ZA200400271B - 4-amino-6-phenyl-pyrrolo[2,3-d]pyrimidine derivatives. - Google Patents
4-amino-6-phenyl-pyrrolo[2,3-d]pyrimidine derivatives. Download PDFInfo
- Publication number
- ZA200400271B ZA200400271B ZA200400271A ZA200400271A ZA200400271B ZA 200400271 B ZA200400271 B ZA 200400271B ZA 200400271 A ZA200400271 A ZA 200400271A ZA 200400271 A ZA200400271 A ZA 200400271A ZA 200400271 B ZA200400271 B ZA 200400271B
- Authority
- ZA
- South Africa
- Prior art keywords
- phenyl
- pyrrolo
- pyrimidin
- amine
- methyl
- Prior art date
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- JSLCFLYSDVRTNX-UHFFFAOYSA-N 6-phenyl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical class C=1C2=C(N)N=CNC2=NC=1C1=CC=CC=C1 JSLCFLYSDVRTNX-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 149
- 150000003839 salts Chemical class 0.000 claims description 50
- 125000000217 alkyl group Chemical group 0.000 claims description 47
- 125000004432 carbon atom Chemical group C* 0.000 claims description 43
- 229910052799 carbon Inorganic materials 0.000 claims description 39
- 239000001257 hydrogen Substances 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 31
- -1 pyrrolidinyi Chemical group 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 21
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- 239000001301 oxygen Substances 0.000 claims description 21
- 230000008569 process Effects 0.000 claims description 21
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 17
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 125000004076 pyridyl group Chemical group 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 150000002367 halogens Chemical group 0.000 claims description 15
- 230000005764 inhibitory process Effects 0.000 claims description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
- 125000003282 alkyl amino group Chemical group 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 239000011593 sulfur Substances 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 125000005936 piperidyl group Chemical group 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 12
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 11
- 239000007858 starting material Substances 0.000 claims description 11
- 125000002757 morpholinyl group Chemical group 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 239000003638 chemical reducing agent Substances 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 125000000524 functional group Chemical group 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 229910006715 Li—O Inorganic materials 0.000 claims description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 54
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims 19
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims 4
- 125000005605 benzo group Chemical group 0.000 claims 2
- YRAATSPCBOVLRX-UHFFFAOYSA-N 1-[4-[4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-n,n-dimethylmethanamine Chemical compound C1=CC(CN(C)C)=CC=C1C(NC1=NC=N2)=CC1=C2OC1=CC=C(NC(C)=C2)C2=C1F YRAATSPCBOVLRX-UHFFFAOYSA-N 0.000 claims 1
- LWLFPYBXHSCBJQ-HXUWFJFHSA-N 2-(4-methylpiperazin-1-yl)-n-[[3-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]methyl]acetamide Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C(C=1)=CC=CC=1CNC(=O)CN1CCN(C)CC1 LWLFPYBXHSCBJQ-HXUWFJFHSA-N 0.000 claims 1
- FTFBSDWSCZFPGA-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)-n-[[4-[4-(4-phenylmethoxyanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]methyl]acetamide Chemical compound C1CN(C)CCN1CC(=O)NCC1=CC=C(C=2NC3=NC=NC(NC=4C=CC(OCC=5C=CC=CC=5)=CC=4)=C3C=2)C=C1 FTFBSDWSCZFPGA-UHFFFAOYSA-N 0.000 claims 1
- YGVOKLMLPAPRSE-QGZVFWFLSA-N 2-(dimethylamino)-n-[[3-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]methyl]acetamide Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=CC(CNC(=O)CN(C)C)=C1 YGVOKLMLPAPRSE-QGZVFWFLSA-N 0.000 claims 1
- JIBWXMKJDYZULM-UHFFFAOYSA-N 2-methoxy-5-[[6-[3-[(4-methylpiperazin-1-yl)methyl]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]phenol Chemical compound C1=C(O)C(OC)=CC=C1NC1=NC=NC2=C1C=C(C=1C=C(CN3CCN(C)CC3)C=CC=1)N2 JIBWXMKJDYZULM-UHFFFAOYSA-N 0.000 claims 1
- JCOQTKKATRMBGY-UHFFFAOYSA-N 2-methoxy-5-[[6-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]phenol Chemical compound C1=C(O)C(OC)=CC=C1NC1=NC=NC2=C1C=C(C=1C=CC(CN3CCN(C)CC3)=CC=1)N2 JCOQTKKATRMBGY-UHFFFAOYSA-N 0.000 claims 1
- IVVQDEMOKGQRMX-HXUWFJFHSA-N 3-(diethylamino)-n-[[4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]methyl]propanamide Chemical compound C1=CC(CNC(=O)CCN(CC)CC)=CC=C1C(NC1=NC=N2)=CC1=C2N[C@H](C)C1=CC=CC=C1 IVVQDEMOKGQRMX-HXUWFJFHSA-N 0.000 claims 1
- HZASJPLZTDZQCT-UHFFFAOYSA-N 4-[[6-[4-(morpholin-4-ylmethyl)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-1h-pyridin-2-one Chemical compound C1=CNC(=O)C=C1NC1=NC=NC2=C1C=C(C=1C=CC(CN3CCOCC3)=CC=1)N2 HZASJPLZTDZQCT-UHFFFAOYSA-N 0.000 claims 1
- MZCPMOIZOBQRSM-UHFFFAOYSA-N 4-[[6-[4-[(dimethylamino)methyl]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-1h-pyridin-2-one Chemical compound C1=CC(CN(C)C)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC(=O)NC=C1 MZCPMOIZOBQRSM-UHFFFAOYSA-N 0.000 claims 1
- FWGFRWILELKXQZ-UHFFFAOYSA-N 5-[[6-[3-[(dimethylamino)methyl]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-2-methoxyphenol Chemical compound C1=C(O)C(OC)=CC=C1NC1=NC=NC2=C1C=C(C=1C=C(CN(C)C)C=CC=1)N2 FWGFRWILELKXQZ-UHFFFAOYSA-N 0.000 claims 1
- RZZHUWWZHXYOEA-UHFFFAOYSA-N 5-[[6-[3-[(dimethylamino)methyl]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-2-methylphenol Chemical compound CN(C)CC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(O)C(C)=CC=4)=C3C=2)=C1 RZZHUWWZHXYOEA-UHFFFAOYSA-N 0.000 claims 1
- WCGWWVHEMGKLRA-UHFFFAOYSA-N 5-[[6-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-1h-pyridin-2-one Chemical compound C1CN(C)CCN1CC1=CC=C(C=2NC3=NC=NC(NC4=CNC(=O)C=C4)=C3C=2)C=C1 WCGWWVHEMGKLRA-UHFFFAOYSA-N 0.000 claims 1
- UFQIDRWSQPCIEQ-UHFFFAOYSA-N 5-[[6-[4-[(dimethylamino)methyl]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-2-methylphenol Chemical compound C1=CC(CN(C)C)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=C(C)C(O)=C1 UFQIDRWSQPCIEQ-UHFFFAOYSA-N 0.000 claims 1
- WXTTVWVQKPFYKX-HXUWFJFHSA-N 6-[3-[(4-ethylpiperazin-1-yl)methyl]phenyl]-n-[(1r)-1-phenylethyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1CN(CC)CCN1CC1=CC=CC(C=2NC3=NC=NC(N[C@H](C)C=4C=CC=CC=4)=C3C=2)=C1 WXTTVWVQKPFYKX-HXUWFJFHSA-N 0.000 claims 1
- OTAINLPPBNSXTJ-LJQANCHMSA-N 6-[3-[(4-methylpiperazin-1-yl)methyl]phenyl]-n-[(1r)-1-phenylethyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C(C=1)=CC=CC=1CN1CCN(C)CC1 OTAINLPPBNSXTJ-LJQANCHMSA-N 0.000 claims 1
- AALYMESKEMSIQZ-UHFFFAOYSA-N 6-[4-(diethylaminomethyl)phenyl]-n-[(3-methoxyphenyl)methyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(CN(CC)CC)=CC=C1C(NC1=NC=N2)=CC1=C2NCC1=CC=CC(OC)=C1 AALYMESKEMSIQZ-UHFFFAOYSA-N 0.000 claims 1
- KENDEWHISLNOER-UHFFFAOYSA-N 6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-n-[(6-methoxypyridin-3-yl)methyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1CN(CC)CCN1CC1=CC=C(C=2NC3=NC=NC(NCC=4C=NC(OC)=CC=4)=C3C=2)C=C1 KENDEWHISLNOER-UHFFFAOYSA-N 0.000 claims 1
- HMELEGZBVLVVAT-UHFFFAOYSA-N 6-[4-[(dimethylamino)methyl]phenyl]-n-(2-methoxypyridin-4-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=NC(OC)=CC(NC=2C=3C=C(NC=3N=CN=2)C=2C=CC(CN(C)C)=CC=2)=C1 HMELEGZBVLVVAT-UHFFFAOYSA-N 0.000 claims 1
- VPXKYUMKBFXCRO-UHFFFAOYSA-N 6-[4-[(dimethylamino)methyl]phenyl]-n-(6-methoxypyridin-3-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=NC(OC)=CC=C1NC1=NC=NC2=C1C=C(C=1C=CC(CN(C)C)=CC=1)N2 VPXKYUMKBFXCRO-UHFFFAOYSA-N 0.000 claims 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- UGMKJZVWTPFHDT-UHFFFAOYSA-N [4-[4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-morpholin-4-ylmethanone Chemical compound C=1C=C2NC(C)=CC2=C(F)C=1OC(C=1C=2)=NC=NC=1NC=2C(C=C1)=CC=C1C(=O)N1CCOCC1 UGMKJZVWTPFHDT-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 229960001867 guaiacol Drugs 0.000 claims 1
- XDTGUTRFUQTJJE-HXUWFJFHSA-N n',n'-diethyl-n-[[4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]methyl]ethane-1,2-diamine Chemical compound C1=CC(CNCCN(CC)CC)=CC=C1C(NC1=NC=N2)=CC1=C2N[C@H](C)C1=CC=CC=C1 XDTGUTRFUQTJJE-HXUWFJFHSA-N 0.000 claims 1
- ZMRQWGOOEGAYKN-UHFFFAOYSA-N n-(1,3-benzodioxol-5-yl)-6-[4-(morpholin-4-ylmethyl)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=1C=C(C=2NC3=NC=NC(NC=4C=C5OCOC5=CC=4)=C3C=2)C=CC=1CN1CCOCC1 ZMRQWGOOEGAYKN-UHFFFAOYSA-N 0.000 claims 1
- JSPLIDXVBSWCRT-UHFFFAOYSA-N n-(1,3-benzodioxol-5-yl)-6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1CN(CC)CCN1CC1=CC=C(C=2NC3=NC=NC(NC=4C=C5OCOC5=CC=4)=C3C=2)C=C1 JSPLIDXVBSWCRT-UHFFFAOYSA-N 0.000 claims 1
- VADZPEBTDDGYRI-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-[3-[(dimethylamino)methyl]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound CN(C)CC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C(F)=CC=4)=C3C=2)=C1 VADZPEBTDDGYRI-UHFFFAOYSA-N 0.000 claims 1
- CZRCGPMKRUUDAR-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1CN(CC)CCN1CC1=CC=C(C=2NC3=NC=NC(NC=4C=C(Cl)C(F)=CC=4)=C3C=2)C=C1 CZRCGPMKRUUDAR-UHFFFAOYSA-N 0.000 claims 1
- QEGSXEQNCZZZDA-UHFFFAOYSA-N n-(3-chlorophenyl)-6-[4-[(dimethylamino)methyl]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.C1=CC(CN(C)C)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 QEGSXEQNCZZZDA-UHFFFAOYSA-N 0.000 claims 1
- VYVOFUYUAUGEAZ-UHFFFAOYSA-N n-(4-phenylmethoxyphenyl)-6-[4-(piperidin-1-ylmethyl)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=1C=CC=CC=1COC(C=C1)=CC=C1NC(C=1C=2)=NC=NC=1NC=2C(C=C1)=CC=C1CN1CCCCC1 VYVOFUYUAUGEAZ-UHFFFAOYSA-N 0.000 claims 1
- COAHCRGSDSNIPV-UHFFFAOYSA-N n-(6-methoxypyridin-3-yl)-6-[4-(morpholin-4-ylmethyl)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=NC(OC)=CC=C1NC1=NC=NC2=C1C=C(C=1C=CC(CN3CCOCC3)=CC=1)N2 COAHCRGSDSNIPV-UHFFFAOYSA-N 0.000 claims 1
- ORDQVBZAMMWELP-UHFFFAOYSA-N n-[(2-chlorophenyl)methyl]-6-[4-[(dimethylamino)methyl]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(CN(C)C)=CC=C1C(NC1=NC=N2)=CC1=C2NCC1=CC=CC=C1Cl ORDQVBZAMMWELP-UHFFFAOYSA-N 0.000 claims 1
- DOTNIKZPLJDULX-UHFFFAOYSA-N n-[(3-chlorophenyl)methyl]-6-[4-(diethylaminomethyl)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(CN(CC)CC)=CC=C1C(NC1=NC=N2)=CC1=C2NCC1=CC=CC(Cl)=C1 DOTNIKZPLJDULX-UHFFFAOYSA-N 0.000 claims 1
- ZBLPQANJCQJTRX-UHFFFAOYSA-N n-[(3-chlorophenyl)methyl]-6-[4-(piperidin-1-ylmethyl)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(CNC=2C=3C=C(NC=3N=CN=2)C=2C=CC(CN3CCCCC3)=CC=2)=C1 ZBLPQANJCQJTRX-UHFFFAOYSA-N 0.000 claims 1
- WEWKUUMCYVMDEQ-UHFFFAOYSA-N n-[(3-methoxyphenyl)methyl]-6-[4-(pyrrolidin-1-ylmethyl)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound COC1=CC=CC(CNC=2C=3C=C(NC=3N=CN=2)C=2C=CC(CN3CCCC3)=CC=2)=C1 WEWKUUMCYVMDEQ-UHFFFAOYSA-N 0.000 claims 1
- LAGMOSJYPZREQG-UHFFFAOYSA-N n-[[3-[4-(3-chloro-4-fluoroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]methyl]-2-(4-methylpiperazin-1-yl)acetamide Chemical compound C1CN(C)CCN1CC(=O)NCC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C(F)=CC=4)=C3C=2)=C1 LAGMOSJYPZREQG-UHFFFAOYSA-N 0.000 claims 1
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- 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
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|---|---|---|---|---|
| CN100351253C (zh) * | 2000-06-26 | 2007-11-28 | 辉瑞产品公司 | 作为免疫抑制剂的吡咯并[2,3－d]嘧啶化合物 |
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