OA10614A - New cryptophycins from synthesis - Google Patents

New cryptophycins from synthesis Download PDF

Info

Publication number: OA10614A
Authority: OA; OAPI
Prior art keywords: compound; cryptophycin; methyl; chloro; double bond
Prior art date: 1995-03-07

Application number

OA70070A

Other languages

English (en)

Inventor

Richard E Moore

Marcus A Tius

Russell A Barrow

Jian Liang

Thomas H Corbett

Frederick A Valeriote

Thomas K Hemscheidt

Golakoti Trimurtulu

Original Assignee

Univ Hawaii

Univ Wayne State

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

1995-03-07

Filing date

1997-09-05

Publication date

2001-03-15

1995-03-07 Priority claimed from US08/400,057 external-priority patent/US6013626A/en

1995-06-07 Priority claimed from US08/482,141 external-priority patent/US5952298A/en

1997-09-05 Application filed by Univ Hawaii, Univ Wayne State filed Critical Univ Hawaii

2001-03-15 Publication of OA10614A publication Critical patent/OA10614A/en

Links

229930188224 Cryptophycin Natural products 0.000 title claims abstract description 345
230000015572 biosynthetic process Effects 0.000 title claims description 18
108010002156 Depsipeptides Proteins 0.000 title abstract description 99
238000003786 synthesis reaction Methods 0.000 title description 13
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 claims abstract description 318
238000000034 method Methods 0.000 claims abstract description 76
239000003814 drug Substances 0.000 claims abstract description 40
210000004962 mammalian cell Anatomy 0.000 claims abstract description 24
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 description 288
150000001875 compounds Chemical class 0.000 claims description 274
108010006226 cryptophycin Proteins 0.000 claims description 249
229910052739 hydrogen Inorganic materials 0.000 claims description 228
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 163
-1 monoalkylamino Chemical group 0.000 claims description 132
210000004027 cell Anatomy 0.000 claims description 119
239000001257 hydrogen Substances 0.000 claims description 84
229910052760 oxygen Inorganic materials 0.000 claims description 83
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 82
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 74
239000001301 oxygen Substances 0.000 claims description 74
239000000203 mixture Substances 0.000 claims description 72
150000002431 hydrogen Chemical group 0.000 claims description 67
229910052799 carbon Inorganic materials 0.000 claims description 55
150000002118 epoxides Chemical group 0.000 claims description 47
239000002253 acid Substances 0.000 claims description 40
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 39
229940079593 drug Drugs 0.000 claims description 36
125000000217 alkyl group Chemical group 0.000 claims description 35
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 27
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229940034982 antineoplastic agent Drugs 0.000 claims description 23
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
125000003118 aryl group Chemical group 0.000 claims description 16
229910052736 halogen Inorganic materials 0.000 claims description 14
150000002367 halogens Chemical class 0.000 claims description 14
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125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 14
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125000004069 aziridinyl group Chemical group 0.000 claims description 13
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125000004414 alkyl thio group Chemical group 0.000 claims description 11
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230000011278 mitosis Effects 0.000 claims description 11
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
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125000006498 halo alkoxy benzyl group Chemical group 0.000 claims description 6
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
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SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 7
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RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium Chemical compound [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 claims 2
XXAXVMUWHZHZMJ-UHFFFAOYSA-N Chymopapain Chemical compound OC1=CC(S(O)(=O)=O)=CC(S(O)(=O)=O)=C1O XXAXVMUWHZHZMJ-UHFFFAOYSA-N 0.000 claims 1
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OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 177
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 130
238000005481 NMR spectroscopy Methods 0.000 description 125
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VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 85
238000002451 electron ionisation mass spectrometry Methods 0.000 description 78
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 76
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HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 57
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 47
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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 45
QCHPKSFMDHPSNR-UHFFFAOYSA-N 3-aminoisobutyric acid Chemical compound NCC(C)C(O)=O QCHPKSFMDHPSNR-UHFFFAOYSA-N 0.000 description 41
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101150041968 CDC13 gene Proteins 0.000 description 40
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238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 38
108010089438 cryptophycin 1 Proteins 0.000 description 37
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239000002243 precursor Substances 0.000 description 33
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 26
102000029749 Microtubule Human genes 0.000 description 26
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239000000377 silicon dioxide Substances 0.000 description 22
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 21
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
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108010090203 cryptophycin 8 Chemical class 0.000 description 17
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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 16
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HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
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125000001041 indolyl group Chemical group 0.000 description 1
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150000007529 inorganic bases Chemical class 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000008101 lactose Substances 0.000 description 1
231100001231 less toxic Toxicity 0.000 description 1
201000002364 leukopenia Diseases 0.000 description 1
239000006193 liquid solution Substances 0.000 description 1
239000006194 liquid suspension Substances 0.000 description 1
208000003747 lymphoid leukemia Diseases 0.000 description 1
150000002678 macrocyclic compounds Chemical class 0.000 description 1
239000003120 macrolide antibiotic agent Substances 0.000 description 1
230000036210 malignancy Effects 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
229960004961 mechlorethamine Drugs 0.000 description 1
HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
229960001924 melphalan Drugs 0.000 description 1
229950009246 mepitiostane Drugs 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
125000004492 methyl ester group Chemical group 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
108091028606 miR-1 stem-loop Proteins 0.000 description 1
244000005700 microbiome Species 0.000 description 1
210000003879 microtubule-organizing center Anatomy 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 1
229960002653 nilutamide Drugs 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
239000012038 nucleophile Substances 0.000 description 1
235000015097 nutrients Nutrition 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000011368 organic material Substances 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
229960003552 other antineoplastic agent in atc Drugs 0.000 description 1
230000002018 overexpression Effects 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
239000006179 pH buffering agent Substances 0.000 description 1
229940116369 pancreatic lipase Drugs 0.000 description 1
230000007170 pathology Effects 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
125000004437 phosphorous atom Chemical group 0.000 description 1
239000006187 pill Substances 0.000 description 1
239000002574 poison Substances 0.000 description 1
231100000614 poison Toxicity 0.000 description 1
229960001298 polyestradiol phosphate Drugs 0.000 description 1
229920001451 polypropylene glycol Polymers 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
230000008569 process Effects 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
230000005522 programmed cell death Effects 0.000 description 1
LJZPPWWHKPGCHS-UHFFFAOYSA-N propargyl chloride Chemical compound ClCC#C LJZPPWWHKPGCHS-UHFFFAOYSA-N 0.000 description 1
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
238000001959 radiotherapy Methods 0.000 description 1
238000006894 reductive elimination reaction Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
231100000916 relative toxicity Toxicity 0.000 description 1
230000004044 response Effects 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000012216 screening Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000012807 shake-flask culturing Methods 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
210000000329 smooth muscle myocyte Anatomy 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
238000003797 solvolysis reaction Methods 0.000 description 1
238000000527 sonication Methods 0.000 description 1
241000894007 species Species 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
238000005556 structure-activity relationship Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229960001603 tamoxifen Drugs 0.000 description 1
BEHTXUBGUDGCNQ-IEAAAIHOSA-N taxol c Chemical compound O([C@@H]1[C@]2(O)C[C@@H](C(=C([C@@H](OC(C)=O)C(=O)[C@]3(C)[C@@H](O)C[C@H]4OC[C@]4([C@H]31)OC(C)=O)C2(C)C)C)OC(=O)[C@H](O)[C@@H](NC(=O)CCCCC)C=1C=CC=CC=1)C(=O)C1=CC=CC=C1 BEHTXUBGUDGCNQ-IEAAAIHOSA-N 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
210000001550 testis Anatomy 0.000 description 1
NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
JGVWCANSWKRBCS-UHFFFAOYSA-N tetramethylrhodamine thiocyanate Chemical compound [Cl-].C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=C(SC#N)C=C1C(O)=O JGVWCANSWKRBCS-UHFFFAOYSA-N 0.000 description 1
108700004921 tetramethylrhodaminylphalloidine Proteins 0.000 description 1
125000006000 trichloroethyl group Chemical group 0.000 description 1
125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
230000004614 tumor growth Effects 0.000 description 1
238000002525 ultrasonication Methods 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
238000010626 work up procedure 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
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
- 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
- A61P5/00—Drugs for disorders of the endocrine system

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Urology & Nephrology (AREA)
Epidemiology (AREA)
Endocrinology (AREA)
Oncology (AREA)
Psychology (AREA)
Diabetes (AREA)
Hematology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Reproductive Health (AREA)
Pulmonology (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)

OA70070A 1995-03-07 1997-09-05 New cryptophycins from synthesis OA10614A (en)

Applications Claiming Priority (2)

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

Publications (1)

Publication Number	Publication Date
OA10614A true OA10614A (en)	2001-03-15

Family

ID=27016884

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA70070A OA10614A (en)	1995-03-07	1997-09-05	New cryptophycins from synthesis

Country Status (22)

Country	Link
EP (1)	EP0830136B1 (pl)
JP (1)	JP4181632B2 (pl)
CN (1)	CN1165337C (pl)
AP (1)	AP737A (pl)
AT (1)	ATE279935T1 (pl)
AU (1)	AU723652B2 (pl)
BG (1)	BG63289B1 (pl)
CZ (1)	CZ278197A3 (pl)
DE (1)	DE69633667T2 (pl)
ES (1)	ES2230561T3 (pl)
FI (1)	FI973591A0 (pl)
GE (1)	GEP20002206B (pl)
HU (1)	HU225041B1 (pl)
MD (1)	MD2196B2 (pl)
NO (1)	NO326685B1 (pl)
NZ (1)	NZ305571A (pl)
OA (1)	OA10614A (pl)
PL (1)	PL185949B1 (pl)
RO (1)	RO118931B1 (pl)
SK (1)	SK119997A3 (pl)
TJ (1)	TJ347B (pl)
WO (1)	WO1996040184A1 (pl)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0850057A4 (en) *	1995-08-30	2001-04-11	Lilly Co Eli	Pharmaceutical compounds
US6680311B1 (en)	1996-08-30	2004-01-20	Eli Lilly And Company	Cryptophycin compounds
AU4233997A (en) *	1996-08-30	1998-03-19	Eli Lilly And Company	Process for preparing pharmaceutical compounds
CA2264063C (en) *	1996-08-30	2007-03-13	Eli Lilly And Company	Cryptophycin compounds
HUP0000291A3 (en) *	1996-09-06	2000-10-30	Lilly Co Eli	Process to prepare cryptophycin compounds
EP0929535A4 (en) *	1996-09-06	2001-05-23	Lilly Co Eli	PROCESS AND NEW INTERMEDIATES
BR9711695A (pt) *	1996-09-06	2000-03-08	Lilly Co Eli	Processo para prepração de composto farmacêuticos
CA2281107A1 (en) *	1997-02-26	1998-09-03	Eli Lilly And Company	Tripeptide and tetrapeptide pharmaceutical compounds
US6143909A (en) *	1997-02-26	2000-11-07	Eli Lilly And Company	Selective epoxidation process for preparing pharmaceutical compounds
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
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
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
AU1123200A (en) *	1998-10-16	2000-05-08	Eli Lilly And Company	Stereoselective process for producing antineoplastic agents
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
WO2021067460A1 (en) *	2019-09-30	2021-04-08	The Regents Of The University Ofmichigan	Biocatalytic synthesis of cryptophycin anticancer agents

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4868208A (en) *	1988-07-15	1989-09-19	Merck & Co., Inc.	Antifungal agent and method
US4946835A (en) *	1988-07-15	1990-08-07	Merck & Co., Inc.	Antifungal fermentation product 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
CA2179490A1 (en) *	1993-12-21	1995-06-29	Trimurtulu Golakoti	New cryptophycins

1996
- 1996-03-07 AU AU53603/96A patent/AU723652B2/en not_active Expired
- 1996-03-07 EP EP96910399A patent/EP0830136B1/en not_active Expired - Lifetime
- 1996-03-07 WO PCT/US1996/003246 patent/WO1996040184A1/en not_active Ceased
- 1996-03-07 HU HU9801880A patent/HU225041B1/hu not_active IP Right Cessation
- 1996-03-07 NZ NZ305571A patent/NZ305571A/xx not_active IP Right Cessation
- 1996-03-07 JP JP50044097A patent/JP4181632B2/ja not_active Expired - Lifetime
- 1996-03-07 CZ CZ972781A patent/CZ278197A3/cs unknown
- 1996-03-07 ES ES96910399T patent/ES2230561T3/es not_active Expired - Lifetime
- 1996-03-07 CN CNB96193140XA patent/CN1165337C/zh not_active Expired - Lifetime
- 1996-03-07 RO RO97-01693A patent/RO118931B1/ro unknown
- 1996-03-07 AP APAP/P/1997/001069A patent/AP737A/en active
- 1996-03-07 PL PL96322507A patent/PL185949B1/pl unknown
- 1996-03-07 TJ TJ97000493A patent/TJ347B/xx unknown
- 1996-03-07 SK SK1199-97A patent/SK119997A3/sk unknown
- 1996-03-07 AT AT96910399T patent/ATE279935T1/de not_active IP Right Cessation
- 1996-03-07 MD MD97-0313A patent/MD2196B2/ro unknown
- 1996-03-07 GE GEAP19963909A patent/GEP20002206B/en unknown
- 1996-03-07 DE DE69633667T patent/DE69633667T2/de not_active Expired - Lifetime
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

Also Published As

Publication number	Publication date
BG101875A (en)	1998-10-30
HUP9801880A3 (en)	1999-08-30
HK1009747A1 (en)	1999-06-11
AP9701069A0 (en)	1997-10-30
CN1183726A (zh)	1998-06-03
HU225041B1 (en)	2006-05-29
AU5360396A (en)	1996-12-30
PL322507A1 (en)	1998-02-02
NZ305571A (en)	1999-02-25
ATE279935T1 (de)	2004-11-15
FI973591A0 (fi)	1997-09-03
BG63289B1 (bg)	2001-09-28
CZ278197A3 (cs)	1998-12-16
WO1996040184A1 (en)	1996-12-19
HUP9801880A2 (hu)	1998-11-30
NO326685B1 (no)	2009-01-26
DE69633667D1 (en)	2004-11-25
AU723652B2 (en)	2000-08-31
DE69633667T2 (de)	2006-03-02
ES2230561T3 (es)	2005-05-01
GEP20002206B (en)	2000-08-25
MD970313A (en)	1999-06-30
TJ347B (en)	2002-10-06
SK119997A3 (en)	1998-12-02
EP0830136A4 (en)	2001-01-24
RO118931B1 (ro)	2004-01-30
EP0830136A1 (en)	1998-03-25
JP4181632B2 (ja)	2008-11-19
NO974105L (no)	1997-11-05
CN1165337C (zh)	2004-09-08
PL185949B1 (pl)	2003-09-30
MD2196B2 (ro)	2003-06-30
EP0830136B1 (en)	2004-10-20
NO974105D0 (no)	1997-09-05
JPH11510476A (ja)	1999-09-14
AP737A (en)	1999-03-15

Publication	Publication Date	Title
US6013626A (en)	2000-01-11	Cryptophycins from synthesis
AU723652B2 (en)	2000-08-31	New cryptophycins from synthesis
KR100459527B1 (ko)	2005-09-30	합성된신규한크립토파이신
CA2230540A1 (en)	1997-03-06	Pharmaceutical compounds
WO1996039829A9 (en)	1997-02-20	New cryptophycins
JP2002514175A (ja)	2002-05-14	医薬化合物群
CA2263420A1 (en)	1998-03-05	Pharmaceutical compounds
EP0869786B1 (en)	2003-03-05	Pharmaceutical compounds
EP0792875B1 (en)	2001-05-09	Cryptophycin derivatives and their use as anti-microtubule agents
US20020128185A1 (en)	2002-09-12	Pharmaceutical compounds
EP0923564A1 (en)	1999-06-23	Pharmaceutical compounds
RU2195458C2 (ru)	2002-12-27	Криптофициновое соединение, фармацевтическая композиция, способ ингибирования пролиферации клеток и способ смягчения патологического состояния
CA2214565C (en)	2007-05-29	New cryptophycins from synthesis
US5955423A (en)	1999-09-21	Cryptophycins
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