LU81733A1 - Peptides apparentes a la somatostatine et leur utilisation therapeutique - Google Patents

Peptides apparentes a la somatostatine et leur utilisation therapeutique Download PDF

Info

Publication number: LU81733A1
Authority: LU; Luxembourg
Prior art keywords: ala; phe; lys; cys; thr
Prior art date: 1978-10-02

Application number

LU81733A

Other languages

English (en)

French (fr)

Inventor

J Shields

Original Assignee

Lilly Co Eli

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.)

1978-10-02

Filing date

1979-09-28

Publication date

1980-01-24

1979-09-28 Application filed by Lilly Co Eli filed Critical Lilly Co Eli

1980-01-24 Publication of LU81733A1 publication Critical patent/LU81733A1/fr

Links

108090000765 processed proteins & peptides Proteins 0.000 title description 84
102000004196 processed proteins & peptides Human genes 0.000 title description 36
230000001225 therapeutic effect Effects 0.000 title 1
238000000034 method Methods 0.000 claims description 27
239000002253 acid Substances 0.000 claims description 14
125000004122 cyclic group Chemical group 0.000 claims description 11
150000001875 compounds Chemical class 0.000 claims description 10
231100000252 nontoxic Toxicity 0.000 claims description 7
230000003000 nontoxic effect Effects 0.000 claims description 7
150000003839 salts Chemical class 0.000 claims description 7
230000028327 secretion Effects 0.000 claims description 7
OMNVYXHOSHNURL-WPRPVWTQSA-N Ala-Phe Chemical group C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 OMNVYXHOSHNURL-WPRPVWTQSA-N 0.000 claims description 6
108010011559 alanylphenylalanine Chemical group 0.000 claims description 6
229940088597 hormone Drugs 0.000 claims description 4
239000005556 hormone Substances 0.000 claims description 4
239000007800 oxidant agent Substances 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 3
238000002360 preparation method Methods 0.000 claims description 3
241000124008 Mammalia Species 0.000 claims description 2
230000002401 inhibitory effect Effects 0.000 claims description 2
AUXMWYRZQPIXCC-KNIFDHDWSA-N (2s)-2-amino-4-methylpentanoic acid;(2s)-2-aminopropanoic acid Chemical group C[C@H](N)C(O)=O.CC(C)C[C@H](N)C(O)=O AUXMWYRZQPIXCC-KNIFDHDWSA-N 0.000 claims 2
101100455752 Caenorhabditis elegans lys-3 gene Proteins 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 claims 1
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 110
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 75
229920005989 resin Polymers 0.000 description 61
239000011347 resin Substances 0.000 description 61
-1 D- Val1 Chemical compound 0.000 description 53
150000001413 amino acids Chemical class 0.000 description 43
229960000583 acetic acid Drugs 0.000 description 40
229940024606 amino acid Drugs 0.000 description 40
235000001014 amino acid Nutrition 0.000 description 40
125000006239 protecting group Chemical group 0.000 description 35
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 32
239000000203 mixture Substances 0.000 description 31
238000004458 analytical method Methods 0.000 description 30
239000000243 solution Substances 0.000 description 28
239000000047 product Substances 0.000 description 27
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 26
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 24
235000018417 cysteine Nutrition 0.000 description 24
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 24
229960000553 somatostatin Drugs 0.000 description 22
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 21
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 20
102000005157 Somatostatin Human genes 0.000 description 19
108010056088 Somatostatin Proteins 0.000 description 19
229920005990 polystyrene resin Polymers 0.000 description 19
NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 17
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 15
239000004472 Lysine Substances 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
238000010586 diagram Methods 0.000 description 14
229920005654 Sephadex Polymers 0.000 description 13
239000012507 Sephadex™ Substances 0.000 description 13
150000002148 esters Chemical class 0.000 description 13
239000002904 solvent Substances 0.000 description 13
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 12
238000002835 absorbance Methods 0.000 description 12
229960003767 alanine Drugs 0.000 description 12
239000007788 liquid Substances 0.000 description 12
239000007787 solid Substances 0.000 description 12
125000003396 thiol group Chemical group [H]S* 0.000 description 12
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 11
239000004473 Threonine Substances 0.000 description 11
230000015572 biosynthetic process Effects 0.000 description 11
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
102000051325 Glucagon Human genes 0.000 description 10
108060003199 Glucagon Proteins 0.000 description 10
108010051696 Growth Hormone Proteins 0.000 description 10
102000004877 Insulin Human genes 0.000 description 10
108090001061 Insulin Proteins 0.000 description 10
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 10
102100038803 Somatotropin Human genes 0.000 description 10
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 10
239000012362 glacial acetic acid Substances 0.000 description 10
MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 10
229960004666 glucagon Drugs 0.000 description 10
229940125396 insulin Drugs 0.000 description 10
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 9
QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 9
QIVBCDIJIAJPQS-SECBINFHSA-N D-tryptophane Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-SECBINFHSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
238000005859 coupling reaction Methods 0.000 description 9
238000001914 filtration Methods 0.000 description 9
239000000122 growth hormone Substances 0.000 description 9
QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
125000000539 amino acid group Chemical group 0.000 description 8
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 8
238000004821 distillation Methods 0.000 description 8
DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 8
238000010348 incorporation Methods 0.000 description 8
238000003786 synthesis reaction Methods 0.000 description 8
238000012360 testing method Methods 0.000 description 8
238000004448 titration Methods 0.000 description 8
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
KZSNJWFQEVHDMF-SCSAIBSYSA-N D-valine Chemical compound CC(C)[C@@H](N)C(O)=O KZSNJWFQEVHDMF-SCSAIBSYSA-N 0.000 description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
210000004899 c-terminal region Anatomy 0.000 description 7
238000001802 infusion Methods 0.000 description 7
229960005190 phenylalanine Drugs 0.000 description 7
229920001184 polypeptide Polymers 0.000 description 7
238000011084 recovery Methods 0.000 description 7
239000000126 substance Substances 0.000 description 7
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 6
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 6
241000700159 Rattus Species 0.000 description 6
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
125000000524 functional group Chemical group 0.000 description 6
230000003647 oxidation Effects 0.000 description 6
238000007254 oxidation reaction Methods 0.000 description 6
239000000725 suspension Substances 0.000 description 6
COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical compound OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 description 5
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 5
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
210000002966 serum Anatomy 0.000 description 5
238000005406 washing Methods 0.000 description 5
RDIKFPRVLJLMER-BQBZGAKWSA-N Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)N RDIKFPRVLJLMER-BQBZGAKWSA-N 0.000 description 4
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
102000001189 Cyclic Peptides Human genes 0.000 description 4
108010069514 Cyclic Peptides Proteins 0.000 description 4
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
239000000908 ammonium hydroxide Substances 0.000 description 4
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
230000008878 coupling Effects 0.000 description 4
238000010168 coupling process Methods 0.000 description 4
239000012153 distilled water Substances 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
238000004108 freeze drying Methods 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 4
239000000463 material Substances 0.000 description 4
238000010992 reflux Methods 0.000 description 4
238000010532 solid phase synthesis reaction Methods 0.000 description 4
238000006467 substitution reaction Methods 0.000 description 4
CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 4
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
229930182831 D-valine Natural products 0.000 description 3
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
125000001176 L-lysyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C([H])([H])C(N([H])[H])([H])[H] 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
102000007079 Peptide Fragments Human genes 0.000 description 3
108010033276 Peptide Fragments Proteins 0.000 description 3
239000004793 Polystyrene Substances 0.000 description 3
PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 3
125000005076 adamantyloxycarbonyl group Chemical group C12(CC3CC(CC(C1)C3)C2)OC(=O)* 0.000 description 3
TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical class [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
230000027326 copulation Effects 0.000 description 3
239000007822 coupling agent Substances 0.000 description 3
230000008030 elimination Effects 0.000 description 3
238000003379 elimination reaction Methods 0.000 description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
238000012986 modification Methods 0.000 description 3
230000004048 modification Effects 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
239000002504 physiological saline solution Substances 0.000 description 3
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 3
239000007790 solid phase Substances 0.000 description 3
BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical group OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 description 2
125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 2
125000001433 C-terminal amino-acid group Chemical group 0.000 description 2
241000282472 Canis lupus familiaris Species 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
239000004201 L-cysteine Substances 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
235000004279 alanine Nutrition 0.000 description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000008280 blood Substances 0.000 description 2
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
ZOAIGCHJWKDIPJ-UHFFFAOYSA-M caesium acetate Chemical compound [Cs+].CC([O-])=O ZOAIGCHJWKDIPJ-UHFFFAOYSA-M 0.000 description 2
238000004891 communication Methods 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
229960003136 leucine Drugs 0.000 description 2
239000011159 matrix material Substances 0.000 description 2
238000006140 methanolysis reaction Methods 0.000 description 2
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
238000003127 radioimmunoassay Methods 0.000 description 2
238000000926 separation method Methods 0.000 description 2
AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
CUNVVZWSABRKAL-ZDUSSCGKSA-N (2r)-3-[(4-methylphenyl)methylsulfanyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC1=CC=C(CSC[C@H](NC(=O)OC(C)(C)C)C(O)=O)C=C1 CUNVVZWSABRKAL-ZDUSSCGKSA-N 0.000 description 1
125000002861 (C1-C4) alkanoyl group Chemical group 0.000 description 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
WCVOGSZTONGSQY-UHFFFAOYSA-N 2,4,6-trichloroanisole Chemical compound COC1=C(Cl)C=C(Cl)C=C1Cl WCVOGSZTONGSQY-UHFFFAOYSA-N 0.000 description 1
125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
125000006185 3,4-dimethyl benzyl group Chemical group [H]C1=C(C([H])=C(C(=C1[H])C([H])([H])[H])C([H])([H])[H])C([H])([H])* 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
206010000599 Acromegaly Diseases 0.000 description 1
CXISPYVYMQWFLE-VKHMYHEASA-N Ala-Gly Chemical compound C[C@H]([NH3+])C(=O)NCC([O-])=O CXISPYVYMQWFLE-VKHMYHEASA-N 0.000 description 1
OMSMPWHEGLNQOD-UWVGGRQHSA-N Asn-Phe Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 OMSMPWHEGLNQOD-UWVGGRQHSA-N 0.000 description 1
229910015900 BF3 Inorganic materials 0.000 description 1
101100328486 Caenorhabditis elegans cni-1 gene Proteins 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
101800001982 Cholecystokinin Proteins 0.000 description 1
102100025841 Cholecystokinin Human genes 0.000 description 1
IOUPEELXVYPCPG-ZCFIWIBFSA-N D-Val-Gly Chemical compound CC(C)[C@@H](N)C(=O)NCC(O)=O IOUPEELXVYPCPG-ZCFIWIBFSA-N 0.000 description 1
125000003941 D-tryptophan group Chemical group [H]C1=C([H])C([H])=C2C(C([C@@](N([H])[H])(C(=O)[*])[H])([H])[H])=C([H])N([H])C2=C1[H] 0.000 description 1
102100038796 E3 ubiquitin-protein ligase TRIM13 Human genes 0.000 description 1
102400000921 Gastrin Human genes 0.000 description 1
108010052343 Gastrins Proteins 0.000 description 1
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
101000664589 Homo sapiens E3 ubiquitin-protein ligase TRIM13 Proteins 0.000 description 1
206010062767 Hypophysitis Diseases 0.000 description 1
239000004395 L-leucine Substances 0.000 description 1
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
241000234435 Lilium Species 0.000 description 1
CXISPYVYMQWFLE-UHFFFAOYSA-N N-D-alanyl-glycine Natural products CC(N)C(=O)NCC(O)=O CXISPYVYMQWFLE-UHFFFAOYSA-N 0.000 description 1
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
102100024819 Prolactin Human genes 0.000 description 1
108010057464 Prolactin Proteins 0.000 description 1
108010086019 Secretin Proteins 0.000 description 1
102100037505 Secretin Human genes 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
NBIIPOKZPUGATB-BWBBJGPYSA-N Thr-Ser-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N)O NBIIPOKZPUGATB-BWBBJGPYSA-N 0.000 description 1
UXZMLECYBHANRH-UHFFFAOYSA-K [B+3].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F Chemical compound [B+3].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F UXZMLECYBHANRH-UHFFFAOYSA-K 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
239000000654 additive Substances 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
108010047495 alanylglycine Proteins 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
150000001408 amides Chemical group 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
238000005915 ammonolysis reaction Methods 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
238000010171 animal model Methods 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
238000003556 assay Methods 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
230000037396 body weight Effects 0.000 description 1
YSMHTFWPDRJCMN-UHFFFAOYSA-N butan-2-yl carbonochloridate Chemical compound CCC(C)OC(Cl)=O YSMHTFWPDRJCMN-UHFFFAOYSA-N 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
229940107137 cholecystokinin Drugs 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
150000003983 crown ethers Chemical class 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
210000003016 hypothalamus Anatomy 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
150000002475 indoles Chemical class 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
210000000936 intestine Anatomy 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
PWPJGUXAGUPAHP-UHFFFAOYSA-N lufenuron Chemical compound C1=C(Cl)C(OC(F)(F)C(C(F)(F)F)F)=CC(Cl)=C1NC(=O)NC(=O)C1=C(F)C=CC=C1F PWPJGUXAGUPAHP-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
239000011707 mineral Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
229960001412 pentobarbital Drugs 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
210000003635 pituitary gland Anatomy 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
229940097325 prolactin Drugs 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
230000001012 protector Effects 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
229960002101 secretin Drugs 0.000 description 1
OWMZNFCDEHGFEP-NFBCVYDUSA-N secretin human Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(N)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)C1=CC=CC=C1 OWMZNFCDEHGFEP-NFBCVYDUSA-N 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
NHXLMOGPVYXJNR-UHFFFAOYSA-N srif Chemical compound N1C(=O)C(C(C)O)NC(=O)C(CCCCN)NC(=O)C(CC=2C3=CC=CC=C3NC=2)NC(=O)C(CC=2C=CC=CC=2)NC(=O)C(CC=2C=CC=CC=2)NC(=O)C(CC(N)=O)NC(=O)C(CCCCN)NC(=O)C(NC(=O)CNC(=O)C(C)N)CSSCC(C(O)=O)NC(=O)C(CO)NC(=O)C(C(O)C)NC(=O)C1CC1=CC=CC=C1 NHXLMOGPVYXJNR-UHFFFAOYSA-N 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000010998 test method Methods 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000004014 thioethyl group Chemical group [H]SC([H])([H])C([H])([H])* 0.000 description 1
125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
238000006257 total synthesis reaction Methods 0.000 description 1
230000001131 transforming effect Effects 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical group C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
239000004474 valine Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/655—Somatostatins
- C07K14/6555—Somatostatins at least 1 amino acid in D-form
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- 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
- Y10S930/16—Somatostatin; related peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
Diabetes (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Endocrinology (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Obesity (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Hematology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Emergency Medicine (AREA)
Toxicology (AREA)
Zoology (AREA)
Gastroenterology & Hepatology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

LU81733A 1978-10-02 1979-09-28 Peptides apparentes a la somatostatine et leur utilisation therapeutique LU81733A1 (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US05/948,117 US4202802A (en)	1978-10-02	1978-10-02	Peptides related to somatostatin
US94811778		1978-10-02

Publications (1)

Publication Number	Publication Date
LU81733A1 true LU81733A1 (fr)	1980-01-24

Family

ID=25487300

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
LU81733A LU81733A1 (fr)	1978-10-02	1979-09-28	Peptides apparentes a la somatostatine et leur utilisation therapeutique

Country Status (9)

Country	Link
US (1)	US4202802A (de)
EP (1)	EP0011366A3 (de)
JP (1)	JPS5549344A (de)
BE (1)	BE879107A (de)
CA (1)	CA1129846A (de)
FR (2)	FR2439181A1 (de)
GB (1)	GB2030572B (de)
IL (1)	IL58337A0 (de)
LU (1)	LU81733A1 (de)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BE883608A (fr) *	1979-06-11	1980-12-03	Lilly Co Eli	Peptides apparentes a la somatostatine leur preparation et leur utilisation therapeutique
US4369179A (en) *	1979-12-14	1983-01-18	Ciba-Geigy Corporation	Acylpeptides
US4585740A (en) *	1983-05-03	1986-04-29	The Whittier Institute For Diabetes And Endocrinology	Prolactin immunoassay using synthetic peptide

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3904594A (en) *	1973-07-02	1975-09-09	Salk Inst For Biological Studi	Somatostatin and acylated des-(ala' 1', gly' 2') derivatives thereof
DE2416048A1 (de) *	1974-04-03	1975-10-30	Hoechst Ag	Neue peptide mit biologischer wirkung
US4372884A (en) *	1975-08-06	1983-02-08	The Salk Institute For Biological Studies	Pharmaceutically active peptides
IL51508A0 (en) *	1976-03-08	1977-06-30	Lilly Co Eli	Sonatostatin analogs and intermediates thereto
US4100117A (en) *	1977-04-21	1978-07-11	Eli Lilly And Company	Somatostatin analogs and intermediates thereto

1978
- 1978-10-02 US US05/948,117 patent/US4202802A/en not_active Expired - Lifetime
1979
- 1979-09-26 IL IL58337A patent/IL58337A0/xx unknown
- 1979-09-26 CA CA336,401A patent/CA1129846A/en not_active Expired
- 1979-09-28 LU LU81733A patent/LU81733A1/fr unknown
- 1979-10-01 JP JP12670479A patent/JPS5549344A/ja active Pending
- 1979-10-01 EP EP79302073A patent/EP0011366A3/de not_active Withdrawn
- 1979-10-01 GB GB7934018A patent/GB2030572B/en not_active Expired
- 1979-10-01 BE BE1/9543A patent/BE879107A/fr unknown
- 1979-10-01 FR FR7924443A patent/FR2439181A1/fr not_active Withdrawn
1980
- 1980-04-04 FR FR8007779A patent/FR2453138A1/fr active Pending

Also Published As

Publication number	Publication date
US4202802A (en)	1980-05-13
IL58337A0 (en)	1979-12-30
CA1129846A (en)	1982-08-17
JPS5549344A (en)	1980-04-09
GB2030572B (en)	1982-10-13
FR2439181A1 (fr)	1980-05-16
BE879107A (fr)	1980-04-01
FR2453138A1 (fr)	1980-10-31
GB2030572A (en)	1980-04-10
EP0011366A3 (de)	1982-02-10
EP0011366A2 (de)	1980-05-28

Publication	Publication Date	Title
US4087390A (en)	1978-05-02	Somatostatin analogs and intermediates thereto
US4093574A (en)	1978-06-06	Somatostatin analogs and intermediates thereto
US4100117A (en)	1978-07-11	Somatostatin analogs and intermediates thereto
JPH0161120B2 (de)	1989-12-27
US4191754A (en)	1980-03-04	Bicyclic somatostatin analogs
JP2514518B2 (ja)	1996-07-10	ヘプタペプチドおよびオクタペプチドのソマトスタチン類似アミド誘導体、それを含有する抗腫瘍剤
FR2465713A1 (fr)	1981-03-27	Nouveaux peptides biologiquement actifs et leur emploi comme medicaments
NO148957B (no)	1983-10-10	Analogifremgangsmaate til fremstilling av terapeutisk aktive cyklopeptider.
IE47421B1 (en)	1984-03-07	Somatostatin analogs,process for their preparation and pharmaceutical compositions containing them
EP0017746B1 (de)	1983-01-26	Peptide mit Somatostatin-Wirkung, sie enthaltende Zusammensetzungen und Verfahren zur Herstellung der Peptide
IE44532B1 (en)	1981-12-30	Somatostatin analogues
FI74711B (fi)	1987-11-30	Foerfarande foer framstaellning av terapeutiskt anvaendbara cykliska hexapeptidfoereningar.
US4162248A (en)	1979-07-24	Somatostatin analogs
Ponsati et al.	1990	Solid-phase approaches to regiospecific double disulfide formation. Application to a fragment of bovine pituitary peptide
Lloyd-Williams et al.	1991	Convergent solid-phase peptide synthesis. X. Synthesis and purification of protected peptide fragments using the photolabile Nbb-resin
GB1574492A (en)	1980-09-10	D-ala2,d-lys4-somatostatin
LU85710A1 (fr)	1986-07-17	Nouveaux derives de la gonadoliberine et procede pour leur preparation
FR2458539A1 (fr)	1981-01-02	Peptides apparentes a la somatostatine, leur preparation et leur utilisation therapeutique
CA1129846A (en)	1982-08-17	Peptides related to somatostatin
FI105816B (fi)	2000-10-13	Menetelmä terapeuttisesti käyttökelpoisten peptidien valmistamiseksi
US4061607A (en)	1977-12-06	Somatostatin analogs and intermediates thereto
KR850000151B1 (ko)	1985-02-28	소마토스타틴 동족체의 제조방법
US4199501A (en)	1980-04-22	Peptides related to somatostatin
FR2524878A1 (fr)	1983-10-14	Peptides a activite biologique et medicament les contenant
KR810000692B1 (ko)	1981-06-22	소마토스타틴(Somatostatin) 동족체의 제조방법