LV10720B - Peptides and pharmaceutical composition containing them - Google Patents
Peptides and pharmaceutical composition containing them Download PDFInfo
- Publication number
- LV10720B LV10720B LVP-92-701A LV920701A LV10720B LV 10720 B LV10720 B LV 10720B LV 920701 A LV920701 A LV 920701A LV 10720 B LV10720 B LV 10720B
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- LV
- Latvia
- Prior art keywords
- arg
- pro
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- gly
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 90
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 39
- 239000008194 pharmaceutical composition Substances 0.000 title claims 2
- -1 aromatic amino acid Chemical class 0.000 claims abstract description 67
- 150000001413 amino acids Chemical class 0.000 claims abstract description 35
- 125000003118 aryl group Chemical group 0.000 claims abstract description 18
- 239000001257 hydrogen Substances 0.000 claims abstract description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 17
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 12
- 102400000967 Bradykinin Human genes 0.000 claims abstract description 9
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 claims abstract description 9
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 claims abstract description 9
- 101800004538 Bradykinin Proteins 0.000 claims abstract description 8
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 6
- 230000001575 pathological effect Effects 0.000 claims abstract description 5
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 3
- 235000001014 amino acid Nutrition 0.000 claims description 37
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 29
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical group NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 26
- 125000006239 protecting group Chemical group 0.000 claims description 26
- 150000001875 compounds Chemical class 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 14
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000003277 amino group Chemical group 0.000 claims description 11
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 9
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 9
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 8
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 8
- 210000004899 c-terminal region Anatomy 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 6
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 6
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 6
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 5
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- 125000003349 3-pyridyl group Chemical class N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 4
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims description 4
- 229960002591 hydroxyproline Drugs 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 claims description 4
- CNMAQBJBWQQZFZ-LURJTMIESA-N (2s)-2-(pyridin-2-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC1=CC=CC=N1 CNMAQBJBWQQZFZ-LURJTMIESA-N 0.000 claims description 3
- PDELQDSYLBLPQO-JGVFFNPUSA-N (3as,7ar)-2,3,3a,4,5,6,7,7a-octahydro-1h-indole Chemical compound C1CCC[C@H]2NCC[C@@H]21 PDELQDSYLBLPQO-JGVFFNPUSA-N 0.000 claims description 3
- NENLYAQPNATJSU-IUCAKERBSA-N (4as,8ar)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline Chemical compound C1NCC[C@@H]2CCCC[C@H]21 NENLYAQPNATJSU-IUCAKERBSA-N 0.000 claims description 3
- NENLYAQPNATJSU-DTWKUNHWSA-N (4as,8as)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline Chemical compound C1NCC[C@@H]2CCCC[C@@H]21 NENLYAQPNATJSU-DTWKUNHWSA-N 0.000 claims description 3
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 3
- CVZZNRXMDCOHBG-UHFFFAOYSA-N 2-azaniumyl-3-(2-chlorophenyl)propanoate Chemical compound OC(=O)C(N)CC1=CC=CC=C1Cl CVZZNRXMDCOHBG-UHFFFAOYSA-N 0.000 claims description 3
- WTOFYLAWDLQMBZ-UHFFFAOYSA-N 2-azaniumyl-3-thiophen-2-ylpropanoate Chemical compound OC(=O)C(N)CC1=CC=CS1 WTOFYLAWDLQMBZ-UHFFFAOYSA-N 0.000 claims description 3
- NYCRCTMDYITATC-UHFFFAOYSA-N 2-fluorophenylalanine Chemical compound OC(=O)C(N)CC1=CC=CC=C1F NYCRCTMDYITATC-UHFFFAOYSA-N 0.000 claims description 3
- 125000000175 2-thienyl group Chemical class S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- JJDJLFDGCUYZMN-QMMMGPOBSA-N 3-chloro-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC(Cl)=C1 JJDJLFDGCUYZMN-QMMMGPOBSA-N 0.000 claims description 3
- XWHHYOYVRVGJJY-QMMMGPOBSA-N 4-fluoro-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(F)C=C1 XWHHYOYVRVGJJY-QMMMGPOBSA-N 0.000 claims description 3
- 125000004203 4-hydroxyphenyl group Chemical class [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 239000004475 Arginine Substances 0.000 claims description 3
- 150000008574 D-amino acids Chemical group 0.000 claims description 3
- NIGWMJHCCYYCSF-UHFFFAOYSA-N Fenclonine Chemical compound OC(=O)C(N)CC1=CC=C(Cl)C=C1 NIGWMJHCCYYCSF-UHFFFAOYSA-N 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 125000001931 aliphatic group Chemical group 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000003435 aroyl group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000000524 functional group Chemical group 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- VWHRYODZTDMVSS-QMMMGPOBSA-N m-fluoro-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC(F)=C1 VWHRYODZTDMVSS-QMMMGPOBSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 230000007935 neutral effect Effects 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- IYKLZBIWFXPUCS-VIFPVBQESA-N (2s)-2-(naphthalen-1-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC=CC2=C1 IYKLZBIWFXPUCS-VIFPVBQESA-N 0.000 claims description 2
- 125000001541 3-thienyl group Chemical class S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical class [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 2
- LEIKGVHQTKHOLM-IUCAKERBSA-N Pro-Pro-Gly Chemical compound OC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 LEIKGVHQTKHOLM-IUCAKERBSA-N 0.000 claims description 2
- 241000534944 Thia Species 0.000 claims description 2
- 235000004279 alanine Nutrition 0.000 claims description 2
- 125000000636 p-nitrophenyl group Chemical class [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
- 108010087846 prolyl-prolyl-glycine Proteins 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims 13
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims 8
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Chemical group NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims 4
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims 3
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims 2
- GEYBMYRBIABFTA-SECBINFHSA-N O-methyl-D-tyrosine Chemical compound COC1=CC=C(C[C@@H]([NH3+])C([O-])=O)C=C1 GEYBMYRBIABFTA-SECBINFHSA-N 0.000 claims 2
- 125000003282 alkyl amino group Chemical group 0.000 claims 2
- 150000002357 guanidines Chemical class 0.000 claims 2
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims 1
- QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical group OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 claims 1
- 125000005418 aryl aryl group Chemical group 0.000 claims 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical class C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims 1
- 125000004076 pyridyl group Chemical class 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 22
- 230000009471 action Effects 0.000 abstract description 7
- 101710097732 Bradykinin-related peptides Proteins 0.000 abstract description 5
- 238000010647 peptide synthesis reaction Methods 0.000 abstract description 5
- 230000001225 therapeutic effect Effects 0.000 abstract description 3
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 230000002459 sustained effect Effects 0.000 abstract 1
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 159
- 239000011347 resin Substances 0.000 description 32
- 229920005989 resin Polymers 0.000 description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- 230000015572 biosynthetic process Effects 0.000 description 20
- 238000003786 synthesis reaction Methods 0.000 description 19
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 16
- 150000003862 amino acid derivatives Chemical class 0.000 description 13
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 12
- 238000005859 coupling reaction Methods 0.000 description 12
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 11
- 230000008878 coupling Effects 0.000 description 10
- 238000010168 coupling process Methods 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- UYRCOTSOPWOSJK-JXTBTVDRSA-N bradykinin antagonist Chemical compound C1C2=CC=CC=C2CC1[C@@H](NC(=O)C(CO)NC(=O)C(NC(=O)CNC(=O)[C@H]1N(C[C@H](O)C1)C(=O)C1N(CCC1)C(=O)C(CCCNC(N)=N)NC(=O)[C@@H](CCCNC(N)=N)NC(=N)CCCCCCC(=N)N[C@H](CCCNC(N)=N)C(=O)NC(CCCNC(N)=N)C(=O)N1C(CCC1)C(=O)N1[C@@H](C[C@@H](O)C1)C(=O)NCC(=O)NC(C1CC2=CC=CC=C2C1)C(=O)NC(CO)C(=O)N[C@H](C1CC2=CC=CC=C2C1)C(=O)N1C2CCCCC2CC1C(=O)NC(CCCNC(N)=N)C(O)=O)C1CC2=CC=CC=C2C1)C(=O)N1C2CCCCC2CC1C(=O)NC(CCCNC(=N)N)C(O)=O UYRCOTSOPWOSJK-JXTBTVDRSA-N 0.000 description 6
- 239000003152 bradykinin antagonist Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 4
- AXEOMQHKTSGLGS-VIFPVBQESA-N (2s)-2-amino-3-(4-hydroxy-2-methylphenyl)propanoic acid Chemical compound CC1=CC(O)=CC=C1C[C@H](N)C(O)=O AXEOMQHKTSGLGS-VIFPVBQESA-N 0.000 description 4
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 4
- 230000003213 activating effect Effects 0.000 description 4
- 230000001476 alcoholic effect Effects 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- 238000010532 solid phase synthesis reaction Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- DVBUCBXGDWWXNY-SFHVURJKSA-N (2s)-5-(diaminomethylideneamino)-2-(9h-fluoren-9-ylmethoxycarbonylamino)pentanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCCN=C(N)N)C(O)=O)C3=CC=CC=C3C2=C1 DVBUCBXGDWWXNY-SFHVURJKSA-N 0.000 description 3
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 108010062796 arginyllysine Proteins 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 3
- 108010054155 lysyllysine Proteins 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229940030966 pyrrole Drugs 0.000 description 3
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 3
- GOUUPUICWUFXPM-XIKOKIGWSA-N (2s,4r)-1-(9h-fluoren-9-ylmethoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid Chemical compound C1[C@H](O)C[C@@H](C(O)=O)N1C(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 GOUUPUICWUFXPM-XIKOKIGWSA-N 0.000 description 2
- DHBXNPKRAUYBTH-UHFFFAOYSA-N 1,1-ethanedithiol Chemical compound CC(S)S DHBXNPKRAUYBTH-UHFFFAOYSA-N 0.000 description 2
- ODSNARDHJFFSRH-UHFFFAOYSA-N 2,3,3a,4,5,6,7,7a-octahydro-1h-isoindole Chemical compound C1CCCC2CNCC21 ODSNARDHJFFSRH-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- OEBIVOHKFYSBPE-UHFFFAOYSA-N 4-Benzyloxybenzyl alcohol Chemical compound C1=CC(CO)=CC=C1OCC1=CC=CC=C1 OEBIVOHKFYSBPE-UHFFFAOYSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- HNDVDQJCIGZPNO-RXMQYKEDSA-N D-histidine Chemical compound OC(=O)[C@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-RXMQYKEDSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
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- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- 235000012245 magnesium oxide Nutrition 0.000 description 1
- MSWIFFGHKBTPMY-VFUQPONKSA-L magnesium;(e)-4-octadecoxy-4-oxobut-2-enoate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCCOC(=O)\C=C\C([O-])=O.CCCCCCCCCCCCCCCCCCOC(=O)\C=C\C([O-])=O MSWIFFGHKBTPMY-VFUQPONKSA-L 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- FFEARJCKVFRZRR-UHFFFAOYSA-N methionine Chemical compound CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 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 1
- IOPLHGOSNCJOOO-UHFFFAOYSA-N methyl 3,4-diaminobenzoate Chemical compound COC(=O)C1=CC=C(N)C(N)=C1 IOPLHGOSNCJOOO-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
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- 239000007923 nasal drop Substances 0.000 description 1
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- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
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- 150000007524 organic acids Chemical class 0.000 description 1
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- 230000036407 pain Effects 0.000 description 1
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- 239000000813 peptide hormone Substances 0.000 description 1
- JLKXXDAJGKKSNK-UHFFFAOYSA-N perchloric acid;pyridine Chemical compound OCl(=O)(=O)=O.C1=CC=NC=C1 JLKXXDAJGKKSNK-UHFFFAOYSA-N 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000005544 phthalimido group Chemical group 0.000 description 1
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- 239000004633 polyglycolic acid Substances 0.000 description 1
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- 229920000642 polymer Polymers 0.000 description 1
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- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 230000036316 preload Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000005588 protonation Effects 0.000 description 1
- ZJOSXOOPEBJBMC-LJRWBPDUSA-N pseudaminic acid Chemical compound CC(=O)N[C@@H]([C@@H](O)C)[C@@H]1O[C@](O)(C(O)=O)C[C@H](O)[C@@H]1NC(C)=O ZJOSXOOPEBJBMC-LJRWBPDUSA-N 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 125000003156 secondary amide group Chemical group 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 230000002226 simultaneous effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 230000019100 sperm motility Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- ZERULLAPCVRMCO-UHFFFAOYSA-N sulfure de di n-propyle Natural products CCCSCCC ZERULLAPCVRMCO-UHFFFAOYSA-N 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000002700 tablet coating Substances 0.000 description 1
- 238000009492 tablet coating Methods 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000009901 transfer hydrogenation reaction Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 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 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N tryptophan Chemical compound C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
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Classifications
-
- 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
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- 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
- C07K7/18—Kallidins; Bradykinins; Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
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Claims (8)
- LV 10720 Izgudrojuma formula 1. Peptīds ar formulu (I): A-B-C-E-F-K- (D)-Tic - G - - M - P- I (I) kurā: Air a1): ūdeņraža atoms, C-^-alkilgrupa, C-ļ^-alkanoilgrupa, C-, _8-alkoksikarbon ilg ru pa, C^-alkilsulfonilgrupa, pie tam šajās grupās 1-3 ūdeņraža atomi var būt aizvietoti ar 1-3 vienādiem vai dažādiem aizvietotājiem no grupas: karboksilgrupa, aminogrupa, C^-alkilgrupa, Cļ^-alkilaminogrupa, hidroksilgrupa, C^-alkoksigrupa, halogēna atoms, (C1.4-alkilgrupa)2N-, karbamoilgrupa, sulfamoilgrupa, Ct.4-alkoksikarbonilgrupa, Ce-12-arilgrupa, ar Ce-ia-arilgrupu aizvietota C-^-alkilgrupa; 1 vai arī viens ūdeņraža atoms aizvietots ar aizvietotāju no grupas: C^-cikloalkilgrupa, C^-alkilsulfonilgrupa, Cļ-4-alkilsulfinilgrupa ar C^-arilgrupu aizvietota C^-alkilsulfonilgrupa, ar C6.12-arilgrupu aizvietota C^-alkilsulfinilgrupa, C6.12-ariloksigrupa, C3.9-heteroarilgrupa, C3.g-heteroariloksigrupa, un 1-2 ūdeņraža atomi aizvietoti ar 1-2 aizvietotājiem no grupas: karboksilgrupa, aminogrupa, C^-alkilaminogrupa, hidroksilgrupa, C-M-alkoksigrupa, halogēna atoms, (C^-alkilgrupa^N-, karbamoilgrupa, sulfamoilgrupa, C-M-alkoksikarbonilgrupa, Ce-12-arilgrupa, ar C6-i2_arilgrupu aizvietota C^s-alkilgrupa; C3.8-cikloalkilgrupa, karbamoilgrupa, kurai pie slāpekļa atoma var būt Cve'alkilgrupa vai Ce-12-arilgrupa, Ce-12-arilgrupa, C7.18-ariloilgrupa 06.12-arilsulfonilrupa, C^g-heteroarilgrupa, C^g-heteroariloilgrupa; pie tam aizvietotājos a1 un a2 minētās heteroarilgrupas, ariloilgrupas, arilsulfonilgrupas un heteroariloilgrupas var būt aizvietotas ar 1-4 vienādiem vai dažādiem aizvietotājiem no grupas: karboksilgrupa, aminogrupa, nitrogrupa, C-,_4-alkilgrupa, C^-alkilaminogrupa, hidroksilgrupa, C^-alkoksigrupa, halogēna atoms, ciāngrupa, 2 LV 10720 (C^-alkilgrupa^N-, karbamoilgrupa, sulfamoilgrupa, C^-alkoksikarbonilgrupa; vai ari ir aizvietotājs ar formulu (II) R2 R3 9 R1 — N —0H —C — (II) kurā: R1 nozīmes ir aizvietotājiem a1un a2 dotās; R2 ir ūdeņraža atoms vai metilgrupa; R3 ir ūdeņraža atoms vai C^-alkilgrupa, sevišķi Cn.4-alkilgrupa, kas var būt aizvietota ar vienu: aminogrupu, aizvietotu aminogrupu, hidroksilgrupu, karbamoilgrupu, guanidīngrupu, aizvietotu guanidīngrupu, ureīdgrupu, merkaptogrupu, metilmerkaptogrupu, fenilgrupu, 4-hlorfenilgrupu, 4-fluorfenilgrupu, 4-nitrofenilgrupu, 4-metoksifenilgrupu, 4-hidroksifenilgrupu, ftalimidgrupu, 4-imidazolilgrupu, 3-indolilgrupu, 2- tienilgrupu, 3- tienilgrupu, 2- piridilgrupu, 3- piridilgrupu, cikloheksilgrupu, pie tam aizvietota aminogruopa apzīmē grupu -NH-A- un aizvietota guanidīngrupa apzīmē savienojumu -NH-C(=NH)-NH-A, kur A nozīmes ir tādas, kā tās dotas aizvietotājiem a1 un a , B ir bāziskā aminoskābe ar L- vai D- konfigurāciju, kas var būt aizvietota sānu virknē; 3 C ir grupa ar formulu (llla) vai (lllb): G’ —G’—Gly (llla) G’ —NH —(CH2)n —CO (lllb) kur G’, neatkarīgi viens no otra, var būt atlikums ar formulu (IV): P1 P5 9 — N—CH—C— (IV) kurā R4 un Rs kopā ar tiem atomiem, pie kuriem tie saistīti, var veidot heterociklisku sistēmu ar 1-3 gredzeniem, kurā ir 2-15 atomi; n = 2-8; E ir aromātiskas aminoskābes palieka; F neatkarīgi viens no otra, ir neitrālas, skābas vai bāziskās alifātiskas vai aromātiskas aminoskābes atlikums, kas var būt aizvietots sānu virknē, vai arī vienkāršā saite; (D)-Tic ir atlikums ar formulu (V):G ir ar tādu pašu nozīmi, kā G’, vai arī vienkāršā saite; F’ ir ar tādu pašu nozīmi, kā F, vai arī grupa _NH-(CH2)n-, kur n = 2-8, vai arī, ja G nav vienkāršā saite, var apzīmēt vienkāršo saiti; I ir -OH, -NH2 vai -NHC2H5; K ir grupa -NH-(CH2)x-CO-, kur x = 1 -4, vai arī apzīmē vienkāršo saiti; M ir tādas pašas nozīmes, kā F; kā arī šo savienojumu fizioloģiski pieņemamās sālīs.
- 2. Peptīris ar formulu (I) pēc 1. punkta, kurā: B ir Arg, Lys, Orn, 2,4-diaminobutiroilgrupa vai L-homoarginīna palieka, pie tam sānu virknes aminogrupa vai guanidīnarupa var būt aizvietota ar aizvietotājiem A, kuru nozīme atbilst a1 un sr nozīmēm punktā 1; 4 LV 10720 E ir aromātiskas L- vai D-aminoskābes palieka, kuras arilgrupā ir 6-14 oglekļa atomi, piemēram, fenilalanins, kas var būt aizvietots ar halogēna atomu 2-, 3- vai 4-stāvoklī, tirozīns.O-metiltirozīns, 2-tienilala-nīns, 2-piridilalanīns, naftilalanīns; F ir bāziskās L- vai D- aminoskābes palieka, piemēram, arginīna vai lizīna palieka, pie tam sānu virknes aminoaruDa vai guanidīngrupa var būt nomainīta ar aizvietotāju A, kura nozīme atbilst' a1 un a2 nozīmēm punktā 1; vai arī grupa -NH-(CH2)n-, kur n = 2-8; K ir grupa -NH-(CH2)x-CO-, kur x = 2-4, vai an apzīmē vienkāršo saiti.
- 3. Peptīds ar formulu (I) pēc 1. vai 2. punkta, kurā: B ir Arg, Lys vai Om atlikums, pie tam sānu virknes aminogrupa vai guanidīngrupa var būt aizvietota ar C^-alkanoilgrupu, C7.13-ariloilgru-pu, C^g-heteroariloilgrupu, C^-alkilsulfonilgrupu, Cg.12-arilsulfonil-grupu, pie tam heteroarilgrupas, ariloilgrupas, arilsulfonilgrupas, aril-grupas un heteroariloilgrupas var būt aizvietotas pie aizvietotāja a2 ar 1- 4 vienādierm vai dažādiem aizvietotājiem; E ir fenilalanīna, 2-hlorfenilalanīna, 3-hlorfenilalanīna, 4-hlorfenilalanīna, 2- fluorfenilalanīna, 3-fluorfenilalanīna, 4-fluorfenilalanīna, tirozīna, O-metiltirozīna, p-(2-tienil)alanīna atlikums; K ir vienkāršā saite; M ir vienkāršā saite.
- 4. Peptīds ar formulu (I) pēc jebkura no iepriekšējiem punktiem, kurā: A ir ūdeņraža atoms, (D)- vai (L)-H-Arg, (D)- vai (L)-H-Lys, (D)- vai (L)-H-Om; B ir ir Arg, Lys vai Om atlikums, pie tam sānu virknes aminogrupa vai guanidīngrupa var būt aizvietota ar C^-alkanoilgrupu, C/.^-ariloil-grupu, C^g-heteroariloilgrupu, C1_s-alkilsulfonifgrupu, C^^-arilsulfonil-grupu, pie tam heteroarilgrupas, ariloilgrupas, arilsulfonilgrupas, aril-grupas un heteroariloilgrupas var būt aizvietotas ar 1-4 vienādierm vai dažādiem aizvietotājiem no grupas: metilgrupa, metoksigrupa, halogēna atoms; C ir Pro-Pro-Gly, Hyp-Pro-Gly vai Pro-Hyp-Gly; E ir Phe vai Thia; F ir Ser, Hser, Lys, Leu, Vai, Nle, lle vai Thr; 5 K ir vienkāršā saite; M ir vienkāršā saite; G ir heterociklisks atlikums ar formulu (IV), jo sevišķi vēlams tāds atlikums, kurā ir pirolidīna (Δ), piperidīna (fi), tetrahidroizohinolīna (C), cis- vai trans-dekahidroizohinolīna (D), cis-endo-oktahidroindola (E), cis-ekso-oktahidroindola (E), trans-oktahidroindola (E), cis-endo-, cis-ekso-trans-oktahidrociklopentano[b]pirola (E) vai hidroksiprolīna (V) heterocikliskā sistēma; F irArg; I ir Otf.
- 5. Paņēmiens peptīda ar formulu (I) pēc jebkura no iepriekšējiem punktiem iegūšanai, kas atšķiras ar to, ka: a) fragmentu ar brīvu C-gala karboksilgrupu, vai tā aktivēto atvasinājumu apstrādā ar atbilstošu fragmentu, kurā ir brīva N-gala aminogrupa, vai b) peptīdu uzbūvē pakāpeniski, un pēc varianta a) vai b) iegūtajā peptīdā, ja nepieciešams, nošķeļ vienas vai otras funkcionālās grupas aizsargāšanai izmantotās aizsarggrupas, un tādā veidā iegūto savienojumu ar formulu (I) pārvērš tā fizioloģiski pieņemamā sālī.
- 6. Peptīda ar formulu (I) pēc jebkura no 1.-4. punktam pielietojums par ārstniecības līdzekli.
- 7. Peptīda ar formulu (I) pēc jebkura no 1.-4. punktam pielietojums ārstniecības līdzekļa ražošanai, kas paredzēts tādu patoloģisko stāvokļu ārstēšanai, kurus izsauc, uztur vai veicina bradikinīns vai tam radniecīgie peptīdi.
- 8. Ārstniecības līdzeklis, kas satur peptīdu ar formulu (I) pēc jebkura no 1.-4. punktam. 6
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE3839581 | 1988-11-24 | ||
DE3916291 | 1989-05-19 | ||
DE3918225 | 1989-06-03 |
Publications (2)
Publication Number | Publication Date |
---|---|
LV10720A LV10720A (lv) | 1995-06-20 |
LV10720B true LV10720B (en) | 1996-02-20 |
Family
ID=27198531
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
LVP-92-701A LV10720B (en) | 1988-11-24 | 1992-12-23 | Peptides and pharmaceutical composition containing them |
Country Status (26)
Country | Link |
---|---|
EP (1) | EP0370453B1 (lv) |
JP (1) | JPH07121956B2 (lv) |
KR (1) | KR0139632B1 (lv) |
CN (1) | CN1035006C (lv) |
AT (1) | ATE107318T1 (lv) |
AU (1) | AU612054B2 (lv) |
CA (1) | CA1340667C (lv) |
CY (2) | CY2028A (lv) |
CZ (1) | CZ282384B6 (lv) |
DE (3) | DE58907889D1 (lv) |
DK (1) | DK175344B1 (lv) |
ES (1) | ES2057071T3 (lv) |
FI (1) | FI94353C (lv) |
HK (1) | HK1006716A1 (lv) |
HU (2) | HU210566B (lv) |
IE (1) | IE63490B1 (lv) |
IL (1) | IL91298A (lv) |
LU (1) | LU91499I2 (lv) |
LV (1) | LV10720B (lv) |
MX (1) | MX9203277A (lv) |
NL (1) | NL300359I2 (lv) |
NO (2) | NO177597C (lv) |
NZ (1) | NZ230244A (lv) |
PH (1) | PH31009A (lv) |
PT (1) | PT91692B (lv) |
SK (1) | SK490689A3 (lv) |
Families Citing this family (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5648333A (en) * | 1988-11-24 | 1997-07-15 | Hoechst Aktiengesellschaft | Peptides having bradykinin antagonist action |
DE4013270A1 (de) * | 1990-04-26 | 1991-10-31 | Hoechst Ag | Peptide mit bradykinin-antagonistischer wirkung |
DE69012142D1 (de) * | 1989-12-08 | 1994-10-06 | Univ Boston | Acylierte bradykininantagonisten und deren verwendung. |
MX9100717A (es) * | 1990-08-24 | 1992-04-01 | Syntex Inc | Antagonistas de la bradiquinina |
US5416191A (en) * | 1991-04-01 | 1995-05-16 | Cortech, Inc. | Bradykinin antagonists |
US5843900A (en) * | 1991-04-01 | 1998-12-01 | Cortech, Inc. | Bradykinin antagonists |
AU1873992A (en) * | 1991-04-19 | 1992-11-17 | Nova Technology Limited Partnership | Bradykinin antagonist peptides |
US6770741B1 (en) | 1991-04-19 | 2004-08-03 | Scios Inc. | Bradykinin antagonist peptides |
CA2106768C (en) | 1991-04-19 | 2000-09-19 | Donald J. Kyle | Bradykinin type peptides |
EP0529499A1 (de) * | 1991-08-22 | 1993-03-03 | Hoechst Aktiengesellschaft | Pharmazeutische Zusammensetzungen enthaltend Bradykinin-Antagonisten zur lokalen Anwendung an Nase und Auge |
US6117974A (en) * | 1991-10-02 | 2000-09-12 | Peptor Limited | Libraries of backbone-cyclized peptidomimetics |
WO1993011789A1 (en) | 1991-12-12 | 1993-06-24 | Scios Nova Inc. | Modified position (7) bradykinin antagonist peptides |
TW199863B (lv) * | 1991-12-21 | 1993-02-11 | Hoechst Ag | |
WO1993017701A1 (en) * | 1992-03-12 | 1993-09-16 | The Administrators Of The Tulane Educational Fund | Endothelin receptor-binding peptides |
TW258739B (lv) * | 1992-04-04 | 1995-10-01 | Hoechst Ag | |
FR2692581B1 (fr) * | 1992-06-18 | 1994-08-19 | Adir | Nouveaux dérivés peptidiques à activité antagoniste de la bradykinine, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent. |
US5610142A (en) * | 1992-10-08 | 1997-03-11 | Scios Inc. | Bradykinin antagonist pseudopeptide derivatives of substituted 4-keto-1,3,8-triazaspiro[4.5]decan-3-alkanoic acids |
US5541286A (en) * | 1992-10-08 | 1996-07-30 | Scios Nova Inc. | Bradykinin antagonist pseudopeptide derivatives of olefinic aminoalkanoic acids |
US5686565A (en) * | 1992-10-08 | 1997-11-11 | Scios Inc. | Bradykinin antagonist pseudopeptide derivatives of aminoalkanoic acids and related olefins |
US5521158A (en) * | 1992-10-08 | 1996-05-28 | Scios Nova Inc. | Pseudopeptide bradykinin receptor antagonists |
IL107400A0 (en) * | 1992-11-10 | 1994-01-25 | Cortech Inc | Bradykinin antagonists |
WO1994019372A1 (en) * | 1993-02-17 | 1994-09-01 | Scios Nova Inc. | Cyclic bradykinin antagonist peptides |
US5817756A (en) * | 1993-09-09 | 1998-10-06 | Scios Inc. | Pseudo- and non-peptide bradykinin receptor antagonists |
DE4345062A1 (de) * | 1993-12-31 | 1995-07-13 | Hoechst Ag | Verwendung von Bradykinin-Antagonisten zur Herstellung von Arzneimitteln zur Behandlung von Viruserkrankungen |
EP0813544B1 (en) * | 1994-03-09 | 2004-10-27 | Cortech, Inc. | Bradykinin antagonist peptides incorporating n-substituted glycines |
IL109943A (en) * | 1994-06-08 | 2006-08-01 | Develogen Israel Ltd | Conformationally constrained backbone cyclized peptide analogs |
US6407059B1 (en) | 1994-06-08 | 2002-06-18 | Peptor Limited | Conformationally constrained backbone cyclized peptide analogs |
AU6044496A (en) * | 1995-06-05 | 1996-12-24 | Cortech, Inc. | Compounds having bradykinin antagonistic activity and mu-opi oid agonistic activity |
US5770687A (en) * | 1995-06-07 | 1998-06-23 | Peptor Limited | Comformationally constrained backbone cyclized somatostatin analogs |
US6051554A (en) * | 1995-06-07 | 2000-04-18 | Peptor Limited | Conformationally constrained backbone cyclized somatostatin analogs |
FR2737408B1 (fr) * | 1995-07-31 | 1997-09-05 | Oreal | Utilisation d'un antagoniste de bradykinine dans une composition cosmetique, pharmaceutique ou dermatologique et composition obtenue |
US5849863A (en) * | 1995-09-08 | 1998-12-15 | University Of Colorado | Cytolytic bradykinin antagonists |
US5834431A (en) * | 1995-09-08 | 1998-11-10 | Cortech, Inc. | Des-Arg9 -BK antagonists |
FR2739553B1 (fr) * | 1995-10-06 | 1998-01-02 | Oreal | Utilisation d'antagonistes de la bradykinine pour stimuler ou induire la pousse des cheveux et/ou stopper leur chute |
US6841533B1 (en) | 1995-12-07 | 2005-01-11 | Peptor Limited | Conformationally constrained backbone cyclized interleukin-6 antagonists |
DE19612067A1 (de) * | 1996-03-27 | 1997-10-02 | Hoechst Ag | Verwendung von Bradykinin-Antagonisten zur Herstellung von Arzneimitteln zur Behandlung von chronisch fibrogenetischen Lebererkrankungen und akuten Lebererkrankungen |
US6355613B1 (en) | 1996-07-31 | 2002-03-12 | Peptor Limited | Conformationally constrained backbone cyclized somatostatin analogs |
DE19642289A1 (de) * | 1996-10-14 | 1998-04-16 | Hoechst Ag | Verwendung von Bradykinin-Antagonisten zur Herstellung von Arzneimitteln zur Behandlung und Prävention der Alzheimer'schen Krankheit |
DE10304994A1 (de) * | 2003-02-07 | 2004-09-02 | Aventis Pharma Deutschland Gmbh | Die Verwendung von Antagonisten des Bradykinin-B2 Rezeptors zur Behandlung von Osteoarthrose |
CN102532267B (zh) * | 2012-02-09 | 2014-06-18 | 深圳翰宇药业股份有限公司 | 一种艾替班特的制备方法 |
CN104043101B (zh) * | 2014-05-23 | 2016-04-20 | 杭州阿德莱诺泰制药技术有限公司 | 一种艾替班特注射用组合物及其制备方法和制剂 |
KR102099509B1 (ko) | 2018-07-27 | 2020-04-09 | 강경순 | 과수용 받침지주 |
CN111944016B (zh) * | 2020-08-25 | 2022-04-29 | 台州吉诺生物科技有限公司 | 一种醋酸艾替班特的制备方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3044236A1 (de) * | 1980-11-25 | 1982-06-16 | Hoechst Ag, 6000 Frankfurt | Aminosaeurederivate und verfahren zu ihrer herstellung |
FR2487829A2 (fr) * | 1979-12-07 | 1982-02-05 | Science Union & Cie | Nouveaux imino acides substitues, leurs procedes de preparation et leur emploi comme inhibiteur d'enzyme |
DE3227055A1 (de) * | 1982-07-20 | 1984-01-26 | Hoechst Ag, 6230 Frankfurt | Neue derivate der 2-aza-bicyclo(2.2.2)octan-3-carbonsaeure, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung sowie 2-aza-bicyclo(2.2.2)octan-3-carbonsaeure als zwischenstufe und verfahren zu deren herstellung |
FR2575753B1 (fr) * | 1985-01-07 | 1987-02-20 | Adir | Nouveaux derives peptidiques a structure polycyclique azotee, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
US4693993A (en) * | 1985-06-13 | 1987-09-15 | Stewart John M | Bradykinin antagonist peptides |
-
1989
- 1989-08-03 IE IE252289A patent/IE63490B1/en not_active IP Right Cessation
- 1989-08-04 DK DK198903840A patent/DK175344B1/da active Protection Beyond IP Right Term
- 1989-08-08 NO NO893193A patent/NO177597C/no not_active IP Right Cessation
- 1989-08-08 FI FI893738A patent/FI94353C/fi active Protection Beyond IP Right Term
- 1989-08-08 NZ NZ230244A patent/NZ230244A/en unknown
- 1989-08-09 CA CA000607853A patent/CA1340667C/en not_active Expired - Lifetime
- 1989-08-09 AU AU39431/89A patent/AU612054B2/en not_active Expired
- 1989-08-11 IL IL9129889A patent/IL91298A/en unknown
- 1989-08-21 SK SK4906-89A patent/SK490689A3/sk unknown
- 1989-08-21 CZ CS894906A patent/CZ282384B6/cs not_active IP Right Cessation
- 1989-08-23 HU HU894323A patent/HU210566B/hu unknown
- 1989-08-28 JP JP1218758A patent/JPH07121956B2/ja not_active Expired - Lifetime
- 1989-09-11 CN CN89107065A patent/CN1035006C/zh not_active Expired - Lifetime
- 1989-09-11 KR KR1019890013102A patent/KR0139632B1/ko not_active IP Right Cessation
- 1989-09-11 PT PT91692A patent/PT91692B/pt not_active IP Right Cessation
- 1989-11-21 ES ES89121498T patent/ES2057071T3/es not_active Expired - Lifetime
- 1989-11-21 EP EP89121498A patent/EP0370453B1/de not_active Expired - Lifetime
- 1989-11-21 DE DE58907889T patent/DE58907889D1/de not_active Expired - Lifetime
- 1989-11-21 DE DE3938751A patent/DE3938751A1/de not_active Withdrawn
- 1989-11-21 AT AT89121498T patent/ATE107318T1/de active
- 1989-11-21 DE DE122008000066C patent/DE122008000066I2/de active Active
-
1990
- 1990-07-30 PH PH40920A patent/PH31009A/en unknown
-
1992
- 1992-06-24 MX MX9203277A patent/MX9203277A/es active IP Right Grant
- 1992-12-23 LV LVP-92-701A patent/LV10720B/en unknown
-
1995
- 1995-01-20 HU HU95P/P00069P patent/HU210712A9/hu active Protection Beyond IP Right Term
-
1998
- 1998-02-20 CY CY202898A patent/CY2028A/xx unknown
- 1998-06-22 HK HK98105867A patent/HK1006716A1/xx not_active IP Right Cessation
-
2008
- 2008-09-09 NL NL300359C patent/NL300359I2/nl unknown
- 2008-10-30 NO NO2008016C patent/NO2008016I2/no unknown
- 2008-11-19 LU LU91499C patent/LU91499I2/xx unknown
- 2008-12-30 CY CY200800022C patent/CY2008022I2/el unknown
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