Related
- 1996-12-06 WO PCT/FR1996/001953 patent/WO1997021682A1/fr active IP Right Grant
- 1996-12-06 JP JP52178697A patent/JP3510270B2/ja not_active Expired - Fee Related
- 1996-12-06 SK SK758-98A patent/SK283706B6/sk not_active IP Right Cessation
- 1996-12-06 HU HU9901244A patent/HUP9901244A3/hu unknown
- 1996-12-06 EE EE9800171A patent/EE04674B1/xx not_active IP Right Cessation
- 1996-12-06 BR BR9611986A patent/BR9611986A/pt not_active IP Right Cessation
- 1996-12-06 ES ES96941716T patent/ES2148820T3/es not_active Expired - Lifetime
- 1996-12-06 TR TR1998/01041T patent/TR199801041T2/xx unknown
- 1996-12-06 PT PT96941716T patent/PT868420E/pt unknown
- 1996-12-06 AR ARP960105525A patent/AR004364A1/es active IP Right Grant
- 1996-12-06 SI SI9630209T patent/SI0868420T1/xx unknown
- 1996-12-07 MY MYPI96005160A patent/MY115228A/en unknown
- 1996-12-07 TW TW085115150A patent/TW402594B/zh active
-
1998
- 1998-06-05 NO NO19982589A patent/NO310683B1/no not_active IP Right Cessation
- 1998-06-08 IS IS4765A patent/IS4765A/is unknown
- 1998-06-08 MX MX9804565A patent/MX9804565A/es not_active IP Right Cessation
-
2000
- 2000-06-07 GR GR20000401312T patent/GR3033626T3/el not_active IP Right Cessation
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