FI62823B - Foerfarande foer framstaellning av terapeutiskt verksamma histidinderivat - Google Patents
Foerfarande foer framstaellning av terapeutiskt verksamma histidinderivat Download PDFInfo
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- FI62823B FI62823B FI760538A FI760538A FI62823B FI 62823 B FI62823 B FI 62823B FI 760538 A FI760538 A FI 760538A FI 760538 A FI760538 A FI 760538A FI 62823 B FI62823 B FI 62823B
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- 150000001875 compounds Chemical class 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 20
- 108010016626 Dipeptides Proteins 0.000 claims description 12
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 150000002410 histidine derivatives Chemical class 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- 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
- 241000772415 Neovison vison Species 0.000 claims 1
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- 239000000243 solution Substances 0.000 description 60
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- VHSFUGXCSGOKJX-JTQLQIEISA-N (2s)-5-oxo-1-phenylmethoxycarbonylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCC(=O)N1C(=O)OCC1=CC=CC=C1 VHSFUGXCSGOKJX-JTQLQIEISA-N 0.000 description 3
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- SEPQTYODOKLVSB-UHFFFAOYSA-N 3-methylbut-2-enal Chemical compound CC(C)=CC=O SEPQTYODOKLVSB-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- AJFFONDFZKSGAZ-MABHGRKGSA-N Cl.C(C1([C@H](NCC1)C(=O)O)C[2H])[2H] Chemical compound Cl.C(C1([C@H](NCC1)C(=O)O)C[2H])[2H] AJFFONDFZKSGAZ-MABHGRKGSA-N 0.000 description 1
- VUBKPVITDNPXES-UHFFFAOYSA-N ClC(COC1=NC=CC1(C)C)Cl Chemical compound ClC(COC1=NC=CC1(C)C)Cl VUBKPVITDNPXES-UHFFFAOYSA-N 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- BXRMEWOQUXOLDH-LURJTMIESA-N L-Histidine methyl ester Chemical compound COC(=O)[C@@H](N)CC1=CN=CN1 BXRMEWOQUXOLDH-LURJTMIESA-N 0.000 description 1
- FEWJPZIEWOKRBE-XIXRPRMCSA-N Mesotartaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-XIXRPRMCSA-N 0.000 description 1
- CYZKJBZEIFWZSR-LURJTMIESA-N N(alpha)-methyl-L-histidine Chemical compound CN[C@H](C(O)=O)CC1=CNC=N1 CYZKJBZEIFWZSR-LURJTMIESA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- GOYHKHMANXXUSB-UHFFFAOYSA-N O.C(C)(C)C(C(=O)O)CC Chemical compound O.C(C)(C)C(C(=O)O)CC GOYHKHMANXXUSB-UHFFFAOYSA-N 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
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- DTCCTIQRPGSLPT-UHFFFAOYSA-N beta-Aethyl-acrolein Natural products CCC=CC=O DTCCTIQRPGSLPT-UHFFFAOYSA-N 0.000 description 1
- 238000009529 body temperature measurement Methods 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- ICCFICYRAVUJNK-UHFFFAOYSA-N cyclohexanamine;dihydrochloride Chemical compound Cl.Cl.NC1CCCCC1 ICCFICYRAVUJNK-UHFFFAOYSA-N 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- VJOLVZZLIHXBLW-UHFFFAOYSA-N hexan-1-amine;dihydrochloride Chemical compound Cl.Cl.CCCCCCN VJOLVZZLIHXBLW-UHFFFAOYSA-N 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- ZUSSTQCWRDLYJA-UHFFFAOYSA-N n-hydroxy-5-norbornene-2,3-dicarboximide Chemical compound C1=CC2CC1C1C2C(=O)N(O)C1=O ZUSSTQCWRDLYJA-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
- XFWCSGJOVUQCME-YUMQZZPRSA-N pEH Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H]1NC(=O)CC1)C1=CNC=N1 XFWCSGJOVUQCME-YUMQZZPRSA-N 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 235000013930 proline Nutrition 0.000 description 1
- 150000003148 prolines Chemical class 0.000 description 1
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 150000003334 secondary amides Chemical class 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- LJFPGBIHDPZHIN-UHFFFAOYSA-N tert-butyl (2,4,5-trichlorophenyl) carbonate Chemical compound CC(C)(C)OC(=O)OC1=CC(Cl)=C(Cl)C=C1Cl LJFPGBIHDPZHIN-UHFFFAOYSA-N 0.000 description 1
- LBVZYIYEWDLJMP-UHFFFAOYSA-N tert-butyl 2-carbamoyl-3,3-dimethylpyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C)(C)C1C(N)=O LBVZYIYEWDLJMP-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
- C07K5/0825—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp and Glp-amino acid; Derivatives thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Life Sciences & Earth Sciences (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Claims (3)
1. R on 1 - 3 hiiliatomia sisältävä alkyyliryhmä; R on vety tai 1-3 hiiliatomia sisältävä alkyyliryhmä; on vety tai syklo- heksyy1iryhmä, tunnettu siitä, että (a) histidiinijohdos, jonka kaava on Λ K!! - CH - COY -n »H ' // N R jossa R on edellä määritelty, Y tarkoittaa suojaryhmää ja A tarkoittaa ryhmää, joka voi muodostaa peptidisidoksen, liitetään yhdisteeseen, jonka kaava bn ^Vcox (III) o n jossa B tarkoittaa vetyatomia tai suojaryhmää ja X tarkoittaa ryhmää, joka voi muodostaa peptidisidoksen, dipeptidin muodostamiseksi, jonka kaava on 19 62823 V CO ·- Nl I - OI - COY ^ N 1 ϋ I " O N .J-l i (5 jossa 8, V ja R on edellä määritelty, minkä jälkeen suojaryhmä V muunnetaan ryhmäksi, joka voi muodostaa peptidisidoksen ja dipeptidi liitetään yhdisteeseen, jonka kaava on O , UN ! ^ 1' ” (IV) CONHfr 12 3 jossa R , R ja R on edellä määritelty, minkä jälkeen suojaryhmä B mahdollisesti poistetaan, tai(b) h istidiinijohdos, jonka kaava o n anh - CM - COY (II) Vj k' jossa R on edellä määritelty, A tarkoittaa N-suojaavaa ryhmää, ja Y tarkoittaa ryhmää, joka voi muodostaa peptidisidoksen, liitetään yhdisteeseen, jonka kaava on HN ^ . muN py· (IV) CONHR5 jossa R1, R2 ja R3 on edellä määritelty, dipeptidin muodostamiseksi, jonka kaava on 20 62823 ΛΝΗ - CM - CO - ] R1 ch2 Jv CONHR5 Ö / R 1 2 3 jossa A, R, R , R ja R on edellä määritelty, minkä jälkeen suojaryhmä A poistetaan ja dipeptidi liitetään yhdisteeseen, jonka kaava on I V- N (III) o jossa B on vetyatomi tai suojaryhmä ja X on ryhmä, joka voi muodostaa peptidisidoksen, minkä jälkeen suojaryhmä B mahdollisesti poistetaan. 21 6282 3 Förfarande for framställning av histidinderivat med den allmanna formeln i'' \ / I I >. CO - NH - CH - CO - tl ir j-.»· I y !l CM- CONHP.J . , | * II) A J Π ' där R betecknar en väteatom eller en alkylgrupp innehällande 1-3 kolatomer, R^ betecknar en alkylgrupp innehällande 1-3 kolatomer, R betecknar en väteatom eller en alkylgrupp innehällande 1-3 kolatomer, och R^ betecknar en väteatom eller en cyklohexyIgrupp, kännetecknat av att (a) ett histidinderivat med formeln A I*.”;! - C!l - COY O! I., ! " (II) \ \ N n - x*'" R där R har ovan angivna betydelse, Y betecknar en skyddsgrupp och A betecknar en grupp som kan bilda en peptidbindning, kopplas med en förening med formelh \— cox ti (111)
0 B där B betecknar en väteatom eller en skyddsgrupp och X betecknar en grupp som kan bilda en peptidbindning, till bildning av en dipeptid med formeln [ CO ~ ΙΊΙI - CH - COY o'- ' 1 ’ λ 0 l\ 22 6 2 8 2 3 dar B, Y och R har ovan angivna betydelser, varefter skyddsgruppen Y omvandlas tili en grupp som kan bilda en peptidbindning och dipeptiden kopplas med en förening med formeln / \ hm : . i' \^~--------(IV) 12 3 där R , R och R har ον/an angivna betydelser, varefter en eventuell skyddsgrupp B avlägsnas; eller att (b) ett histidinderivat med formeln ANN - Cl I - qov OH, f 11> N n' där R har ovan angivna betydelse, A betecknar en N-skyddande grupp, och Y betecknar en grupp som kan bilda en peptidbindning, kopplas med en förening med formeln I?1 HN ^ K (IV) CONHR3 12 3 där R , R och R har ovan angivna betydelser, tili bildning av dipeptid med formeln ani-i - cm - CO - N R1 CH2 λ ,
1 CONHR^ f - R
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1014475 | 1975-03-08 | ||
| GB10144/75A GB1523598A (en) | 1975-03-08 | 1975-03-08 | Tripeptides |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI760538A FI760538A (sv) | 1976-09-09 |
| FI62823B true FI62823B (fi) | 1982-11-30 |
| FI62823C FI62823C (fi) | 1983-03-10 |
Family
ID=9962321
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI760538A FI62823C (fi) | 1975-03-08 | 1976-03-02 | Foerfarande foer framstaellning av terapeutiskt verksamma histidinderivat |
Country Status (32)
| Country | Link |
|---|---|
| US (1) | US4060603A (sv) |
| JP (1) | JPS5940144B2 (sv) |
| AR (1) | AR208361A1 (sv) |
| AT (1) | AT352918B (sv) |
| BE (1) | BE839187A (sv) |
| CA (1) | CA1059994A (sv) |
| CH (1) | CH608484A5 (sv) |
| CS (1) | CS197268B2 (sv) |
| DE (1) | DE2609154C2 (sv) |
| DK (1) | DK97376A (sv) |
| EG (1) | EG13624A (sv) |
| ES (1) | ES445763A1 (sv) |
| FI (1) | FI62823C (sv) |
| FR (1) | FR2303559A1 (sv) |
| GB (1) | GB1523598A (sv) |
| GR (1) | GR59891B (sv) |
| HU (1) | HU175652B (sv) |
| IE (1) | IE42784B1 (sv) |
| IL (1) | IL49122A (sv) |
| LU (1) | LU74483A1 (sv) |
| MX (1) | MX3055E (sv) |
| NL (1) | NL7602257A (sv) |
| NO (1) | NO144604C (sv) |
| OA (1) | OA05260A (sv) |
| PH (1) | PH11727A (sv) |
| PL (1) | PL101401B1 (sv) |
| PT (1) | PT64853B (sv) |
| SE (1) | SE411671B (sv) |
| SU (1) | SU619101A3 (sv) |
| YU (1) | YU58176A (sv) |
| ZA (1) | ZA761062B (sv) |
| ZM (1) | ZM2576A1 (sv) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5920647B2 (ja) * | 1976-10-01 | 1984-05-15 | 武田薬品工業株式会社 | 注射剤 |
| US4182856A (en) * | 1978-04-25 | 1980-01-08 | Miles Laboratories, Inc. | Reagents for use in binding assays to determine diphenylhydantoin |
| CA1256650A (en) * | 1983-03-25 | 1989-06-27 | Toshinari Tamura | Process of producing 2-azetidinone-4-substituted compounds, and medicaments containing the compounds |
| JPS59195038U (ja) * | 1983-06-14 | 1984-12-25 | 株式会社村上開明堂 | バツクミラ− |
| JPS59195037U (ja) * | 1983-06-14 | 1984-12-25 | 株式会社村上開明堂 | バツクミラ− |
| GB2146026A (en) * | 1983-09-07 | 1985-04-11 | Tanabe Seiyaku Co | Peptides and process for preparing the same |
| FR2622581B1 (fr) * | 1987-11-03 | 1990-02-16 | Inorgan Sa Rech Develop Pharm | Nouveaux derives de l-proline, leur preparation et leurs applications biologiques |
| FR2649110B1 (fr) * | 1989-06-29 | 1994-10-21 | Adir | Nouveaux derives peptidiques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| DK437289D0 (da) * | 1989-09-04 | 1989-09-04 | Hans Bundgaard | Prodrug derivatives of thyrotropin-releasing hormone (trh) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2343035C2 (de) * | 1973-08-25 | 1982-04-01 | Hoechst Ag, 6000 Frankfurt | Pyroglutamyl-histidyl-prolinamide, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel |
| US3959248A (en) * | 1974-04-03 | 1976-05-25 | Merck & Co., Inc. | Analogs of thyrotropin-releasing hormone |
-
1975
- 1975-03-08 GB GB10144/75A patent/GB1523598A/en not_active Expired
-
1976
- 1976-01-01 AR AR262475A patent/AR208361A1/es active
- 1976-02-20 CA CA246,250A patent/CA1059994A/en not_active Expired
- 1976-02-20 US US05/659,913 patent/US4060603A/en not_active Expired - Lifetime
- 1976-02-23 SE SE7602165A patent/SE411671B/sv not_active IP Right Cessation
- 1976-02-24 ZA ZA761062A patent/ZA761062B/xx unknown
- 1976-02-27 PT PT64853A patent/PT64853B/pt unknown
- 1976-02-29 IL IL49122A patent/IL49122A/xx unknown
- 1976-03-02 FI FI760538A patent/FI62823C/fi not_active IP Right Cessation
- 1976-03-02 PH PH18163A patent/PH11727A/en unknown
- 1976-03-03 JP JP51023063A patent/JPS5940144B2/ja not_active Expired
- 1976-03-03 ZM ZM25/76A patent/ZM2576A1/xx unknown
- 1976-03-03 GR GR50233A patent/GR59891B/el unknown
- 1976-03-04 NO NO760741A patent/NO144604C/no unknown
- 1976-03-04 BE BE164854A patent/BE839187A/xx not_active IP Right Cessation
- 1976-03-04 NL NL7602257A patent/NL7602257A/xx not_active Application Discontinuation
- 1976-03-04 ES ES445763A patent/ES445763A1/es not_active Expired
- 1976-03-05 DK DK97376*#A patent/DK97376A/da not_active Application Discontinuation
- 1976-03-05 SU SU762331353A patent/SU619101A3/ru active
- 1976-03-05 OA OA55754A patent/OA05260A/xx unknown
- 1976-03-05 PL PL1976187742A patent/PL101401B1/pl unknown
- 1976-03-05 DE DE2609154A patent/DE2609154C2/de not_active Expired
- 1976-03-05 CH CH282376A patent/CH608484A5/xx not_active IP Right Cessation
- 1976-03-05 LU LU74483A patent/LU74483A1/xx unknown
- 1976-03-05 FR FR7606369A patent/FR2303559A1/fr active Granted
- 1976-03-08 MX MX000050U patent/MX3055E/es unknown
- 1976-03-08 HU HU76RE580A patent/HU175652B/hu unknown
- 1976-03-08 AT AT169776A patent/AT352918B/de not_active IP Right Cessation
- 1976-03-08 IE IE477/76A patent/IE42784B1/en unknown
- 1976-03-08 YU YU00581/76A patent/YU58176A/xx unknown
- 1976-03-08 CS CS761513A patent/CS197268B2/cs unknown
- 1976-03-09 EG EG139/76A patent/EG13624A/xx active
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