CA2262421C - Substituted pyrrolopyrimidines and processes for their preparation - Google Patents
Substituted pyrrolopyrimidines and processes for their preparation Download PDFInfo
- Publication number
- CA2262421C CA2262421C CA002262421A CA2262421A CA2262421C CA 2262421 C CA2262421 C CA 2262421C CA 002262421 A CA002262421 A CA 002262421A CA 2262421 A CA2262421 A CA 2262421A CA 2262421 C CA2262421 C CA 2262421C
- Authority
- CA
- Canada
- Prior art keywords
- formula
- pyrrolo
- pyrimidine
- pharmaceutically acceptable
- acceptable salt
- 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 - Fee Related
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- 238000000034 method Methods 0.000 title claims description 52
- 238000002360 preparation method Methods 0.000 title claims description 47
- 230000008569 process Effects 0.000 title claims description 39
- 150000004944 pyrrolopyrimidines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 218
- JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical class N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 claims abstract description 6
- -1 cyano, amino Chemical group 0.000 claims description 242
- 125000000217 alkyl group Chemical group 0.000 claims description 163
- 150000003839 salts Chemical class 0.000 claims description 114
- 125000006239 protecting group Chemical group 0.000 claims description 79
- 125000001424 substituent group Chemical group 0.000 claims description 60
- 125000003282 alkyl amino group Chemical group 0.000 claims description 45
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 44
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 40
- 125000003545 alkoxy group Chemical group 0.000 claims description 37
- 125000000524 functional group Chemical group 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
- 229910052736 halogen Inorganic materials 0.000 claims description 28
- 150000002367 halogens Chemical group 0.000 claims description 28
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 22
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 22
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 22
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 125000003277 amino group Chemical group 0.000 claims description 20
- 125000004423 acyloxy group Chemical group 0.000 claims description 19
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 206010028980 Neoplasm Diseases 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 16
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 14
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 14
- 239000000460 chlorine Substances 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 12
- 125000005281 alkyl ureido group Chemical group 0.000 claims description 12
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 241001465754 Metazoa Species 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- BYYLPECJKOEHBV-UHFFFAOYSA-N 4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidine-6-carbaldehyde Chemical compound ClC1=CC=CC(NC=2C=3C=C(C=O)NC=3N=CN=2)=C1 BYYLPECJKOEHBV-UHFFFAOYSA-N 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 239000011593 sulfur Substances 0.000 claims description 8
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 7
- 229910052783 alkali metal Inorganic materials 0.000 claims description 6
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 6
- 150000001448 anilines Chemical class 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Chemical group 0.000 claims description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 5
- BNMRACHWXQYRHO-UHFFFAOYSA-N 4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidine-6-carbothioamide Chemical compound N1=CN=C2NC(C(=S)N)=CC2=C1NC1=CC=CC(Cl)=C1 BNMRACHWXQYRHO-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 239000012024 dehydrating agents Substances 0.000 claims description 4
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 claims description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000000972 4,5-dimethylthiazol-2-yl group Chemical group [H]C([H])([H])C1=C(N=C(*)S1)C([H])([H])[H] 0.000 claims description 3
- OGEBYZFAAZVIHT-UHFFFAOYSA-N N-(3-chlorophenyl)-6-(2H-tetrazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C=3C=C(NC=3N=CN=2)C=2NN=NN=2)=C1 OGEBYZFAAZVIHT-UHFFFAOYSA-N 0.000 claims description 3
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims description 3
- 150000001351 alkyl iodides Chemical class 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 150000002443 hydroxylamines Chemical class 0.000 claims description 3
- 239000012948 isocyanate Substances 0.000 claims description 3
- 150000003512 tertiary amines Chemical class 0.000 claims description 3
- LDUVGYTUBRSPKL-UBKPWBPPSA-N (NE)-N-[[4-(3-chloroanilino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]methylidene]hydroxylamine Chemical compound N1=CN=C2NC(/C=N/O)=CC2=C1NC1=CC=CC(Cl)=C1 LDUVGYTUBRSPKL-UBKPWBPPSA-N 0.000 claims description 2
- YYELWCZQXDCXCI-UHFFFAOYSA-N 1-[3-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-3-ethylurea Chemical compound CCNC(=O)NC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 YYELWCZQXDCXCI-UHFFFAOYSA-N 0.000 claims description 2
- UTIXVEICQYJJRY-UHFFFAOYSA-N 1-[3-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-3-methylthiourea Chemical compound CNC(=S)NC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 UTIXVEICQYJJRY-UHFFFAOYSA-N 0.000 claims description 2
- UCRKSQGCZVGBGX-UHFFFAOYSA-N 1-[4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-3-methylthiourea Chemical compound C1=CC(NC(=S)NC)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 UCRKSQGCZVGBGX-UHFFFAOYSA-N 0.000 claims description 2
- CGSVJQVCEGIWCF-OAHLLOKOSA-N 1-ethyl-3-[3-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]urea Chemical compound CCNC(=O)NC1=CC=CC(C=2NC3=NC=NC(N[C@H](C)C=4C=CC=CC=4)=C3C=2)=C1 CGSVJQVCEGIWCF-OAHLLOKOSA-N 0.000 claims description 2
- YPCURGZEPMFYLX-OAHLLOKOSA-N 1-ethyl-3-[4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(NC1=NC=N2)=CC1=C2N[C@H](C)C1=CC=CC=C1 YPCURGZEPMFYLX-OAHLLOKOSA-N 0.000 claims description 2
- VEJBANJNCNEZHG-CQSZACIVSA-N 1-methyl-3-[3-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]thiourea Chemical compound CNC(=S)NC1=CC=CC(C=2NC3=NC=NC(N[C@H](C)C=4C=CC=CC=4)=C3C=2)=C1 VEJBANJNCNEZHG-CQSZACIVSA-N 0.000 claims description 2
- IKELJGAIXVSXJM-CQSZACIVSA-N 1-methyl-3-[4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]thiourea Chemical compound C1=CC(NC(=S)NC)=CC=C1C(NC1=NC=N2)=CC1=C2N[C@H](C)C1=CC=CC=C1 IKELJGAIXVSXJM-CQSZACIVSA-N 0.000 claims description 2
- PWHGHAZYGUIHSJ-UHFFFAOYSA-N 2-[[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]methyl-(2-hydroxyethyl)amino]ethanol Chemical compound N1=CN=C2NC(CN(CCO)CCO)=CC2=C1NC1=CC=CC(Cl)=C1 PWHGHAZYGUIHSJ-UHFFFAOYSA-N 0.000 claims description 2
- JEWOIKNJTXJTGH-UHFFFAOYSA-N 4-(4-anilino-7h-pyrrolo[2,3-d]pyrimidin-6-yl)-2-methoxyphenol;hydrochloride Chemical compound Cl.C1=C(O)C(OC)=CC(C=2NC3=NC=NC(NC=4C=CC=CC=4)=C3C=2)=C1 JEWOIKNJTXJTGH-UHFFFAOYSA-N 0.000 claims description 2
- WXZNMFZVZMNGIO-UHFFFAOYSA-N 4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-2-methoxyphenol;hydrochloride Chemical compound Cl.C1=C(O)C(OC)=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 WXZNMFZVZMNGIO-UHFFFAOYSA-N 0.000 claims description 2
- GECLSTHOYOAGFD-UHFFFAOYSA-N 4-[[[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]methylamino]methyl]phenol Chemical compound C1=CC(O)=CC=C1CNCC(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 GECLSTHOYOAGFD-UHFFFAOYSA-N 0.000 claims description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- QOLIVYYSALQXGF-LJQANCHMSA-N 6-[3-(benzylamino)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=1NCC1=CC=CC=C1 QOLIVYYSALQXGF-LJQANCHMSA-N 0.000 claims description 2
- NIFHYNGZYDVDBU-UHFFFAOYSA-N 6-[4-(benzylamino)phenyl]-n-(3-chlorophenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C=3C=C(NC=3N=CN=2)C=2C=CC(NCC=3C=CC=CC=3)=CC=2)=C1 NIFHYNGZYDVDBU-UHFFFAOYSA-N 0.000 claims description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 2
- QOPHSBUZTVLVBJ-UHFFFAOYSA-N N-(3-chlorophenyl)-6-(1-methyltetrazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound CN1N=NN=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 QOPHSBUZTVLVBJ-UHFFFAOYSA-N 0.000 claims description 2
- BCZCVGXQOLPACI-UHFFFAOYSA-N N-(3-chlorophenyl)-6-(2-methyltetrazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound CN1N=NC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=N1 BCZCVGXQOLPACI-UHFFFAOYSA-N 0.000 claims description 2
- GAABGZUDSKAVGH-UHFFFAOYSA-N N-(3-chlorophenyl)-6-(4,5-dimethyl-1,3-thiazol-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound S1C(C)=C(C)N=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 GAABGZUDSKAVGH-UHFFFAOYSA-N 0.000 claims description 2
- ZRSLTYRSYOZHIR-UHFFFAOYSA-N N-(3-chlorophenyl)-6-(4-ethyl-1,3-thiazol-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound CCC1=CSC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=N1 ZRSLTYRSYOZHIR-UHFFFAOYSA-N 0.000 claims description 2
- BPEIBTXCKPKWLE-UHFFFAOYSA-N N-(3-chlorophenyl)-6-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1C1=CSC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=N1 BPEIBTXCKPKWLE-UHFFFAOYSA-N 0.000 claims description 2
- LNPXDMGETBINDL-UHFFFAOYSA-N [4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 LNPXDMGETBINDL-UHFFFAOYSA-N 0.000 claims description 2
- KJCWFUJEFVWZSE-UHFFFAOYSA-N [4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-morpholin-4-ylmethanone Chemical compound ClC1=CC=CC(NC=2C=3C=C(NC=3N=CN=2)C(=O)N2CCOCC2)=C1 KJCWFUJEFVWZSE-UHFFFAOYSA-N 0.000 claims description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 150000002513 isocyanates Chemical class 0.000 claims description 2
- 150000002540 isothiocyanates Chemical class 0.000 claims description 2
- ROZJWSLFOMITNR-UHFFFAOYSA-N methyl n-[4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]carbamate Chemical compound C1=CC(NC(=O)OC)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 ROZJWSLFOMITNR-UHFFFAOYSA-N 0.000 claims description 2
- BRBPDQKNOPJHDS-UHFFFAOYSA-N n'-[3-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-n,n-diethylmethanimidamide Chemical compound CCN(CC)C=NC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 BRBPDQKNOPJHDS-UHFFFAOYSA-N 0.000 claims description 2
- HYSPQBYMQIZTMH-UHFFFAOYSA-N n'-[3-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-n,n-dimethylmethanimidamide Chemical compound CN(C)C=NC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 HYSPQBYMQIZTMH-UHFFFAOYSA-N 0.000 claims description 2
- YBZDNHCFYNZPHI-UHFFFAOYSA-N n'-[4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-n,n-dimethylmethanimidamide Chemical compound C1=CC(N=CN(C)C)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 YBZDNHCFYNZPHI-UHFFFAOYSA-N 0.000 claims description 2
- SDSLGPIDULPJQG-MRXNPFEDSA-N n,n-dimethyl-n'-[3-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]methanimidamide Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=CC(N=CN(C)C)=C1 SDSLGPIDULPJQG-MRXNPFEDSA-N 0.000 claims description 2
- UNUHIYOQLRIQNQ-MRXNPFEDSA-N n,n-dimethyl-n'-[4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]methanimidamide Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=C(N=CN(C)C)C=C1 UNUHIYOQLRIQNQ-MRXNPFEDSA-N 0.000 claims description 2
- OHTCWCLASYCDQT-UHFFFAOYSA-N n-(3-chlorophenyl)-6-(morpholin-4-ylmethyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C=3C=C(CN4CCOCC4)NC=3N=CN=2)=C1 OHTCWCLASYCDQT-UHFFFAOYSA-N 0.000 claims description 2
- DUXRXJPIRNVGEO-UHFFFAOYSA-N n-(3-chlorophenyl)-6-[(4-methylpiperazin-1-yl)methyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1CN(C)CCN1CC(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 DUXRXJPIRNVGEO-UHFFFAOYSA-N 0.000 claims description 2
- MIZGMBWXPIRGEE-UHFFFAOYSA-N n-(3-chlorophenyl)-6-[3-(morpholin-4-ylmethylideneamino)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C=3C=C(NC=3N=CN=2)C=2C=C(C=CC=2)N=CN2CCOCC2)=C1 MIZGMBWXPIRGEE-UHFFFAOYSA-N 0.000 claims description 2
- GBCGNNNFIRWGCW-UHFFFAOYSA-N n-(3-chlorophenyl)-6-[4-[(4-methylpiperazin-1-yl)methylideneamino]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1CN(C)CCN1C=NC1=CC=C(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)C=C1 GBCGNNNFIRWGCW-UHFFFAOYSA-N 0.000 claims description 2
- SIZKLLRWNREFDZ-UHFFFAOYSA-N n-(3-chlorophenyl)-6-[[(4-methoxyphenyl)methylamino]methyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1CNCC(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 SIZKLLRWNREFDZ-UHFFFAOYSA-N 0.000 claims description 2
- RBEFWIDYHAIBSL-UHFFFAOYSA-N n-[3-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 RBEFWIDYHAIBSL-UHFFFAOYSA-N 0.000 claims description 2
- WVICNPJYDFMIGL-OAHLLOKOSA-N n-[3-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]ethanesulfonamide Chemical compound CCS(=O)(=O)NC1=CC=CC(C=2NC3=NC=NC(N[C@H](C)C=4C=CC=CC=4)=C3C=2)=C1 WVICNPJYDFMIGL-OAHLLOKOSA-N 0.000 claims description 2
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- 150000008163 sugars Chemical class 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid group Chemical class S(N)(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
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- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 150000004072 triols Chemical class 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 238000010518 undesired secondary reaction Methods 0.000 description 1
- ACWBQPMHZXGDFX-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=NN1 ACWBQPMHZXGDFX-QFIPXVFZSA-N 0.000 description 1
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Classifications
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH207196 | 1996-08-23 | ||
| CH2071/96 | 1996-08-23 | ||
| PCT/EP1997/004564 WO1998007726A1 (en) | 1996-08-23 | 1997-08-21 | Substituted pyrrolopyrimidines and processes for their preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2262421A1 CA2262421A1 (en) | 1998-02-26 |
| CA2262421C true CA2262421C (en) | 2007-10-02 |
Family
ID=4225221
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002262421A Expired - Fee Related CA2262421C (en) | 1996-08-23 | 1997-08-21 | Substituted pyrrolopyrimidines and processes for their preparation |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US6180636B1 (OSRAM) |
| EP (1) | EP0938486B1 (OSRAM) |
| JP (1) | JP4242928B2 (OSRAM) |
| AT (1) | ATE384062T1 (OSRAM) |
| AU (1) | AU720429B2 (OSRAM) |
| CA (1) | CA2262421C (OSRAM) |
| DE (1) | DE69738468T2 (OSRAM) |
| DK (1) | DK0938486T3 (OSRAM) |
| ES (1) | ES2297864T3 (OSRAM) |
| PT (1) | PT938486E (OSRAM) |
| WO (1) | WO1998007726A1 (OSRAM) |
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| CA2102780C (en) | 1991-05-10 | 2007-01-09 | Alfred P. Spada | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit egf and/or pdgf receptor tyrosine kinase |
| US5679683A (en) * | 1994-01-25 | 1997-10-21 | Warner-Lambert Company | Tricyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family |
| IL112249A (en) * | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
| IL112248A0 (en) | 1994-01-25 | 1995-03-30 | Warner Lambert Co | Tricyclic heteroaromatic compounds and pharmaceutical compositions containing them |
| ATE159257T1 (de) | 1994-05-03 | 1997-11-15 | Ciba Geigy Ag | Pyrrolopyrimidinderivate mit antiproliferativer wirkung |
| EP0783505B1 (en) | 1994-09-29 | 2001-03-07 | Novartis AG | PYRROLO[2,3-d]PYRIMIDINES AND THEIR USE |
| ATE195123T1 (de) | 1995-04-03 | 2000-08-15 | Novartis Erfind Verwalt Gmbh | Pyrazolderivate und verfahren zu deren herstellung |
| US6403599B1 (en) | 1995-11-08 | 2002-06-11 | Pfizer Inc | Corticotropin releasing factor antagonists |
| EP0831829B1 (en) | 1995-06-07 | 2003-08-20 | Pfizer Inc. | Heterocyclic ring-fused pyrimidine derivatives |
| NZ312665A (en) | 1995-07-06 | 1999-08-30 | Novartis Ag | Rrolopyrimidines(7h-pyrrolo[2,3-d]pyrimidine and preparation of these |
| WO1997027199A1 (en) | 1996-01-23 | 1997-07-31 | Novartis Ag | Pyrrolopyrimidines and processes for their preparation |
| GB9604361D0 (en) | 1996-02-29 | 1996-05-01 | Pharmacia Spa | 4-Substituted pyrrolopyrimidine compounds as tyrosine kinase inhibitors |
| EP0929553B1 (en) | 1996-10-02 | 2005-03-16 | Novartis AG | Pyrimidine derivatives and processes for the preparation thereof |
| WO1998014449A1 (en) | 1996-10-02 | 1998-04-09 | Novartis Ag | Fused pyrazole derivatives and processes for their preparation |
-
1997
- 1997-08-21 US US09/242,592 patent/US6180636B1/en not_active Expired - Fee Related
- 1997-08-21 PT PT97940108T patent/PT938486E/pt unknown
- 1997-08-21 DK DK97940108T patent/DK0938486T3/da active
- 1997-08-21 AT AT97940108T patent/ATE384062T1/de not_active IP Right Cessation
- 1997-08-21 CA CA002262421A patent/CA2262421C/en not_active Expired - Fee Related
- 1997-08-21 JP JP51042598A patent/JP4242928B2/ja not_active Expired - Fee Related
- 1997-08-21 WO PCT/EP1997/004564 patent/WO1998007726A1/en not_active Ceased
- 1997-08-21 DE DE69738468T patent/DE69738468T2/de not_active Expired - Lifetime
- 1997-08-21 ES ES97940108T patent/ES2297864T3/es not_active Expired - Lifetime
- 1997-08-21 EP EP97940108A patent/EP0938486B1/en not_active Expired - Lifetime
- 1997-08-21 AU AU42064/97A patent/AU720429B2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| EP0938486B1 (en) | 2008-01-16 |
| JP2000516626A (ja) | 2000-12-12 |
| US6180636B1 (en) | 2001-01-30 |
| ES2297864T3 (es) | 2008-05-01 |
| DK0938486T3 (da) | 2008-07-07 |
| PT938486E (pt) | 2008-03-27 |
| DE69738468D1 (de) | 2008-03-06 |
| JP4242928B2 (ja) | 2009-03-25 |
| DE69738468T2 (de) | 2009-01-08 |
| AU4206497A (en) | 1998-03-06 |
| AU720429B2 (en) | 2000-06-01 |
| ATE384062T1 (de) | 2008-02-15 |
| WO1998007726A1 (en) | 1998-02-26 |
| EP0938486A1 (en) | 1999-09-01 |
| CA2262421A1 (en) | 1998-02-26 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |