JP2019515880A5 - - Google Patents

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Publication number

JP2019515880A5

JP2019515880A5 JP2018549266A JP2018549266A JP2019515880A5 JP 2019515880 A5 JP2019515880 A5 JP 2019515880A5 JP 2018549266 A JP2018549266 A JP 2018549266A JP 2018549266 A JP2018549266 A JP 2018549266A JP 2019515880 A5 JP2019515880 A5 JP 2019515880A5

Authority

JP

Japan

Prior art keywords

alkyl

alkynyl

alkenyl

group

independently

Prior art date

2017-03-16

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Pending

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• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 27
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 26
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 18
• 150000003839 salts Chemical class 0.000 claims 18
• 229910052799 carbon Inorganic materials 0.000 claims 17
• 229910052739 hydrogen Inorganic materials 0.000 claims 16
• 125000003118 aryl group Chemical group 0.000 claims 14
• 125000001072 heteroaryl group Chemical group 0.000 claims 14
• 229910052736 halogen Inorganic materials 0.000 claims 12
• 150000002367 halogens Chemical class 0.000 claims 12
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims 12
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 9
• DLKUYSQUHXBYPB-NSSHGSRYSA-N (2s,4r)-4-[[2-[(1r,3r)-1-acetyloxy-4-methyl-3-[3-methylbutanoyloxymethyl-[(2s,3s)-3-methyl-2-[[(2r)-1-methylpiperidine-2-carbonyl]amino]pentanoyl]amino]pentyl]-1,3-thiazole-4-carbonyl]amino]-2-methyl-5-(4-methylphenyl)pentanoic acid Chemical compound N([C@@H]([C@@H](C)CC)C(=O)N(COC(=O)CC(C)C)[C@H](C[C@@H](OC(C)=O)C=1SC=C(N=1)C(=O)N[C@H](C[C@H](C)C(O)=O)CC=1C=CC(C)=CC=1)C(C)C)C(=O)[C@H]1CCCCN1C DLKUYSQUHXBYPB-NSSHGSRYSA-N 0.000 claims 6
• 125000000217 alkyl group Chemical group 0.000 claims 6
• 229930184737 tubulysin Natural products 0.000 claims 6
• 125000000304 alkynyl group Chemical group 0.000 claims 5
• 125000003342 alkenyl group Chemical group 0.000 claims 4
• 150000001413 amino acids Chemical class 0.000 claims 3
• 229940079593 drug Drugs 0.000 claims 3
• 239000003814 drug Substances 0.000 claims 3
• 239000008194 pharmaceutical composition Substances 0.000 claims 3
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims 2
• 206010028980 Neoplasm Diseases 0.000 claims 2
• 201000011510 cancer Diseases 0.000 claims 2
• 125000004093 cyano group Chemical group *C#N 0.000 claims 2
• 125000000753 cycloalkyl group Chemical group 0.000 claims 2
• 239000003446 ligand Substances 0.000 claims 2
• 238000000034 method Methods 0.000 claims 2
• UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims 2
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 2
• -1 thiobortezomib Chemical compound 0.000 claims 2
• NZCNGJHOIKMMCG-UZRVFEFTSA-N (2S,4R)-4-[[2-[(1R,3R)-1-acetyloxy-4-methyl-3-[[(2S,3S)-3-methyl-2-[[(2R)-1-methylpiperidine-2-carbonyl]amino]pentanoyl]-(propanoyloxymethyl)amino]pentyl]-1,3-thiazole-4-carbonyl]amino]-5-(4-hydroxyphenyl)-2-methylpentanoic acid Chemical compound N([C@@H]([C@@H](C)CC)C(=O)N(COC(=O)CC)[C@H](C[C@@H](OC(C)=O)C=1SC=C(N=1)C(=O)N[C@H](C[C@H](C)C(O)=O)CC=1C=CC(O)=CC=1)C(C)C)C(=O)[C@H]1CCCCN1C NZCNGJHOIKMMCG-UZRVFEFTSA-N 0.000 claims 1
• TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 claims 1
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims 1
• 101800002638 Alpha-amanitin Proteins 0.000 claims 1
• FRYULLIZUDQONW-IMJSIDKUSA-N Asp-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(O)=O FRYULLIZUDQONW-IMJSIDKUSA-N 0.000 claims 1
• VPSHHQXIWLGVDD-ZLUOBGJFSA-N Asp-Asp-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O VPSHHQXIWLGVDD-ZLUOBGJFSA-N 0.000 claims 1
• 229930188224 Cryptophycin Natural products 0.000 claims 1
• ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 claims 1
• KYHUYMLIVQFXRI-SJPGYWQQSA-N Didemnin B Chemical compound CN([C@H](CC(C)C)C(=O)N[C@@H]1C(=O)N[C@@H]([C@H](CC(=O)O[C@H](C(=O)[C@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N2CCC[C@H]2C(=O)N(C)[C@@H](CC=2C=CC(OC)=CC=2)C(=O)O[C@@H]1C)C(C)C)O)[C@@H](C)CC)C(=O)[C@@H]1CCCN1C(=O)[C@H](C)O KYHUYMLIVQFXRI-SJPGYWQQSA-N 0.000 claims 1
• HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims 1
• JRZJKWGQFNTSRN-UHFFFAOYSA-N Geldanamycin Natural products C1C(C)CC(OC)C(O)C(C)C=C(C)C(OC(N)=O)C(OC)CCC=C(C)C(=O)NC2=CC(=O)C(OC)=C1C2=O JRZJKWGQFNTSRN-UHFFFAOYSA-N 0.000 claims 1
• 208000008839 Kidney Neoplasms Diseases 0.000 claims 1
• 239000002067 L01XE06 - Dasatinib Substances 0.000 claims 1
• 229930126263 Maytansine Natural products 0.000 claims 1
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims 1
• 229930012538 Paclitaxel Natural products 0.000 claims 1
• 206010038389 Renal cancer Diseases 0.000 claims 1
• RXGJTYFDKOHJHK-UHFFFAOYSA-N S-deoxo-amaninamide Natural products CCC(C)C1NC(=O)CNC(=O)C2Cc3c(SCC(NC(=O)CNC1=O)C(=O)NC(CC(=O)N)C(=O)N4CC(O)CC4C(=O)NC(C(C)C(O)CO)C(=O)N2)[nH]c5ccccc35 RXGJTYFDKOHJHK-UHFFFAOYSA-N 0.000 claims 1
• IBEDDHUHZBDXGB-UHFFFAOYSA-N Tubulysin A Natural products N=1C(C(=O)NC(CC(C)C(O)=O)CC=2C=CC(O)=CC=2)=CSC=1C(OC(C)=O)CC(C(C)C)N(COC(=O)CC(C)C)C(=O)C(C(C)CC)NC(=O)C1CCCCN1C IBEDDHUHZBDXGB-UHFFFAOYSA-N 0.000 claims 1
• IBEDDHUHZBDXGB-OEJISELMSA-N Tubulysin A Chemical compound N([C@@H]([C@@H](C)CC)C(=O)N(COC(=O)CC(C)C)[C@H](C[C@@H](OC(C)=O)C=1SC=C(N=1)C(=O)N[C@H](C[C@H](C)C(O)=O)CC=1C=CC(O)=CC=1)C(C)C)C(=O)[C@H]1CCCCN1C IBEDDHUHZBDXGB-OEJISELMSA-N 0.000 claims 1
• HWCIETDQUHYHGQ-YHVCZDCZSA-N Tubulysin B Chemical compound C([C@@H](C[C@H](C)C(O)=O)NC(=O)C=1N=C(SC=1)[C@H](OC(C)=O)C[C@@H](N(COC(=O)CCC)C(=O)[C@@H](NC(=O)[C@@H]1N(CCCC1)C)[C@@H](C)CC)C(C)C)C1=CC=C(O)C=C1 HWCIETDQUHYHGQ-YHVCZDCZSA-N 0.000 claims 1
• SAJNCFZAPSBQTQ-HZZFHOQESA-N Tubulysin D Chemical compound N([C@@H]([C@@H](C)CC)C(=O)N(COC(=O)CC(C)C)[C@H](C[C@@H](OC(C)=O)C=1SC=C(N=1)C(=O)N[C@H](C[C@H](C)C(O)=O)CC=1C=CC=CC=1)C(C)C)C(=O)[C@H]1CCCCN1C SAJNCFZAPSBQTQ-HZZFHOQESA-N 0.000 claims 1
• SEIXESXDPXDGRK-CAPJTEJHSA-N Tubulysin E Chemical compound C([C@@H](C[C@H](C)C(O)=O)NC(=O)C=1N=C(SC=1)[C@H](OC(C)=O)C[C@@H](N(COC(=O)CCC)C(=O)[C@@H](NC(=O)[C@@H]1N(CCCC1)C)[C@@H](C)CC)C(C)C)C1=CC=CC=C1 SEIXESXDPXDGRK-CAPJTEJHSA-N 0.000 claims 1
• 229940122803 Vinca alkaloid Drugs 0.000 claims 1
• 239000004007 alpha amanitin Substances 0.000 claims 1
• CIORWBWIBBPXCG-SXZCQOKQSA-N alpha-amanitin Chemical compound O=C1N[C@@H](CC(N)=O)C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H]([C@@H](C)[C@@H](O)CO)C(=O)N[C@@H](C2)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@H]1C[S@@](=O)C1=C2C2=CC=C(O)C=C2N1 CIORWBWIBBPXCG-SXZCQOKQSA-N 0.000 claims 1
• CIORWBWIBBPXCG-UHFFFAOYSA-N alpha-amanitin Natural products O=C1NC(CC(N)=O)C(=O)N2CC(O)CC2C(=O)NC(C(C)C(O)CO)C(=O)NC(C2)C(=O)NCC(=O)NC(C(C)CC)C(=O)NCC(=O)NC1CS(=O)C1=C2C2=CC=C(O)C=C2N1 CIORWBWIBBPXCG-UHFFFAOYSA-N 0.000 claims 1
• 229960003896 aminopterin Drugs 0.000 claims 1
• 108010040443 aspartyl-aspartic acid Proteins 0.000 claims 1
• GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims 1
• 229960001467 bortezomib Drugs 0.000 claims 1
• 210000004556 brain Anatomy 0.000 claims 1
• 210000000481 breast Anatomy 0.000 claims 1
• 125000004432 carbon atom Chemical group C* 0.000 claims 1
• 210000003679 cervix uteri Anatomy 0.000 claims 1
• 239000003795 chemical substances by application Substances 0.000 claims 1
• 108010006226 cryptophycin Proteins 0.000 claims 1
• PSNOPSMXOBPNNV-VVCTWANISA-N cryptophycin 1 Chemical compound C1=C(Cl)C(OC)=CC=C1C[C@@H]1C(=O)NC[C@@H](C)C(=O)O[C@@H](CC(C)C)C(=O)O[C@H]([C@H](C)[C@@H]2[C@H](O2)C=2C=CC=CC=2)C/C=C/C(=O)N1 PSNOPSMXOBPNNV-VVCTWANISA-N 0.000 claims 1
• PSNOPSMXOBPNNV-UHFFFAOYSA-N cryptophycin-327 Natural products C1=C(Cl)C(OC)=CC=C1CC1C(=O)NCC(C)C(=O)OC(CC(C)C)C(=O)OC(C(C)C2C(O2)C=2C=CC=CC=2)CC=CC(=O)N1 PSNOPSMXOBPNNV-UHFFFAOYSA-N 0.000 claims 1
• 229960002448 dasatinib Drugs 0.000 claims 1
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims 1
• 229960000975 daunorubicin Drugs 0.000 claims 1
• KYHUYMLIVQFXRI-UHFFFAOYSA-N didemnin B Natural products CC1OC(=O)C(CC=2C=CC(OC)=CC=2)N(C)C(=O)C2CCCN2C(=O)C(CC(C)C)NC(=O)C(C)C(=O)C(C(C)C)OC(=O)CC(O)C(C(C)CC)NC(=O)C1NC(=O)C(CC(C)C)N(C)C(=O)C1CCCN1C(=O)C(C)O KYHUYMLIVQFXRI-UHFFFAOYSA-N 0.000 claims 1
• 108010061297 didemnins Proteins 0.000 claims 1
• 229960003668 docetaxel Drugs 0.000 claims 1
• 229960004679 doxorubicin Drugs 0.000 claims 1
• 229930013356 epothilone Natural products 0.000 claims 1
• 150000003883 epothilone derivatives Chemical class 0.000 claims 1
• 229960005167 everolimus Drugs 0.000 claims 1
• QTQAWLPCGQOSGP-GBTDJJJQSA-N geldanamycin Chemical compound N1C(=O)\C(C)=C/C=C\[C@@H](OC)[C@H](OC(N)=O)\C(C)=C/[C@@H](C)[C@@H](O)[C@H](OC)C[C@@H](C)CC2=C(OC)C(=O)C=C1C2=O QTQAWLPCGQOSGP-GBTDJJJQSA-N 0.000 claims 1
• 210000003128 head Anatomy 0.000 claims 1
• 208000014829 head and neck neoplasm Diseases 0.000 claims 1
• 239000012216 imaging agent Substances 0.000 claims 1
• 238000003384 imaging method Methods 0.000 claims 1
• 238000000338 in vitro Methods 0.000 claims 1
• 201000010982 kidney cancer Diseases 0.000 claims 1
• 210000004072 lung Anatomy 0.000 claims 1
• 208000026037 malignant tumor of neck Diseases 0.000 claims 1
• WKPWGQKGSOKKOO-RSFHAFMBSA-N maytansine Chemical compound CO[C@@H]([C@@]1(O)C[C@](OC(=O)N1)([C@H]([C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(C)=O)CC(=O)N1C)C)[H])\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 WKPWGQKGSOKKOO-RSFHAFMBSA-N 0.000 claims 1
• 210000000214 mouth Anatomy 0.000 claims 1
• 210000003739 neck Anatomy 0.000 claims 1
• 201000005443 oral cavity cancer Diseases 0.000 claims 1
• 210000001672 ovary Anatomy 0.000 claims 1
• 229960001592 paclitaxel Drugs 0.000 claims 1
• 210000000496 pancreas Anatomy 0.000 claims 1
• 239000000546 pharmaceutical excipient Substances 0.000 claims 1
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims 1
• 239000001022 rhodamine dye Substances 0.000 claims 1
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims 1
• 229960002930 sirolimus Drugs 0.000 claims 1
• 210000002784 stomach Anatomy 0.000 claims 1
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims 1
• 108010061145 tubulysin A Proteins 0.000 claims 1
• HWCIETDQUHYHGQ-UHFFFAOYSA-N tubulysin B Natural products C1CCCN(C)C1C(=O)NC(C(C)CC)C(=O)N(COC(=O)CCC)C(C(C)C)CC(OC(C)=O)C(SC=1)=NC=1C(=O)NC(CC(C)C(O)=O)CC1=CC=C(O)C=C1 HWCIETDQUHYHGQ-UHFFFAOYSA-N 0.000 claims 1
• 108010061146 tubulysin B Proteins 0.000 claims 1
• SAJNCFZAPSBQTQ-UHFFFAOYSA-N tubulysin D Natural products N=1C(C(=O)NC(CC(C)C(O)=O)CC=2C=CC=CC=2)=CSC=1C(OC(C)=O)CC(C(C)C)N(COC(=O)CC(C)C)C(=O)C(C(C)CC)NC(=O)C1CCCCN1C SAJNCFZAPSBQTQ-UHFFFAOYSA-N 0.000 claims 1
• 108010061212 tubulysin D Proteins 0.000 claims 1
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims 1
• 239000005483 tyrosine kinase inhibitor Substances 0.000 claims 1
• 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 claims 1
• 210000003932 urinary bladder Anatomy 0.000 claims 1
• 229960005502 α-amanitin Drugs 0.000 claims 1
• 0 C*(CC*(C)N(CC(***)=O)CC(*c1ccccc1)=O)N(C*)CC(*c1ccccc1)=O Chemical compound C*(CC*(C)N(CC(***)=O)CC(*c1ccccc1)=O)N(C*)CC(*c1ccccc1)=O 0.000 description 2