CA2274117A1 - Novel compounds with analgesic effect - Google Patents
Novel compounds with analgesic effect Download PDFInfo
- Publication number
- CA2274117A1 CA2274117A1 CA002274117A CA2274117A CA2274117A1 CA 2274117 A1 CA2274117 A1 CA 2274117A1 CA 002274117 A CA002274117 A CA 002274117A CA 2274117 A CA2274117 A CA 2274117A CA 2274117 A1 CA2274117 A1 CA 2274117A1
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- CA
- Canada
- Prior art keywords
- formula
- compound
- independently
- compound according
- mmol
- 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.)
- Abandoned
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 78
- 230000000202 analgesic effect Effects 0.000 title description 5
- 208000002193 Pain Diseases 0.000 claims abstract description 11
- 230000036407 pain Effects 0.000 claims abstract description 10
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- -1 pyrryl Chemical group 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 208000020339 Spinal injury Diseases 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical group C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 4
- 238000006254 arylation reaction Methods 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000000651 prodrug Substances 0.000 claims description 4
- 229940002612 prodrug Drugs 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 108010029485 Protein Isoforms Proteins 0.000 claims description 3
- 102000001708 Protein Isoforms Human genes 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 239000000032 diagnostic agent Substances 0.000 claims description 3
- 229940039227 diagnostic agent Drugs 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 238000006268 reductive amination reaction Methods 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical group C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 claims description 2
- 101150047265 COR2 gene Proteins 0.000 claims description 2
- 101100467189 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) QCR2 gene Proteins 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 2
- 150000004982 aromatic amines Chemical class 0.000 claims description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- 150000002576 ketones Chemical class 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 210000002820 sympathetic nervous system Anatomy 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 2
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 6
- 101100134922 Gallus gallus COR5 gene Proteins 0.000 claims 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 1
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 1
- 208000010643 digestive system disease Diseases 0.000 claims 1
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 claims 1
- 230000002496 gastric effect Effects 0.000 claims 1
- 208000018685 gastrointestinal system disease Diseases 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 80
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- 238000005481 NMR spectroscopy Methods 0.000 description 29
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 29
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 28
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 22
- 238000004587 chromatography analysis Methods 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 235000019439 ethyl acetate Nutrition 0.000 description 21
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 19
- 239000000706 filtrate Substances 0.000 description 16
- 239000012074 organic phase Substances 0.000 description 16
- 238000010992 reflux Methods 0.000 description 16
- 229910017974 NH40H Inorganic materials 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000003921 oil Substances 0.000 description 14
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 13
- 239000012267 brine Substances 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 239000000538 analytical sample Substances 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 8
- 210000002683 foot Anatomy 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
- 239000012458 free base Substances 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 239000007983 Tris buffer Substances 0.000 description 6
- 210000004209 hair Anatomy 0.000 description 6
- 235000015320 potassium carbonate Nutrition 0.000 description 6
- 239000002287 radioligand Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 239000010936 titanium Substances 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
- 229940125904 compound 1 Drugs 0.000 description 5
- 239000008188 pellet Substances 0.000 description 5
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000000730 antalgic agent Substances 0.000 description 4
- 239000006286 aqueous extract Substances 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 210000003497 sciatic nerve Anatomy 0.000 description 4
- 230000009870 specific binding Effects 0.000 description 4
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 3
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 3
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 3
- SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 description 3
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- 206010002091 Anaesthesia Diseases 0.000 description 3
- KCBAMQOKOLXLOX-BSZYMOERSA-N CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O Chemical compound CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O KCBAMQOKOLXLOX-BSZYMOERSA-N 0.000 description 3
- 208000004454 Hyperalgesia Diseases 0.000 description 3
- 208000028257 Joubert syndrome with oculorenal defect Diseases 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 206010053552 allodynia Diseases 0.000 description 3
- 230000037005 anaesthesia Effects 0.000 description 3
- 229940035676 analgesics Drugs 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 229940125810 compound 20 Drugs 0.000 description 3
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- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0446—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0455—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/56—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2123/00—Preparations for testing in vivo
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Optics & Photonics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9604786-5 | 1996-12-20 | ||
| SE9604786A SE9604786D0 (sv) | 1996-12-20 | 1996-12-20 | New compounds |
| PCT/SE1997/002051 WO1998028270A1 (en) | 1996-12-20 | 1997-12-09 | Novel compounds with analgesic effect |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2274117A1 true CA2274117A1 (en) | 1998-07-02 |
Family
ID=20405139
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002274117A Abandoned CA2274117A1 (en) | 1996-12-20 | 1997-12-09 | Novel compounds with analgesic effect |
Country Status (31)
| Country | Link |
|---|---|
| US (3) | US6153626A (enExample) |
| EP (2) | EP0946510B1 (enExample) |
| JP (1) | JP2001507021A (enExample) |
| KR (1) | KR20000069600A (enExample) |
| CN (2) | CN1154635C (enExample) |
| AR (1) | AR010378A1 (enExample) |
| AT (1) | ATE266638T1 (enExample) |
| AU (1) | AU738002B2 (enExample) |
| BR (1) | BR9713785A (enExample) |
| CA (1) | CA2274117A1 (enExample) |
| CZ (1) | CZ220099A3 (enExample) |
| DE (1) | DE69729115T2 (enExample) |
| DK (1) | DK0946510T3 (enExample) |
| EE (1) | EE03966B1 (enExample) |
| ES (1) | ES2219783T3 (enExample) |
| HU (1) | HUP0000613A3 (enExample) |
| ID (1) | ID21662A (enExample) |
| IL (1) | IL130536A0 (enExample) |
| IS (1) | IS5078A (enExample) |
| MY (1) | MY132705A (enExample) |
| NO (1) | NO313632B1 (enExample) |
| NZ (1) | NZ336028A (enExample) |
| PL (1) | PL188945B1 (enExample) |
| PT (1) | PT946510E (enExample) |
| RU (1) | RU2193030C2 (enExample) |
| SE (1) | SE9604786D0 (enExample) |
| SK (1) | SK283300B6 (enExample) |
| TR (1) | TR199901411T2 (enExample) |
| UA (1) | UA54481C2 (enExample) |
| WO (1) | WO1998028270A1 (enExample) |
| ZA (1) | ZA9711049B (enExample) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9504661D0 (sv) | 1995-12-22 | 1995-12-22 | Astra Pharma Inc | New compounds |
| US6974825B1 (en) | 1996-12-20 | 2005-12-13 | Astrazeneca Canada Inc. | Compounds with analgesic effect |
| TW548271B (en) * | 1996-12-20 | 2003-08-21 | Astra Pharma Inc | Novel piperidine derivatives having an exocyclic double bond with analgesic effects |
| SE9604786D0 (sv) | 1996-12-20 | 1996-12-20 | Astra Pharma Inc | New compounds |
| AU2003220725B2 (en) * | 1997-12-24 | 2006-06-01 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)] aminobenzamides which bind to the delta-opioid receptor |
| WO1999033806A1 (en) * | 1997-12-24 | 1999-07-08 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)] aminobenzamides which bind to the delta-opioid receptor |
| US6900228B1 (en) | 1998-03-10 | 2005-05-31 | Research Triangle Institute | Opiate compounds, methods of making and methods of use |
| AU756983B2 (en) * | 1998-03-10 | 2003-01-30 | Research Triangle Institute | Novel opiate compounds, methods of making and methods of use |
| US6436959B1 (en) | 1998-12-23 | 2002-08-20 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)]aminobenzamides |
| SE9904673D0 (sv) | 1999-12-20 | 1999-12-20 | Astra Pharma Inc | Novel compounds |
| SE9904674D0 (sv) * | 1999-12-20 | 1999-12-20 | Astra Pharma Inc | Novel compounds |
| SE9904675D0 (sv) | 1999-12-20 | 1999-12-20 | Astra Pharma Inc | Novel compounds |
| EP1242421A1 (en) | 1999-12-22 | 2002-09-25 | Ortho-McNeil Pharmaceutical, Inc. | 4-[aryl(8-azabicyclo[3.2.1] octan-3-yl)] aminobenzoic acid derivatives |
| CA2400640A1 (en) * | 2000-02-18 | 2001-08-23 | Meiji Seika Kaisha, Ltd. | Phenoxyalkylamine derivatives useful as opioid .delta. receptor ligands |
| IL151550A0 (en) | 2000-03-03 | 2003-04-10 | Ortho Mcneil Pharm Inc | 3-(diarylmethylene)-8-azabicyclo [3.2.1] octane derivatives |
| CA2404280A1 (en) | 2000-03-24 | 2002-09-23 | Meiji Seika Kaisha, Ltd. | Diphenylalkylamine derivatives useful as opioid .delta. receptor agonists |
| SE0001209D0 (sv) | 2000-04-04 | 2000-04-04 | Astrazeneca Canada Inc | Novel compounds |
| AU2002234010A1 (en) * | 2000-12-14 | 2002-06-24 | Ortho-Mcneil Pharmaceutical, Inc. | Benzamidine derivatives |
| AU2002222879B2 (en) * | 2000-12-15 | 2006-02-02 | Astrazeneca Ab | New process for the preparation diaryl-4-amino-piperidinyl compounds |
| SE0101773D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101771D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| US7229994B2 (en) | 2001-05-18 | 2007-06-12 | Astrazeneca Ab | 4(phenyl-piperazinyl-methyl) benzamide derivatives and their use for the treatment of pain anxiety or gastrointestinal disorders |
| SE0101770D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101769D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| EA006507B1 (ru) | 2001-10-15 | 2005-12-29 | Янссен Фармацевтика Н.В. | Новые замещенные 4-фенил-4-[1h-имидазол-2-ил] пиперидиновые производные и их применение в качестве селективных непептидных агонистов дельта-опиоидов |
| US7501417B2 (en) * | 2002-03-13 | 2009-03-10 | Janssen Pharmaceutica, N.V. | Aminocarbonyl-derivatives as novel inhibitors of histone deacetylase |
| EP2399903A1 (en) | 2002-05-24 | 2011-12-28 | Millennium Pharmaceuticals, Inc. | Ccr9 inhibitors and methods of use thereof |
| SE0203303D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| SE0203302D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| SE0203300D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| US7227035B2 (en) | 2002-11-18 | 2007-06-05 | Chemocentryx | Bis-aryl sulfonamides |
| US7741519B2 (en) | 2007-04-23 | 2010-06-22 | Chemocentryx, Inc. | Bis-aryl sulfonamides |
| PT1562940E (pt) | 2002-11-18 | 2007-07-23 | Chemocentryx Inc | Sulfonamidas de arilo. |
| US7420055B2 (en) | 2002-11-18 | 2008-09-02 | Chemocentryx, Inc. | Aryl sulfonamides |
| ES2314362T3 (es) * | 2003-01-16 | 2009-03-16 | Acadia Pharmaceuticals Inc. | Agonistas inversos selectivos de los receptores 2a o 2c de serotonina utilizados como agentes terapeuticos contra enfermedades neurodegenerativas. |
| EP1644373A1 (en) | 2003-06-27 | 2006-04-12 | Janssen Pharmaceutica N.V. | Tricyclic delta opioid modulators |
| WO2005075472A1 (en) | 2004-02-03 | 2005-08-18 | Janssen Pharmaceutica, N.V. | 3-(diheteroarylnethylene)-8-azabicyclo[3.2.1]octane and 3-(aryl)(heteroaryl)methylene)-8-azabicyclo[3.2.1]octane derivatives |
| HRP20120343T1 (hr) | 2004-08-02 | 2012-05-31 | Astrazeneca Ab | Derivati diarilmetil piperazina, njihovi pripravci i njihova uporaba |
| BRPI0513075A (pt) * | 2004-08-05 | 2008-04-22 | Janssen Pharmaceutica Nv | moduladores gama-opióides tricìclicos |
| AU2005319059A1 (en) * | 2004-12-22 | 2006-06-29 | Janssen Pharmaceutica N.V. | Tricyclic delta-opioid modulators |
| MX2007007626A (es) * | 2004-12-22 | 2008-01-28 | Johnson & Johnson | Moduladores delta-opioides triciclicos. |
| CA2592464A1 (en) * | 2004-12-22 | 2006-06-29 | Janssen Pharmaceutica N.V. | Tricyclic .delta.-opioid modulators |
| CA2594347A1 (en) * | 2005-01-06 | 2006-07-13 | Janssen Pharmaceutica N.V. | Tricyclic d-opioid modulators |
| TWI449692B (zh) | 2005-05-13 | 2014-08-21 | Otsuka Pharma Co Ltd | 吡咯烷化合物（三） |
| JP2008543866A (ja) * | 2005-06-16 | 2008-12-04 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 三環式オピオイドモジュレーター |
| JP5219465B2 (ja) * | 2006-11-10 | 2013-06-26 | 大塚製薬株式会社 | 医薬 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4091096A (en) * | 1976-03-19 | 1978-05-23 | Eli Lilly And Company | Dinitroanilines for the control of phytopathogens |
| EG12406A (en) * | 1976-08-12 | 1979-03-31 | Janssen Pharmaceutica Nv | Process for preparing of novel n-aryl-n-(1-l-4-piperidinyl)-arylacetamides |
| SE441448B (sv) * | 1977-05-23 | 1985-10-07 | Pfizer | Sett att framstella hexahydro-gamma-karbolinforeningar |
| DE3200304A1 (de) * | 1981-01-16 | 1982-08-26 | Sandoz-Patent-GmbH, 7850 Lörrach | 3-aminopropoxyaryl-derivate, ihre herstellung und sie enthaltende arzneimittel |
| DE3563964D1 (en) * | 1984-10-16 | 1988-09-01 | Synthelabo | Piperidine derivatives, their preparation and their therapeutical application |
| YU150489A (sh) | 1989-08-10 | 1992-12-21 | W.L. Gore & Co. Gmbh. | Uređaj za ispitivanje odevnih predmeta na nepromočivost |
| KR940003491B1 (ko) | 1989-08-10 | 1994-04-23 | 리히터 게데온 베기에스제티 기아르 알.티 | 4,4-이중 치환된 피페리딘 유도체와 그 제조방법 및 상기 화합물을 함유하는 약제학적 조성물 |
| SE8904298D0 (sv) * | 1989-12-21 | 1989-12-21 | Astra Ab | New compounds |
| GB9202238D0 (en) * | 1992-02-03 | 1992-03-18 | Wellcome Found | Compounds |
| US5854245A (en) * | 1996-06-28 | 1998-12-29 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
| SE9604786D0 (sv) | 1996-12-20 | 1996-12-20 | Astra Pharma Inc | New compounds |
| TW548271B (en) * | 1996-12-20 | 2003-08-21 | Astra Pharma Inc | Novel piperidine derivatives having an exocyclic double bond with analgesic effects |
| WO1999033806A1 (en) * | 1997-12-24 | 1999-07-08 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)] aminobenzamides which bind to the delta-opioid receptor |
| AU756983B2 (en) | 1998-03-10 | 2003-01-30 | Research Triangle Institute | Novel opiate compounds, methods of making and methods of use |
| US6436959B1 (en) | 1998-12-23 | 2002-08-20 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)]aminobenzamides |
-
1996
- 1996-12-20 SE SE9604786A patent/SE9604786D0/xx unknown
-
1997
- 1997-09-12 UA UA99074131A patent/UA54481C2/uk unknown
- 1997-12-09 EE EEP199900261A patent/EE03966B1/xx not_active IP Right Cessation
- 1997-12-09 BR BR9713785-5A patent/BR9713785A/pt unknown
- 1997-12-09 EP EP97950539A patent/EP0946510B1/en not_active Expired - Lifetime
- 1997-12-09 SK SK763-99A patent/SK283300B6/sk unknown
- 1997-12-09 ID IDW990536A patent/ID21662A/id unknown
- 1997-12-09 NZ NZ336028A patent/NZ336028A/en unknown
- 1997-12-09 CN CNB971808376A patent/CN1154635C/zh not_active Expired - Fee Related
- 1997-12-09 AT AT97950539T patent/ATE266638T1/de not_active IP Right Cessation
- 1997-12-09 US US09/029,468 patent/US6153626A/en not_active Expired - Lifetime
- 1997-12-09 CA CA002274117A patent/CA2274117A1/en not_active Abandoned
- 1997-12-09 AU AU53513/98A patent/AU738002B2/en not_active Ceased
- 1997-12-09 IL IL13053697A patent/IL130536A0/xx unknown
- 1997-12-09 WO PCT/SE1997/002051 patent/WO1998028270A1/en not_active Ceased
- 1997-12-09 ES ES97950539T patent/ES2219783T3/es not_active Expired - Lifetime
- 1997-12-09 CZ CZ992200A patent/CZ220099A3/cs unknown
- 1997-12-09 ZA ZA9711049A patent/ZA9711049B/xx unknown
- 1997-12-09 CN CNA2004100324204A patent/CN1539824A/zh active Pending
- 1997-12-09 DE DE69729115T patent/DE69729115T2/de not_active Expired - Fee Related
- 1997-12-09 DK DK97950539T patent/DK0946510T3/da active
- 1997-12-09 PL PL97334370A patent/PL188945B1/pl not_active IP Right Cessation
- 1997-12-09 JP JP52867098A patent/JP2001507021A/ja not_active Ceased
- 1997-12-09 HU HU0000613A patent/HUP0000613A3/hu unknown
- 1997-12-09 PT PT97950539T patent/PT946510E/pt unknown
- 1997-12-09 RU RU99115746/04A patent/RU2193030C2/ru not_active IP Right Cessation
- 1997-12-09 KR KR1019997005586A patent/KR20000069600A/ko not_active Ceased
- 1997-12-09 TR TR1999/01411T patent/TR199901411T2/xx unknown
- 1997-12-09 EP EP04002901A patent/EP1428821A1/en not_active Withdrawn
- 1997-12-19 MY MYPI97006174A patent/MY132705A/en unknown
- 1997-12-19 AR ARP970106076A patent/AR010378A1/es active IP Right Grant
-
1999
- 1999-06-11 IS IS5078A patent/IS5078A/is unknown
- 1999-06-18 NO NO19993023A patent/NO313632B1/no unknown
-
2000
- 2000-08-25 US US09/645,565 patent/US6399635B1/en not_active Expired - Fee Related
-
2002
- 2002-04-15 US US10/121,683 patent/US6710179B2/en not_active Expired - Fee Related
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| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Discontinued |