DE69737039T2 - Anandamid-amidaseinhibitoren als analgetika - Google Patents
Anandamid-amidaseinhibitoren als analgetika Download PDFInfo
- Publication number
- DE69737039T2 DE69737039T2 DE69737039T DE69737039T DE69737039T2 DE 69737039 T2 DE69737039 T2 DE 69737039T2 DE 69737039 T DE69737039 T DE 69737039T DE 69737039 T DE69737039 T DE 69737039T DE 69737039 T2 DE69737039 T2 DE 69737039T2
- Authority
- DE
- Germany
- Prior art keywords
- group
- substituted
- compound
- aryl
- lower alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 108010084714 arachidonoylethanolamide synthase Proteins 0.000 title description 25
- 239000003112 inhibitor Substances 0.000 title description 19
- -1 thioether ethers Chemical class 0.000 claims description 42
- 150000001875 compounds Chemical class 0.000 claims description 31
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- 241001465754 Metazoa Species 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000003107 substituted aryl group Chemical group 0.000 claims description 9
- 108700023418 Amidases Proteins 0.000 claims description 8
- 102000005922 amidase Human genes 0.000 claims description 8
- 230000036592 analgesia Effects 0.000 claims description 8
- 230000027455 binding Effects 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 206010028813 Nausea Diseases 0.000 claims description 6
- 230000008693 nausea Effects 0.000 claims description 6
- 230000000269 nucleophilic effect Effects 0.000 claims description 6
- 230000001225 therapeutic effect Effects 0.000 claims description 6
- 230000036528 appetite Effects 0.000 claims description 5
- 235000019789 appetite Nutrition 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 210000000987 immune system Anatomy 0.000 claims description 4
- 230000004410 intraocular pressure Effects 0.000 claims description 4
- SNVLJLYUUXKWOJ-UHFFFAOYSA-N methylidenecarbene Chemical group C=[C] SNVLJLYUUXKWOJ-UHFFFAOYSA-N 0.000 claims description 4
- 229920001281 polyalkylene Polymers 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 206010039897 Sedation Diseases 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- 230000036280 sedation Effects 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000003367 polycyclic group Chemical group 0.000 claims description 2
- 125000006413 ring segment Chemical group 0.000 claims description 2
- 230000001629 suppression Effects 0.000 claims description 2
- 150000003573 thiols Chemical class 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- 230000000202 analgesic effect Effects 0.000 claims 1
- 150000002170 ethers Chemical class 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 230000001737 promoting effect Effects 0.000 claims 1
- 239000000932 sedative agent Substances 0.000 claims 1
- 230000001624 sedative effect Effects 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- LGEQQWMQCRIYKG-DOFZRALJSA-N anandamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCO LGEQQWMQCRIYKG-DOFZRALJSA-N 0.000 description 37
- LGEQQWMQCRIYKG-UHFFFAOYSA-N arachidonic acid ethanolamide Natural products CCCCCC=CCC=CCC=CCC=CCCCC(=O)NCCO LGEQQWMQCRIYKG-UHFFFAOYSA-N 0.000 description 27
- 210000004027 cell Anatomy 0.000 description 21
- 230000000694 effects Effects 0.000 description 16
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 16
- QIVFMUVBIHIZAM-UHFFFAOYSA-N hexadecane-1-sulfonyl fluoride Chemical compound CCCCCCCCCCCCCCCCS(F)(=O)=O QIVFMUVBIHIZAM-UHFFFAOYSA-N 0.000 description 15
- 102000009132 CB1 Cannabinoid Receptor Human genes 0.000 description 14
- 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 description 14
- 229930003827 cannabinoid Natural products 0.000 description 12
- 239000003557 cannabinoid Substances 0.000 description 12
- 229940065144 cannabinoids Drugs 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 102000009135 CB2 Cannabinoid Receptor Human genes 0.000 description 8
- 108010073376 CB2 Cannabinoid Receptor Proteins 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 150000002430 hydrocarbons Chemical group 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 206010029260 Neuroblastoma Diseases 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 5
- 108050007331 Cannabinoid receptor Proteins 0.000 description 5
- 102100033868 Cannabinoid receptor 1 Human genes 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- VQFQXLQALUCXND-UHFFFAOYSA-N icosane-1-sulfonyl fluoride Chemical compound CCCCCCCCCCCCCCCCCCCCS(F)(=O)=O VQFQXLQALUCXND-UHFFFAOYSA-N 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- OBTWBSRJZRCYQV-UHFFFAOYSA-N sulfuryl difluoride Chemical compound FS(F)(=O)=O OBTWBSRJZRCYQV-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000036407 pain Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 2
- 208000037415 AIDS wasting syndrome Diseases 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-M Arachidonate Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC([O-])=O YZXBAPSDXZZRGB-DOFZRALJSA-M 0.000 description 2
- 101150065749 Churc1 gene Proteins 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 2
- 208000010412 Glaucoma Diseases 0.000 description 2
- 208000003577 HIV wasting syndrome Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 102100038239 Protein Churchill Human genes 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229940114078 arachidonate Drugs 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- UVLRFDMRDPQRSM-UHFFFAOYSA-N dodecane-1-sulfonyl fluoride Chemical compound CCCCCCCCCCCCS(F)(=O)=O UVLRFDMRDPQRSM-UHFFFAOYSA-N 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 150000004668 long chain fatty acids Chemical class 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- SZXIBISKCHYMAR-UHFFFAOYSA-N octadecane-1-sulfonyl fluoride Chemical compound CCCCCCCCCCCCCCCCCCS(F)(=O)=O SZXIBISKCHYMAR-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Chemical group 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000000506 psychotropic effect Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical class O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 229910052717 sulfur Chemical group 0.000 description 2
- 239000011593 sulfur Chemical group 0.000 description 2
- QKRWHXNZSPRRMB-UHFFFAOYSA-N tetradecane-1-sulfonyl fluoride Chemical compound CCCCCCCCCCCCCCS(F)(=O)=O QKRWHXNZSPRRMB-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- YPYQDMBJZJZFQL-LLZYVPLJSA-N (6s,6ar,9r,10ar)-6-methyl-3-[(2r)-5-phenylpentan-2-yl]oxy-5,6,6a,7,8,9,10,10a-octahydrophenanthridine-1,9-diol Chemical compound C([C@@H](C)OC=1C=C2N[C@@H](C)[C@@H]3CC[C@@H](O)C[C@H]3C2=C(O)C=1)CCC1=CC=CC=C1 YPYQDMBJZJZFQL-LLZYVPLJSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- VLEIUWBSEKKKFX-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid Chemical compound OCC(N)(CO)CO.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O VLEIUWBSEKKKFX-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical class C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- PLWROONZUDKYKG-DOFZRALJSA-N AACOCF3 Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)C(F)(F)F PLWROONZUDKYKG-DOFZRALJSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 0 C*(CC(N1OS(*)(=O)=O)=O)C1=O Chemical compound C*(CC(N1OS(*)(=O)=O)=O)C1=O 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 description 1
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 235000019750 Crude protein Nutrition 0.000 description 1
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 1
- DKMROQRQHGEIOW-UHFFFAOYSA-N Diethyl succinate Chemical compound CCOC(=O)CCC(=O)OCC DKMROQRQHGEIOW-UHFFFAOYSA-N 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 238000001061 Dunnett's test Methods 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000010909 Monoamine Oxidase Human genes 0.000 description 1
- 108010062431 Monoamine oxidase Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108010081690 Pertussis Toxin Proteins 0.000 description 1
- URBYTNAFBOUEQN-UHFFFAOYSA-N S(=O)(=O)=[ClH] Chemical compound S(=O)(=O)=[ClH] URBYTNAFBOUEQN-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 241000144290 Sigmodon hispidus Species 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 238000006600 Stobbe condensation reaction Methods 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 125000004097 arachidonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])/C([H])=C([H])\C([H])([H])/C([H])=C([H])\C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- LOLKAJARZKDJTD-UHFFFAOYSA-N butanedioic acid monoethyl ester Natural products CCOC(=O)CCC(O)=O LOLKAJARZKDJTD-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000003375 cannabimimetic effect Effects 0.000 description 1
- 239000003554 cannabinoid 1 receptor agonist Substances 0.000 description 1
- 239000003556 cannabinoid 2 receptor agonist Substances 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- VBZWSGALLODQNC-UHFFFAOYSA-N hexafluoroacetone Chemical class FC(F)(F)C(=O)C(F)(F)F VBZWSGALLODQNC-UHFFFAOYSA-N 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 206010021654 increased appetite Diseases 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 238000005567 liquid scintillation counting Methods 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000013223 sprague-dawley female rat Methods 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000011044 succinic acid Nutrition 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/255—Esters, e.g. nitroglycerine, selenocyanates of sulfoxy acids or sulfur analogues thereof
-
- 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
-
- 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
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- 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]
-
- 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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- 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
- C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Emergency Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Transplantation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US658949 | 1984-10-09 | ||
| US08/658,949 US5688825A (en) | 1996-05-31 | 1996-05-31 | Anandamide amidase inhibitors as analgesic agents |
| PCT/US1997/009613 WO1997045407A1 (en) | 1996-05-31 | 1997-05-30 | Novel anandamide amidase inhibitors as analgesic agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69737039D1 DE69737039D1 (de) | 2007-01-11 |
| DE69737039T2 true DE69737039T2 (de) | 2007-06-21 |
Family
ID=24643395
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69737039T Expired - Lifetime DE69737039T2 (de) | 1996-05-31 | 1997-05-30 | Anandamid-amidaseinhibitoren als analgetika |
Country Status (8)
| Country | Link |
|---|---|
| US (4) | US5688825A (enExample) |
| EP (2) | EP1021406B1 (enExample) |
| JP (1) | JP2000511540A (enExample) |
| AU (1) | AU3229097A (enExample) |
| CA (1) | CA2255620C (enExample) |
| DE (1) | DE69737039T2 (enExample) |
| ES (1) | ES2278391T3 (enExample) |
| WO (1) | WO1997045407A1 (enExample) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5688825A (en) * | 1996-05-31 | 1997-11-18 | University Of Connecticut | Anandamide amidase inhibitors as analgesic agents |
| WO1999057107A2 (en) * | 1998-05-04 | 1999-11-11 | The University Of Connecticut | Cannabinoids selective for the cb2 receptor |
| WO1999057106A1 (en) * | 1998-05-04 | 1999-11-11 | The University Of Connecticut | Novel analgesic and immunomodulatory cannabinoids |
| US7897598B2 (en) * | 1998-06-09 | 2011-03-01 | Alexandros Makriyannis | Inhibitors of the anandamide transporter |
| EP1084098A4 (en) * | 1998-06-09 | 2004-12-22 | Univ Connecticut | INHIBITORS OF THE ANANDAMIDE TRANSPORTER AS ANALGETIC AGENT |
| US7589220B2 (en) | 1998-06-09 | 2009-09-15 | University Of Connecticut | Inhibitors of the anandamide transporter |
| US7276613B1 (en) * | 1998-11-24 | 2007-10-02 | University Of Connecticut | Retro-anandamides, high affinity and stability cannabinoid receptor ligands |
| US7161016B1 (en) | 1998-11-24 | 2007-01-09 | University Of Connecticut | Cannabimimetic lipid amides as useful medications |
| ATE428495T1 (de) | 1999-04-28 | 2009-05-15 | Toray Industries | Stoffe zur enternung von cannabinoiden und säulen mit diesen stoffen zur entfernung von cannabinoiden |
| GB9923738D0 (en) * | 1999-10-07 | 1999-12-08 | Nestle Sa | Nutritional composition |
| US7393842B2 (en) * | 2001-08-31 | 2008-07-01 | University Of Connecticut | Pyrazole analogs acting on cannabinoid receptors |
| CA2387846A1 (en) * | 1999-10-18 | 2001-04-26 | University Of Connecticut | Retro-anandamides, high affinity and stability cannabinoid receptor ligands |
| US6900236B1 (en) * | 1999-10-18 | 2005-05-31 | University Of Connecticut | Cannabimimetic indole derivatives |
| 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 |
| MXPA02005103A (es) | 1999-10-18 | 2003-09-25 | Alexipharma Inc | Ligandos selectivos del receptor de canabinoide (cb2) perifericos. |
| US7741365B2 (en) * | 1999-10-18 | 2010-06-22 | University Of Connecticut | Peripheral cannabinoid receptor (CB2) selective ligands |
| US8084467B2 (en) * | 1999-10-18 | 2011-12-27 | University Of Connecticut | Pyrazole derivatives as cannabinoid receptor antagonists |
| ES2174716B1 (es) * | 2000-07-28 | 2004-08-01 | Universidad Complutense De Madrid | Nuevos derivados de acido araquidonico con afinidad por el transportador de anandamida. |
| ES2181601B2 (es) * | 2001-07-27 | 2004-04-01 | Univ Madrid Complutense | Derivados de acido araquidonico con afinidad por el transportador de anandamida |
| AU2001284061A1 (en) * | 2000-07-28 | 2002-02-18 | Universidad Complutense De Madrid | Novel araquidonic acid derivatives with affinity toward the anandamide transporter |
| WO2002058636A2 (en) * | 2001-01-26 | 2002-08-01 | University Of Connecticut | Novel cannabimimetic ligands |
| JP2005503998A (ja) | 2001-01-29 | 2005-02-10 | ユニバーシティ オブ コネチカット | 受容体選択性のカンナビミメティックアミノアルキルインドール |
| EP1385520A4 (en) * | 2001-02-08 | 2007-03-21 | Nps Pharma Inc | METHODS AND COMPOUNDS FOR THE TREATMENT OF NEUROLOGICAL AND NEUROPSYCHIATRICAL DISEASES AND FOR THE IDENTIFICATION OF COMPOUNDS FOR THE TREATMENT THEREOF |
| WO2003005960A2 (en) * | 2001-07-13 | 2003-01-23 | University Of Connecticut | Novel bicyclic and tricyclic cannabinoids |
| EP2147679B1 (en) | 2001-07-25 | 2014-06-25 | Raptor Pharmaceutical, Inc. | Compositions for blood-brain barrier transport |
| CN1589269A (zh) * | 2001-10-26 | 2005-03-02 | 康涅狄格大学 | 杂1,2－二氢化茚:一类新型有效的大麻配体 |
| EP1482917B1 (en) * | 2002-02-01 | 2019-05-08 | GW Pharma Limited | Compositions comprising cannabidiolic acid for treatment of nausea, vomiting, emesis, motion sickness or like conditions |
| US20040063726A1 (en) * | 2002-02-08 | 2004-04-01 | Artman Linda D | Methods and compounds for treating neurologic or neuropsychiatric disorders and identifying compounds to treat the same |
| IL148244A0 (en) | 2002-02-19 | 2002-09-12 | Yissum Res Dev Co | Anti-nausea and anti-vomiting activity of cannabidiol compounds |
| WO2003092676A1 (en) * | 2002-04-29 | 2003-11-13 | The General Hospital Corporation | Compositions and methods for preventing abuse of orally administered medications |
| MXPA04011390A (es) | 2002-05-16 | 2005-02-17 | Sepracor Inc | Aminas que inhiben un transportador de anandamida de mamifero, y metodos de uso de las mismas. |
| DE60320784D1 (de) * | 2002-06-06 | 2008-06-19 | Yissum Res Dev Co | Stände zur modulierung des knochenwachstums |
| AU2003265663A1 (en) | 2002-08-23 | 2004-03-11 | University Of Connecticut | Keto cannabinoids with therapeutic indications |
| GB0403864D0 (en) | 2004-02-20 | 2004-03-24 | Ucl Ventures | Modulator |
| EP2392258B1 (en) | 2005-04-28 | 2014-10-08 | Proteus Digital Health, Inc. | Pharma-informatics system |
| CN101594878A (zh) | 2006-09-18 | 2009-12-02 | 雷普特药品公司 | 通过给予受体相关蛋白（rap）-缀合物对肝病症的治疗 |
| US7781650B2 (en) * | 2007-04-30 | 2010-08-24 | Monsanto Technology Llc | Plants and seeds of corn variety CV202909 |
| WO2009052319A1 (en) * | 2007-10-16 | 2009-04-23 | Northeastern University | Monoacylglycerol lipase inhibitors for modulation of cannabinoid activity |
| PL3395372T3 (pl) | 2009-02-20 | 2022-07-25 | EnhanX Biopharm Inc. | Układ do dostarczania leków na bazie glutationu |
| CN102458374A (zh) | 2009-05-06 | 2012-05-16 | 实验室护肤股份有限公司 | 包含活性剂-磷酸钙颗粒复合物的皮肤递送组合物及其使用方法 |
| US20120077778A1 (en) | 2010-09-29 | 2012-03-29 | Andrea Bourdelais | Ladder-Frame Polyether Conjugates |
| CN106659700B (zh) * | 2014-06-06 | 2020-07-10 | 斯克里普斯研究所 | 氟化硫(vi)化合物及其制备方法 |
| CN112121852B (zh) * | 2020-08-27 | 2021-09-24 | 中山大学 | 催化剂组合物及催化剂组合物或催化剂用于催化亲核取代反应的用途 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3577458A (en) * | 1966-11-14 | 1971-05-04 | Allied Chem | Process for the preparation of isocyanates |
| US3465024A (en) * | 1966-11-14 | 1969-09-02 | Allied Chem | Process for the preparation of isocyanates |
| US5804601A (en) * | 1995-04-10 | 1998-09-08 | Takeda Chemical Industries, Ltd. | Aromatic hydroxamic acid compounds, their production and use |
| US5688825A (en) * | 1996-05-31 | 1997-11-18 | University Of Connecticut | Anandamide amidase inhibitors as analgesic agents |
-
1996
- 1996-05-31 US US08/658,949 patent/US5688825A/en not_active Expired - Lifetime
-
1997
- 1997-05-30 JP JP09543074A patent/JP2000511540A/ja active Pending
- 1997-05-30 DE DE69737039T patent/DE69737039T2/de not_active Expired - Lifetime
- 1997-05-30 WO PCT/US1997/009613 patent/WO1997045407A1/en not_active Ceased
- 1997-05-30 CA CA002255620A patent/CA2255620C/en not_active Expired - Fee Related
- 1997-05-30 ES ES97927958T patent/ES2278391T3/es not_active Expired - Lifetime
- 1997-05-30 EP EP97927958A patent/EP1021406B1/en not_active Expired - Lifetime
- 1997-05-30 EP EP06024572A patent/EP1775286A1/en not_active Withdrawn
- 1997-05-30 AU AU32290/97A patent/AU3229097A/en not_active Abandoned
- 1997-11-12 US US08/967,847 patent/US5874459A/en not_active Expired - Lifetime
-
2000
- 2000-04-20 US US09/553,499 patent/US6391909B1/en not_active Expired - Fee Related
-
2002
- 2002-02-06 US US10/068,588 patent/US6579900B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US6579900B2 (en) | 2003-06-17 |
| EP1021406B1 (en) | 2006-11-29 |
| CA2255620C (en) | 2008-01-29 |
| EP1021406A1 (en) | 2000-07-26 |
| US5874459A (en) | 1999-02-23 |
| US20020091153A1 (en) | 2002-07-11 |
| US6391909B1 (en) | 2002-05-21 |
| AU3229097A (en) | 1998-01-05 |
| WO1997045407A1 (en) | 1997-12-04 |
| ES2278391T3 (es) | 2007-08-01 |
| JP2000511540A (ja) | 2000-09-05 |
| EP1775286A1 (en) | 2007-04-18 |
| US5688825A (en) | 1997-11-18 |
| DE69737039D1 (de) | 2007-01-11 |
| CA2255620A1 (en) | 1997-12-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69737039T2 (de) | Anandamid-amidaseinhibitoren als analgetika | |
| DE60209504T2 (de) | Carbocyclische hydrazino-hemmer von kupferhaltigen aminoxidasen | |
| DE69809726T2 (de) | Substituierte analoge von indol-3-carbinol und von diindolmethan als antiestrogene | |
| DE60027648T2 (de) | Sulfonamide enthaltende indolderivate | |
| EP0846685B1 (de) | 3-Hydroxy-Pyridin-2-carbonsäureamidester, ihre Herstellung und ihre Verwendung als Arzneimittel | |
| DE60312155T2 (de) | 1-(aminoalkyl)-3-sulfonylazaindole als 5-hydroxytryptamin-6 liganden | |
| DE60023686T2 (de) | Verwendung von selektiven alpha-adrenergischen rezeptorantagonisten zur behandlung sexueller störungen | |
| DE69530933T2 (de) | Verwendung von 5-(tetradecyloxy)-2-furan carbonsäure für die behandlung von alzheimer krankheit oder psychosis | |
| DE69323185T2 (de) | Proteinkinase c-inhibitor | |
| WO1997041103A1 (de) | 3-alkoxypyridin-2-carbonsäureamidester, ihre herstellung und ihre verwendung als arzneimittel | |
| DE69731038T2 (de) | Screening-test zur identifikation von inhibitoren des makrophagenmigrationshemmenden faktors | |
| EP0214058A2 (fr) | Composition pharmaceutique contenant des dérivés de l'histamine | |
| DE60224276T2 (de) | Krebsmetastasen-hemmer mit carbacyclischen phosphatidinsäurederivaten | |
| EP0474597B1 (de) | Arachidonsäurestoffwechselhemmende Diphenylverbindungen und ihre Verwendung in pharmazeutischen Zusammensetzungen | |
| DE3109335C2 (de) | Ebelacton A und B, Verfahren zu deren Herstellung und diese Verbindungen enthaltende pharmazeutische Mittel | |
| DE69911755T2 (de) | Synthetische endogene cannabinoidanaloge und ihre verwendungen | |
| DE60029954T2 (de) | Dermale anästhetika | |
| DE69412073T2 (de) | Xanthinderivate als adenosin-a1 rezeptor antagonisten | |
| DE1643279A1 (de) | Aromatische Sulfamoylverbindungen | |
| DE69208569T2 (de) | Thioharnstoffderivate und sie enthaltendes, antimikrobielles und antiulcerogenes Mittel | |
| DE69320367T2 (de) | Therapeutische verbindungen für die behandlung von krankheiten, die mit einem glutathion-defizit assoziiert sind, herstellungsprozess und diese enthaltene pharmazeutische zusammensetzungen | |
| US4540709A (en) | Method for treatment of diseases mediated by PAF using 5-allyl-2-(3,4-Dimethoxyphenyl)-3a,α-methoxy-3-methyl-2,3,3a,6-tetrahydro-6-oxobenzofuran | |
| WO2001074753A1 (de) | Synthetische derivate von lunularsäure, arzneimittel enthaltend diese verbindungen, verfahren zur herstellung der lunularsäurederivate sowie deren verwendung | |
| DE60207257T2 (de) | Heterocarpin, ein protein, das humanes ghrh bindet | |
| DE3410848C2 (de) | Verwendung von Flunarizin zur Behandlung von Tumoren |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |