ZA200306237B - Epothilone derivatives for the treatment of refractory tumors. - Google Patents

Epothilone derivatives for the treatment of refractory tumors. Download PDF

Info

Publication number: ZA200306237B
Authority: ZA; South Africa
Prior art keywords: group; methyl; dihydroxy; thiazolyl; dione
Prior art date: 2001-02-20

Application number

ZA200306237A

Other languages

English (en)

Inventor

Francis Y F Lee

Original Assignee

Bristol Myers Squibb Co

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.)

2001-02-20

Filing date

2003-08-12

Publication date

2004-12-23

2003-08-12 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

2004-12-23 Publication of ZA200306237B publication Critical patent/ZA200306237B/en

Links

206010028980 Neoplasm Diseases 0.000 title claims description 61
238000011282 treatment Methods 0.000 title claims description 34
150000003883 epothilone derivatives Chemical class 0.000 title description 16
125000000217 alkyl group Chemical group 0.000 claims description 86
125000000547 substituted alkyl group Chemical group 0.000 claims description 78
150000001875 compounds Chemical class 0.000 claims description 71
-1 epothilone compound Chemical class 0.000 claims description 41
125000002252 acyl group Chemical group 0.000 claims description 36
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
125000003118 aryl group Chemical group 0.000 claims description 35
125000003107 substituted aryl group Chemical group 0.000 claims description 28
238000000034 method Methods 0.000 claims description 25
229930013356 epothilone Natural products 0.000 claims description 23
229910052739 hydrogen Inorganic materials 0.000 claims description 23
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 20
239000000203 mixture Substances 0.000 claims description 18
125000000623 heterocyclic group Chemical group 0.000 claims description 17
125000005843 halogen group Chemical group 0.000 claims description 16
LZWPOLSJFGLQCE-UHFFFAOYSA-N heptadecane-5,9-dione Chemical compound CCCCCCCCC(=O)CCCC(=O)CCCC LZWPOLSJFGLQCE-UHFFFAOYSA-N 0.000 claims description 16
229940127089 cytotoxic agent Drugs 0.000 claims description 15
150000002118 epoxides Chemical class 0.000 claims description 15
239000002246 antineoplastic agent Substances 0.000 claims description 14
239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 14
229910052736 halogen Inorganic materials 0.000 claims description 12
150000002367 halogens Chemical class 0.000 claims description 12
201000011510 cancer Diseases 0.000 claims description 8
201000010099 disease Diseases 0.000 claims description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 8
238000011275 oncology therapy Methods 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
229910052757 nitrogen Inorganic materials 0.000 claims description 6
229910052717 sulfur Inorganic materials 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
230000003287 optical effect Effects 0.000 claims description 5
230000002062 proliferating effect Effects 0.000 claims description 5
241000124008 Mammalia Species 0.000 claims description 4
125000003147 glycosyl group Chemical group 0.000 claims description 4
125000004430 oxygen atom Chemical group O* 0.000 claims description 4
125000004434 sulfur atom Chemical group 0.000 claims description 4
150000004677 hydrates Chemical class 0.000 claims description 3
239000012453 solvate Substances 0.000 claims description 3
125000000335 thiazolyl group Chemical group 0.000 claims description 3
150000001204 N-oxides Chemical class 0.000 claims description 2
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
125000004705 ethylthio group Chemical group C(C)S* 0.000 claims description 2
125000001072 heteroaryl group Chemical group 0.000 claims description 2
DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 2
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
210000004027 cell Anatomy 0.000 description 25
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 25
229930012538 Paclitaxel Natural products 0.000 description 24
229960001592 paclitaxel Drugs 0.000 description 24
238000012360 testing method Methods 0.000 description 18
239000003795 chemical substances by application Substances 0.000 description 14
239000003814 drug Substances 0.000 description 13
125000001424 substituent group Chemical group 0.000 description 13
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 description 10
206010033128 Ovarian cancer Diseases 0.000 description 9
229940123237 Taxane Drugs 0.000 description 9
230000000259 anti-tumor effect Effects 0.000 description 9
229940079593 drug Drugs 0.000 description 9
DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
239000000546 pharmaceutical excipient Substances 0.000 description 8
241001465754 Metazoa Species 0.000 description 7
230000000694 effects Effects 0.000 description 7
231100000682 maximum tolerated dose Toxicity 0.000 description 7
239000003981 vehicle Substances 0.000 description 7
102000004243 Tubulin Human genes 0.000 description 6
108090000704 Tubulin Proteins 0.000 description 6
125000003710 aryl alkyl group Chemical group 0.000 description 6
125000004432 carbon atom Chemical group C* 0.000 description 6
125000004122 cyclic group Chemical group 0.000 description 6
239000000243 solution Substances 0.000 description 6
238000002560 therapeutic procedure Methods 0.000 description 6
241000699670 Mus sp. Species 0.000 description 5
125000003545 alkoxy group Chemical group 0.000 description 5
239000002254 cytotoxic agent Substances 0.000 description 5
239000003085 diluting agent Substances 0.000 description 5
125000005842 heteroatom Chemical group 0.000 description 5
238000000338 in vitro Methods 0.000 description 5
230000002611 ovarian Effects 0.000 description 5
239000003381 stabilizer Substances 0.000 description 5
238000007920 subcutaneous administration Methods 0.000 description 5
239000000725 suspension Substances 0.000 description 5
210000004881 tumor cell Anatomy 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
230000001093 anti-cancer Effects 0.000 description 4
239000011230 binding agent Substances 0.000 description 4
125000001589 carboacyl group Chemical group 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
231100000599 cytotoxic agent Toxicity 0.000 description 4
230000001472 cytotoxic effect Effects 0.000 description 4
230000003013 cytotoxicity Effects 0.000 description 4
231100000135 cytotoxicity Toxicity 0.000 description 4
HESCAJZNRMSMJG-HGYUPSKWSA-N epothilone A Natural products O=C1[C@H](C)[C@H](O)[C@H](C)CCC[C@H]2O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C HESCAJZNRMSMJG-HGYUPSKWSA-N 0.000 description 4
239000000796 flavoring agent Substances 0.000 description 4
238000009472 formulation Methods 0.000 description 4
230000035772 mutation Effects 0.000 description 4
238000007911 parenteral administration Methods 0.000 description 4
230000003389 potentiating effect Effects 0.000 description 4
239000003755 preservative agent Substances 0.000 description 4
230000004044 response Effects 0.000 description 4
239000003826 tablet Substances 0.000 description 4
229940124597 therapeutic agent Drugs 0.000 description 4
PFJFPBDHCFMQPN-RGJAOAFDSA-N (1s,3s,7s,10r,11s,12s,16r)-3-[(e)-1-[2-(aminomethyl)-1,3-thiazol-4-yl]prop-1-en-2-yl]-7,11-dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(CN)=N1 PFJFPBDHCFMQPN-RGJAOAFDSA-N 0.000 description 3
MQLACMBJVPINKE-UHFFFAOYSA-N 10-[(3-hydroxy-4-methoxyphenyl)methylidene]anthracen-9-one Chemical compound C1=C(O)C(OC)=CC=C1C=C1C2=CC=CC=C2C(=O)C2=CC=CC=C21 MQLACMBJVPINKE-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
108091003079 Bovine Serum Albumin Proteins 0.000 description 3
201000008808 Fibrosarcoma Diseases 0.000 description 3
125000005236 alkanoylamino group Chemical group 0.000 description 3
230000000118 anti-neoplastic effect Effects 0.000 description 3
230000037396 body weight Effects 0.000 description 3
210000000481 breast Anatomy 0.000 description 3
230000003021 clonogenic effect Effects 0.000 description 3
230000000052 comparative effect Effects 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 3
238000013265 extended release Methods 0.000 description 3
239000012091 fetal bovine serum Substances 0.000 description 3
235000019634 flavors Nutrition 0.000 description 3
239000012729 immediate-release (IR) formulation Substances 0.000 description 3
239000007943 implant Substances 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
230000007246 mechanism Effects 0.000 description 3
239000002609 medium Substances 0.000 description 3
201000001441 melanoma Diseases 0.000 description 3
208000008443 pancreatic carcinoma Diseases 0.000 description 3
239000008194 pharmaceutical composition Substances 0.000 description 3
239000008389 polyethoxylated castor oil Substances 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
238000006116 polymerization reaction Methods 0.000 description 3
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 3
230000001988 toxicity Effects 0.000 description 3
231100000419 toxicity Toxicity 0.000 description 3
PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 2
208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
201000009030 Carcinoma Diseases 0.000 description 2
206010009944 Colon cancer Diseases 0.000 description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 2
QXRSDHAAWVKZLJ-OXZHEXMSSA-N Epothilone B Natural products O=C1[C@H](C)[C@H](O)[C@@H](C)CCC[C@@]2(C)O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C QXRSDHAAWVKZLJ-OXZHEXMSSA-N 0.000 description 2
208000032612 Glial tumor Diseases 0.000 description 2
206010018338 Glioma Diseases 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
206010025323 Lymphomas Diseases 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
229920000168 Microcrystalline cellulose Polymers 0.000 description 2
102000029749 Microtubule Human genes 0.000 description 2
108091022875 Microtubule Proteins 0.000 description 2
206010029260 Neuroblastoma Diseases 0.000 description 2
208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
201000010208 Seminoma Diseases 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
206010070863 Toxicity to various agents Diseases 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
125000004423 acyloxy group Chemical group 0.000 description 2
125000004453 alkoxycarbonyl 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
125000001691 aryl alkyl amino group Chemical group 0.000 description 2
125000001769 aryl amino group Chemical group 0.000 description 2
125000004104 aryloxy group Chemical group 0.000 description 2
230000008901 benefit Effects 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
125000002619 bicyclic group Chemical group 0.000 description 2
238000001574 biopsy Methods 0.000 description 2
239000002775 capsule Substances 0.000 description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
150000001721 carbon Chemical group 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
235000010980 cellulose Nutrition 0.000 description 2
210000001072 colon Anatomy 0.000 description 2
238000010293 colony formation assay Methods 0.000 description 2
125000006310 cycloalkyl amino group Chemical group 0.000 description 2
125000005366 cycloalkylthio group Chemical group 0.000 description 2
231100000433 cytotoxic Toxicity 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
QXRSDHAAWVKZLJ-PVYNADRNSA-N epothilone B Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 QXRSDHAAWVKZLJ-PVYNADRNSA-N 0.000 description 2
238000011156 evaluation Methods 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000012634 fragment Substances 0.000 description 2
125000002541 furyl group Chemical group 0.000 description 2
201000005787 hematologic cancer Diseases 0.000 description 2
208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
125000004476 heterocycloamino group Chemical group 0.000 description 2
125000004356 hydroxy functional group Chemical group O* 0.000 description 2
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
125000002883 imidazolyl group Chemical group 0.000 description 2
238000011534 incubation Methods 0.000 description 2
125000001041 indolyl group Chemical group 0.000 description 2
230000001939 inductive effect Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 2
239000008101 lactose Substances 0.000 description 2
210000004185 liver Anatomy 0.000 description 2
239000000314 lubricant Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
238000005259 measurement Methods 0.000 description 2
239000008108 microcrystalline cellulose Substances 0.000 description 2
229940016286 microcrystalline cellulose Drugs 0.000 description 2
235000019813 microcrystalline cellulose Nutrition 0.000 description 2
210000004688 microtubule Anatomy 0.000 description 2
125000002950 monocyclic group Chemical group 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
230000002335 preservative effect Effects 0.000 description 2
230000008569 process Effects 0.000 description 2
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
125000004076 pyridyl group Chemical group 0.000 description 2
125000000714 pyrimidinyl group Chemical group 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
230000035945 sensitivity Effects 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000002904 solvent Substances 0.000 description 2
239000000829 suppository Substances 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
208000001608 teratocarcinoma Diseases 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
125000003396 thiol group Chemical class [H]S* 0.000 description 2
210000001685 thyroid gland Anatomy 0.000 description 2
230000000699 topical effect Effects 0.000 description 2
239000003558 transferase inhibitor Substances 0.000 description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 description 1
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 description 1
WLXGQMVCYPUOLM-UHFFFAOYSA-N 1-hydroxyethanesulfonic acid Chemical compound CC(O)S(O)(=O)=O WLXGQMVCYPUOLM-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
KFXDYZXVIHNBFD-UHFFFAOYSA-N 2-(thian-2-ylsulfonyl)thiane Chemical compound C1CCCSC1S(=O)(=O)C1CCCCS1 KFXDYZXVIHNBFD-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 1
125000004635 2-oxazepinyl group Chemical group O1N(CC=CC=C1)* 0.000 description 1
125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
125000004610 3,4-dihydro-4-oxo-quinazolinyl group Chemical group O=C1NC(=NC2=CC=CC=C12)* 0.000 description 1
125000005986 4-piperidonyl group Chemical group 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
108010024976 Asparaginase Proteins 0.000 description 1
206010003571 Astrocytoma Diseases 0.000 description 1
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical class C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
208000003950 B-cell lymphoma Diseases 0.000 description 1
208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
108010006654 Bleomycin Proteins 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 group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
JWBOIMRXGHLCPP-UHFFFAOYSA-N Chloditan Chemical compound C=1C=CC=C(Cl)C=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 JWBOIMRXGHLCPP-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
208000001333 Colorectal Neoplasms Diseases 0.000 description 1
229920000858 Cyclodextrin Polymers 0.000 description 1
108010092160 Dactinomycin Proteins 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
101000835651 Echinococcus multilocularis Tubulin beta-2 chain Proteins 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
206010053155 Epigastric discomfort Diseases 0.000 description 1
239000004606 Fillers/Extenders Substances 0.000 description 1
229940123414 Folate antagonist Drugs 0.000 description 1
108700012941 GNRH1 Proteins 0.000 description 1
239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
208000012766 Growth delay Diseases 0.000 description 1
208000017604 Hodgkin disease Diseases 0.000 description 1
208000021519 Hodgkin lymphoma Diseases 0.000 description 1
208000010747 Hodgkins lymphoma Diseases 0.000 description 1
241000282412 Homo Species 0.000 description 1
101000956263 Homo sapiens Uncharacterized protein C19orf48 Proteins 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
206010023347 Keratoacanthoma Diseases 0.000 description 1
206010027476 Metastases Diseases 0.000 description 1
229930192392 Mitomycin Natural products 0.000 description 1
241001529936 Murinae Species 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
241000699660 Mus musculus Species 0.000 description 1
208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
125000004633 N-oxo-pyridyl group Chemical group 0.000 description 1
238000011794 NU/NU nude mouse Methods 0.000 description 1
206010028813 Nausea Diseases 0.000 description 1
208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
108010016076 Octreotide Proteins 0.000 description 1
239000005642 Oleic acid Substances 0.000 description 1
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
206010061535 Ovarian neoplasm Diseases 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
241000700159 Rattus Species 0.000 description 1
241000283984 Rodentia Species 0.000 description 1
230000018199 S phase Effects 0.000 description 1
229920002125 Sokalan® Polymers 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
206010042971 T-cell lymphoma Diseases 0.000 description 1
208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
102100038573 Uncharacterized protein C19orf48 Human genes 0.000 description 1
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 1
229940122803 Vinca alkaloid Drugs 0.000 description 1
238000001793 Wilcoxon signed-rank test Methods 0.000 description 1
201000006083 Xeroderma Pigmentosum Diseases 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
229940124532 absorption promoter Drugs 0.000 description 1
239000002253 acid Substances 0.000 description 1
RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
150000008052 alkyl sulfonates Chemical class 0.000 description 1
125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
229960000473 altretamine Drugs 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
239000003098 androgen Substances 0.000 description 1
229940030486 androgens Drugs 0.000 description 1
229940045799 anthracyclines and related substance Drugs 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000002280 anti-androgenic effect Effects 0.000 description 1
230000003474 anti-emetic effect Effects 0.000 description 1
229940046836 anti-estrogen Drugs 0.000 description 1
230000001833 anti-estrogenic effect Effects 0.000 description 1
230000001387 anti-histamine Effects 0.000 description 1
230000000340 anti-metabolite Effects 0.000 description 1
239000000051 antiandrogen Substances 0.000 description 1
229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
229940125683 antiemetic agent Drugs 0.000 description 1
239000002111 antiemetic agent Substances 0.000 description 1
229940125715 antihistaminic agent Drugs 0.000 description 1
239000000739 antihistaminic agent Substances 0.000 description 1
229940100197 antimetabolite Drugs 0.000 description 1
239000002256 antimetabolite Substances 0.000 description 1
229940045686 antimetabolites antineoplastic purine analogs Drugs 0.000 description 1
229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
229940045688 antineoplastic antimetabolites pyrimidine analogues Drugs 0.000 description 1
229940041181 antineoplastic drug Drugs 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000005140 aralkylsulfonyl group Chemical group 0.000 description 1
125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
125000005239 aroylamino group Chemical group 0.000 description 1
125000004659 aryl alkyl thio group Chemical group 0.000 description 1
125000004391 aryl sulfonyl group Chemical group 0.000 description 1
125000005110 aryl thio group Chemical group 0.000 description 1
238000003556 assay Methods 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
125000002785 azepinyl group Chemical group 0.000 description 1
150000001541 aziridines Chemical class 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000004602 benzodiazinyl group Chemical group N1=NC(=CC2=C1C=CC=C2)* 0.000 description 1
125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 description 1
125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
125000004599 benzpyrazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N beta-hydroxyethanesulfonic acid Natural products OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
125000006267 biphenyl group Chemical group 0.000 description 1
OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical class N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
201000008275 breast carcinoma Diseases 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
244000309466 calf Species 0.000 description 1
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
229960004562 carboplatin Drugs 0.000 description 1
125000004181 carboxyalkyl group Chemical group 0.000 description 1
230000022131 cell cycle Effects 0.000 description 1
230000010261 cell growth Effects 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
210000003679 cervix uteri Anatomy 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000000460 chlorine Chemical group 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 description 1
125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
229960004316 cisplatin Drugs 0.000 description 1
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
208000029742 colonic neoplasm Diseases 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000007398 colorimetric assay Methods 0.000 description 1
238000013329 compounding Methods 0.000 description 1
239000007891 compressed tablet Substances 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
239000006071 cream Substances 0.000 description 1
125000000000 cycloalkoxy group Chemical group 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
229940097362 cyclodextrins Drugs 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
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 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
238000002784 cytotoxicity assay Methods 0.000 description 1
231100000263 cytotoxicity test Toxicity 0.000 description 1
229960000640 dactinomycin Drugs 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
125000004598 dihydrobenzofuryl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
125000004586 dihydrobenzopyranyl group Chemical group O1C(CCC2=C1C=CC=C2)* 0.000 description 1
125000004582 dihydrobenzothienyl group Chemical group S1C(CC2=C1C=CC=C2)* 0.000 description 1
125000004597 dihydrobenzothiopyranyl group Chemical group S1C(CCC2=C1C=CC=C2)* 0.000 description 1
WOKPSXJEBSRSAT-UHFFFAOYSA-N dihydrobenzothiopyranyl sulfone group Chemical group S1C(CCC2=C1C=CC=C2)S(=O)(=O)C2SC1=C(CC2)C=CC=C1 WOKPSXJEBSRSAT-UHFFFAOYSA-N 0.000 description 1
125000004611 dihydroisoindolyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
125000000532 dioxanyl group Chemical group 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
238000009826 distribution Methods 0.000 description 1
239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
239000003623 enhancer Substances 0.000 description 1
229940088598 enzyme Drugs 0.000 description 1
229940011871 estrogen Drugs 0.000 description 1
239000000262 estrogen Substances 0.000 description 1
239000000328 estrogen antagonist Substances 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
230000003325 follicular Effects 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
UPBDXRPQPOWRKR-UHFFFAOYSA-N furan-2,5-dione;methoxyethene Chemical compound COC=C.O=C1OC(=O)C=C1 UPBDXRPQPOWRKR-UHFFFAOYSA-N 0.000 description 1
125000004615 furo[2,3-b]pyridinyl group Chemical group O1C(=CC=2C1=NC=CC2)* 0.000 description 1
125000004613 furo[2,3-c]pyridinyl group Chemical group O1C(=CC=2C1=CN=CC2)* 0.000 description 1
125000004614 furo[3,1-b]pyridinyl group Chemical group 0.000 description 1
125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
230000014509 gene expression Effects 0.000 description 1
239000003862 glucocorticoid Substances 0.000 description 1
125000005456 glyceride group Chemical group 0.000 description 1
239000008187 granular material Substances 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
230000036541 health Effects 0.000 description 1
125000004470 heterocyclooxy group Chemical group 0.000 description 1
UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 1
229940125697 hormonal agent Drugs 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
230000003463 hyperproliferative effect Effects 0.000 description 1
230000009610 hypersensitivity Effects 0.000 description 1
125000002632 imidazolidinyl group Chemical group 0.000 description 1
125000002636 imidazolinyl group Chemical group 0.000 description 1
125000001841 imino group Chemical group [H]N=* 0.000 description 1
239000000367 immunologic factor Substances 0.000 description 1
230000005917 in vivo anti-tumor Effects 0.000 description 1
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
238000001802 infusion Methods 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000011630 iodine Chemical group 0.000 description 1
229910052740 iodine Chemical group 0.000 description 1
125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000003971 isoxazolinyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
229960002014 ixabepilone Drugs 0.000 description 1
FABUFPQFXZVHFB-CFWQTKTJSA-N ixabepilone Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@H](C)C(=O)C(C)(C)[C@H](O)CC(=O)N1)O)C)=C\C1=CSC(C)=N1 FABUFPQFXZVHFB-CFWQTKTJSA-N 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
239000007788 liquid Substances 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
239000003120 macrolide antibiotic agent Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229940057948 magnesium stearate Drugs 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
229960004857 mitomycin Drugs 0.000 description 1
229960000350 mitotane Drugs 0.000 description 1
230000036456 mitotic arrest Effects 0.000 description 1
239000007932 molded tablet Substances 0.000 description 1
125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
239000007922 nasal spray Substances 0.000 description 1
230000008693 nausea Effects 0.000 description 1
208000007538 neurilemmoma Diseases 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
231100000344 non-irritating Toxicity 0.000 description 1
239000012457 nonaqueous media Substances 0.000 description 1
238000011580 nude mouse model Methods 0.000 description 1
229960001494 octreotide acetate Drugs 0.000 description 1
239000002674 ointment Substances 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
230000000771 oncological effect Effects 0.000 description 1
230000000174 oncolytic effect Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
201000008968 osteosarcoma Diseases 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
230000002018 overexpression Effects 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
125000000160 oxazolidinyl group Chemical group 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
125000003566 oxetanyl group Chemical group 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
210000001428 peripheral nervous system Anatomy 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
229960005235 piperonyl butoxide Drugs 0.000 description 1
125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229960003171 plicamycin Drugs 0.000 description 1
239000004584 polyacrylic acid Substances 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
229960000624 procarbazine Drugs 0.000 description 1
239000000047 product Substances 0.000 description 1
239000000583 progesterone congener Substances 0.000 description 1
230000000644 propagated effect Effects 0.000 description 1
125000003373 pyrazinyl 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
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000004590 pyridopyridyl group Chemical group N1=C(C=CC2=C1C=CC=N2)* 0.000 description 1
150000003230 pyrimidines Chemical class 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000006085 pyrrolopyridyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
125000004620 quinolinyl-N-oxide group Chemical group 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
238000001959 radiotherapy Methods 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000012064 sodium phosphate buffer Substances 0.000 description 1
230000003381 solubilizing effect Effects 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
206010041823 squamous cell carcinoma Diseases 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
229940032147 starch Drugs 0.000 description 1
238000007619 statistical method Methods 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
229940037128 systemic glucocorticoids Drugs 0.000 description 1
RCINICONZNJXQF-XAZOAEDWSA-N taxol® Chemical compound O([C@@H]1[C@@]2(CC(C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3(C21)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-XAZOAEDWSA-N 0.000 description 1
125000006092 tetrahydro-1,1-dioxothienyl group Chemical group 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
125000004589 thienofuryl group Chemical group O1C(=CC2=C1C=CS2)* 0.000 description 1
125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
125000004587 thienothienyl group Chemical group S1C(=CC2=C1C=CS2)* 0.000 description 1
125000002053 thietanyl group Chemical group 0.000 description 1
125000001730 thiiranyl group Chemical group 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
WCNFFKHKJLERFM-UHFFFAOYSA-N thiomorpholinyl sulfone group Chemical group N1(CCSCC1)S(=O)(=O)N1CCSCC1 WCNFFKHKJLERFM-UHFFFAOYSA-N 0.000 description 1
229940044693 topoisomerase inhibitor Drugs 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
230000007704 transition Effects 0.000 description 1
150000004654 triazenes Chemical class 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
230000004614 tumor growth Effects 0.000 description 1
210000003932 urinary bladder Anatomy 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
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 1
238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Chemical & Material Sciences (AREA)
General Health & Medical Sciences (AREA)
Epidemiology (AREA)
Organic Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Plural Heterocyclic Compounds (AREA)

ZA200306237A 2001-02-20 2003-08-12 Epothilone derivatives for the treatment of refractory tumors. ZA200306237B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US26985801P	2001-02-20	2001-02-20

Publications (1)

Publication Number	Publication Date
ZA200306237B true ZA200306237B (en)	2004-12-23

Family

ID=23028941

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200306237A ZA200306237B (en)	2001-02-20	2003-08-12	Epothilone derivatives for the treatment of refractory tumors.

Country Status (18)

Country	Link
US (1)	US6727276B2 (et)
EP (1)	EP1368030A1 (et)
JP (1)	JP2004522771A (et)
KR (1)	KR20040028720A (et)
CN (1)	CN1610549A (et)
BG (1)	BG108072A (et)
BR (1)	BR0207316A (et)
CA (1)	CA2438598A1 (et)
EE (1)	EE200300397A (et)
HU (1)	HUP0400041A2 (et)
IL (1)	IL157128A0 (et)
IS (1)	IS6917A (et)
MX (1)	MXPA03007423A (et)
NO (1)	NO20033682L (et)
PL (1)	PL363363A1 (et)
RU (1)	RU2003128312A (et)
WO (1)	WO2002066033A1 (et)
ZA (1)	ZA200306237B (et)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6204388B1 (en) *	1996-12-03	2001-03-20	Sloan-Kettering Institute For Cancer Research	Synthesis of epothilones, intermediates thereto and analogues thereof
JP4579351B2 (ja)	1996-12-03	2010-11-10	スローン−ケッタリングインスティトュートフォアキャンサーリサーチ	エポチロンの合成とその中間体及びその類似物並びにその使用
US20050043376A1 (en) *	1996-12-03	2005-02-24	Danishefsky Samuel J.	Synthesis of epothilones, intermediates thereto, analogues and uses thereof
US6780620B1 (en) *	1998-12-23	2004-08-24	Bristol-Myers Squibb Company	Microbial transformation method for the preparation of an epothilone
US20020058286A1 (en) *	1999-02-24	2002-05-16	Danishefsky Samuel J.	Synthesis of epothilones, intermediates thereto and analogues thereof
ES2384789T3 (es) *	2001-03-14	2012-07-12	Bristol-Myers Squibb Company	Combinación de un análogo de epotilona y agentes quimioterapéuticos para el tratamiento de enfermedades proliferativas
TW200403994A (en) *	2002-04-04	2004-03-16	Bristol Myers Squibb Co	Oral administration of EPOTHILONES
TW200400191A (en) *	2002-05-15	2004-01-01	Bristol Myers Squibb Co	Pharmaceutical compositions and methods of using C-21 modified epothilone derivatives
US6921769B2 (en)	2002-08-23	2005-07-26	Sloan-Kettering Institute For Cancer Research	Synthesis of epothilones, intermediates thereto and analogues thereof
US7384964B2 (en) *	2002-08-23	2008-06-10	Sloan-Kettering Institute For Cancer Research	Synthesis of epothilones, intermediates thereto, analogues and uses thereof
NZ538522A (en)	2002-08-23	2008-03-28	Sloan Kettering Inst Cancer	Synthesis of epothilones, intermediates thereto, analogues and uses thereof
US7649006B2 (en)	2002-08-23	2010-01-19	Sloan-Kettering Institute For Cancer Research	Synthesis of epothilones, intermediates thereto and analogues thereof
EP1551425A4 (en)	2002-10-09	2006-09-20	Kosan Biosciences Inc	THERAPEUTIC FORMULATIONS
US20050171167A1 (en) *	2003-11-04	2005-08-04	Haby Thomas A.	Process and formulation containing epothilones and analogs thereof
US20050215604A1 (en) *	2004-03-26	2005-09-29	Kosan Biosciences, Inc.	Combination therapies with epothilones and carboplatin
WO2006055742A1 (en) *	2004-11-18	2006-05-26	Bristol-Myers Squibb Company	Enteric coated bead comprising epothilone or epothilone analog, and preparation and administration thereof
CA2588400A1 (en) *	2004-11-18	2006-05-26	Bristol-Myers Squibb Company	Enteric coated bead comprising ixabepilone, and preparation thereof
WO2007086879A2 (en)	2005-02-11	2007-08-02	University Of Southern California	Method of expressing proteins with disulfide bridges
JP4954983B2 (ja)	2005-05-18	2012-06-20	ファーマサイエンス・インコーポレイテッド	Ｂｉｒドメイン結合化合物
WO2007130501A2 (en)	2006-05-01	2007-11-15	University Of Southern California	Combination therapy for treatment of cancer
SG171682A1 (en)	2006-05-16	2011-06-29	Aegera Therapeutics Inc	Iap bir domain binding compounds
WO2010056901A2 (en)	2008-11-13	2010-05-20	University Of Southern California	Method of expressing proteins with disulfide bridges with enhanced yields and activity
KR20120140658A (ko)	2010-02-12	2012-12-31	파마사이언스 인크.	Ｉａｐｂｉｒ 도메인 결합 화합물
US20110300150A1 (en)	2010-05-18	2011-12-08	Scott Eliasof	Compositions and methods for treatment of autoimmune and other disease
CN110105368B (zh) *	2019-05-09	2022-01-07	上海大学	去氧紫杉烷类似物及其制备方法

Family Cites Families (37)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE4138042C2 (de)	1991-11-19	1993-10-14	Biotechnolog Forschung Gmbh	Epothilone, deren Herstellungsverfahren sowie diese Verbindungen enthaltende Mittel
DE19639456A1 (de)	1996-09-25	1998-03-26	Biotechnolog Forschung Gmbh	Epothilon-Derivate, Herstellung und Mittel
PT873341E (pt)	1995-11-17	2004-02-27	Biotechnolog Forschung Mbh Gbf	Derivados de epotilona preparacao e utilizacao
DE19542986A1 (de)	1995-11-17	1997-05-22	Biotechnolog Forschung Gmbh	Epothilon-Derivate und deren Verwendung
DE19645361A1 (de)	1996-08-30	1998-04-30	Ciba Geigy Ag	Zwischenprodukte innerhalb der Totalsynthese von Epothilon A und B, Teil II
US5969145A (en) *	1996-08-30	1999-10-19	Novartis Ag	Process for the production of epothilones and intermediate products within the process
DE19645362A1 (de)	1996-10-28	1998-04-30	Ciba Geigy Ag	Verfahren zur Herstellung von Epothilon A und B und Derivaten
AU716610B2 (en)	1996-08-30	2000-03-02	Novartis Ag	Method for producing epothilones, and intermediate products obtained during the production process
WO1998022461A1 (de)	1996-11-18	1998-05-28	GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF)	Epothilone c, d, e und f, deren herstellung und deren verwendung als cytostatische mittel bzw. als pflanzenschutzmittel
US6515016B2 (en)	1996-12-02	2003-02-04	Angiotech Pharmaceuticals, Inc.	Composition and methods of paclitaxel for treating psoriasis
US6204388B1 (en)	1996-12-03	2001-03-20	Sloan-Kettering Institute For Cancer Research	Synthesis of epothilones, intermediates thereto and analogues thereof
JP4579351B2 (ja)	1996-12-03	2010-11-10	スローン−ケッタリングインスティトュートフォアキャンサーリサーチ	エポチロンの合成とその中間体及びその類似物並びにその使用
US6441186B1 (en)	1996-12-13	2002-08-27	The Scripps Research Institute	Epothilone analogs
US6380394B1 (en)	1996-12-13	2002-04-30	The Scripps Research Institute	Epothilone analogs
DE19701758A1 (de)	1997-01-20	1998-07-23	Wessjohann Ludgar A Dr	Epothilone-Synthesebausteine
HU228851B1 (en)	1997-02-25	2013-06-28	Biotechnolog Forschung Gmbh	Process for preparing epothilones with a modified side chain and compounds prepared by this process
DE19713970B4 (de)	1997-04-04	2006-08-31	R&D-Biopharmaceuticals Gmbh	Epothilone-Synthesebausteine II - Prenylderivate
ATE225783T1 (de)	1997-04-18	2002-10-15	Studiengesellschaft Kohle Mbh	Selektive olefinmetathese von bi- oder polyfunktionellen substraten in komprimiertem kohlendioxid als reaktionsmedium
DE19821954A1 (de)	1997-05-15	1998-11-19	Biotechnolog Forschung Gmbh	Verfahren zur Herstellung eines Epothilon-Derivats
DE19720312A1 (de)	1997-05-15	1998-11-19	Hoechst Ag	Zubereitung mit erhöhter in vivo Verträglichkeit
DE19726627A1 (de)	1997-06-17	1998-12-24	Schering Ag	Zwischenprodukte, Verfahren zu ihrer Herstellung und ihre Verwendung zur Herstellung von Epothilon
US6605599B1 (en)	1997-07-08	2003-08-12	Bristol-Myers Squibb Company	Epothilone derivatives
DK1001951T3 (da)	1997-07-16	2002-12-23	Schering Ag	Thiazolderivater, fremgangsmåde til fremstilling deraf og anvendelse af disse
EP1005465B1 (de)	1997-08-09	2007-07-25	Bayer Schering Pharma Aktiengesellschaft	Neue epothilon-derivate, verfahren zu deren herstellung und ihre pharmazeutische verwendung
US6365749B1 (en)	1997-12-04	2002-04-02	Bristol-Myers Squibb Company	Process for the preparation of ring-opened epothilone intermediates which are useful for the preparation of epothilone analogs
WO1999039694A2 (en)	1998-02-05	1999-08-12	Novartis Ag	Compositions containing organic compounds
US6194181B1 (en)	1998-02-19	2001-02-27	Novartis Ag	Fermentative preparation process for and crystal forms of cytostatics
EP1058679B1 (en)	1998-02-25	2005-10-19	Sloan-Kettering Institute For Cancer Research	Synthesis of epothilones, intermediates thereto and analogues therof
FR2775187B1 (fr)	1998-02-25	2003-02-21	Novartis Ag	Utilisation de l'epothilone b pour la fabrication d'une preparation pharmaceutique antiproliferative et d'une composition comprenant l'epothilone b comme agent antiproliferatif in vivo
US6399638B1 (en)	1998-04-21	2002-06-04	Bristol-Myers Squibb Company	12,13-modified epothilone derivatives
AU5036999A (en)	1998-06-30	2000-01-17	Schering Aktiengesellschaft	Epothilon derivatives, their preparation process, intermediate products and their pharmaceutical use
CA2350189A1 (en)	1998-11-20	2000-06-02	Kosan Biosciences, Inc.	Recombinant methods and materials for producing epothilone and epothilone derivatives
JP2002533346A (ja)	1998-12-22	2002-10-08	ノバルティスアクチエンゲゼルシャフト	エポシロン誘導体およびそれらの抗腫瘍剤としての使用
ATE370946T1 (de)	1999-02-18	2007-09-15	Bayer Schering Pharma Ag	16-halogen-epothilon-derivate, verfahren zu deren herstellung und ihre pharmazeutische verwendung
KR100685336B1 (ko) *	1999-02-22	2007-02-23	게젤샤프트 퓌어 비오테크놀로기쉐 포르슝 엠베하(게베에프)	Ｃ-21 변형 에포틸론
US6211412B1 (en)	1999-03-29	2001-04-03	The University Of Kansas	Synthesis of epothilones
PE20010116A1 (es)	1999-04-30	2001-02-15	Schering Ag	Derivados de 6-alquenil-, 6-alquinil- y 6-epoxi-epotilona, procedimientos para su preparacion

2002
- 2002-02-06 RU RU2003128312/14A patent/RU2003128312A/ru not_active Application Discontinuation
- 2002-02-06 EE EEP200300397A patent/EE200300397A/et unknown
- 2002-02-06 IL IL15712802A patent/IL157128A0/xx unknown
- 2002-02-06 KR KR10-2003-7010872A patent/KR20040028720A/ko not_active Withdrawn
- 2002-02-06 MX MXPA03007423A patent/MXPA03007423A/es unknown
- 2002-02-06 JP JP2002565591A patent/JP2004522771A/ja active Pending
- 2002-02-06 PL PL02363363A patent/PL363363A1/xx not_active Application Discontinuation
- 2002-02-06 EP EP02724940A patent/EP1368030A1/en not_active Withdrawn
- 2002-02-06 HU HU0400041A patent/HUP0400041A2/hu unknown
- 2002-02-06 WO PCT/US2002/004247 patent/WO2002066033A1/en not_active Ceased
- 2002-02-06 CN CNA028052447A patent/CN1610549A/zh active Pending
- 2002-02-06 BR BR0207316-1A patent/BR0207316A/pt not_active Application Discontinuation
- 2002-02-06 CA CA002438598A patent/CA2438598A1/en not_active Abandoned
- 2002-02-08 US US10/071,988 patent/US6727276B2/en not_active Expired - Fee Related
2003
- 2003-08-07 BG BG108072A patent/BG108072A/xx unknown
- 2003-08-12 ZA ZA200306237A patent/ZA200306237B/en unknown
- 2003-08-18 IS IS6917A patent/IS6917A/is unknown
- 2003-08-19 NO NO20033682A patent/NO20033682L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
MXPA03007423A (es)	2003-11-18
PL363363A1 (en)	2004-11-15
NO20033682D0 (no)	2003-08-19
CA2438598A1 (en)	2002-08-29
WO2002066033A1 (en)	2002-08-29
JP2004522771A (ja)	2004-07-29
RU2003128312A (ru)	2005-02-10
BG108072A (en)	2005-04-30
US20020165257A1 (en)	2002-11-07
BR0207316A (pt)	2004-02-10
IL157128A0 (en)	2004-02-08
KR20040028720A (ko)	2004-04-03
EE200300397A (et)	2003-12-15
CN1610549A (zh)	2005-04-27
HUP0400041A2 (hu)	2004-04-28
IS6917A (is)	2003-08-18
US6727276B2 (en)	2004-04-27
NO20033682L (no)	2003-08-19
EP1368030A1 (en)	2003-12-10

Publication	Publication Date	Title
US6727276B2 (en)	2004-04-27	Epothilone derivatives for the treatment of refractory tumors
USRE41393E1 (en)	2010-06-22	Treatment of refractory tumors using epothilone derivatives
CA2681962C (en)	2012-06-12	Methods of administering epothilone analogs for the treatment of cancer
US6670384B2 (en)	2003-12-30	Methods of administering epothilone analogs for the treatment of cancer
SK11082003A3 (sk)	2004-08-03	Kombinácia analógov epotilónu a chemoterapeutických činidiel na liečenie proliferatívnych ochorení
US6936628B2 (en)	2005-08-30	Oral administration of epothilones
US6719540B2 (en)	2004-04-13	C3-cyano epothilone derivatives
AU2002248542A1 (en)	2003-03-20	Combination of epothilone analogs and chemotherapeutic agents for the treatment of proliferative diseases
AU2002245296B2 (en)	2006-12-21	Methods of administering epothilone analogs for the treatment of cancer
AU2002245296A1 (en)	2003-02-06	Methods of administering epothilone analogs for the treatment of cancer
AU2002255539A1 (en)	2002-09-04	Epothilone derivatives for the treatment of refractory tumors
AU2002247123A1 (en)	2002-09-04	Treatment of refractory tumors using epothilone derivatives
AU2002243548A1 (en)	2002-08-19	Parenteral formulation containing epothilone analogs