ZA200407611B - Hemiasterlin derivatives and uses thereof in the treatment of cancer - Google Patents
Hemiasterlin derivatives and uses thereof in the treatment of cancer Download PDFInfo
- Publication number
- ZA200407611B ZA200407611B ZA200407611A ZA200407611A ZA200407611B ZA 200407611 B ZA200407611 B ZA 200407611B ZA 200407611 A ZA200407611 A ZA 200407611A ZA 200407611 A ZA200407611 A ZA 200407611A ZA 200407611 B ZA200407611 B ZA 200407611B
- Authority
- ZA
- South Africa
- Prior art keywords
- aryl
- substituted
- unsubstituted
- moiety
- hydrogen
- Prior art date
Links
- KQODQNJLJQHFQV-MKWZWQCGSA-N (e,4s)-4-[[(2s)-3,3-dimethyl-2-[[(2s)-3-methyl-2-(methylamino)-3-(1-methylindol-3-yl)butanoyl]amino]butanoyl]-methylamino]-2,5-dimethylhex-2-enoic acid Chemical class C1=CC=C2C(C(C)(C)[C@@H](C(=O)N[C@H](C(=O)N(C)[C@H](\C=C(/C)C(O)=O)C(C)C)C(C)(C)C)NC)=CN(C)C2=C1 KQODQNJLJQHFQV-MKWZWQCGSA-N 0.000 title description 14
- 206010028980 Neoplasm Diseases 0.000 title description 7
- 201000011510 cancer Diseases 0.000 title description 6
- 125000003118 aryl group Chemical group 0.000 claims description 299
- 229910052739 hydrogen Inorganic materials 0.000 claims description 240
- 239000001257 hydrogen Substances 0.000 claims description 234
- 150000001875 compounds Chemical class 0.000 claims description 218
- 125000000217 alkyl group Chemical group 0.000 claims description 165
- 125000002723 alicyclic group Chemical group 0.000 claims description 146
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 136
- 125000004122 cyclic group Chemical group 0.000 claims description 121
- 125000001931 aliphatic group Chemical group 0.000 claims description 110
- 125000002015 acyclic group Chemical group 0.000 claims description 98
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 94
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 81
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 41
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 29
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 27
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 18
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- 150000002431 hydrogen Chemical group 0.000 claims 7
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000001072 heteroaryl group Chemical group 0.000 description 246
- 229920006395 saturated elastomer Polymers 0.000 description 99
- 125000004404 heteroalkyl group Chemical group 0.000 description 85
- -1 heteroalicyclic Chemical group 0.000 description 66
- 125000001424 substituent group Chemical group 0.000 description 34
- 125000000623 heterocyclic group Chemical group 0.000 description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 29
- 229910052757 nitrogen Inorganic materials 0.000 description 27
- 229910052799 carbon Inorganic materials 0.000 description 25
- 125000002252 acyl group Chemical group 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 22
- 150000001721 carbon Chemical group 0.000 description 21
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 21
- 125000004433 nitrogen atom Chemical group N* 0.000 description 20
- 125000003545 alkoxy group Chemical group 0.000 description 17
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 17
- 229940002612 prodrug Drugs 0.000 description 16
- 239000000651 prodrug Substances 0.000 description 16
- 229910052736 halogen Inorganic materials 0.000 description 15
- 150000002367 halogens Chemical class 0.000 description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 15
- 229910052717 sulfur Inorganic materials 0.000 description 15
- 125000003342 alkenyl group Chemical group 0.000 description 14
- 125000000304 alkynyl group Chemical group 0.000 description 14
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 14
- 125000000753 cycloalkyl group Chemical group 0.000 description 14
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 14
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 14
- 229910052760 oxygen Inorganic materials 0.000 description 14
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 14
- 125000006239 protecting group Chemical group 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 12
- 125000004093 cyano group Chemical group *C#N 0.000 description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- 125000004414 alkyl thio group Chemical group 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
- CHBRHODLKOZEPZ-UHFFFAOYSA-N Clotiazepam Chemical compound S1C(CC)=CC2=C1N(C)C(=O)CN=C2C1=CC=CC=C1Cl CHBRHODLKOZEPZ-UHFFFAOYSA-N 0.000 description 8
- 125000002877 alkyl aryl group Chemical group 0.000 description 8
- 125000005213 alkyl heteroaryl group Chemical group 0.000 description 8
- 150000001408 amides Chemical class 0.000 description 8
- 125000004429 atom Chemical group 0.000 description 8
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 8
- 238000010189 synthetic method Methods 0.000 description 8
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 7
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 7
- 125000000524 functional group Chemical group 0.000 description 7
- 229930187626 hemiasterlin Natural products 0.000 description 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 6
- 125000005842 heteroatom Chemical group 0.000 description 6
- KQODQNJLJQHFQV-UHFFFAOYSA-N (-)-hemiasterlin Natural products C1=CC=C2C(C(C)(C)C(C(=O)NC(C(=O)N(C)C(C=C(C)C(O)=O)C(C)C)C(C)(C)C)NC)=CN(C)C2=C1 KQODQNJLJQHFQV-UHFFFAOYSA-N 0.000 description 5
- 229910019567 Re Re Inorganic materials 0.000 description 5
- 125000005110 aryl thio group Chemical group 0.000 description 5
- 125000004104 aryloxy group Chemical group 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 238000010511 deprotection reaction Methods 0.000 description 5
- 108010057806 hemiasterlin Proteins 0.000 description 5
- 125000004405 heteroalkoxy group Chemical group 0.000 description 5
- 125000005553 heteroaryloxy group Chemical group 0.000 description 5
- 125000005368 heteroarylthio group Chemical group 0.000 description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 5
- 125000001041 indolyl group Chemical group 0.000 description 5
- 125000006413 ring segment Chemical group 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 125000001984 thiazolidinyl group Chemical group 0.000 description 5
- AQTFKGDWFRRIHR-UHFFFAOYSA-L 3-[18-(2-carboxylatoethyl)-8,13-bis(ethenyl)-3,7,12,17-tetramethylporphyrin-21,24-diid-2-yl]propanoate;cobalt(2+);hydron Chemical compound [Co+2].[N-]1C(C=C2C(=C(C)C(C=C3C(=C(C)C(=C4)[N-]3)C=C)=N2)C=C)=C(C)C(CCC(O)=O)=C1C=C1C(CCC(O)=O)=C(C)C4=N1 AQTFKGDWFRRIHR-UHFFFAOYSA-L 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 125000001183 hydrocarbyl group Chemical group 0.000 description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 150000002894 organic compounds Chemical class 0.000 description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 4
- 125000000168 pyrrolyl group Chemical group 0.000 description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 3
- 125000003047 N-acetyl group Chemical group 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 125000004442 acylamino group Chemical group 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 238000002399 angioplasty Methods 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 229930014626 natural product Natural products 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- 125000003367 polycyclic group Chemical group 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 208000037803 restenosis Diseases 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- WZZUQWBUVSVLRT-SECBINFHSA-N tert-butyl n-methyl-n-[(2s)-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound CC(C)[C@@H](C=O)N(C)C(=O)OC(C)(C)C WZZUQWBUVSVLRT-SECBINFHSA-N 0.000 description 3
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 101150053424 CRYGC gene Proteins 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 241000611009 Nematalosa come Species 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 125000004103 aminoalkyl group Chemical group 0.000 description 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 125000001691 aryl alkyl amino group Chemical group 0.000 description 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 2
- 125000001769 aryl amino group Chemical group 0.000 description 2
- 150000001733 carboxylic acid esters Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 150000001923 cyclic compounds Chemical class 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 150000005217 methyl ethers Chemical class 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- KJTULOVPMGUBJS-UHFFFAOYSA-N tert-butyl-[tert-butyl(diphenyl)silyl]oxy-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](C=1C=CC=CC=1)(C(C)(C)C)O[Si](C(C)(C)C)(C=1C=CC=CC=1)C1=CC=CC=C1 KJTULOVPMGUBJS-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 125000004001 thioalkyl group Chemical group 0.000 description 2
- WILBTFWIBAOWLN-UHFFFAOYSA-N triethyl(triethylsilyloxy)silane Chemical compound CC[Si](CC)(CC)O[Si](CC)(CC)CC WILBTFWIBAOWLN-UHFFFAOYSA-N 0.000 description 2
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 2
- ABYZSYDGJGVCHS-ZETCQYMHSA-N (2s)-2-acetamido-n-(4-nitrophenyl)propanamide Chemical compound CC(=O)N[C@@H](C)C(=O)NC1=CC=C([N+]([O-])=O)C=C1 ABYZSYDGJGVCHS-ZETCQYMHSA-N 0.000 description 1
- LRFZIPCTFBPFLX-SSDOTTSWSA-N (2s)-3,3-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)C(C)(C)C LRFZIPCTFBPFLX-SSDOTTSWSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- CWGCIGQBFBEZLP-AULKDKKBSA-N (e,4s)-4-[[(2s)-2-[[(2s)-3-(1h-indol-3-yl)-3-methyl-2-(methylamino)butanoyl]amino]-3,3-dimethylbutanoyl]-methylamino]-2,5-dimethylhex-2-enoic acid Chemical compound C1=CC=C2C(C(C)(C)[C@@H](C(=O)N[C@H](C(=O)N(C)[C@H](\C=C(/C)C(O)=O)C(C)C)C(C)(C)C)NC)=CNC2=C1 CWGCIGQBFBEZLP-AULKDKKBSA-N 0.000 description 1
- STWMUTMEDIGCPZ-PUMSQASDSA-N (e,4s)-4-[[(2s)-2-[[(2s)-3-(1h-indol-3-yl)-3-methyl-2-(methylamino)butanoyl]amino]-3-methylbutanoyl]-methylamino]-2,5-dimethylhex-2-enoic acid Chemical compound C1=CC=C2C(C(C)(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@H](\C=C(/C)C(O)=O)C(C)C)NC)=CNC2=C1 STWMUTMEDIGCPZ-PUMSQASDSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- UUAKOKFSMXRGJP-UHFFFAOYSA-N 1-methoxy-4-[(4-methoxyphenyl)methoxymethoxymethoxymethyl]benzene Chemical compound C1=CC(OC)=CC=C1COCOCOCC1=CC=C(OC)C=C1 UUAKOKFSMXRGJP-UHFFFAOYSA-N 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004917 3-methyl-2-butyl group Chemical group CC(C(C)*)C 0.000 description 1
- KBSDLBVPAHQCRY-UHFFFAOYSA-N 307496-19-1 Chemical group C1CC=CCC1CC[Si](O1)(O2)O[Si](O3)(C4CCCC4)O[Si](O4)(C5CCCC5)O[Si]1(C1CCCC1)O[Si](O1)(C5CCCC5)O[Si]2(C2CCCC2)O[Si]3(C2CCCC2)O[Si]41C1CCCC1 KBSDLBVPAHQCRY-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical group NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 101150018425 Cr1l gene Proteins 0.000 description 1
- 241001673468 Cymbastela Species 0.000 description 1
- 101000869592 Daucus carota Major allergen Dau c 1 Proteins 0.000 description 1
- 241000243143 Demospongiae Species 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 101100289061 Drosophila melanogaster lili gene Proteins 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical class CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 241000796658 Hemiasterella Species 0.000 description 1
- 101001061851 Homo sapiens V(D)J recombination-activating protein 2 Proteins 0.000 description 1
- 101000650136 Homo sapiens WAS/WASL-interacting protein family member 3 Proteins 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- BPSLZWSRHTULGU-UHFFFAOYSA-N Methylpipecolic acid Chemical class CN1CCCCC1C(O)=O BPSLZWSRHTULGU-UHFFFAOYSA-N 0.000 description 1
- 235000015429 Mirabilis expansa Nutrition 0.000 description 1
- 244000294411 Mirabilis expansa Species 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- UQVKZNNCIHJZLS-UHFFFAOYSA-N PhIP Chemical compound C1=C2N(C)C(N)=NC2=NC=C1C1=CC=CC=C1 UQVKZNNCIHJZLS-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 101150107341 RERE gene Proteins 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 241000949477 Toona ciliata Species 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 102100029591 V(D)J recombination-activating protein 2 Human genes 0.000 description 1
- 244000047670 Viola x wittrockiana Species 0.000 description 1
- 235000004031 Viola x wittrockiana Nutrition 0.000 description 1
- 102100027539 WAS/WASL-interacting protein family member 3 Human genes 0.000 description 1
- XOCUXOWLYLLJLV-UHFFFAOYSA-N [O].[S] Chemical compound [O].[S] XOCUXOWLYLLJLV-UHFFFAOYSA-N 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000007824 aliphatic compounds Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000002927 anti-mitotic effect Effects 0.000 description 1
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000005998 bromoethyl group Chemical group 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- GWXLDORMOJMVQZ-UHFFFAOYSA-N cerium Chemical compound [Ce] GWXLDORMOJMVQZ-UHFFFAOYSA-N 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 229910052729 chemical element Inorganic materials 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 125000006310 cycloalkyl amino group Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical class C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 229940120124 dichloroacetate Drugs 0.000 description 1
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 108010060754 hemiasterlin A Proteins 0.000 description 1
- CWGCIGQBFBEZLP-UHFFFAOYSA-N hemiasterlin A Natural products C1=CC=C2C(C(C)(C)C(C(=O)NC(C(=O)N(C)C(C=C(C)C(O)=O)C(C)C)C(C)(C)C)NC)=CNC2=C1 CWGCIGQBFBEZLP-UHFFFAOYSA-N 0.000 description 1
- 108010060756 hemiasterlin B Proteins 0.000 description 1
- STWMUTMEDIGCPZ-UHFFFAOYSA-N hemiasterlin B Natural products C1=CC=C2C(C(C)(C)C(C(=O)NC(C(C)C)C(=O)N(C)C(C=C(C)C(O)=O)C(C)C)NC)=CNC2=C1 STWMUTMEDIGCPZ-UHFFFAOYSA-N 0.000 description 1
- 108010060696 hemiasterlin C Proteins 0.000 description 1
- 125000004366 heterocycloalkenyl group Chemical group 0.000 description 1
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 1
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- NSPJNIDYTSSIIY-UHFFFAOYSA-N methoxy(methoxymethoxy)methane Chemical compound COCOCOC NSPJNIDYTSSIIY-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- CPZBTYRIGVOOMI-UHFFFAOYSA-N methylsulfanyl(methylsulfanylmethoxy)methane Chemical compound CSCOCSC CPZBTYRIGVOOMI-UHFFFAOYSA-N 0.000 description 1
- 235000013536 miso Nutrition 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- 125000001298 n-hexoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000005429 oxyalkyl group Chemical group 0.000 description 1
- 150000002926 oxygen Chemical class 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
- TYZYRCHEVXXLSJ-UHFFFAOYSA-N phenylmethoxymethoxymethoxymethylbenzene Chemical compound C=1C=CC=CC=1COCOCOCC1=CC=CC=C1 TYZYRCHEVXXLSJ-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000004585 polycyclic heterocycle group Chemical group 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 238000010583 slow cooling Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000005032 thiofuranyl group Chemical group S1C(=CC=C1)* 0.000 description 1
- LGSAOJLQTXCYHF-UHFFFAOYSA-N tri(propan-2-yl)-tri(propan-2-yl)silyloxysilane Chemical compound CC(C)[Si](C(C)C)(C(C)C)O[Si](C(C)C)(C(C)C)C(C)C LGSAOJLQTXCYHF-UHFFFAOYSA-N 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/30—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
- C07D211/32—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/07—Tetrapeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- 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
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06156—Dipeptides with the first amino acid being heterocyclic and Trp-amino acid; Derivatives thereof
-
- 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
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06165—Dipeptides with the first amino acid being heterocyclic and Pro-amino acid; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
- C07K5/0823—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp and Pro-amino acid; Derivatives thereof
-
- 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
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Steroid Compounds (AREA)
- Materials For Medical Uses (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US36659202P | 2002-03-22 | 2002-03-22 |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200407611B true ZA200407611B (en) | 2008-02-27 |
Family
ID=28675269
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200407611A ZA200407611B (en) | 2002-03-22 | 2004-09-21 | Hemiasterlin derivatives and uses thereof in the treatment of cancer |
Country Status (19)
Country | Link |
---|---|
US (5) | US7192972B2 (pl) |
EP (2) | EP2374454B1 (pl) |
JP (3) | JP5042444B2 (pl) |
KR (1) | KR101208266B1 (pl) |
CN (1) | CN1633289A (pl) |
AU (1) | AU2003228354B8 (pl) |
BR (1) | BRPI0308606B8 (pl) |
CA (1) | CA2479764C (pl) |
HK (1) | HK1162948A1 (pl) |
IL (2) | IL163868A0 (pl) |
MX (1) | MXPA04009209A (pl) |
NO (1) | NO334803B1 (pl) |
NZ (2) | NZ555951A (pl) |
PH (1) | PH12013500123A1 (pl) |
PL (1) | PL219737B1 (pl) |
RU (1) | RU2342399C2 (pl) |
TW (1) | TWI332835B (pl) |
WO (1) | WO2003082268A2 (pl) |
ZA (1) | ZA200407611B (pl) |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7064211B2 (en) | 2002-03-22 | 2006-06-20 | Eisai Co., Ltd. | Hemiasterlin derivatives and uses thereof |
NZ555951A (en) * | 2002-03-22 | 2009-01-31 | Eisai Co Ltd | Hemiasterlin derivatives and uses thereof |
US7390910B2 (en) * | 2003-08-08 | 2008-06-24 | Wyeth | Compounds for treating tumors |
US7317019B2 (en) | 2003-08-21 | 2008-01-08 | Bristol Myers Squibb Co. | N-alkylated diaminopropane derivatives as modulators of chemokine receptor activity |
JP2008522624A (ja) * | 2004-12-09 | 2008-07-03 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ヘミアスタリン(hemiasterlin)アナログを使用する癌治療におけるチューブリンのアイソタイプのスクリーニング |
US8663210B2 (en) | 2009-05-13 | 2014-03-04 | Novian Health, Inc. | Methods and apparatus for performing interstitial laser therapy and interstitial brachytherapy |
WO2014145314A2 (en) | 2013-03-15 | 2014-09-18 | Cancer Research Technology, Llc | Methods and compositions for gamma-glutamyl cycle modulation |
PL2968440T3 (pl) * | 2013-03-15 | 2019-12-31 | Zymeworks Inc. | Związki cytotoksyczne i antymitotyczne oraz sposoby ich stosowania |
US10675355B2 (en) | 2013-12-27 | 2020-06-09 | Var2 Pharmaceuticals Aps | VAR2CSA-drug conjugates |
EP3086815B1 (en) | 2013-12-27 | 2022-02-09 | Zymeworks Inc. | Sulfonamide-containing linkage systems for drug conjugates |
RS62860B1 (sr) | 2014-09-17 | 2022-02-28 | Zymeworks Inc | Citotoksična i antimitotička jedinjenja, i postupci upotrebe istih |
US10844090B2 (en) | 2015-01-30 | 2020-11-24 | Sutro Biopharma, Inc. | Hemiasterlin derivatives for conjugation and therapy |
US10517958B2 (en) | 2016-10-04 | 2019-12-31 | Zymeworks Inc. | Compositions and methods for the treatment of platinum-drug resistant cancer |
WO2018128745A1 (en) | 2017-01-06 | 2018-07-12 | The Board Of Trustees Of The Leland Stanford Junior University | Ciliary neurotrophic factor receptor ligands and methods of using the same |
US20200247845A1 (en) | 2017-08-10 | 2020-08-06 | Sumitomo Dainippon Pharma Co., Ltd. | Hemiasterlin Derivatives and Antibody-Drug Conjugates Including Same |
WO2019031614A1 (ja) | 2017-08-10 | 2019-02-14 | 大日本住友製薬株式会社 | ヘミアスタリン誘導体を含む抗体薬物複合体 |
CN113412271A (zh) | 2019-02-13 | 2021-09-17 | 大日本住友制药株式会社 | 具有半胱氨酸残基的哈米特林衍生物 |
WO2020166613A1 (ja) * | 2019-02-13 | 2020-08-20 | 大日本住友製薬株式会社 | 多能性幹細胞の除去剤 |
EP4079327A1 (en) | 2021-04-22 | 2022-10-26 | Centaurus Polytherapeutics | Payloads for drug-conjugates and their use for treating cancer |
CN114195684B (zh) * | 2021-12-21 | 2023-10-20 | 马鞍山诺恩特医药科技有限公司 | 一种氨基保护基n-取代手性氨基酸的合成方法 |
Family Cites Families (50)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4768523A (en) | 1981-04-29 | 1988-09-06 | Lifecore Biomedical, Inc. | Hydrogel adhesive |
US4733665C2 (en) | 1985-11-07 | 2002-01-29 | Expandable Grafts Partnership | Expandable intraluminal graft and method and apparatus for implanting an expandable intraluminal graft |
US5041126A (en) | 1987-03-13 | 1991-08-20 | Cook Incorporated | Endovascular stent and delivery system |
US5328471A (en) | 1990-02-26 | 1994-07-12 | Endoluminal Therapeutics, Inc. | Method and apparatus for treatment of focal disease in hollow tubular organs and other tissue lumens |
US5213580A (en) | 1988-08-24 | 1993-05-25 | Endoluminal Therapeutics, Inc. | Biodegradable polymeric endoluminal sealing process |
US5089606A (en) | 1989-01-24 | 1992-02-18 | Minnesota Mining And Manufacturing Company | Water-insoluble polysaccharide hydrogel foam for medical applications |
US5052998A (en) | 1990-04-04 | 1991-10-01 | Zimmon David S | Indwelling stent and method of use |
DE4016994A1 (de) * | 1990-05-26 | 1991-11-28 | Bayer Ag | Neue anhydro-statin-phosphonopyrrolidine und -piperidine, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel gegen retroviren |
US5064435A (en) | 1990-06-28 | 1991-11-12 | Schneider (Usa) Inc. | Self-expanding prosthesis having stable axial length |
US5147370A (en) | 1991-06-12 | 1992-09-15 | Mcnamara Thomas O | Nitinol stent for hollow body conduits |
US5176626A (en) | 1992-01-15 | 1993-01-05 | Wilson-Cook Medical, Inc. | Indwelling stent |
US5798355A (en) | 1995-06-07 | 1998-08-25 | Gpi Nil Holdings, Inc. | Inhibitors of rotamase enzyme activity |
JPH073444A (ja) * | 1993-06-17 | 1995-01-06 | Mitsubishi Materials Corp | 耐割損性のすぐれた半導体装置の誘電薄膜形成用スパッタリング焼結ターゲット材 |
JPH0873444A (ja) | 1994-09-02 | 1996-03-19 | Fujisawa Pharmaceut Co Ltd | ベンゾジアゼピン誘導体 |
US6231600B1 (en) | 1995-02-22 | 2001-05-15 | Scimed Life Systems, Inc. | Stents with hybrid coating for medical devices |
US5837313A (en) | 1995-04-19 | 1998-11-17 | Schneider (Usa) Inc | Drug release stent coating process |
GB9508195D0 (en) * | 1995-04-20 | 1995-06-07 | Univ British Columbia | Novel biologically active compounds and compositions,their use and derivation |
US5661175A (en) * | 1995-06-20 | 1997-08-26 | Kashman; Yoel | Hemiasterlin and geodiamolide TA |
CA2254343A1 (en) * | 1996-05-14 | 1997-11-20 | Agouron Pharmaceuticals, Inc. | Inhibitors of picornavirus 3c proteases and methods for their use and preparation |
US6057297A (en) * | 1996-08-06 | 2000-05-02 | Polifarma S.P.A. | Inhibitor compounds of zinc-dependent metalloproteinases associated with pathological conditions, and therapeutic use thereof |
DE19638870B4 (de) | 1996-09-23 | 2009-05-14 | Helmholtz-Zentrum für Infektionsforschung GmbH | Tubulysine, Verfahren zu ihrer Gewinnung und sie enthaltende Mittel |
ZA9710342B (en) | 1996-11-25 | 1998-06-10 | Alza Corp | Directional drug delivery stent and method of use. |
US6515016B2 (en) | 1996-12-02 | 2003-02-04 | Angiotech Pharmaceuticals, Inc. | Composition and methods of paclitaxel for treating psoriasis |
US6273913B1 (en) | 1997-04-18 | 2001-08-14 | Cordis Corporation | Modified stent useful for delivery of drugs along stent strut |
US6143721A (en) | 1997-07-18 | 2000-11-07 | Basf Aktiengesellschaft | Dolastatin 15 derivatives |
US5891507A (en) | 1997-07-28 | 1999-04-06 | Iowa-India Investments Company Limited | Process for coating a surface of a metallic stent |
US5962487A (en) * | 1997-12-16 | 1999-10-05 | Agouron Pharmaceuticals, Inc. | Antipicornaviral compounds and methods for their use and preparation |
CA2225325A1 (en) * | 1997-12-19 | 1999-06-19 | The University Of British Columbia | Hemiasterlin analogs |
DE69806812T2 (de) * | 1997-12-19 | 2003-03-13 | Unilever Nv | Olivenöl enthaltende nahrungsmittelzusammensetzung |
WO1999051613A1 (en) | 1998-04-03 | 1999-10-14 | Medivir Ab | Prodrugs of phosphorous-containing pharmaceuticals |
EP2272839B1 (en) | 1998-06-17 | 2012-08-22 | Eisai R&D Management Co., Ltd. | Intermediate compounds for the preparation of halichondrin analogs |
WO1999065299A1 (en) * | 1998-06-19 | 1999-12-23 | Smithkline Beecham Corporation | Compositions and methods for expansion of hematopoietic cells |
US6153252A (en) | 1998-06-30 | 2000-11-28 | Ethicon, Inc. | Process for coating stents |
US6248127B1 (en) | 1998-08-21 | 2001-06-19 | Medtronic Ave, Inc. | Thromboresistant coated medical device |
US7022677B1 (en) * | 1999-02-18 | 2006-04-04 | Kaken Pharmaceutical Co., Ltd. | Amide derivatives as growth hormone secretagogues |
KR100699404B1 (ko) * | 1999-02-18 | 2007-03-23 | 가켄 세야쿠 가부시키가이샤 | 성장 호르몬 분비촉진제로서의 신규 아미드 유도체 |
US6258121B1 (en) | 1999-07-02 | 2001-07-10 | Scimed Life Systems, Inc. | Stent coating |
US6323315B1 (en) * | 1999-09-10 | 2001-11-27 | Basf Aktiengesellschaft | Dolastatin peptides |
US6203551B1 (en) | 1999-10-04 | 2001-03-20 | Advanced Cardiovascular Systems, Inc. | Chamber for applying therapeutic substances to an implant device |
US6251136B1 (en) | 1999-12-08 | 2001-06-26 | Advanced Cardiovascular Systems, Inc. | Method of layering a three-coated stent using pharmacological and polymeric agents |
PE20011277A1 (es) | 2000-04-14 | 2002-01-07 | Agouron Pharma | Compuestos y composiciones antipicornavirales, sus usos farmaceuticos y los materiales para su sintesis |
US6737409B2 (en) * | 2001-07-19 | 2004-05-18 | Hoffmann-La Roche Inc. | Dolastatin 10 derivatives |
US6517889B1 (en) | 2001-11-26 | 2003-02-11 | Swaminathan Jayaraman | Process for coating a surface of a stent |
NZ555951A (en) * | 2002-03-22 | 2009-01-31 | Eisai Co Ltd | Hemiasterlin derivatives and uses thereof |
US7064211B2 (en) | 2002-03-22 | 2006-06-20 | Eisai Co., Ltd. | Hemiasterlin derivatives and uses thereof |
DE10230874A1 (de) | 2002-07-09 | 2004-01-22 | Morphochem AG Aktiengesellschaft für kombinatorische Chemie | Neue Tubulysinanaloga |
AU2003294463A1 (en) | 2002-11-21 | 2004-06-18 | Wyeth | Cells resistant to chemotherapeutic compounds and uses thereof |
AU2003295808A1 (en) | 2002-11-21 | 2004-06-18 | Wyeth | Hemiasterlin affinity probes and their uses |
JP2008522624A (ja) | 2004-12-09 | 2008-07-03 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ヘミアスタリン(hemiasterlin)アナログを使用する癌治療におけるチューブリンのアイソタイプのスクリーニング |
WO2006121857A2 (en) | 2005-05-05 | 2006-11-16 | Eisai Co., Ltd. | Unsolvated and host-guest solvated crystalline forms of (2e,4s)-4-[(n-{[(2r)-1-isopropylpiperidin-2-yl]-carbonyl}-3-methyl-l-valyl)(methyl)amino]-2,5-dimethylhex-2-enoic acid and their pharmaceutical uses |
-
2003
- 2003-03-21 NZ NZ555951A patent/NZ555951A/en not_active IP Right Cessation
- 2003-03-21 EP EP10191039.6A patent/EP2374454B1/en not_active Expired - Lifetime
- 2003-03-21 JP JP2003579806A patent/JP5042444B2/ja not_active Expired - Lifetime
- 2003-03-21 EP EP03726101A patent/EP1490054A2/en not_active Withdrawn
- 2003-03-21 KR KR1020047014555A patent/KR101208266B1/ko active IP Right Grant
- 2003-03-21 AU AU2003228354A patent/AU2003228354B8/en not_active Expired
- 2003-03-21 NZ NZ535139A patent/NZ535139A/en not_active IP Right Cessation
- 2003-03-21 MX MXPA04009209A patent/MXPA04009209A/es active IP Right Grant
- 2003-03-21 IL IL16386803A patent/IL163868A0/xx unknown
- 2003-03-21 CA CA2479764A patent/CA2479764C/en not_active Expired - Lifetime
- 2003-03-21 PL PL373572A patent/PL219737B1/pl unknown
- 2003-03-21 WO PCT/US2003/008888 patent/WO2003082268A2/en active Search and Examination
- 2003-03-21 CN CNA038067005A patent/CN1633289A/zh active Pending
- 2003-03-21 BR BRPI0308606A patent/BRPI0308606B8/pt not_active IP Right Cessation
- 2003-03-21 RU RU2004131218/04A patent/RU2342399C2/ru active
- 2003-03-21 US US10/508,607 patent/US7192972B2/en not_active Expired - Lifetime
- 2003-03-24 TW TW092106495A patent/TWI332835B/zh not_active IP Right Cessation
-
2004
- 2004-09-01 IL IL163868A patent/IL163868A/en active IP Right Grant
- 2004-09-21 ZA ZA200407611A patent/ZA200407611B/en unknown
- 2004-10-21 NO NO20044526A patent/NO334803B1/no not_active IP Right Cessation
-
2007
- 2007-02-02 US US11/701,969 patent/US7528152B2/en not_active Expired - Lifetime
- 2007-08-30 JP JP2007224880A patent/JP2007332160A/ja not_active Withdrawn
-
2009
- 2009-02-27 US US12/394,882 patent/US8129407B2/en not_active Expired - Fee Related
-
2012
- 2012-02-03 US US13/365,728 patent/US8633224B2/en not_active Expired - Fee Related
- 2012-04-12 HK HK12103605.7A patent/HK1162948A1/zh not_active IP Right Cessation
-
2013
- 2013-01-17 PH PH12013500123A patent/PH12013500123A1/en unknown
- 2013-03-05 JP JP2013042550A patent/JP2013166754A/ja not_active Withdrawn
- 2013-11-12 US US14/077,660 patent/US20140309174A1/en not_active Abandoned
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ZA200407611B (en) | Hemiasterlin derivatives and uses thereof in the treatment of cancer | |
ES2291642T3 (es) | Hidroxinaftiridinoncarboxamidas utiles como inhibidores de la integrasa de vih. | |
KR100312444B1 (ko) | 트리플루오로메틸피롤로인돌카르복실산에스테르유도체및그의제조방법 | |
BR9909488B1 (pt) | ecteinascidinas semi-sintéticas e composição farmacêutica. | |
JP2008505976A (ja) | テトラペプチド類似体 | |
PL186869B1 (pl) | Nowe heterocykliczne N-podstawione pochodne kwasów alfa-iminohydroksamowych i karboksylowych, sposób ich wytwarzania, środek farmaceutyczny i ich zastosowanie | |
SA96160637B1 (ar) | مشتقات aroy1- piperidine | |
ES2929208T3 (es) | Compuestos de imidazotiadiazol como inhibidores de PAR4 | |
JP6251236B2 (ja) | 癌を治療するための官能性チエノ−インドール誘導体 | |
CZ272098A3 (cs) | Isochinoliny vhodné jako analgetika | |
JPH0826036B2 (ja) | 生理活性物質k−252の誘導体 | |
JP4167806B2 (ja) | メビノリン誘導体 | |
WO2023143236A1 (zh) | 2h-吲唑-7-甲酰胺类化合物、制备方法、药物组合物和应用 | |
ES2911183T3 (es) | Compuesto para inhibir selectivamente quinasas y uso del mismo | |
US6664285B1 (en) | Use of cell membrane penetrating indigoid bisindole derivatives | |
JP6758282B2 (ja) | ヒト免疫プロテアソーム阻害剤としてのジペプチド模倣薬 | |
TWI331151B (en) | Esters in position 20 of camptothecins | |
ES2235844T3 (es) | Agentes antibacterianos. | |
CZ280952B6 (cs) | N-(alfa-substituovaný pyridinyl) karbonyldipeptidy, způsob jejich výroby a farmaceutické přípravky na jejich bázi | |
ES2332976B2 (es) | Compuesto tetrahidro-quinolin-sulfonamida sustituidos, su preparaciony uso como medicamentos. | |
US6992207B2 (en) | Melphalan derivatives and their use as cancer chemotherapeutic drugs | |
OGAWA et al. | Synthesis and Antiarrhythmic Activity of 2, 5-Disubstituted 2, 3-Dihydro-1, 2, 5-benzothiadiazepin-4 (5H)-one 1, 1-Dioxides | |
JPWO2017086392A1 (ja) | 新規なグルタミン酸誘導体とブロック共重合体を含有する組成物及びその用途 | |
JP4369229B2 (ja) | 抗腫瘍活性を有する多環式化合物 | |
PT98766B (pt) | Processo de preparacao de derivados de quinobenzoxazina quinobenzotiazina e pirido-acridina e de composicoes farmaceuticas que os contem |