TW200942233A

TW200942233A - Compositions of hydrophobic taxane derivatives and uses thereof

Compositions of hydrophobic taxane derivatives and uses thereof Download PDF

Info

Publication number: TW200942233A
Authority: TW; Taiwan
Prior art keywords: composition; group; unsubstituted; hydrophobic; cancer
Prior art date: 2008-04-10

Application number

TW097135271A

Other languages

English (en)

Chinese (zh)

Inventor

Neil P Desai

Chunlin Tao

Tapas De

Sherry Xiaopei Ci

Vuong Trieu

Original Assignee

Abraxis Bioscience Llc

Priority date

2008-04-10

Filing date

2008-09-12

Publication date

2009-10-16

2008-09-12 Application filed by Abraxis Bioscience Llc filed Critical Abraxis Bioscience Llc

2009-10-16 Publication of TW200942233A publication Critical patent/TW200942233A/zh

Links

239000000203 mixture Substances 0.000 title claims abstract description 372
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 title claims abstract description 224
230000002209 hydrophobic effect Effects 0.000 title claims abstract description 218
239000002105 nanoparticle Substances 0.000 claims abstract description 181
206010028980 Neoplasm Diseases 0.000 claims abstract description 94
238000000034 method Methods 0.000 claims abstract description 80
102000014914 Carrier Proteins Human genes 0.000 claims abstract description 74
108010078791 Carrier Proteins Proteins 0.000 claims abstract description 74
201000011510 cancer Diseases 0.000 claims abstract description 51
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 27
201000010099 disease Diseases 0.000 claims abstract description 26
125000003118 aryl group Chemical group 0.000 claims description 71
102000009027 Albumins Human genes 0.000 claims description 70
108010088751 Albumins Proteins 0.000 claims description 70
125000000217 alkyl group Chemical group 0.000 claims description 66
239000002245 particle Substances 0.000 claims description 63
229940123237 Taxane Drugs 0.000 claims description 50
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
102000008100 Human Serum Albumin Human genes 0.000 claims description 42
108091006905 Human Serum Albumin Proteins 0.000 claims description 42
238000009472 formulation Methods 0.000 claims description 35
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
230000000694 effects Effects 0.000 claims description 27
125000001165 hydrophobic group Chemical group 0.000 claims description 26
150000003839 salts Chemical class 0.000 claims description 24
229910052799 carbon Inorganic materials 0.000 claims description 23
238000004090 dissolution Methods 0.000 claims description 23
239000003795 chemical substances by application Substances 0.000 claims description 20
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125000001072 heteroaryl group Chemical group 0.000 claims description 19
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102000004169 proteins and genes Human genes 0.000 claims description 19
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
125000003342 alkenyl group Chemical group 0.000 claims description 14
239000000651 prodrug Substances 0.000 claims description 14
229940002612 prodrug Drugs 0.000 claims description 14
125000000304 alkynyl group Chemical group 0.000 claims description 13
210000004369 blood Anatomy 0.000 claims description 13
239000008280 blood Substances 0.000 claims description 13
208000029742 colonic neoplasm Diseases 0.000 claims description 13
239000002904 solvent Substances 0.000 claims description 13
208000026310 Breast neoplasm Diseases 0.000 claims description 12
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125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 claims description 12
238000004128 high performance liquid chromatography Methods 0.000 claims description 12
239000000463 material Substances 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
206010006187 Breast cancer Diseases 0.000 claims description 10
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 10
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125000004446 heteroarylalkyl group Chemical group 0.000 claims description 8
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125000003396 thiol group Chemical group [H]S* 0.000 claims description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
240000007594 Oryza sativa Species 0.000 claims description 6
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229920001222 biopolymer Polymers 0.000 claims 1
208000035475 disorder Diseases 0.000 claims 1
125000004426 substituted alkynyl group Chemical group 0.000 claims 1
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 153
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229940079593 drug Drugs 0.000 description 28
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YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 13
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RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
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230000000875 corresponding effect Effects 0.000 description 10
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WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
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125000005842 heteroatom Chemical group 0.000 description 9
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RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
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229910052786 argon Inorganic materials 0.000 description 8
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HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
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