AP737A - New cryptophycins from synthesis. - Google Patents
New cryptophycins from synthesis. Download PDFInfo
- Publication number
- AP737A AP737A APAP/P/1997/001069A AP9701069A AP737A AP 737 A AP737 A AP 737A AP 9701069 A AP9701069 A AP 9701069A AP 737 A AP737 A AP 737A
- Authority
- AP
- ARIPO
- Prior art keywords
- taken together
- group
- methyl
- compound
- double bond
- Prior art date
Links
- 229930188224 Cryptophycin Natural products 0.000 title abstract description 32
- 108010002156 Depsipeptides Proteins 0.000 title abstract description 23
- 230000015572 biosynthetic process Effects 0.000 title description 4
- 238000003786 synthesis reaction Methods 0.000 title description 2
- PSNOPSMXOBPNNV-VVCTWANISA-N cryptophycin 1 Chemical class 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 abstract description 18
- 239000003814 drug Substances 0.000 abstract description 8
- 206010028980 Neoplasm Diseases 0.000 abstract description 5
- 230000035755 proliferation Effects 0.000 abstract description 4
- 238000010189 synthetic method Methods 0.000 abstract description 4
- 210000004962 mammalian cell Anatomy 0.000 abstract description 2
- 230000009826 neoplastic cell growth Effects 0.000 abstract description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 36
- 150000001875 compounds Chemical class 0.000 description 35
- -1 monoalkylamino Chemical group 0.000 description 27
- 125000000217 alkyl group Chemical group 0.000 description 17
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 13
- 102000029749 Microtubule Human genes 0.000 description 12
- 108091022875 Microtubule Proteins 0.000 description 12
- 210000004688 microtubule Anatomy 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- 150000002118 epoxides Chemical group 0.000 description 11
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 10
- 229960003048 vinblastine Drugs 0.000 description 10
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 10
- 108010006226 cryptophycin Proteins 0.000 description 9
- 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 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 229910052736 halogen Inorganic materials 0.000 description 6
- 150000002367 halogens Chemical class 0.000 description 6
- 210000005170 neoplastic cell Anatomy 0.000 description 6
- 230000002194 synthesizing effect Effects 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 5
- 102000004243 Tubulin Human genes 0.000 description 5
- 108090000704 Tubulin Proteins 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 150000001261 hydroxy acids Chemical group 0.000 description 5
- QCHPKSFMDHPSNR-UHFFFAOYSA-N 3-aminoisobutyric acid Chemical compound NCC(C)C(O)=O QCHPKSFMDHPSNR-UHFFFAOYSA-N 0.000 description 4
- 206010059866 Drug resistance Diseases 0.000 description 4
- 206010048723 Multiple-drug resistance Diseases 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 125000004423 acyloxy group Chemical group 0.000 description 4
- 125000001183 hydrocarbyl group Chemical group 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 125000000468 ketone group Chemical group 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000000394 mitotic effect Effects 0.000 description 4
- 125000004430 oxygen atom Chemical group O* 0.000 description 4
- 150000003553 thiiranes Chemical group 0.000 description 4
- IOOMXAQUNPWDLL-UHFFFAOYSA-N 2-[6-(diethylamino)-3-(diethyliminiumyl)-3h-xanthen-9-yl]-5-sulfobenzene-1-sulfonate Chemical compound C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(S(O)(=O)=O)C=C1S([O-])(=O)=O IOOMXAQUNPWDLL-UHFFFAOYSA-N 0.000 description 3
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 3
- 229930012538 Paclitaxel Natural products 0.000 description 3
- 125000004069 aziridinyl group Chemical group 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 125000001072 heteroaryl group Chemical group 0.000 description 3
- 125000006289 hydroxybenzyl group Chemical group 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 229960001592 paclitaxel Drugs 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 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 description 3
- 229960004528 vincristine Drugs 0.000 description 3
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 3
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 3
- ATKRDMWWPRZLSY-BJJCRNJMSA-N (3s,10r,13e,16s)-10-[(3-chloro-4-methoxyphenyl)methyl]-3-(2-methylpropyl)-16-[(1s)-1-[(2r,3r)-3-phenyloxiran-2-yl]ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone Chemical class C1=C(Cl)C(OC)=CC=C1C[C@@H]1C(=O)NCCC(=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 ATKRDMWWPRZLSY-BJJCRNJMSA-N 0.000 description 2
- YFGZFQNBPSCWPN-FOLMERSESA-N (3s,6r,10r,13e,16s)-10-[(4-methoxyphenyl)methyl]-6-methyl-3-(2-methylpropyl)-16-[(1s)-1-[(2r,3r)-3-phenyloxiran-2-yl]ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone Chemical class C1=CC(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 YFGZFQNBPSCWPN-FOLMERSESA-N 0.000 description 2
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 2
- JCCRURJDQIVIFI-UHFFFAOYSA-N Cryptophycin G Natural products C1=C(Cl)C(OC)=CC=C1CC(C(O)=O)NC(=O)C=CCC(O)C(C)C(O)C(O)C1=CC=CC=C1 JCCRURJDQIVIFI-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 125000006307 alkoxy benzyl group Chemical group 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 125000003275 alpha amino acid group Chemical group 0.000 description 2
- 229940044684 anti-microtubule agent Drugs 0.000 description 2
- 239000003080 antimitotic agent Substances 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- YFGZFQNBPSCWPN-UHFFFAOYSA-N cryptophycin 52 Chemical class C1=CC(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 YFGZFQNBPSCWPN-UHFFFAOYSA-N 0.000 description 2
- 210000004292 cytoskeleton Anatomy 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 125000006498 halo alkoxy benzyl group Chemical group 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- BXGDNKQFNQZCLG-UHFFFAOYSA-N methyl 3-amino-2-methylpropanoate Chemical compound COC(=O)C(C)CN BXGDNKQFNQZCLG-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 125000005208 trialkylammonium group Chemical group 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- NNJPGOLRFBJNIW-HNNXBMFYSA-N (-)-demecolcine Chemical compound C1=C(OC)C(=O)C=C2[C@@H](NC)CCC3=CC(OC)=C(OC)C(OC)=C3C2=C1 NNJPGOLRFBJNIW-HNNXBMFYSA-N 0.000 description 1
- WNKVYYZASJQZMX-YFBMXWBHSA-N (3S,6R,10R,13E,16S)-10-[(3,5-dichloro-4-hydroxyphenyl)methyl]-6-methyl-3-(2-methylpropyl)-16-[(1S)-1-[(2R,3R)-3-phenyloxiran-2-yl]ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone Chemical class C([C@@H]1C(=O)NC[C@@H](C)C(=O)O[C@H](C(O[C@@H](C/C=C/C(=O)N1)[C@H](C)[C@@H]1[C@H](O1)C=1C=CC=CC=1)=O)CC(C)C)C1=CC(Cl)=C(O)C(Cl)=C1 WNKVYYZASJQZMX-YFBMXWBHSA-N 0.000 description 1
- TVIRNGFXQVMMGB-OFWIHYRESA-N (3s,6r,10r,13e,16s)-16-[(2r,3r,4s)-4-chloro-3-hydroxy-4-phenylbutan-2-yl]-10-[(3-chloro-4-methoxyphenyl)methyl]-6-methyl-3-(2-methylpropyl)-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone Chemical class 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](O)[C@@H](Cl)C=2C=CC=CC=2)C/C=C/C(=O)N1 TVIRNGFXQVMMGB-OFWIHYRESA-N 0.000 description 1
- LVRFTAZAXQPQHI-RXMQYKEDSA-N (R)-2-hydroxy-4-methylpentanoic acid Chemical compound CC(C)C[C@@H](O)C(O)=O LVRFTAZAXQPQHI-RXMQYKEDSA-N 0.000 description 1
- LVRFTAZAXQPQHI-UHFFFAOYSA-N 2-hydroxy-4-methylvaleric acid Chemical compound CC(C)CC(O)C(O)=O LVRFTAZAXQPQHI-UHFFFAOYSA-N 0.000 description 1
- MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical group C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- NNJPGOLRFBJNIW-UHFFFAOYSA-N Demecolcine Natural products C1=C(OC)C(=O)C=C2C(NC)CCC3=CC(OC)=C(OC)C(OC)=C3C2=C1 NNJPGOLRFBJNIW-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- YVHMMVIXYJJXOL-UHFFFAOYSA-N [C].[C].[O].[O].[S] Chemical group [C].[C].[O].[O].[S] YVHMMVIXYJJXOL-UHFFFAOYSA-N 0.000 description 1
- TXFVLGPKPCACOV-UHFFFAOYSA-N [O].[P].[O].[C].[C] Chemical group [O].[P].[O].[C].[C] TXFVLGPKPCACOV-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 108010077391 arenastatin A Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000009134 cell regulation Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- CCZRCVCMUDRTLT-MQIHADEYSA-N cryptophycin 18 Chemical class N1C(=O)\C=C\CC(C(C)\C=C\C=2C=CC=CC=2)OC(=O)C(C(C)CC)OC(=O)C(C)CNC(=O)C1CC1=CC=C(OC)C(Cl)=C1 CCZRCVCMUDRTLT-MQIHADEYSA-N 0.000 description 1
- OVOJAAKFACTXHX-BBXOWAOSSA-N cryptophycin 19 Chemical class C1=C(Cl)C(OC)=CC=C1CC1C(=O)NCC(C)C(=O)OC(C(C)C)C(=O)OC(C(C)\C=C\C=2C=CC=CC=2)C/C=C/C(=O)N1 OVOJAAKFACTXHX-BBXOWAOSSA-N 0.000 description 1
- GPUHMLPBKTYERL-UHFFFAOYSA-N cryptophycin 24 Chemical class C1=CC(OC)=CC=C1CC1C(=O)NCCC(=O)OC(CC(C)C)C(=O)OC(C(C)C2C(O2)C=2C=CC=CC=2)CC=CC(=O)N1 GPUHMLPBKTYERL-UHFFFAOYSA-N 0.000 description 1
- IEYSWBYGDJSUEZ-UHFFFAOYSA-N cryptophycin 4 Chemical class C1=CC(OC)=CC=C1CC1C(=O)NCC(C)C(=O)OC(CC(C)C)C(=O)OC(C(C)C=CC=2C=CC=CC=2)CC=CC(=O)N1 IEYSWBYGDJSUEZ-UHFFFAOYSA-N 0.000 description 1
- 108010090203 cryptophycin 8 Chemical class 0.000 description 1
- VIMVAIVZDDHRDJ-UHFFFAOYSA-N cryptophycin F methyl ester Chemical class C=1C=CC=CC=1C(O)C(O)C(C)C(O)CC=CC(=O)NC(C(=O)NCC(C)C(=O)OC)CC1=CC=C(OC)C(Cl)=C1 VIMVAIVZDDHRDJ-UHFFFAOYSA-N 0.000 description 1
- XUZKJXAKKMKMBV-UHFFFAOYSA-N cryptophycin-17 Chemical class N1C(=O)C=CCC(C(C)C=CC=2C=CC=CC=2)OC(=O)C(CC(C)C)OC(=O)C(C)CNC(=O)C1CC1=CC=C(O)C(Cl)=C1 XUZKJXAKKMKMBV-UHFFFAOYSA-N 0.000 description 1
- CCZRCVCMUDRTLT-UHFFFAOYSA-N cryptophycin-18 Chemical class N1C(=O)C=CCC(C(C)C=CC=2C=CC=CC=2)OC(=O)C(C(C)CC)OC(=O)C(C)CNC(=O)C1CC1=CC=C(OC)C(Cl)=C1 CCZRCVCMUDRTLT-UHFFFAOYSA-N 0.000 description 1
- OVOJAAKFACTXHX-UHFFFAOYSA-N cryptophycin-19 Chemical class C1=C(Cl)C(OC)=CC=C1CC1C(=O)NCC(C)C(=O)OC(C(C)C)C(=O)OC(C(C)C=CC=2C=CC=CC=2)CC=CC(=O)N1 OVOJAAKFACTXHX-UHFFFAOYSA-N 0.000 description 1
- WNKVYYZASJQZMX-UHFFFAOYSA-N cryptophycin-23 Chemical class N1C(=O)C=CCC(C(C)C2C(O2)C=2C=CC=CC=2)OC(=O)C(CC(C)C)OC(=O)C(C)CNC(=O)C1CC1=CC(Cl)=C(O)C(Cl)=C1 WNKVYYZASJQZMX-UHFFFAOYSA-N 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 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
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Reproductive Health (AREA)
- Psychology (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epoxy Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Furan Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/400,057 US6013626A (en) | 1993-12-21 | 1995-03-07 | Cryptophycins from synthesis |
| US08/482,141 US5952298A (en) | 1993-12-21 | 1995-06-07 | Cryptophycins |
| PCT/US1996/003246 WO1996040184A1 (en) | 1995-03-07 | 1996-03-07 | New cryptophycins from synthesis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AP9701069A0 AP9701069A0 (en) | 1997-10-30 |
| AP737A true AP737A (en) | 1999-03-15 |
Family
ID=27016884
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| APAP/P/1997/001069A AP737A (en) | 1995-03-07 | 1996-03-07 | New cryptophycins from synthesis. |
Country Status (22)
| Country | Link |
|---|---|
| EP (1) | EP0830136B1 (ro) |
| JP (1) | JP4181632B2 (ro) |
| CN (1) | CN1165337C (ro) |
| AP (1) | AP737A (ro) |
| AT (1) | ATE279935T1 (ro) |
| AU (1) | AU723652B2 (ro) |
| BG (1) | BG63289B1 (ro) |
| CZ (1) | CZ278197A3 (ro) |
| DE (1) | DE69633667T2 (ro) |
| ES (1) | ES2230561T3 (ro) |
| FI (1) | FI973591A0 (ro) |
| GE (1) | GEP20002206B (ro) |
| HU (1) | HU225041B1 (ro) |
| MD (1) | MD2196B2 (ro) |
| NO (1) | NO326685B1 (ro) |
| NZ (1) | NZ305571A (ro) |
| OA (1) | OA10614A (ro) |
| PL (1) | PL185949B1 (ro) |
| RO (1) | RO118931B1 (ro) |
| SK (1) | SK119997A3 (ro) |
| TJ (1) | TJ347B (ro) |
| WO (1) | WO1996040184A1 (ro) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000501067A (ja) * | 1995-08-30 | 2000-02-02 | イーライ・リリー・アンド・カンパニー | 医薬化合物 |
| AU4233997A (en) * | 1996-08-30 | 1998-03-19 | Eli Lilly And Company | Process for preparing pharmaceutical compounds |
| US6680311B1 (en) | 1996-08-30 | 2004-01-20 | Eli Lilly And Company | Cryptophycin compounds |
| CZ64599A3 (cs) * | 1996-08-30 | 1999-10-13 | Eli Lilly And Company | Farmaceutické sloučeniny |
| WO1998009601A2 (en) * | 1996-09-06 | 1998-03-12 | Eli Lilly And Company | Process to prepare pharmaceutical compounds |
| EP0929535A4 (en) * | 1996-09-06 | 2001-05-23 | Lilly Co Eli | PROCESS AND NEW INTERMEDIATES |
| CA2264245A1 (en) * | 1996-09-06 | 1998-03-12 | Eli Lilly And Company | Process to prepare pharmaceutical compounds |
| JP2001513775A (ja) * | 1997-02-26 | 2001-09-04 | イーライ・リリー・アンド・カンパニー | トリペプチドおよびテトラペプチド医薬化合物 |
| CN1252788A (zh) * | 1997-02-26 | 2000-05-10 | 伊莱利利公司 | 制备药用化合物的方法 |
| EP0870506A1 (en) * | 1997-04-11 | 1998-10-14 | Eli Lilly And Company | Compositions comprising a cryptophycin compound in combination with a synchronizing or activating agent for treating cancer |
| EP0870501A1 (en) * | 1997-04-11 | 1998-10-14 | Eli Lilly And Company | Use of specific cryptophycin derivatives for the manufacture of a medicament in the treatment of fungal infections |
| EP0870510A3 (en) * | 1997-04-11 | 1999-09-15 | Eli Lilly And Company | Synergistic combination comprising cryptophycin derivatives and microtubule synergizing agents |
| AU1123200A (en) * | 1998-10-16 | 2000-05-08 | Eli Lilly And Company | Stereoselective process for producing antineoplastic agents |
| US6376230B1 (en) | 1998-10-16 | 2002-04-23 | Eli Lilly And Company | Stereoselective process for producing intermediates of cryptophycins |
| US6103913A (en) * | 1998-10-16 | 2000-08-15 | Eli Lilly And Company | Process for preparing enollactone derivatives |
| WO2000034252A2 (en) * | 1998-12-07 | 2000-06-15 | Eli Lilly And Company | Process for the preparation of cryptophycin derivatives |
| US6372936B1 (en) * | 1999-06-09 | 2002-04-16 | Eli Lilly And Company | Optical resolution of aminoisobobutyric acid |
| FR2947269B1 (fr) | 2009-06-29 | 2013-01-18 | Sanofi Aventis | Nouveaux composes anticancereux |
| US11530204B2 (en) * | 2019-09-30 | 2022-12-20 | The Regents Of The University Of Michigan | Biocatalytic synthesis of cryptophycin anticancer agents |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4946835A (en) * | 1988-07-15 | 1990-08-07 | Merck & Co., Inc. | Antifungal fermentation product and method |
| US4868208A (en) * | 1988-07-15 | 1989-09-19 | Merck & Co., Inc. | Antifungal agent and method |
| US4845086A (en) * | 1988-08-09 | 1989-07-04 | Merck & Co., Inc. | Antifungal agent |
| US4845085A (en) * | 1988-08-09 | 1989-07-04 | Merck & Co., Inc. | Antifungal agent |
| AU695873B2 (en) * | 1993-12-21 | 1998-08-27 | University Of Hawaii | New cryptophycins |
-
1996
- 1996-03-07 HU HU9801880A patent/HU225041B1/hu not_active IP Right Cessation
- 1996-03-07 TJ TJ97000493A patent/TJ347B/xx unknown
- 1996-03-07 GE GEAP19963909A patent/GEP20002206B/en unknown
- 1996-03-07 AU AU53603/96A patent/AU723652B2/en not_active Expired
- 1996-03-07 AT AT96910399T patent/ATE279935T1/de not_active IP Right Cessation
- 1996-03-07 WO PCT/US1996/003246 patent/WO1996040184A1/en not_active Ceased
- 1996-03-07 SK SK1199-97A patent/SK119997A3/sk unknown
- 1996-03-07 ES ES96910399T patent/ES2230561T3/es not_active Expired - Lifetime
- 1996-03-07 CZ CZ972781A patent/CZ278197A3/cs unknown
- 1996-03-07 AP APAP/P/1997/001069A patent/AP737A/en active
- 1996-03-07 MD MD97-0313A patent/MD2196B2/ro unknown
- 1996-03-07 JP JP50044097A patent/JP4181632B2/ja not_active Expired - Lifetime
- 1996-03-07 PL PL96322507A patent/PL185949B1/pl unknown
- 1996-03-07 DE DE69633667T patent/DE69633667T2/de not_active Expired - Lifetime
- 1996-03-07 NZ NZ305571A patent/NZ305571A/xx not_active IP Right Cessation
- 1996-03-07 CN CNB96193140XA patent/CN1165337C/zh not_active Expired - Lifetime
- 1996-03-07 EP EP96910399A patent/EP0830136B1/en not_active Expired - Lifetime
- 1996-03-07 RO RO97-01693A patent/RO118931B1/ro unknown
-
1997
- 1997-09-03 FI FI973591A patent/FI973591A0/fi not_active Application Discontinuation
- 1997-09-04 BG BG101875A patent/BG63289B1/bg unknown
- 1997-09-05 NO NO19974105A patent/NO326685B1/no not_active IP Right Cessation
- 1997-09-05 OA OA70070A patent/OA10614A/en unknown
Non-Patent Citations (2)
| Title |
|---|
| CHEMICAL PHARMACEUTICAL BULLETIN, 42(10), ISSUED 1994, KOBAYASHI et al., "The Absolute Stereostructure of Arenastatin A, A Potent Cytotoxic Depsipeptide from the Okinawan Marine Sponge Dysidea Arenaria", pages 2196-2198 * |
| FEBS Letters, issued 1995 KERKSIEK et al., "Interaction fo Cryptophycin 1 with Tubulin and Microtubules", pages 59-61 * |
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