CH627151A5 - - Google Patents

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Info

Publication number: CH627151A5
Authority: CH; Switzerland
Prior art keywords: mmol; tyr; ser; trp; arg
Prior art date: 1976-05-11

Application number

CH578677A

Other languages

German (de)

English (en)

Inventor

Anand Swaroop Dutta

Barrington John Albert Furr

Michael Brian Giles

Original Assignee

Ici Ltd

Priority date (The priority date 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 date listed.)

1976-05-11

Filing date

1977-05-09

Publication date

1981-12-31

1977-05-09 Application filed by Ici Ltd filed Critical Ici Ltd

1981-12-31 Publication of CH627151A5 publication Critical patent/CH627151A5/de

Links

OUYCCCASQSFEME-MRVPVSSYSA-N D-tyrosine Chemical compound OC(=O)[C@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-MRVPVSSYSA-N 0.000 claims description 22
108090000765 processed proteins & peptides Proteins 0.000 claims description 21
MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 claims description 20
238000000034 method Methods 0.000 claims description 17
COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical compound OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 claims description 12
102000004196 processed proteins & peptides Human genes 0.000 claims description 11
QIVBCDIJIAJPQS-SECBINFHSA-N D-tryptophane Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-SECBINFHSA-N 0.000 claims description 10
229920001184 polypeptide Polymers 0.000 claims description 10
230000008569 process Effects 0.000 claims description 9
XJODGRWDFZVTKW-LURJTMIESA-N (2s)-4-methyl-2-(methylamino)pentanoic acid Chemical group CN[C@H](C(O)=O)CC(C)C XJODGRWDFZVTKW-LURJTMIESA-N 0.000 claims description 8
239000002253 acid Substances 0.000 claims description 7
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 7
QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims description 5
150000001540 azides Chemical class 0.000 claims description 5
150000003839 salts Chemical class 0.000 claims description 5
238000005897 peptide coupling reaction Methods 0.000 claims description 4
150000001450 anions Chemical class 0.000 claims description 2
238000002360 preparation method Methods 0.000 claims description 2
HKTRDWYCAUTRRL-YUMQZZPRSA-N Glu-His Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 HKTRDWYCAUTRRL-YUMQZZPRSA-N 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 180
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 149
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 62
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
239000000243 solution Substances 0.000 description 54
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 50
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
239000000203 mixture Substances 0.000 description 24
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
150000001875 compounds Chemical class 0.000 description 21
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 18
229910000041 hydrogen chloride Inorganic materials 0.000 description 18
239000011541 reaction mixture Substances 0.000 description 17
101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 15
XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 15
239000002904 solvent Substances 0.000 description 14
239000000047 product Substances 0.000 description 13
238000003756 stirring Methods 0.000 description 13
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
239000003054 catalyst Substances 0.000 description 11
238000010898 silica gel chromatography Methods 0.000 description 11
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 10
229940024606 amino acid Drugs 0.000 description 10
102000009151 Luteinizing Hormone Human genes 0.000 description 9
108010073521 Luteinizing Hormone Proteins 0.000 description 9
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 9
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
238000010531 catalytic reduction reaction Methods 0.000 description 9
229940040129 luteinizing hormone Drugs 0.000 description 9
238000001953 recrystallisation Methods 0.000 description 9
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
150000001413 amino acids Chemical class 0.000 description 8
238000005859 coupling reaction Methods 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 8
239000003208 petroleum Substances 0.000 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
108010016626 Dipeptides Proteins 0.000 description 7
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 7
-1 ethylamino radical Chemical class 0.000 description 7
239000000741 silica gel Substances 0.000 description 7
229910002027 silica gel Inorganic materials 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 6
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 5
102000012673 Follicle Stimulating Hormone Human genes 0.000 description 5
108010079345 Follicle Stimulating Hormone Proteins 0.000 description 5
241000700159 Rattus Species 0.000 description 5
230000008878 coupling Effects 0.000 description 5
238000010168 coupling process Methods 0.000 description 5
238000000354 decomposition reaction Methods 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
238000001914 filtration Methods 0.000 description 5
229940028334 follicle stimulating hormone Drugs 0.000 description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
238000010626 work up procedure Methods 0.000 description 5
MCRMUCXATQAAMN-HNNXBMFYSA-N (2s)-3-(4-hydroxyphenyl)-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C1=CC=C(O)C=C1 MCRMUCXATQAAMN-HNNXBMFYSA-N 0.000 description 4
ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 4
125000003440 L-leucyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C(C([H])([H])[H])([H])C([H])([H])[H] 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
239000003480 eluent Substances 0.000 description 4
238000010348 incorporation Methods 0.000 description 4
230000016087 ovulation Effects 0.000 description 4
238000007911 parenteral administration Methods 0.000 description 4
239000000725 suspension Substances 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
239000000556 agonist Substances 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
230000000694 effects Effects 0.000 description 3
230000012173 estrus Effects 0.000 description 3
210000001672 ovary Anatomy 0.000 description 3
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 3
JXGVXCZADZNAMJ-NSHDSACASA-N (2s)-1-phenylmethoxycarbonylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)OCC1=CC=CC=C1 JXGVXCZADZNAMJ-NSHDSACASA-N 0.000 description 2
ZNCVCDONTDKDNY-YUMQZZPRSA-N (2s)-n-[(2s)-1-hydrazinyl-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]-5-oxopyrrolidine-2-carboxamide Chemical compound C([C@@H](C(=O)NN)NC(=O)[C@H]1NC(=O)CC1)C1=CN=CN1 ZNCVCDONTDKDNY-YUMQZZPRSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
206010062767 Hypophysitis Diseases 0.000 description 2
206010067482 No adverse event Diseases 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
238000009395 breeding Methods 0.000 description 2
230000001488 breeding effect Effects 0.000 description 2
BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
239000002775 capsule Substances 0.000 description 2
OWIUPIRUAQMTTK-UHFFFAOYSA-N carbazic acid Chemical compound NNC(O)=O OWIUPIRUAQMTTK-UHFFFAOYSA-N 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
238000001962 electrophoresis Methods 0.000 description 2
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
238000007429 general method Methods 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 2
QVDXUKJJGUSGLS-LURJTMIESA-N methyl L-leucinate Chemical compound COC(=O)[C@@H](N)CC(C)C QVDXUKJJGUSGLS-LURJTMIESA-N 0.000 description 2
150000004702 methyl esters Chemical class 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000000624 ovulatory effect Effects 0.000 description 2
210000003635 pituitary gland Anatomy 0.000 description 2
210000002381 plasma Anatomy 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
230000007704 transition Effects 0.000 description 2
DZUXGQBLFALXCR-UHFFFAOYSA-N (+)-(9alpha,11alpha,13E,15S)-9,11,15-trihydroxyprost-13-en-1-oic acid Natural products CCCCCC(O)C=CC1C(O)CC(O)C1CCCCCCC(O)=O DZUXGQBLFALXCR-UHFFFAOYSA-N 0.000 description 1
AHYFYYVVAXRMKB-QGZVFWFLSA-N (2r)-3-(1h-indol-3-yl)-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound N([C@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)OCC1=CC=CC=C1 AHYFYYVVAXRMKB-QGZVFWFLSA-N 0.000 description 1
IPAODWFPTVIUSZ-QFIPXVFZSA-N (2s)-2-(phenylmethoxycarbonylamino)-3-(4-phenylmethoxyphenyl)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C(C=C1)=CC=C1OCC1=CC=CC=C1 IPAODWFPTVIUSZ-QFIPXVFZSA-N 0.000 description 1
AHYFYYVVAXRMKB-KRWDZBQOSA-N (2s)-3-(1h-indol-3-yl)-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)OCC1=CC=CC=C1 AHYFYYVVAXRMKB-KRWDZBQOSA-N 0.000 description 1
PTSTYNLPDWVGLZ-RGMNGODLSA-N (2s)-n-ethylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.CCNC(=O)[C@@H]1CCCN1 PTSTYNLPDWVGLZ-RGMNGODLSA-N 0.000 description 1
ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
OVBRGKZTKQSNRM-JTRKXDDTSA-N 2-[[(9s,12s,15s,21s,30s,33s)-9-[(3-amino-4-hydroxyphenyl)methyl]-33-(2-amino-2-oxoethyl)-21-carbamoyl-12-(2-methylpropyl)-8,11,14,17,19,23,29,32,35-nonaoxo-30-propan-2-yl-19$l^{4}-thia-7,10,13,16,22,28,31,34-octazaspiro[5.29]pentatriacontan-15-yl]methyl]p Chemical compound N([C@@H](CC(N)=O)C(=O)N[C@H](C(=O)NCCCCC(=O)N[C@H](C[S+]([O-])CC(=O)N[C@@H](CC(C(O)=O)C(O)=O)C(=O)N[C@H](C(N[C@@H](CC=1C=C(N)C(O)=CC=1)C(=O)N1)=O)CC(C)C)C(N)=O)C(C)C)C(=O)C21CCCCC2 OVBRGKZTKQSNRM-JTRKXDDTSA-N 0.000 description 1
UJTTUOLQLCQZEA-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-(4-hydroxybutyl)carbamate Chemical compound C1=CC=C2C(COC(=O)NCCCCO)C3=CC=CC=C3C2=C1 UJTTUOLQLCQZEA-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
125000001711 D-phenylalanine group Chemical group [H]N([H])[C@@]([H])(C(=O)[*])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
ZGKXAUIVGIBISK-SZMVWBNQSA-N Glu-His-Trp Chemical compound N[C@@H](CCC(O)=O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(O)=O ZGKXAUIVGIBISK-SZMVWBNQSA-N 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
FBTYOQIYBULKEH-ZFWWWQNUSA-N His-Trp Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C1=CNC=N1 FBTYOQIYBULKEH-ZFWWWQNUSA-N 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
USPFMEKVPDBMCG-LBPRGKRZSA-M N-benzyloxycarbonyl-L-leucinate Chemical compound CC(C)C[C@@H](C([O-])=O)NC(=O)OCC1=CC=CC=C1 USPFMEKVPDBMCG-LBPRGKRZSA-M 0.000 description 1
239000007832 Na2SO4 Substances 0.000 description 1
IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
102000006877 Pituitary Hormones Human genes 0.000 description 1
108010047386 Pituitary Hormones Proteins 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
NHUHCSRWZMLRLA-UHFFFAOYSA-N Sulfisoxazole Chemical compound CC1=NOC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1C NHUHCSRWZMLRLA-UHFFFAOYSA-N 0.000 description 1
PDMMFKSKQVNJMI-BLQWBTBKSA-N Testosterone propionate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CC)[C@@]1(C)CC2 PDMMFKSKQVNJMI-BLQWBTBKSA-N 0.000 description 1
MYVYPSWUSKCCHG-JQWIXIFHSA-N Trp-Ser Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CO)C(O)=O)=CNC2=C1 MYVYPSWUSKCCHG-JQWIXIFHSA-N 0.000 description 1
IYUKFAFDFHZKPI-AENDTGMFSA-N [(2r)-1-methoxy-1-oxopropan-2-yl]azanium;chloride Chemical compound Cl.COC(=O)[C@@H](C)N IYUKFAFDFHZKPI-AENDTGMFSA-N 0.000 description 1
KPKLNNIUKPNZAY-WCCKRBBISA-N [[(2s)-pyrrolidine-2-carbonyl]amino]urea;hydrochloride Chemical compound Cl.NC(=O)NNC(=O)[C@@H]1CCCN1 KPKLNNIUKPNZAY-WCCKRBBISA-N 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
125000000539 amino acid group Chemical group 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
239000003098 androgen Substances 0.000 description 1
239000003957 anion exchange resin Substances 0.000 description 1
230000001174 ascending effect Effects 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
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
238000009835 boiling Methods 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
210000004246 corpus luteum Anatomy 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
230000003205 diastolic effect Effects 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
235000013601 eggs Nutrition 0.000 description 1
239000002024 ethyl acetate extract Substances 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000000284 extract Substances 0.000 description 1
ZFKJVJIDPQDDFY-UHFFFAOYSA-N fluorescamine Chemical compound C12=CC=CC=C2C(=O)OC1(C1=O)OC=C1C1=CC=CC=C1 ZFKJVJIDPQDDFY-UHFFFAOYSA-N 0.000 description 1
238000009472 formulation Methods 0.000 description 1
238000002523 gelfiltration Methods 0.000 description 1
BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical group NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
239000000960 hypophysis hormone Substances 0.000 description 1
210000003016 hypothalamus Anatomy 0.000 description 1
239000012535 impurity Substances 0.000 description 1
208000000509 infertility Diseases 0.000 description 1
230000036512 infertility Effects 0.000 description 1
231100000535 infertility Toxicity 0.000 description 1
238000001802 infusion Methods 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
230000001592 luteinising effect Effects 0.000 description 1
230000035800 maturation Effects 0.000 description 1
NDBQJIBNNUJNHA-DFWYDOINSA-N methyl (2s)-2-amino-3-hydroxypropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CO NDBQJIBNNUJNHA-DFWYDOINSA-N 0.000 description 1
DODCBMODXGJOKD-RGMNGODLSA-N methyl (2s)-2-amino-4-methylpentanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CC(C)C DODCBMODXGJOKD-RGMNGODLSA-N 0.000 description 1
210000004400 mucous membrane Anatomy 0.000 description 1
210000003097 mucus Anatomy 0.000 description 1
239000007923 nasal drop Substances 0.000 description 1
229940100662 nasal drops Drugs 0.000 description 1
239000007922 nasal spray Substances 0.000 description 1
229940097496 nasal spray Drugs 0.000 description 1
FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
210000003101 oviduct Anatomy 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
238000004810 partition chromatography Methods 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
150000003180 prostaglandins Chemical class 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
238000003127 radioimmunoassay Methods 0.000 description 1
239000003488 releasing hormone Substances 0.000 description 1
230000027272 reproductive process Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000011343 solid material Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000013589 supplement Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229960001603 tamoxifen Drugs 0.000 description 1
238000012360 testing method Methods 0.000 description 1
229960001712 testosterone propionate Drugs 0.000 description 1
150000003852 triazoles Chemical class 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
- C07K5/06—Dipeptides
- C07K5/06086—Dipeptides with the first amino acid being basic
- C07K5/06095—Arg-amino acid
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/23—Luteinising hormone-releasing hormone [LHRH]; Related peptides
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S930/00—Peptide or protein sequence
- Y10S930/01—Peptide or protein sequence
- Y10S930/13—Luteinizing hormone-releasing hormone; related peptides

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Biophysics (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Biochemistry (AREA)
Endocrinology (AREA)
Pharmacology & Pharmacy (AREA)
Reproductive Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Fodder In General (AREA)
Medicines Containing Plant Substances (AREA)

CH578677A 1976-05-11 1977-05-09 CH627151A5 (sv)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB19327/76A GB1524747A (en)	1976-05-11	1976-05-11	Polypeptide

Publications (1)

Publication Number	Publication Date
CH627151A5 true CH627151A5 (sv)	1981-12-31

Family

ID=10127509

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
CH578677A CH627151A5 (sv)	1976-05-11	1977-05-09
CH447281A CH629475A5 (de)	1976-05-11	1981-07-07	Verfahren zur herstellung von polypeptiden.

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
CH447281A CH629475A5 (de)	1976-05-11	1981-07-07	Verfahren zur herstellung von polypeptiden.

Country Status (27)

Country	Link
US (1)	US4100274A (sv)
JP (1)	JPS52136172A (sv)
AT (2)	AT379400B (sv)
AU (1)	AU508025B2 (sv)
BE (1)	BE854467A (sv)
BG (1)	BG60740B2 (sv)
CA (1)	CA1101844A (sv)
CH (2)	CH627151A5 (sv)
CS (1)	CS199673B2 (sv)
DD (1)	DD136738A5 (sv)
DE (1)	DE2720245C2 (sv)
DK (1)	DK149596C (sv)
ES (1)	ES458691A1 (sv)
FI (1)	FI64139C (sv)
FR (1)	FR2351092A1 (sv)
GB (1)	GB1524747A (sv)
HU (1)	HU179990B (sv)
IE (1)	IE44426B1 (sv)
IL (1)	IL52014A (sv)
NL (2)	NL191793C (sv)
NO (2)	NO147304C (sv)
NZ (1)	NZ183931A (sv)
PL (2)	PL108860B1 (sv)
SE (2)	SE437837B (sv)
SU (1)	SU910116A3 (sv)
YU (1)	YU40672B (sv)
ZA (1)	ZA772433B (sv)

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1976
- 1976-05-11 GB GB19327/76A patent/GB1524747A/en not_active Expired
1977
- 1977-04-20 IE IE808/77A patent/IE44426B1/en not_active IP Right Cessation
- 1977-04-22 ZA ZA00772433A patent/ZA772433B/xx unknown
- 1977-04-22 US US05/790,003 patent/US4100274A/en not_active Expired - Lifetime
- 1977-04-26 CA CA277,003A patent/CA1101844A/en not_active Expired
- 1977-04-26 NZ NZ183931A patent/NZ183931A/xx unknown
- 1977-04-28 AU AU24681/77A patent/AU508025B2/en not_active Expired
- 1977-05-04 HU HU77IE777A patent/HU179990B/hu unknown
- 1977-05-05 PL PL1977212706A patent/PL108860B1/pl unknown
- 1977-05-05 IL IL52014A patent/IL52014A/xx unknown
- 1977-05-05 CS CS772980A patent/CS199673B2/cs unknown
- 1977-05-05 PL PL1977197889A patent/PL104362B1/pl unknown
- 1977-05-05 DE DE2720245A patent/DE2720245C2/de not_active Expired
- 1977-05-09 CH CH578677A patent/CH627151A5/de not_active IP Right Cessation
- 1977-05-09 YU YU1172/77A patent/YU40672B/xx unknown
- 1977-05-10 FI FI771480A patent/FI64139C/fi not_active IP Right Cessation
- 1977-05-10 NL NL7705130A patent/NL191793C/xx not_active IP Right Cessation
- 1977-05-10 SE SE7705432A patent/SE437837B/sv not_active IP Right Cessation
- 1977-05-10 BE BE177448A patent/BE854467A/xx not_active IP Right Cessation
- 1977-05-10 NO NO771644A patent/NO147304C/no unknown
- 1977-05-10 FR FR7714262A patent/FR2351092A1/fr active Granted
- 1977-05-11 ES ES458691A patent/ES458691A1/es not_active Expired
- 1977-05-11 DD DD77198869A patent/DD136738A5/xx unknown
- 1977-05-11 JP JP5418677A patent/JPS52136172A/ja active Granted
- 1977-05-11 SU SU772480485A patent/SU910116A3/ru active
- 1977-05-11 AT AT0335877A patent/AT379400B/de not_active IP Right Cessation
- 1977-05-11 DK DK207977A patent/DK149596C/da not_active IP Right Cessation
1979
- 1979-03-23 AT AT0217979A patent/AT365562B/de not_active IP Right Cessation
1980
- 1980-11-05 SE SE8007763A patent/SE437993B/sv not_active IP Right Cessation
1981
- 1981-07-07 CH CH447281A patent/CH629475A5/de not_active IP Right Cessation
1982
- 1982-09-03 NO NO822984A patent/NO149586C/no unknown
1993
- 1993-09-24 BG BG098123A patent/BG60740B2/bg unknown
1997
- 1997-01-15 NL NL970002C patent/NL970002I2/nl unknown

Also Published As

Publication number	Publication date
FI64139C (fi)	1983-10-10
NO771644L (no)	1977-11-14
IE44426L (en)	1977-11-11
JPS52136172A (en)	1977-11-14
YU40672B (en)	1986-04-30
FI771480A7 (sv)	1977-11-12
JPS6113480B2 (sv)	1986-04-14
PL108860B1 (en)	1980-05-31
FR2351092B1 (sv)	1980-02-22
HU179990B (en)	1983-01-28
DE2720245C2 (de)	1986-09-25
NL191793B (nl)	1996-04-01
DK207977A (da)	1977-11-12
CS199673B2 (en)	1980-07-31
DE2720245A1 (de)	1977-11-24
IE44426B1 (en)	1981-11-18
IL52014A (en)	1979-11-30
ATA217979A (de)	1981-06-15
ZA772433B (en)	1978-03-29
DK149596C (da)	1987-01-05
US4100274A (en)	1978-07-11
NL191793C (nl)	1996-08-02
NO149586B (no)	1984-02-06
SE7705432L (sv)	1977-11-12
ES458691A1 (es)	1978-08-16
AT365562B (de)	1982-01-25
ATA335877A (de)	1985-05-15
SE437993B (sv)	1985-03-25
BG60740B2 (bg)	1996-01-31
AT379400B (de)	1985-12-27
SE8007763L (sv)	1980-11-05
DD136738A5 (de)	1979-07-25
YU117277A (en)	1983-02-28
AU2468177A (en)	1978-11-02
PL104362B1 (pl)	1979-08-31
DK149596B (da)	1986-08-04
NO149586C (no)	1984-05-16
IL52014A0 (en)	1977-07-31
PL197889A1 (pl)	1978-02-13
NL970002I2 (nl)	1997-05-01
FR2351092A1 (fr)	1977-12-09
NO147304C (no)	1983-03-16
BE854467A (fr)	1977-11-10
NO147304B (no)	1982-12-06
CA1101844A (en)	1981-05-26
NZ183931A (en)	1979-03-16
NL7705130A (nl)	1977-11-15
SU910116A3 (ru)	1982-02-28
GB1524747A (en)	1978-09-13
NO822984L (no)	1977-11-14
SE437837B (sv)	1985-03-18
FI64139B (fi)	1983-06-30
AU508025B2 (en)	1980-03-06
CH629475A5 (de)	1982-04-30
NL970002I1 (nl)	1997-03-03

Publication	Publication Date	Title
CH627151A5 (sv)	1981-12-31
DE2617646C2 (de)	1986-07-31	Nonapeptid-amide und Decapeptid-amide mit Gonadoliberin-Wirkung, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende pharmazeutische Präparate
DE3854159T2 (de)	1996-02-15	Effektive antagonisten für den das luteinisierende hormon freisetzenden faktor mit unbedeutender histaminfreisetzung.
US3992365A (en)	1976-11-16	Agonist analogues of luteinizing hormone releasing hormone
DE2435027A1 (de)	1975-02-06	Nonapeptideamide und verfahren zu ihrer herstellung
DE2649146A1 (de)	1977-05-12	Nonapeptide
DE4034829A1 (de)	1992-05-07	Cyclopeptide
DE2726276C2 (de)	1986-08-21	Luliberin-Antagonisten, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Zusammensetzungen
DE2547721A1 (de)	1976-04-29	Biologisch aktive amide
AT394727B (de)	1992-06-10	Verfahren zur herstellung von neuen gonadoliberin-derivaten
US4083967A (en)	1978-04-11	Nona- and decapeptides
AT389704B (de)	1990-01-25	Verfahren zur herstellung von neuen gonadoliberin-derivaten
DE3700166A1 (de)	1987-07-09	In der 6-stellung einen aromatischen aminocarbonsaeurerest aufweisende nonapeptidaethylamide beziehungsweise decapeptidamide, verfahren zur herstellung derselben und diese enthaltende arzneimittel beziehungsweise vermehrungsbiologisch wirksame mittel sowie ihre verwendung
CH658661A5 (de)	1986-11-28	Peptidverbindungen.
DE2649114A1 (de)	1977-05-12	Octapeptide
CH658662A5 (de)	1986-11-28	Gonadotrop hochwirksame luteinierungs- und follikelstimulierungshormon-liberationsfaktoranaloge und verfahren zu deren herstellung.
EP0373545B1 (de)	1994-02-16	Kompetitive Gonadoliberin-Antagonisten
DE2648829A1 (de)	1977-06-16	Nonapeptide, verfahren zu deren herstellung und diese enthaltende arzneimittel
DE2347456A1 (de)	1974-04-11	Polypeptide und verfahren zu deren herstellung
DE2727048C2 (de)	1984-06-07	8-Norleucyl-ceruletide
AT379818B (de)	1986-03-10	Verfahren zur herstellung eines neuen polypeptids
EP0424670B1 (de)	1995-02-22	Neue ZNS-aktive Hexapeptide mit antiamnestischer Wirkung
DE1493559C3 (de)	1976-08-19	Neue Peptide mit adrenocorticotroper Wirkung und Verfahren zu ihrer Herstellung
DE2025791C2 (de)	1982-06-03	Dotriacontapeptide, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel
CH509980A (de)	1971-07-15	Verfahren zur Herstellung eines bisher unbekannten Polypeptidderivates

Legal Events

Date	Code	Title	Description
1994-05-31	PUE	Assignment	Owner name: ZENECA LIMITED
1996-05-31	SPCF	Supplementary protection certificate filed	Free format text: IKS 48159/900628, 960219
1996-08-30	SPCC	Certificates - corrections	Free format text: IKS 48159/900628, 960219
1996-08-30	SPCG	Supplementary protection certificate granted	Free format text: IKS 48159/900628, 960219, EXPIRES:20020508
1998-08-14	PL	Patent ceased
2001-01-31	SPCM	Certificates - modification of assignment	Free format text: ZENECA LIMITED 15 STANHOPE GATE LONDON (GB)TRANSFER-ASTRA ZENECA AB SODERTÄLJE (SE)
2002-05-31	SPCL	Supplementary protection certificate deletion