CN101370497B - 包含parp抑制剂和细胞毒性剂的联合产品及用途 - Google Patents
包含parp抑制剂和细胞毒性剂的联合产品及用途 Download PDFInfo
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Abstract
Description
化合物 | PARP抑制作用 K<sub>i</sub>(nM) |
2-(2-甲基吡咯烷-2-基)-1H-苯并咪唑-4-甲酰胺 | 4.3 |
2-[(2R)-吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 8 |
2-[(2R)-2-甲基吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 5.4 |
2-[(2S)-2-吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 28.4 |
2-[(2S)-2-甲基吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 5.1 |
2-[(2S)-1-甲基吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 30.8 |
2-[(2R)-1-甲基吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 7.3 |
2-(1,2-二甲基吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 6.2 |
2-[(2S)-1-乙基吡咯烷-2-基]-H-苯并咪唑-4-甲酰胺 | 49 |
2-(1-乙基-2-甲基吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 6 |
2-[(2S)-1-丙基吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 129 |
2-[(2R)-1-丙基吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 146 |
2-(2-甲基-1-丙基吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 18.7 |
2-[(2R)-1-异丙基吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 12.8 |
2-[(2S)-1-异丙基吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 19.3 |
2-(1-异丙基-2-甲基吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 17.5 |
2-[(2S)-1-环丁基吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 338 |
2-[(2R)-1-环丁基吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 142 |
2-(1-环丁基-2-甲基吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 31.3 |
2-吡咯烷-3-基-1H-苯并咪唑-4-甲酰胺 | 3.9 |
2-(3-甲基吡咯烷-3-基)-1H-苯并咪唑-4-甲酰胺 | 3.9 |
2-(1-丙基吡咯烷-3-基)-1H-苯并咪唑-4-甲酰胺 | 8.1 |
2-(3-甲基-1-丙基吡咯烷-3-基)-1H-苯并咪唑-4-甲酰胺 | 4.2 |
2-[1-(环丙基甲基)吡咯烷-3-基]-1H-苯并咪唑-4-甲酰胺 | 5.2 |
2-[1-(环丙基甲基)-3-甲基吡咯烷-3-基]-1H-苯并咪唑 -4-甲酰胺 | 5 |
2-(1-异丁基吡咯烷-3-基)-1H-苯并咪唑-4-甲酰胺 | 7.4 |
2-(1-异丁基-3-甲基吡咯烷-3-基)-1H-苯并咪唑-4-甲 酰胺 | 3.8 |
2-(1-异丙基吡咯烷-3-基)-1H-苯并咪唑-4-甲酰胺 | 9.2 |
2-(1-异丙基-3-甲基吡咯烷-3-基)-1H-苯并咪唑-4-甲 酰胺 | 4.4 |
2-(1-环丁基吡咯烷-3-基)-1H-苯并咪唑-4-甲酰胺 | 6.8 |
2-(1-环丁基-3-甲基吡咯烷-3-基)-1H-苯并咪唑-4-甲 酰胺 | 4 |
2-(1-环戊基吡咯烷-3-基)-1H-苯并咪唑-4-甲酰胺 | 5.5 |
2-(1-环戊基-3-甲基吡咯烷-3-基)-1H-苯并咪唑-4-甲 酰胺 | 3.4 |
2-(1-环己基吡咯烷-3-基)-1H-苯并咪唑-4-甲酰胺 | 7 |
2-(1-环己基-3-甲基吡咯烷-3-基)-1H-苯并咪唑-4-甲 酰胺 | 5.8 |
2-(1-异丙基-2-甲基吡咯烷-2-基]-1H-苯并咪唑-4-甲酰胺 | 17.5 |
2-(1-四氢-2H-吡喃-4-基吡咯烷-3-基)-1H-苯并咪唑-4- 甲酰胺 | 8.2 |
2-(3-甲基-1-四氢-2H-吡喃-4-基吡咯烷-3-基)-1H-苯 并咪唑-4-甲酰胺 | 7.2 |
2-[1-(吡啶-4-基甲基)吡咯烷-3-基]-1H-苯并咪唑-4- 甲酰胺 | 14.2 |
2-[3-甲基-1-(吡啶-4-基甲基)吡咯烷-3-基]-1H-苯并 咪唑-4-甲酰胺 | 8.9 |
2-[1-(2-苯乙基)吡咯烷-3-基]-1H-苯并咪唑-4-甲酰胺 | 9.1 |
2-[3-甲基-1-(2-苯乙基)吡咯烷-3-基]-1H-苯并咪唑-4- 甲酰胺 | 10.5 |
2-[1-(1-甲基-3-苯丙基)吡咯烷-3-基]-1H-苯并咪唑-4- 甲酰胺 | 13.2 |
2-[3-甲基-1-(1-甲基-3-苯丙基)吡咯烷-3-基]-1H-苯并 咪唑-4-甲酰胺 | 12 |
2-氮杂环丁-2-基-1H-苯并咪唑-4-甲酰胺 | 34 |
2-(2-甲基氮杂环丁-2-基)-1H-苯并咪唑-4-甲酰胺 | 14.1 |
2-(1-异丙基氮杂环丁-2-基)-1H-苯并咪唑-4-甲酰胺 | 118 |
2-(1-异丙基-2-甲基氮杂环丁-2-基)-1H-苯并咪唑-4- 甲酰胺 | 41.6 |
2-(1-环丁基氮杂环丁-2-基)-1H-苯并咪唑-4-甲酰胺 | 80 |
2-(1-环丁基-2-甲基氮杂环丁-2-基)-1H-苯并咪唑-4- 甲酰胺 | 33.3 |
2-(1-环戊基氮杂环丁-2-基)-1H-苯并咪唑-4-甲酰胺 | 176 |
2-(1-环戊基-2-甲基氮杂环丁-2-基)-1H-苯并咪唑-4- 甲酰胺 | 31.1 |
2-(1-环己基氮杂环丁-2-基)-1H-苯并咪唑-4-甲酰胺 | 245 |
2-(1-环己基-2-甲基氮杂环丁-2-基)-1H-苯并咪唑-4- 甲酰胺 | 27.7 |
2-氮杂环丁-3-基-1H-苯并咪唑-4-甲酰胺 | 6 |
2-(3-甲基氮杂环丁-3-基)-1H-苯并咪唑-4-甲酰胺 | 4.4 |
2-(1-丙基氮杂环丁-3-基)-1H-苯并咪唑-4-甲酰胺 | 14.1 |
2-(3-甲基-1-丙基氮杂环丁-3-基)-1H-苯并咪唑-4-甲 酰胺 | 6.9 |
2-[1-(环丙基甲基)氮杂环丁-3-基]-1H-苯并咪唑-4- 甲酰胺 | 19 |
2-[1-(环丙基甲基)-3-甲基氮杂环丁-3-基]-1H-苯并咪 唑-4-甲酰胺 | 8 |
2-(1-异丁基氮杂环丁-3-基)-1H-苯并咪唑-4-甲酰胺 | 14.4 |
2-(1-异丁基-3-甲基氮杂环丁-3-基)-1H-苯并咪唑-4- 甲酰胺 | 5.6 |
2-(1-环丁基氮杂环丁-3-基)-1H-苯并咪唑-4-甲酰胺 | 16.4 |
2-(1-环丁基-3-甲基氮杂环丁-3-基)-1H-苯并咪唑-4- 甲酰胺 | 6.1 |
2-(1-环戊基氮杂环丁-3-基)-1H-苯并咪唑-4-甲酰胺 | 14 |
2-(1-环戊基-3-甲基氮杂环丁-3-基)-1H-苯并咪唑-4- 甲酰胺 | 4 |
2-(1-环己基氮杂环丁-3-基)-1H-苯并咪唑-4-甲酰胺 | 16 |
2-(1-环己基-3-甲基氮杂环丁-3-基)-1H-苯并咪唑-4- 甲酰胺 | 5.6 |
2-(1-四氢-2H-吡喃-4-基氮杂环丁-3-基)-1H-苯并咪 唑-4-甲酰胺 | 45.6 |
2-(3-甲基-1-四氢-2H-吡喃-4-基氮杂环丁-3-基)-1H- 苯并咪唑-4-甲酰胺 | 12.7 |
2-{1-[(二甲基氨基)磺酰基]氮杂环丁-3-基}-1H-苯并 咪唑-4-甲酰胺 | 16 |
2-{1-[(二甲基氨基)磺酰基]-3-甲基氮杂环丁-3- 基}-1H-苯并咪唑-4-甲酰胺 | 7 |
2-[(2S)-哌啶-2-基]-1H-苯并咪唑-4-甲酰胺 | 46.1 |
2-[(2R)-哌啶-2-基]-1H-苯并咪唑-4-甲酰胺 | 47.4 |
2-[哌啶-2-基]-1H-苯并咪唑-4-甲酰胺 | 32.2 |
2-(2-甲基哌啶-2-基)-1H-苯并咪唑-4-甲酰胺 | 4.6 |
2-(1-丙基哌啶-2-基)-1H-苯并咪唑-4-甲酰胺 | 120 |
2-(2-甲基-1-丙基哌啶-2-基)-1H-苯并咪唑-4-甲酰胺 | 18.7 |
2-{1-[(二甲基氨基)磺酰基]哌啶-4-基}-1H-苯并咪唑 -4-甲酰胺 | 31.1 |
2-{1-[(二甲基氨基)磺酰基]-4-甲基哌啶-4-基}-1H- 苯并咪唑-4-甲酰胺 | 8.8 |
2-(1-环丁基哌啶-4-基)-1H-苯并咪唑-4-甲酰胺 | 6.3 |
2-{1-[(二甲基氨基)磺酰基]哌啶-4-基}-1H-苯并咪唑 -4-甲酰胺 | 31.1 |
2-(1-环丁基-4-甲基哌啶-4-基)-1H-苯并咪唑-4-甲酰 胺 | 9.2 |
2-(1-异丙基哌啶-4-基)-1H-苯并咪唑-4-甲酰胺 | 6 |
2-(1-异丙基-4-甲基哌啶-4-基)-1H-苯并咪唑-4-甲酰胺 | 8 |
2-(N-丙基哌啶-4-基)苯并咪唑-4-甲酰胺 | 8.6 |
2-(4-甲基-1-丙基哌啶-4-基)-1H-苯并咪唑-4-甲酰胺 | 13.5 |
2-氮杂环庚-4-基-1H-苯并咪唑-4-甲酰胺 | 5.7 |
2-(4-甲基氮杂环庚-4-基)-1H-苯并咪唑-4-甲酰胺 | 3.3 |
2-(1-环戊基氮杂环庚-4-基)-1H-苯并咪唑-4-甲酰胺 | 3.9 |
2-(1-环戊基-4-甲基氮杂环庚-4-基)-1H-苯并咪唑-4- 甲酰胺 | 7.3 |
2-(1-环己基氮杂环庚-4-基)-1H-苯并咪唑-4-甲酰胺 | 4.8 |
2-(1-环己基-4-甲基氮杂环庚-4-基)-1H-苯并咪唑-4- 甲酰胺 | 11.9 |
第29天ANC和/或血小板计数500≤ANC< 50,000≤PIt<1000/μl 100,000/μl500≤ANC< 50,000≤PIt<1000/μl 100,000/μlANC<500 PIt<50,000/ml | 恢复 前一周期开始后 第42天之前 前一周期开始第 42天后 无数据 | 剂量调节 恢复TMZ,无剂 量调节 减小TMZ,剂量 25mg/m<sup>2</sup>/天 减小TMZ,剂量 25mg/m<sup>2</sup>/天 |
如果在第28天ANC≥500/μl和血小板计数≥20,000/μl,继续治疗方案 |
如果在第42天ANC≥500/μl和血小板计数≥20,000/μl,减少TMZ25mg/m<sup>2</sup>/天 |
如果在第42天ANC≤500/μl和/或血小板计数≤20,000/μl,骨髓<25%成骨细胞 |
延长治疗,直到ANC≥500/μl和血小板计数≥20,000/μl |
减少TMZ 25mg/m<sup>2</sup>/天 |
Claims (6)
Applications Claiming Priority (11)
Application Number | Priority Date | Filing Date | Title |
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US75944506P | 2006-01-17 | 2006-01-17 | |
US60/759,445 | 2006-01-17 | ||
US80411206P | 2006-06-07 | 2006-06-07 | |
US60/804,112 | 2006-06-07 | ||
US85004206P | 2006-10-06 | 2006-10-06 | |
US60/850,042 | 2006-10-06 | ||
US82926106P | 2006-10-12 | 2006-10-12 | |
US60/829,261 | 2006-10-12 | ||
US86751806P | 2006-11-28 | 2006-11-28 | |
US60/867,518 | 2006-11-28 | ||
PCT/US2007/001189 WO2007084532A2 (en) | 2006-01-17 | 2007-01-17 | Combination therapy with parp inhibitors |
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WO2006110683A1 (en) * | 2005-04-11 | 2006-10-19 | Abbott Laboratories | 2-substituted-1h-benzimidazole-4-carboxamides are parp inhibitors |
CA2612979A1 (en) * | 2005-06-10 | 2006-12-21 | Bipar Sciences, Inc. | Parp modulators and treatment of cancer |
ZA200800907B (en) | 2005-07-18 | 2010-04-28 | Bipar Sciences Inc | Treatment of cancer |
CA2623822C (en) * | 2005-09-29 | 2013-11-12 | Abbott Laboratories | 1h-benzimidazole-4-carboxamides substituted with phenyl at the 2-position are potent parp inhibitors |
CN101309908A (zh) * | 2005-11-15 | 2008-11-19 | 艾博特公司 | 作为有效parp抑制剂的取代的1h-苯并咪唑-4-甲酰胺化合物 |
MX2008014004A (es) * | 2006-05-02 | 2008-11-12 | Abbott Lab | 1h-benzimidazol-4-carboxamidas sustituidas son inhibidores de parp potentes. |
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RS53082B (en) | 2014-06-30 |
WO2007084532A3 (en) | 2007-09-07 |
JP2017160216A (ja) | 2017-09-14 |
CA2635691A1 (en) | 2007-07-26 |
CA2635691C (en) | 2013-10-29 |
CN101370497A (zh) | 2009-02-18 |
JP2013136605A (ja) | 2013-07-11 |
EP2338487A1 (en) | 2011-06-29 |
HRP20131180T1 (hr) | 2014-01-31 |
EP2329818A1 (en) | 2011-06-08 |
JP2015187114A (ja) | 2015-10-29 |
US20070265324A1 (en) | 2007-11-15 |
EP1976515A2 (en) | 2008-10-08 |
ME02121B (me) | 2014-06-30 |
US20110152336A1 (en) | 2011-06-23 |
JP2009523801A (ja) | 2009-06-25 |
JP6147799B2 (ja) | 2017-06-14 |
JP5289060B2 (ja) | 2013-09-11 |
SI2338487T1 (sl) | 2014-01-31 |
US20110151023A1 (en) | 2011-06-23 |
WO2007084532A2 (en) | 2007-07-26 |
ES2437132T3 (es) | 2014-01-09 |
DK2338487T3 (da) | 2013-12-09 |
EP2338487B1 (en) | 2013-09-11 |
PL2338487T3 (pl) | 2014-03-31 |
PT2338487E (pt) | 2013-12-16 |
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