NO313962B1 - Pyrrolo[2,3]pyrimidiner, deres fremstilling og anvendelse og farmasöytiskepreparater inneholdende dem - Google Patents

Info

Publication number

NO313962B1

NO313962B1 NO19994509A NO994509A NO313962B1 NO 313962 B1 NO313962 B1 NO 313962B1 NO 19994509 A NO19994509 A NO 19994509A NO 994509 A NO994509 A NO 994509A NO 313962 B1 NO313962 B1 NO 313962B1

Authority

NO

Norway

Prior art keywords

phenyl

pyrrolo

pyrimidin

amino

formula

Prior art date

1997-03-19

Links

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• 239000000825 pharmaceutical preparation Substances 0.000 title claims description 10
• 238000002360 preparation method Methods 0.000 title description 22
• KCTZOTUQSGYWLV-UHFFFAOYSA-N N1C=NC=C2N=CC=C21 Chemical class N1C=NC=C2N=CC=C21 KCTZOTUQSGYWLV-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 172
• -1 2-phenyl-1,3-dioxan-5-yl Chemical group 0.000 claims abstract description 139
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 84
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 84
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 48
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 37
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 33
• 239000001257 hydrogen Substances 0.000 claims abstract description 33
• 238000000034 method Methods 0.000 claims abstract description 32
• 150000003839 salts Chemical class 0.000 claims abstract description 25
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 23
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 18
• 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 17
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 12
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 11
• 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims abstract description 9
• 230000002062 proliferating effect Effects 0.000 claims abstract description 8
• 210000000987 immune system Anatomy 0.000 claims abstract description 6
• 230000008569 process Effects 0.000 claims abstract description 6
• 208000037765 diseases and disorders Diseases 0.000 claims abstract description 3
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract 5
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 33
• 229910052736 halogen Inorganic materials 0.000 claims description 30
• 150000002367 halogens Chemical class 0.000 claims description 30
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 22
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 21
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 20
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
• 201000010099 disease Diseases 0.000 claims description 17
• 229910021529 ammonia Inorganic materials 0.000 claims description 15
• 238000006243 chemical reaction Methods 0.000 claims description 14
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 13
• 150000002431 hydrogen Chemical class 0.000 claims description 13
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 12
• 125000003545 alkoxy group Chemical group 0.000 claims description 11
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
• OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 9
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 9
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
• 239000000460 chlorine Substances 0.000 claims description 8
• 229910052801 chlorine Inorganic materials 0.000 claims description 8
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 7
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 6
• METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims description 6
• 239000003054 catalyst Substances 0.000 claims description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
• LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical compound NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 claims description 4
• NFSWHYRUVWRUDN-UHFFFAOYSA-N 5-(4-phenoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2NC=C1C(C=C1)=CC=C1OC1=CC=CC=C1 NFSWHYRUVWRUDN-UHFFFAOYSA-N 0.000 claims description 4
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 230000001613 neoplastic effect Effects 0.000 claims description 4
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• ZCBPGURKZDCEFP-UHFFFAOYSA-N 2-[4-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)phenoxy]-5-nitrobenzoic acid Chemical compound C12=C(N)N=CN=C2N(C(C)C)C=C1C(C=C1)=CC=C1OC1=CC=C([N+]([O-])=O)C=C1C(O)=O ZCBPGURKZDCEFP-UHFFFAOYSA-N 0.000 claims description 3
• VPDWAEBGKFDQTQ-UHFFFAOYSA-N 5-[4-(benzenesulfonyl)phenyl]-7-tert-butylpyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1)=CC=C1S(=O)(=O)C1=CC=CC=C1 VPDWAEBGKFDQTQ-UHFFFAOYSA-N 0.000 claims description 3
• PAHKLGUKLSFIBQ-UHFFFAOYSA-N 7-cyclopentyl-5-(2-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2N(C2CCCC2)C=C1C1=CC=CC=C1OC1=CC=CC=C1 PAHKLGUKLSFIBQ-UHFFFAOYSA-N 0.000 claims description 3
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
• DAGSDOGBZLLVLH-UHFFFAOYSA-N n-[4-(4-amino-7-cyclopentylpyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl]-4-tert-butylbenzenesulfonamide Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCCC3)C=2)=CC=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 DAGSDOGBZLLVLH-UHFFFAOYSA-N 0.000 claims description 3
• ZYUVGYBAPZYKSA-UHFFFAOYSA-N 5-(3-hydroxybutan-2-yl)-4-methylbenzene-1,3-diol Chemical compound CC(O)C(C)C1=CC(O)=CC(O)=C1C ZYUVGYBAPZYKSA-UHFFFAOYSA-N 0.000 claims description 2
• GQMYAXSHDAEFGH-UHFFFAOYSA-N C(C)(C)(C)N1C=C(C2=C1N=CN=C2N)C2=CC=C(C=C2)S(=O)C2=CC=CC=C2.C(C)(C)(C)N2C=C(C1=C2N=CN=C1N)C1=CC=C(C=C1)OC1=CC=C(C=C1)OC Chemical compound C(C)(C)(C)N1C=C(C2=C1N=CN=C2N)C2=CC=C(C=C2)S(=O)C2=CC=CC=C2.C(C)(C)(C)N2C=C(C1=C2N=CN=C1N)C1=CC=C(C=C1)OC1=CC=C(C=C1)OC GQMYAXSHDAEFGH-UHFFFAOYSA-N 0.000 claims description 2
• 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 2
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
• 150000003863 ammonium salts Chemical class 0.000 claims description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
• 238000009833 condensation Methods 0.000 claims description 2
• 230000005494 condensation Effects 0.000 claims description 2
• NHADDZMCASKINP-HTRCEHHLSA-N decarboxydihydrocitrinin Natural products C1=C(O)C(C)=C2[C@H](C)[C@@H](C)OCC2=C1O NHADDZMCASKINP-HTRCEHHLSA-N 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
• 229910052717 sulfur Inorganic materials 0.000 claims description 2
• 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 2
• KYDZEZNYRFJCSA-UHFFFAOYSA-N 4-tert-butylbenzenesulfonamide Chemical compound CC(C)(C)C1=CC=C(S(N)(=O)=O)C=C1 KYDZEZNYRFJCSA-UHFFFAOYSA-N 0.000 claims 1
• HJJXVPUOMJYVPN-UHFFFAOYSA-N C1(CCCC1)N1C=C(C2=C1N=CN=C2N)C2=CC=C(C=C2)OC2=CC=CC=C2.C(C)(C)N2C=C(C1=C2N=CN=C1N)C1=CC=C(C=C1)OC1=CC=CC=C1 Chemical compound C1(CCCC1)N1C=C(C2=C1N=CN=C2N)C2=CC=C(C=C2)OC2=CC=CC=C2.C(C)(C)N2C=C(C1=C2N=CN=C1N)C1=CC=C(C=C1)OC1=CC=CC=C1 HJJXVPUOMJYVPN-UHFFFAOYSA-N 0.000 claims 1
• IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 claims 1
• 229920000219 Ethylene vinyl alcohol Polymers 0.000 claims 1
• WNYKZALHSGWGLX-UHFFFAOYSA-N NC1=C(OC2=CC=C(C=C2)C2=CN(C=3N=CN=C(C32)N)C(C)C)C=CC=C1.NC=1C=C(OC3=CC=C(C=C3)C3=CN(C=2N=CN=C(C23)N)C(C)(C)C)C=CC1 Chemical compound NC1=C(OC2=CC=C(C=C2)C2=CN(C=3N=CN=C(C32)N)C(C)C)C=CC=C1.NC=1C=C(OC3=CC=C(C=C3)C3=CN(C=2N=CN=C(C23)N)C(C)(C)C)C=CC1 WNYKZALHSGWGLX-UHFFFAOYSA-N 0.000 claims 1
• IZZRYPGIYWRQCJ-UHFFFAOYSA-N n-[4-(4-amino-7-cyclopentylpyrrolo[2,3-d]pyrimidin-5-yl)-2-hydroxyphenyl]benzenesulfonamide Chemical compound C1=2C(N)=NC=NC=2N(C2CCCC2)C=C1C(C=C1O)=CC=C1NS(=O)(=O)C1=CC=CC=C1 IZZRYPGIYWRQCJ-UHFFFAOYSA-N 0.000 claims 1
• 229940124530 sulfonamide Drugs 0.000 claims 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 4
• 241000124008 Mammalia Species 0.000 abstract description 2
• 125000001475 halogen functional group Chemical group 0.000 abstract 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 2
• 125000002947 alkylene group Chemical group 0.000 abstract 1
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 abstract 1
• 125000000623 heterocyclic group Chemical group 0.000 abstract 1
• 239000008194 pharmaceutical composition Substances 0.000 abstract 1
• 125000005544 phthalimido group Chemical group 0.000 abstract 1
• 125000003226 pyrazolyl group Chemical group 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 172
• 239000000203 mixture Substances 0.000 description 149
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
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• JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 21
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• 239000002904 solvent Substances 0.000 description 8
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