DE60207241T2 - 5-amino-5-phenyl-7-cyclobutyl-pyrrolo(2,3-d)pyrimidin-derivate - Google Patents
5-amino-5-phenyl-7-cyclobutyl-pyrrolo(2,3-d)pyrimidin-derivate Download PDFInfo
- Publication number
- DE60207241T2 DE60207241T2 DE60207241T DE60207241T DE60207241T2 DE 60207241 T2 DE60207241 T2 DE 60207241T2 DE 60207241 T DE60207241 T DE 60207241T DE 60207241 T DE60207241 T DE 60207241T DE 60207241 T2 DE60207241 T2 DE 60207241T2
- Authority
- DE
- Germany
- Prior art keywords
- amino
- lower alkyl
- benzyloxyphenyl
- pyrimidin
- pyrrolo
- 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.)
- Expired - Lifetime
Links
- ZINWLBJDJOKZAP-UHFFFAOYSA-N 7-cyclobutyl-5-phenyl-6H-pyrrolo[2,3-d]pyrimidin-5-amine Chemical class NC1(CN(C=2N=CN=CC=21)C1CCC1)C1=CC=CC=C1 ZINWLBJDJOKZAP-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 321
- 125000000217 alkyl group Chemical group 0.000 claims description 319
- -1 heterocyclic radical Chemical class 0.000 claims description 227
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 107
- 150000003839 salts Chemical class 0.000 claims description 69
- 229910052757 nitrogen Inorganic materials 0.000 claims description 64
- 238000000034 method Methods 0.000 claims description 62
- 239000001301 oxygen Substances 0.000 claims description 60
- 229910052760 oxygen Inorganic materials 0.000 claims description 60
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 57
- 150000003254 radicals Chemical class 0.000 claims description 57
- 125000003545 alkoxy group Chemical group 0.000 claims description 47
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 47
- 229910052736 halogen Inorganic materials 0.000 claims description 46
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 46
- 238000006243 chemical reaction Methods 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 150000002367 halogens Chemical class 0.000 claims description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 38
- 238000002360 preparation method Methods 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 37
- 125000003282 alkyl amino group Chemical group 0.000 claims description 36
- MINLECAKOASWQA-UHFFFAOYSA-N 7-[3-(aminomethyl)cyclobutyl]-5-(3-phenylmethoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1C(CN)CC1N1C2=NC=NC(N)=C2C(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=C1 MINLECAKOASWQA-UHFFFAOYSA-N 0.000 claims description 32
- 201000010099 disease Diseases 0.000 claims description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 29
- 238000011282 treatment Methods 0.000 claims description 29
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 22
- 229910052717 sulfur Inorganic materials 0.000 claims description 22
- 239000011593 sulfur Chemical group 0.000 claims description 22
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 21
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 20
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 20
- 239000007858 starting material Substances 0.000 claims description 20
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 17
- 230000005764 inhibitory process Effects 0.000 claims description 16
- 125000002757 morpholinyl group Chemical group 0.000 claims description 15
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 13
- 230000008569 process Effects 0.000 claims description 12
- 241001465754 Metazoa Species 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 125000006239 protecting group Chemical group 0.000 claims description 11
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 10
- 230000004663 cell proliferation Effects 0.000 claims description 10
- 230000001419 dependent effect Effects 0.000 claims description 10
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000004423 acyloxy group Chemical group 0.000 claims description 8
- 239000004202 carbamide Substances 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- 125000001589 carboacyl group Chemical group 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 125000005936 piperidyl group Chemical group 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000000524 functional group Chemical group 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 3
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- CZAXYMOAFIXZDY-UHFFFAOYSA-N 1-[[3-[4-amino-5-(3-phenylmethoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclobutyl]methyl]-3-propan-2-ylurea Chemical compound C1C(CNC(=O)NC(C)C)CC1N1C2=NC=NC(N)=C2C(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=C1 CZAXYMOAFIXZDY-UHFFFAOYSA-N 0.000 claims description 2
- GQGMUKOYILWOIQ-UHFFFAOYSA-N 6-methyl-5-(3-phenylmethoxyphenyl)-7-[3-(pyrrolidin-1-ylmethyl)cyclobutyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C2CC(CN3CCCC3)C2)C(C)=C1C(C=1)=CC=CC=1OCC1=CC=CC=C1 GQGMUKOYILWOIQ-UHFFFAOYSA-N 0.000 claims description 2
- AECDBHGVIIRMOI-UHFFFAOYSA-N 7-[3-(azetidin-1-ylmethyl)cyclobutyl]-5-(3-phenylmethoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2N(C2CC(CN3CCC3)C2)C=C1C(C=1)=CC=CC=1OCC1=CC=CC=C1 AECDBHGVIIRMOI-UHFFFAOYSA-N 0.000 claims description 2
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- 230000003612 virological effect Effects 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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| GB0111764 | 2001-05-14 | ||
| GB0111764A GB0111764D0 (en) | 2001-05-14 | 2001-05-14 | Organic compounds |
| GB0204752A GB0204752D0 (en) | 2002-02-28 | 2002-02-28 | Organic compounds |
| GB0204752 | 2002-02-28 | ||
| PCT/EP2002/005239 WO2002092599A1 (en) | 2001-05-14 | 2002-05-13 | 4-amino-5-phenyl-7-cyclobutyl-pyrrolo (2,3-d) pyrimidine derivatives |
Publications (2)
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|---|---|
| DE60207241D1 DE60207241D1 (de) | 2005-12-15 |
| DE60207241T2 true DE60207241T2 (de) | 2006-07-27 |
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| DE60207241T Expired - Lifetime DE60207241T2 (de) | 2001-05-14 | 2002-05-13 | 5-amino-5-phenyl-7-cyclobutyl-pyrrolo(2,3-d)pyrimidin-derivate |
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