JPS6012981A - オピオイド分解酵素阻害剤 - Google Patents
オピオイド分解酵素阻害剤Info
- Publication number
- JPS6012981A JPS6012981A JP11985683A JP11985683A JPS6012981A JP S6012981 A JPS6012981 A JP S6012981A JP 11985683 A JP11985683 A JP 11985683A JP 11985683 A JP11985683 A JP 11985683A JP S6012981 A JPS6012981 A JP S6012981A
- Authority
- JP
- Japan
- Prior art keywords
- opioid
- compound
- present
- morphine
- agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229940124036 Hydrolase inhibitor Drugs 0.000 title abstract 2
- 239000004093 hydrolase inhibitor Substances 0.000 title abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- 239000002075 main ingredient Substances 0.000 claims description 10
- 150000002291 germanium compounds Chemical class 0.000 claims description 9
- 230000000593 degrading effect Effects 0.000 claims description 8
- 229940125532 enzyme inhibitor Drugs 0.000 claims description 2
- 239000002532 enzyme inhibitor Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- -1 organogermanium compound Chemical class 0.000 abstract description 7
- 239000002775 capsule Substances 0.000 abstract description 2
- 238000002347 injection Methods 0.000 abstract description 2
- 239000007924 injection Substances 0.000 abstract description 2
- 239000000843 powder Substances 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 abstract description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract 1
- 239000003112 inhibitor Substances 0.000 abstract 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 abstract 1
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 24
- 102000004190 Enzymes Human genes 0.000 description 13
- 108090000790 Enzymes Proteins 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 12
- 229960005181 morphine Drugs 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 229940005483 opioid analgesics Drugs 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- 241000283690 Bos taurus Species 0.000 description 4
- URLZCHNOLZSCCA-VABKMULXSA-N Leu-enkephalin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 URLZCHNOLZSCCA-VABKMULXSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 108010036928 Thiorphan Proteins 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- LJJKNPQAGWVLDQ-SNVBAGLBSA-N thiorphan Chemical compound OC(=O)CNC(=O)[C@@H](CS)CC1=CC=CC=C1 LJJKNPQAGWVLDQ-SNVBAGLBSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- NLIJOIUVZBYQRS-UHFFFAOYSA-N 3-trichlorogermylpropanoic acid Chemical compound OC(=O)CC[Ge](Cl)(Cl)Cl NLIJOIUVZBYQRS-UHFFFAOYSA-N 0.000 description 2
- 102000015427 Angiotensins Human genes 0.000 description 2
- 108010064733 Angiotensins Proteins 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 102000003729 Neprilysin Human genes 0.000 description 2
- 108090000028 Neprilysin Proteins 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- 230000036592 analgesia Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- GIEAINOVPLDQPT-UHFFFAOYSA-N ethylgermanium Chemical compound CC[Ge] GIEAINOVPLDQPT-UHFFFAOYSA-N 0.000 description 2
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 102000004400 Aminopeptidases Human genes 0.000 description 1
- 108090000915 Aminopeptidases Proteins 0.000 description 1
- 206010005746 Blood pressure fluctuation Diseases 0.000 description 1
- COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical compound OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 description 1
- 229930182832 D-phenylalanine Natural products 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000000114 Pain Threshold Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 238000001467 acupuncture Methods 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000006477 desulfuration reaction Methods 0.000 description 1
- 230000023556 desulfurization Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000008531 maintenance mechanism Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000003533 narcotic effect Effects 0.000 description 1
- 230000037040 pain threshold Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002315 pressor effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000036454 renin-angiotensin system Effects 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- VLZFWMHRXCHTLY-UHFFFAOYSA-N trichloro(ethyl)germane Chemical class CC[Ge](Cl)(Cl)Cl VLZFWMHRXCHTLY-UHFFFAOYSA-N 0.000 description 1
- FEFXFMQVSDTSPA-UHFFFAOYSA-N trichloro(methyl)germane Chemical class C[Ge](Cl)(Cl)Cl FEFXFMQVSDTSPA-UHFFFAOYSA-N 0.000 description 1
- YITSIQZHKDXQEI-UHFFFAOYSA-N trichlorogermanium Chemical compound Cl[Ge](Cl)Cl YITSIQZHKDXQEI-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Enzymes And Modification Thereof (AREA)
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11985683A JPS6012981A (ja) | 1983-07-01 | 1983-07-01 | オピオイド分解酵素阻害剤 |
| CH315384A CH660192B (enExample) | 1983-07-01 | 1984-06-29 | |
| GB08416614A GB2142635B (en) | 1983-07-01 | 1984-06-29 | Organogermanium compound and an opioid peptide-degrading enzyme inhibitor containing the same |
| FR8410392A FR2548187B1 (fr) | 1983-07-01 | 1984-06-29 | Composes d'organo-germanium et leurs utilisations therapeutiques en tant qu'inhibiteurs des enzymes qui degradent les peptides opioides |
| DE3424107A DE3424107A1 (de) | 1983-07-01 | 1984-06-29 | Organogermaniumverbindung und diese als wirkstoff enthaltender opioidpeptidaseinhibitor |
| US06/626,787 US4681960A (en) | 1983-07-01 | 1984-07-02 | Organogermanium compound |
| US06/930,561 US4748187A (en) | 1983-07-01 | 1986-11-14 | Opioid peptide-degrading enzyme inhibitor with a germanium compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11985683A JPS6012981A (ja) | 1983-07-01 | 1983-07-01 | オピオイド分解酵素阻害剤 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6012981A true JPS6012981A (ja) | 1985-01-23 |
| JPH0144168B2 JPH0144168B2 (enExample) | 1989-09-26 |
Family
ID=14771963
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11985683A Granted JPS6012981A (ja) | 1983-07-01 | 1983-07-01 | オピオイド分解酵素阻害剤 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6012981A (enExample) |
-
1983
- 1983-07-01 JP JP11985683A patent/JPS6012981A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0144168B2 (enExample) | 1989-09-26 |
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