JP2007528343A - ピロロ[2,1−c][1,4]ベンゾジアゼピン・ハイブリッドの調製方法 - Google Patents
ピロロ[2,1−c][1,4]ベンゾジアゼピン・ハイブリッドの調製方法 Download PDFInfo
- Publication number
- JP2007528343A JP2007528343A JP2005512761A JP2005512761A JP2007528343A JP 2007528343 A JP2007528343 A JP 2007528343A JP 2005512761 A JP2005512761 A JP 2005512761A JP 2005512761 A JP2005512761 A JP 2005512761A JP 2007528343 A JP2007528343 A JP 2007528343A
- Authority
- JP
- Japan
- Prior art keywords
- general formula
- pyrrolo
- benzo
- imidazol
- methoxy
- Prior art date
- 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
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- MSNVESLISHTIRS-UHFFFAOYSA-N 9h-pyrrolo[2,1-c][1,4]benzodiazepine Chemical compound N1=C2C=CC=CC2=CN2CC=CC2=C1 MSNVESLISHTIRS-UHFFFAOYSA-N 0.000 title claims abstract description 37
- 238000000034 method Methods 0.000 title claims abstract description 19
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- 229940079593 drug Drugs 0.000 claims abstract description 4
- 239000003814 drug Substances 0.000 claims abstract description 4
- -1 1H-benzo [d] imidazol-2-yl Chemical group 0.000 claims description 33
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 30
- CRMGITHMNVPUPY-UHFFFAOYSA-N 2-[ethoxy(ethylsulfanyl)methyl]pyrrolidine Chemical compound CCOC(SCC)C1CCCN1 CRMGITHMNVPUPY-UHFFFAOYSA-N 0.000 claims description 23
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 18
- 239000003960 organic solvent Substances 0.000 claims description 12
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- REOGMBVECOGANJ-UHFFFAOYSA-N chembl377740 Chemical compound C1=CC(O)=CC=C1C1=NC2=CC=CC=C2N1 REOGMBVECOGANJ-UHFFFAOYSA-N 0.000 claims description 6
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- 229940049706 benzodiazepine Drugs 0.000 claims description 4
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- 125000000217 alkyl group Chemical group 0.000 claims description 3
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 claims description 2
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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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
- A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
- A61K31/5517—1,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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Abstract
Description
1.7-メトキシ-8-{3-[4-(1H-ベンゾ[d]イミダゾル-2-イル)フェノキシ]プロポキシ}-(11aS)-1,2,3-11a-テトラヒドロ-5H-ピロロ[2,1-c][1,4]ベンゾジアゼピン-5-オン
2.7-メトキシ-8-{4-[4-(1H-ベンゾ[d]イミダゾル-2-イル)フェノキシ]ブトキシ}-(11aS)-1,2,3-11a-テトラヒドロ-5H-ピロロ[2,1-c][1,4]ベンゾジアゼピン-5-オン
3.7-メトキシ-8-{5-[4-(1H-ベンゾ[d]イミダゾル-2-イル)フェノキシ]ペンチルオキシ}-(11aS)-1,2,3-11a-テトラヒドロ-5H-ピロロ[2,1-c][1,4]ベンゾジアゼピン-5-オン
4.7-メトキシ-8-(3-{4-[6-(4-メチルヘキサヒドロ-1-ピラジニル)-1H-ベンゾ[d]イミダゾル-2-イル)フェノキシ]プロポキシ}-(11aS)-1,2,3-11a-テトラヒドロ-5H-ピロロ[2,1-c][1,4]ベンゾジアゼピン-5-オン
5.7-メトキシ-8-(4-{4-[6-(4-メチルヘキサヒドロ-1-ピラジニル)-1H-ベンゾ[d]イミダゾル-2-イル)フェノキシ]ブトキシ}-(11aS)-1,2,3-11a-テトラヒドロ-5H-ピロロ[2,1-c][1,4]ベンゾジアゼピン-5-オン
6.7-メトキシ-8-{5-{4-[6-(4-メチルヘキサヒドロ-1-ピラジニル)-1H-ベンゾ[d]イミダゾル-2-イル)フェノキシ]ペンチルオキシ}-(11aS)-1,2,3-11a-テトラヒドロ-5H-ピロロ[2,1-c][1,4]ベンゾジアゼピン-5-オン
7.7-メトキシ-8-(3-{4-[6-(4-エチルヘキサヒドロ-1-ピラジニル)-1H-ベンゾ[d]イミダゾル-2-イル]フェノキシ}プロポキシ)-(11aS)-1,2,3-11a-テトラヒドロ-5H-ピロロ[2,1-c][1,4]ベンゾジアゼピン-5-オン
8.7-メトキシ-8-(4-{4-[6-(4-エチルヘキサヒドロ-1-ピラジニル)-1H-ベンゾ[d]イミダゾル-2-イル]フェノキシ}ブトキシ)-(11aS)-1,2,3-11a-テトラヒドロ-5H-ピロロ[2,1-c][1,4]ベンゾジアゼピン-5-オン
9.7-メトキシ-8-(5-{4-[6-(4-エチルヘキサヒドロ-1-ピラジニル)-1H-ベンゾ[d]イミダゾル-2-イル]フェノキシ}ペンチルオキシ)-(11aS)-1,2,3-11a-テトラヒドロ-5H-ピロロ[2,1-c][1,4]ベンゾジアゼピン-5-オン
1.置換された2-フェノキシベンゾイミダゾール部分を有するDC-81中間体のC8位置におけるエーテル結合
2.還流温度までの温度での反応混合物の12〜48時間にわたる加熱
3.C8位置で結合したPBD抗腫瘍抗生物質ハイブリッド・イミンの合成
4.さまざまな溶媒(例えば酢酸エチル、ヘキサン、ジクロロメタン、クロロホルム、メタノール)を用いたカラム・クロマトグラフィによる精製
Claims (17)
- 一般式(V):
- 一般式(IX)のピロロ[2,1-c][1,4]ベンゾジアゼピン・ハイブリッド:
- 一般式(XIII)のピロロ[2,1-c][1,4]ベンゾジアゼピン・ハイブリッド:
- 請求項1〜10のいずれか1項に記載のピロロ[2,1-c][1,4]ベンゾジアゼピン・ハイブリッドを利用して腫瘍の治療に役立つ薬を調製する方法。
- 請求項1〜10のいずれか1項に記載のピロロ[2,1-c][1,4]ベンゾジアゼピン・ハイブリッドが有効量含まれていて、抗腫瘍薬として使用される医薬組成物。
- 哺乳動物の治療法であって、請求項1〜10のいずれか1項に記載のピロロ[2,1-c][1,4]ベンゾジアゼピン・ハイブリッドを有効量投与する操作を含む方法。
- 哺乳動物の治療法であって、請求項15に記載の医薬組成物を有効量投与する操作を含む方法。
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PCT/IN2003/000462 WO2005063759A1 (en) | 2003-12-31 | 2003-12-31 | PROCESS FOR PREPARING PYRROLO[2, 1-c] [1, 4] BENZODIAZEPINE HYBRIDS |
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JP2007528343A true JP2007528343A (ja) | 2007-10-11 |
JP4520411B2 JP4520411B2 (ja) | 2010-08-04 |
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JP (1) | JP4520411B2 (ja) |
AU (1) | AU2003300718A1 (ja) |
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WO (1) | WO2005063759A1 (ja) |
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DE112005003752T5 (de) * | 2005-11-10 | 2008-11-13 | Council Of Scientific & Industrial Research | Neues Pyrrolo[2,1-c][1,4]benzodiapezinhybrid und ein Verfahren zu dessen Herstellung |
WO2008099416A2 (en) * | 2007-02-13 | 2008-08-21 | Council Of Scientific & Industrial Research | Novel benzothiazole and benzoxazole linked pyrrolo[2,1-c] [1, 4] benzodiazepine hybrids as novel antitumour agents and process for the preparation thereof |
US8288387B2 (en) * | 2008-03-05 | 2012-10-16 | Council Of Scientific & Industrial Research | Napthalimide-benzimidazole hybrids as potential antitumor agents and process for the preparation thereof |
WO2009113085A1 (en) * | 2008-03-11 | 2009-09-17 | Council Of Scientific & Industrial Research | Novel benzimidazole linked pyrrolo[2,1-q[1,4] benzodiazepine hybrids as potential antitumour agents and process for the preparation thereof |
WO2009118748A1 (en) * | 2008-03-26 | 2009-10-01 | Council Of Scientific & Industrial Research | Isoxazoline linked pyrrolo[2,1-c[1,4]benzodiazepine hybrids as potential anticancer agents and the process for preparation thereof |
EP2358719B1 (en) | 2008-11-19 | 2014-10-01 | Council Of Scientific & Industrial Research | Novel pyrrolo[2,1-c][1,4]benzodiazepine derivatives with dithiocarbamate side chains and process for the preparation thereof |
IL283355B (en) | 2015-07-21 | 2022-08-01 | Immunogen Inc | Methods for the preparation of cytotoxic benzodiazepine compounds |
Citations (1)
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WO2000012508A2 (en) * | 1998-08-27 | 2000-03-09 | Spirogen Limited | Pyrrolbenzodiazepines |
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- 2003-12-31 AU AU2003300718A patent/AU2003300718A1/en not_active Abandoned
- 2003-12-31 GB GB0614750A patent/GB2424883B/en not_active Expired - Fee Related
- 2003-12-31 WO PCT/IN2003/000462 patent/WO2005063759A1/en active Application Filing
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WO2000012508A2 (en) * | 1998-08-27 | 2000-03-09 | Spirogen Limited | Pyrrolbenzodiazepines |
Non-Patent Citations (2)
Title |
---|
JPN6010002436, Ahmed Kamal et al., "Design, Synthesis, and Evaluation of New Noncross−Linking Pyrrolobenzodiazepine Dimers with Efficien", Journal of Medicinal Chemistry, 2002, Vol.45, No.21, p.4679−4688 * |
JPN6010002440, Moana Tercel et al., "Unsymmetrical DNA Cross−Linking Agents: combination of the CBI and PBD Pharmacophores", Journal of Medicinal Chemistry, 200304, Vol.46, No.11, p.2132−2151 * |
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AU2003300718A1 (en) | 2005-07-21 |
GB2424883B (en) | 2008-10-22 |
WO2005063759A1 (en) | 2005-07-14 |
GB0614750D0 (en) | 2006-09-06 |
GB2424883A (en) | 2006-10-11 |
JP4520411B2 (ja) | 2010-08-04 |
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