AU2009246402B2 - Pyrrolopyridines as kinase inhibitors - Google Patents
Pyrrolopyridines as kinase inhibitors Download PDFInfo
- Publication number
- AU2009246402B2 AU2009246402B2 AU2009246402A AU2009246402A AU2009246402B2 AU 2009246402 B2 AU2009246402 B2 AU 2009246402B2 AU 2009246402 A AU2009246402 A AU 2009246402A AU 2009246402 A AU2009246402 A AU 2009246402A AU 2009246402 B2 AU2009246402 B2 AU 2009246402B2
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- Australia
- Prior art keywords
- alkyl
- hydrogen
- phenyl
- compound
- membered
- 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.)
- Ceased
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- 229940043355 kinase inhibitor Drugs 0.000 title description 3
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 3
- 150000005255 pyrrolopyridines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 217
- 238000000034 method Methods 0.000 claims abstract description 111
- 150000003839 salts Chemical class 0.000 claims abstract description 47
- 125000000217 alkyl group Chemical group 0.000 claims description 588
- 229910052739 hydrogen Inorganic materials 0.000 claims description 322
- 239000001257 hydrogen Substances 0.000 claims description 318
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 259
- -1 6-methylpyridin-3-yl Chemical group 0.000 claims description 226
- 229910052736 halogen Inorganic materials 0.000 claims description 193
- 150000002367 halogens Chemical class 0.000 claims description 165
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 141
- 125000004429 atom Chemical group 0.000 claims description 132
- 150000002431 hydrogen Chemical class 0.000 claims description 132
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 121
- 125000001072 heteroaryl group Chemical group 0.000 claims description 108
- 238000006243 chemical reaction Methods 0.000 claims description 99
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 97
- 229920006395 saturated elastomer Polymers 0.000 claims description 94
- 125000003118 aryl group Chemical group 0.000 claims description 91
- 125000000623 heterocyclic group Chemical group 0.000 claims description 79
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 76
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 68
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 62
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 45
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- 201000010099 disease Diseases 0.000 claims description 39
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- 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 35
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 35
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 34
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- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 28
- 229910052731 fluorine Inorganic materials 0.000 claims description 28
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- 230000003463 hyperproliferative effect Effects 0.000 claims description 26
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- 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 claims description 8
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- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 6
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 6
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- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 6
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 6
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- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound 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 6
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- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims description 6
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 6
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- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 6
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 6
- 125000004262 quinoxalin-2-yl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N=C1* 0.000 claims description 6
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- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000001847 2-phenylcyclopropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1([H])C([H])([H])C1([H])* 0.000 claims description 3
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A61P9/00—Drugs for disorders of the cardiovascular system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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| JP2009256298A (ja) * | 2008-03-26 | 2009-11-05 | Sumitomo Chemical Co Ltd | ピペリジン−３−イルカーバメート化合物の光学分割方法およびその中間体 |
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| US8481557B2 (en) * | 2009-04-11 | 2013-07-09 | Array Biopharma Inc. | Method of treatment using checkpoint kinase 1 inhibitors |
| EP2416773B1 (en) * | 2009-04-11 | 2016-09-28 | Array Biopharma, Inc. | Checkpoint kinase 1 inhibitors for potentiating dna damaging agents |
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Patent Citations (1)
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| WO2003028724A1 (en) * | 2001-10-04 | 2003-04-10 | Smithkline Beecham Corporation | Chk1 kinase inhibitors |
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