JP2000506537A - 新規なN―7―ヘテロサイクリル―ピロロ[2,3―d]ピリミジンおよびこれらの使用 - Google Patents
新規なN―7―ヘテロサイクリル―ピロロ[2,3―d]ピリミジンおよびこれらの使用Info
- Publication number
- JP2000506537A JP2000506537A JP9533081A JP53308197A JP2000506537A JP 2000506537 A JP2000506537 A JP 2000506537A JP 9533081 A JP9533081 A JP 9533081A JP 53308197 A JP53308197 A JP 53308197A JP 2000506537 A JP2000506537 A JP 2000506537A
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- lower alkyl
- pyrrolo
- amino
- pyrimidin
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 131
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims abstract description 9
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims abstract description 9
- 241001465754 Metazoa Species 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 106
- 125000003545 alkoxy group Chemical group 0.000 claims description 73
- 150000003839 salts Chemical class 0.000 claims description 63
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 53
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 38
- 239000000203 mixture Substances 0.000 claims description 38
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 19
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 17
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 12
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 9
- 238000007363 ring formation reaction Methods 0.000 claims description 9
- 125000005529 alkyleneoxy group Chemical group 0.000 claims description 8
- 238000009472 formulation Methods 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 6
- 230000001629 suppression Effects 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
- 201000010099 disease Diseases 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 208000020084 Bone disease Diseases 0.000 abstract 1
- 230000005764 inhibitory process Effects 0.000 abstract 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 abstract 1
- -1 methylene, ethylene, propylene Chemical group 0.000 description 110
- 238000005160 1H NMR spectroscopy Methods 0.000 description 74
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 54
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 54
- 238000000034 method Methods 0.000 description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 30
- 125000003282 alkyl amino group Chemical group 0.000 description 26
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 241000610375 Sparisoma viride Species 0.000 description 23
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 22
- 239000013543 active substance Substances 0.000 description 22
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 20
- 239000000047 product Substances 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- 150000003973 alkyl amines Chemical class 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 239000002585 base Substances 0.000 description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 14
- 239000002253 acid Substances 0.000 description 13
- 150000002148 esters Chemical class 0.000 description 13
- 238000001914 filtration Methods 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- 125000004423 acyloxy group Chemical group 0.000 description 10
- 125000005236 alkanoylamino group Chemical group 0.000 description 10
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 9
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 8
- UHDSSJJGBUOKBN-UHFFFAOYSA-N 5-(4-phenylmethoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2NC=C1C(C=C1)=CC=C1OCC1=CC=CC=C1 UHDSSJJGBUOKBN-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 210000000988 bone and bone Anatomy 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 125000002883 imidazolyl group Chemical group 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 125000004076 pyridyl group Chemical group 0.000 description 8
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 125000001425 triazolyl group Chemical group 0.000 description 8
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
- 125000004414 alkyl thio group Chemical group 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 125000002757 morpholinyl group Chemical group 0.000 description 7
- 239000003208 petroleum Substances 0.000 description 7
- 125000004193 piperazinyl group Chemical group 0.000 description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 7
- 125000000168 pyrrolyl group Chemical group 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- 239000000454 talc Substances 0.000 description 7
- 229910052623 talc Inorganic materials 0.000 description 7
- 235000012222 talc Nutrition 0.000 description 7
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 6
- 108010010803 Gelatin Proteins 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 239000008273 gelatin Substances 0.000 description 6
- 229920000159 gelatin Polymers 0.000 description 6
- 235000019322 gelatine Nutrition 0.000 description 6
- 235000011852 gelatine desserts Nutrition 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 6
- 229920002261 Corn starch Polymers 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000008120 corn starch Substances 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 5
- 125000003386 piperidinyl group Chemical group 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- KARPLIRWOJABFB-UHFFFAOYSA-N 5-(3-methoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound COC1=CC=CC(C=2C3=C(N)N=CN=C3NC=2)=C1 KARPLIRWOJABFB-UHFFFAOYSA-N 0.000 description 4
- RTNKTMKZMYPBGZ-UHFFFAOYSA-N 5-(4-methoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1C1=CNC2=NC=NC(N)=C12 RTNKTMKZMYPBGZ-UHFFFAOYSA-N 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- 208000006386 Bone Resorption Diseases 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 125000005530 alkylenedioxy group Chemical group 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 230000024279 bone resorption Effects 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 238000005342 ion exchange Methods 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 210000002997 osteoclast Anatomy 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 229920001592 potato starch Polymers 0.000 description 4
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- 239000007858 starting material Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- IBCLKOLOJLBQDZ-UHFFFAOYSA-N 1-o-tert-butyl 2-o-ethyl pyrrolidine-1,2-dicarboxylate Chemical compound CCOC(=O)C1CCCN1C(=O)OC(C)(C)C IBCLKOLOJLBQDZ-UHFFFAOYSA-N 0.000 description 3
- PEHVGBZKEYRQSX-UHFFFAOYSA-N 7-deaza-adenine Chemical class NC1=NC=NC2=C1C=CN2 PEHVGBZKEYRQSX-UHFFFAOYSA-N 0.000 description 3
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- 208000013038 Hypocalcemia Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 description 3
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- 238000003556 assay Methods 0.000 description 3
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 3
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- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
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- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
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- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 3
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- 238000011200 topical administration Methods 0.000 description 3
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 2
- MKYMYZJJFMPDOA-UHFFFAOYSA-N 1-(4-phenylmethoxyphenyl)ethanone Chemical compound C1=CC(C(=O)C)=CC=C1OCC1=CC=CC=C1 MKYMYZJJFMPDOA-UHFFFAOYSA-N 0.000 description 2
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- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
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- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 2
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- 206010027476 Metastases Diseases 0.000 description 2
- 241001024304 Mino Species 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 2
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Classifications
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- 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
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- A61P17/06—Antipsoriatics
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A—HUMAN NECESSITIES
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- 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
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- A—HUMAN NECESSITIES
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.次式(I): (式中、R1はアリールを示し、R2とR3は同時にもしくは相互に独立して水素 原子、低級アルキルもしくはハロゲン原子を示し、R4は水素原子、ヒドロキシ 、非置換もしくは置換低級アルキル、低級アルコキシ、低級アルキルオキシ低級 アルケニル、非置換もしくは置換低級アルコキシカルボニル、N−低級アルキル アミノカルボニルもしくはN,N−ジ低級アルキルアミノカルボニルを示し、R5 は水素原子もしくは非置換もしくは置換低級アルキル、低級アルキルカルボニル もしくは低級アルコキシカルボニルを示し、mは1もしくは2を示し、nは0〜6 の数を示す) で表される化合物または該化合物の塩。 2.R1が非置換フェニルまたは低級アルキル、ヒドロキシ低級アルキル、フェ ニル、低級アルコキシ、フェニル低級アルコキシ、C1〜C3−アルキレンジオキ シ、シアノおよびハロゲン原子から成る群から選択される1個、2個もしくは3 個の置換基によって置換されたフェニルを示し、R2およびR3が同時にもしくは 相互に独立して水素原子、低級アルキルもしくはハロゲン原子を示し、R4が水 素原子、ヒドロキシ、非置換もしくは置換低級アルキル、低級アルコキシ、低級 アルキレンオキシ低級アルキル、非置換もしくは置換低級アルコキシカルボニル 、N−低級アルキルアミノカルボニルまたはN,N−ジ低級アルキルアミノカル ボニルを示し、R5が水素原子もしくは非置換もしくは置換低級アルキル、低級 アルキルカルボニルまたは低級アルコキシカルボニルを示し、mが1または2を 示し、nが0〜4の数を示す請求項1記載の化合物または該化合物の塩。 3.R1が非置換フェニルまたは低級アルキル、ヒドロキシ低級アルキル、フェ ニル、低級アルコキシ、フェニル低級アルコキシ、C1〜C3−アルキレンジオキ シ、シアノおよびハロゲン原子から成る群から選択される1個、2個もしくは3 個の置換基によって置換されたフェニルを示し、R2およびR3が水素原子を示し 、R4が水素原子、ヒドロキシ、非置換もしくは置換低級アルキル、低級アルコ キシ、低級アルキレンオキシ低級アルキル、非置換もしくは置換低級アルコキシ カルボニル、N−低級アルキルアミノカルボニルまたはN,N−ジ低級アルキル アミノカルボニルを示し、R5が水素原子もしくは非置換もしくは置換低級アル キル、低級アルキルカルボニルまたは低級アルコキシカルボニルを示し、mが1 または2を示し、nが0〜4の数を示す請求項1記載の化合物または該化合物の 塩。 4.R1が非置換フェニルまたは低級アルキル、ヒドロキシ低級アルキル、フェ ニル、低級アルコキシ、フェニル低級アルコキシ、C1〜C3−アルキレンジオキ シ、シアノおよびハロゲン原子から成る群から選択される1個、2個もしくは3 個の置換基によって置換されたフェニルを示し、R2およびR3が水素原子を示し 、R4が水素原子、非置換もしくは置換低級アルキル、低級アルコキシ、低級ア ルキレンオキシ低級アルキルまたは非置換もしくは置換低級アルコキシカルボニ ルを示し、R5が水素原子もしくは非置換もしくは置換低級アルキル、低級アル キルカルボニルまたは低級アルコキシカルボニルを示し、mが1または2を示し 、nが0または1を示す請求項1記載の化合物または該化合物の塩。 5.R1が非置換フェニルまたは低級アルキル、ヒドロキシ低級アルキル、フェ ニル、低級アルコキシ、フェニル低級アルコキシ、C1〜C3−アルキレンジオキ シ、シアノおよびハロゲン原子から成る群から選択される1個、2個もしくは3 個の置換基によって置換されたフェニルを示し、R2およびR3が水素原子を示し 、R4が水素原子、非置換もしくは置換低級アルキル、低級アルコキシ、低級ア ルキレンオキシ低級アルキルまたは非置換もしくは置換低級アルコキシカルボニ ルを示し、R5が水素原子もしくは非置換もしくは置換低級アルキル、低級アル キルカルボニルまたは低級アルコキシカルボニルを示し、mが1または2を示し 、nが0を示す請求項1記載の化合物または薬学的に使用可能な該化合物 の塩。 6.請求項1から5いずれかに記載の化合物および少なくとも1種の薬学的に 使用可能なキャリヤーを含有する薬剤。 7.人体もしくは動物体の治療的処置に使用するための請求項1から5いずれ かに記載の化合物。 8.タンパク質−チロシン−キナーゼpp60c-srcの活性抑制に影響される疾患 の処置に使用するための請求項1から5いずれかに記載の化合物。 9.製剤を製造するための請求項1から5いずれかに記載の化合物の使用。 10.タンパク質−チロシン−キナーゼpp60c-srcの活性抑制に影響される疾患 の処置用製剤を製造するための請求項1から5いずれかに記載の化合物の使用。 11.下記の過程(a)、(b)、(c)または(d)を含む請求項1記載の化合物(I)の製 造方法[この場合、所望により式(I)で表される不特定の化合物を式(I)で表さ れる別の化合物に変換してもよく、および/または所望により得られる塩を遊離 の化合物もしくは別の塩に変換してもよく、および/または、所望により得られ る式(I)で表される遊離の塩形成性化合物を塩に変換してもよい]: (a)次式(II): で表される化合物をピリミジン環の形成を伴う閉環反応に付す。 (b)次式(III):で表される化合物をピリミジン環の形成を伴う閉環反応に付す。 (c)次式(IV): で表される化合物を次式(V): (式中、Xは脱離基を示す) で表される化合物と反応させる。 (d)次式(VI): (式中、Y1およびY2は適当な脱離基を示す) で表される化合物を次式(VII): R5−NH2 (VII) で表される化合物と反応させる。
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Family Cites Families (1)
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CA2100863A1 (en) * | 1991-01-23 | 1992-07-24 | David A. Bullough | Adenosine kinase inhibitors |
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1997
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- 1997-03-05 DK DK97914189T patent/DK0888353T3/da active
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- 1997-03-05 BR BRPI9709443-9A patent/BR9709443B1/pt not_active IP Right Cessation
- 1997-03-05 KR KR1019980707280A patent/KR20000064601A/ko not_active Application Discontinuation
- 1997-03-05 AU AU21534/97A patent/AU716383B2/en not_active Ceased
- 1997-03-05 AT AT97914189T patent/ATE244719T1/de active
- 1997-03-05 CN CN97193839A patent/CN1079796C/zh not_active Expired - Fee Related
- 1997-03-05 ES ES97914189T patent/ES2203793T3/es not_active Expired - Lifetime
- 1997-03-05 WO PCT/EP1997/001095 patent/WO1997034895A1/de not_active Application Discontinuation
- 1997-03-05 CA CA002249739A patent/CA2249739A1/en not_active Abandoned
- 1997-03-05 EP EP97914189A patent/EP0888353B1/de not_active Expired - Lifetime
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Cited By (6)
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WO2005080392A1 (ja) * | 2004-02-19 | 2005-09-01 | Takeda Pharmaceutical Company Limited | ピラゾロキノロン誘導体およびその用途 |
US7842701B2 (en) | 2004-02-19 | 2010-11-30 | Takeda Pharmaceutical Company Limited | Pyrazoloquinolone derivative and use thereof |
JP2009522284A (ja) * | 2005-12-29 | 2009-06-11 | アボット・ラボラトリーズ | タンパク質キナーゼ阻害薬 |
JP2009528991A (ja) * | 2006-02-14 | 2009-08-13 | バーテックス ファーマシューティカルズ インコーポレイテッド | プロテインキナーゼの阻害剤として有用なピロロ(3,2−c)ピリジン |
JP2019073522A (ja) * | 2012-06-29 | 2019-05-16 | ファイザー・インク | LRRK2阻害薬としての新規な4−(置換アミノ)−7H−ピロロ[2,3−d]ピリミジン |
JP2019521992A (ja) * | 2016-06-16 | 2019-08-08 | 上海 インスティテュート オブ マテリア メディカ、チャイニーズ アカデミー オブ サイエンシーズShanghai Institute Of Materia Medica, Chinese Academy Of Sciences | Fgfr阻害活性を有する新規な化合物およびその製造と使用 |
Also Published As
Publication number | Publication date |
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BR9709443A (pt) | 1999-08-10 |
AU716383B2 (en) | 2000-02-24 |
NZ331804A (en) | 2000-04-28 |
EP0888353A1 (de) | 1999-01-07 |
BR9709443B1 (pt) | 2009-05-05 |
KR20000064601A (ko) | 2000-11-06 |
NO984199L (no) | 1998-11-05 |
CA2249739A1 (en) | 1997-09-25 |
WO1997034895A1 (de) | 1997-09-25 |
DE59710417D1 (de) | 2003-08-14 |
CN1216544A (zh) | 1999-05-12 |
JP4326024B2 (ja) | 2009-09-02 |
NO984199D0 (no) | 1998-09-11 |
NO313239B1 (no) | 2002-09-02 |
CN1079796C (zh) | 2002-02-27 |
AU2153497A (en) | 1997-10-10 |
US6051577A (en) | 2000-04-18 |
ATE244719T1 (de) | 2003-07-15 |
ES2203793T3 (es) | 2004-04-16 |
PT888353E (pt) | 2003-11-28 |
DK0888353T3 (da) | 2003-10-27 |
EP0888353B1 (de) | 2003-07-09 |
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