JP2011530597A5 - - Google Patents

Info

Publication number

JP2011530597A5

JP2011530597A5 JP2011522993A JP2011522993A JP2011530597A5 JP 2011530597 A5 JP2011530597 A5 JP 2011530597A5 JP 2011522993 A JP2011522993 A JP 2011522993A JP 2011522993 A JP2011522993 A JP 2011522993A JP 2011530597 A5 JP2011530597 A5 JP 2011530597A5

Authority

JP

Japan

Prior art keywords

arm

polymer conjugate

conjugate according

poly

polymer

Prior art date

2009-08-11

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

Granted

Links

• Espacenet
• Global Dossier
• Discuss

• 229920000642 polymer Polymers 0.000 claims description 90
• 239000000562 conjugate Substances 0.000 claims description 88
• 125000005647 linker group Chemical group 0.000 claims description 16
• 239000000203 mixture Substances 0.000 claims description 16
• 238000000034 method Methods 0.000 claims description 15
• 206010028980 Neoplasm Diseases 0.000 claims description 14
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 12
• 125000004429 atom Chemical group 0.000 claims description 10
• 125000000217 alkyl group Chemical group 0.000 claims description 8
• 125000004432 carbon atom Chemical group C* 0.000 claims description 8
• 238000010276 construction Methods 0.000 claims description 8
• 125000006575 electron-withdrawing group Chemical group 0.000 claims description 8
• 150000002148 esters Chemical class 0.000 claims description 8
• 229940126586 small molecule drug Drugs 0.000 claims description 8
• 125000006850 spacer group Chemical group 0.000 claims description 8
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 6
• 239000002246 antineoplastic agent Substances 0.000 claims description 6
• 229960003668 docetaxel Drugs 0.000 claims description 6
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 6
• 150000003384 small molecules Chemical class 0.000 claims description 6
• 229920003169 water-soluble polymer Polymers 0.000 claims description 6
• 206010060862 Prostate cancer Diseases 0.000 claims description 4
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
• 238000010171 animal model Methods 0.000 claims description 4
• 201000011510 cancer Diseases 0.000 claims description 4
• 239000003153 chemical reaction reagent Substances 0.000 claims description 4
• 229940079593 drug Drugs 0.000 claims description 4
• 239000003814 drug Substances 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000000524 functional group Chemical group 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 239000000580 polymer-drug conjugate Substances 0.000 claims description 4
• 230000004614 tumor growth Effects 0.000 claims description 4
• XLPJNCYCZORXHG-UHFFFAOYSA-N 1-morpholin-4-ylprop-2-en-1-one Chemical compound C=CC(=O)N1CCOCC1 XLPJNCYCZORXHG-UHFFFAOYSA-N 0.000 claims description 2
• 206010006187 Breast cancer Diseases 0.000 claims description 2
• 208000026310 Breast neoplasm Diseases 0.000 claims description 2
• 206010009944 Colon cancer Diseases 0.000 claims description 2
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 2
• 229930012538 Paclitaxel Natural products 0.000 claims description 2
• 229920001389 Poly(hydroxyalkylmethacrylamide) Polymers 0.000 claims description 2
• 239000002202 Polyethylene glycol Substances 0.000 claims description 2
• 241000700159 Rattus Species 0.000 claims description 2
• 229920002125 Sokalan® Polymers 0.000 claims description 2
• 229940123237 Taxane Drugs 0.000 claims description 2
• ZJCCRDAZUWHFQH-UHFFFAOYSA-N Trimethylolpropane Chemical compound CCC(CO)(CO)CO ZJCCRDAZUWHFQH-UHFFFAOYSA-N 0.000 claims description 2
• 150000001336 alkenes Chemical class 0.000 claims description 2
• 229940061720 alpha hydroxy acid Drugs 0.000 claims description 2
• 150000001280 alpha hydroxy acids Chemical class 0.000 claims description 2
• VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical group C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 2
• 150000001720 carbohydrates Chemical class 0.000 claims description 2
• 125000002843 carboxylic acid group Chemical group 0.000 claims description 2
• 230000021615 conjugation Effects 0.000 claims description 2
• 229920001577 copolymer Polymers 0.000 claims description 2
• 125000004122 cyclic group Chemical group 0.000 claims description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
• LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 2
• 150000004820 halides Chemical class 0.000 claims description 2
• 230000007062 hydrolysis Effects 0.000 claims description 2
• 238000006460 hydrolysis reaction Methods 0.000 claims description 2
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 2
• 230000003993 interaction Effects 0.000 claims description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 230000017066 negative regulation of growth Effects 0.000 claims description 2
• 150000002825 nitriles Chemical class 0.000 claims description 2
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 2
• JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 2
• 229960001592 paclitaxel Drugs 0.000 claims description 2
• WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 claims description 2
• -1 poly (alkylene glycol Chemical compound 0.000 claims description 2
• 229920000765 poly(2-oxazolines) Polymers 0.000 claims description 2
• 229920001390 poly(hydroxyalkylmethacrylate) Polymers 0.000 claims description 2
• 229920002627 poly(phosphazenes) Polymers 0.000 claims description 2
• 229920000768 polyamine Polymers 0.000 claims description 2
• 229920001223 polyethylene glycol Polymers 0.000 claims description 2
• 229920005862 polyol Polymers 0.000 claims description 2
• 150000003077 polyols Chemical class 0.000 claims description 2
• 229920006295 polythiol Polymers 0.000 claims description 2
• 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 150000003333 secondary alcohols Chemical class 0.000 claims description 2
• 239000000600 sorbitol Substances 0.000 claims description 2
• 238000006467 substitution reaction Methods 0.000 claims description 2
• 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 claims description 2
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 2
• 229920001897 terpolymer Polymers 0.000 claims description 2
• 150000003509 tertiary alcohols Chemical class 0.000 claims description 2
• 230000001988 toxicity Effects 0.000 claims description 2
• 231100000419 toxicity Toxicity 0.000 claims description 2
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 2
• 239000007787 solid Substances 0.000 claims 1