JP2006515886A - 化合物、組成物、および方法 - Google Patents

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Publication number

JP2006515886A

JP2006515886A JP2006501021A JP2006501021A JP2006515886A JP 2006515886 A JP2006515886 A JP 2006515886A JP 2006501021 A JP2006501021 A JP 2006501021A JP 2006501021 A JP2006501021 A JP 2006501021A JP 2006515886 A JP2006515886 A JP 2006515886A

Authority

JP

Japan

Prior art keywords

optionally substituted

alkyl

hydrogen

compound

substituted

Prior art date

2003-01-17

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.)

Pending

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 317
• 238000000034 method Methods 0.000 title claims description 66
• 239000000203 mixture Substances 0.000 title claims description 61
• 230000000694 effects Effects 0.000 claims abstract description 45
• 230000002062 proliferating effect Effects 0.000 claims abstract description 13
• -1 amino, amino Chemical group 0.000 claims description 369
• 229910052739 hydrogen Inorganic materials 0.000 claims description 136
• 239000001257 hydrogen Substances 0.000 claims description 132
• 125000000217 alkyl group Chemical group 0.000 claims description 100
• 150000002431 hydrogen Chemical class 0.000 claims description 76
• 125000001072 heteroaryl group Chemical group 0.000 claims description 73
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 68
• 125000003107 substituted aryl group Chemical group 0.000 claims description 67
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 61
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 55
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 52
• 102000010638 Kinesin Human genes 0.000 claims description 51
• 108010063296 Kinesin Proteins 0.000 claims description 51
• 150000003839 salts Chemical class 0.000 claims description 51
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 50
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 46
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 44
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 37
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
• 125000003545 alkoxy group Chemical group 0.000 claims description 34
• 125000000623 heterocyclic group Chemical group 0.000 claims description 34
• 206010028980 Neoplasm Diseases 0.000 claims description 30
• 229910052760 oxygen Inorganic materials 0.000 claims description 30
• 239000012453 solvate Substances 0.000 claims description 29
• 229910052717 sulfur Inorganic materials 0.000 claims description 28
• 125000005842 heteroatom Chemical group 0.000 claims description 27
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 24
• 125000006178 methyl benzyl group Chemical group 0.000 claims description 24
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 23
• 239000003814 drug Substances 0.000 claims description 23
• 201000011510 cancer Diseases 0.000 claims description 22
• 125000004803 chlorobenzyl group Chemical group 0.000 claims description 22
• 125000002946 cyanobenzyl group Chemical group 0.000 claims description 22
• 125000006289 hydroxybenzyl group Chemical group 0.000 claims description 22
• 229910052757 nitrogen Inorganic materials 0.000 claims description 21
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 18
• 208000035475 disorder Diseases 0.000 claims description 17
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 16
• 125000002947 alkylene group Chemical group 0.000 claims description 15
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 15
• 125000002883 imidazolyl group Chemical group 0.000 claims description 14
• 125000001424 substituent group Chemical group 0.000 claims description 13
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
• 125000002252 acyl group Chemical group 0.000 claims description 11
• 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 11
• 125000003386 piperidinyl group Chemical group 0.000 claims description 11
• 125000004076 pyridyl group Chemical group 0.000 claims description 11
• 125000003944 tolyl group Chemical group 0.000 claims description 11
• 239000002246 antineoplastic agent Substances 0.000 claims description 10
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 10
• 125000001624 naphthyl group Chemical group 0.000 claims description 10
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
• 125000002541 furyl group Chemical group 0.000 claims description 9
• 125000005415 substituted alkoxy group Chemical group 0.000 claims description 9
• 230000002401 inhibitory effect Effects 0.000 claims description 8
• 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims description 8
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
• 125000002636 imidazolinyl group Chemical group 0.000 claims description 7
• 125000002757 morpholinyl group Chemical group 0.000 claims description 7
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 6
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
• 201000010099 disease Diseases 0.000 claims description 6
• 125000001041 indolyl group Chemical group 0.000 claims description 6
• 125000004193 piperazinyl group Chemical class 0.000 claims description 6
• 125000001544 thienyl group Chemical class 0.000 claims description 6
• 206010061218 Inflammation Diseases 0.000 claims description 5
• 229940123237 Taxane Drugs 0.000 claims description 5
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
• 125000002393 azetidinyl group Chemical group 0.000 claims description 5
• 229940127089 cytotoxic agent Drugs 0.000 claims description 5
• DHZYXWMZLAKTQV-UHFFFAOYSA-N diazepin-3-one Chemical class O=C1C=CC=CN=N1 DHZYXWMZLAKTQV-UHFFFAOYSA-N 0.000 claims description 5
• 125000006286 dichlorobenzyl group Chemical group 0.000 claims description 5
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
• 230000004054 inflammatory process Effects 0.000 claims description 5
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 4
• 206010007572 Cardiac hypertrophy Diseases 0.000 claims description 4
• 208000006029 Cardiomegaly Diseases 0.000 claims description 4
• MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 claims description 4
• 125000004104 aryloxy group Chemical group 0.000 claims description 4
• 125000004799 bromophenyl group Chemical group 0.000 claims description 4
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 4
• 125000004802 cyanophenyl group Chemical group 0.000 claims description 4
• 125000005059 halophenyl group Chemical group 0.000 claims description 4
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
• 206010020718 hyperplasia Diseases 0.000 claims description 4
• 208000026278 immune system disease Diseases 0.000 claims description 4
• 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 claims description 4
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 4
• 125000006513 pyridinyl methyl group Chemical group 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical class 0.000 claims description 4
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
• 208000037803 restenosis Diseases 0.000 claims description 4
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 3
• 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 claims description 3
• 239000000365 Topoisomerase I Inhibitor Substances 0.000 claims description 3
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
• 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 3
• 125000004414 alkyl thio group Chemical group 0.000 claims description 3
• 125000000499 benzofuranyl group Chemical class O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
• 150000003857 carboxamides Chemical class 0.000 claims description 3
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
• 125000000068 chlorophenyl group Chemical group 0.000 claims description 3
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
• 125000006202 diisopropylaminoethyl group Chemical group [H]C([H])([H])C([H])(N(C([H])([H])C([H])([H])*)C([H])(C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
• 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 3
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
• HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims description 3
• 125000002098 pyridazinyl group Chemical class 0.000 claims description 3
• 229940122803 Vinca alkaloid Drugs 0.000 claims description 2
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 2
• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 2
• 125000005874 benzothiadiazolyl group Chemical group 0.000 claims description 2
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
• 125000005048 dihydroisoxazolyl group Chemical class O1N(CC=C1)* 0.000 claims description 2
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
• 125000004372 methylthioethyl group Chemical group [H]C([H])([H])SC([H])([H])C([H])([H])* 0.000 claims description 2
• 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 2
• PGAWFZNQHGVJDJ-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-(3-benzyl-4-oxopyrido[1,2-a]pyrimidin-2-yl)-2-methylpropyl]-4-methylbenzamide Chemical compound N1=C2C=CC=CN2C(=O)C(CC=2C=CC=CC=2)=C1C(C(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 PGAWFZNQHGVJDJ-UHFFFAOYSA-N 0.000 claims description 2
• CUWXSSDSZFPYID-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-(5-benzyl-1,2-dimethyl-6-oxopyrimidin-4-yl)-2-methylpropyl]-4-methylbenzamide Chemical compound N1=C(C)N(C)C(=O)C(CC=2C=CC=CC=2)=C1C(C(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 CUWXSSDSZFPYID-UHFFFAOYSA-N 0.000 claims description 2
• DMCQQNWUZYMBLF-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-(5-benzyl-2-methyl-4-oxo-1h-pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide Chemical compound N1=C(C)NC(=O)C(CC=2C=CC=CC=2)=C1C(C(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 DMCQQNWUZYMBLF-UHFFFAOYSA-N 0.000 claims description 2
• DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims 6
• 125000003047 N-acetyl group Chemical group 0.000 claims 2
• UHBGYFCCKRAEHA-UHFFFAOYSA-N P-toluamide Chemical compound CC1=CC=C(C(N)=O)C=C1 UHBGYFCCKRAEHA-UHFFFAOYSA-N 0.000 claims 2
• 238000004519 manufacturing process Methods 0.000 claims 2
• 125000005958 tetrahydrothienyl group Chemical class 0.000 claims 1
• 208000037765 diseases and disorders Diseases 0.000 abstract description 2
• 239000000243 solution Substances 0.000 description 102
• 238000006243 chemical reaction Methods 0.000 description 98
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 70
• 210000004027 cell Anatomy 0.000 description 63
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
• 239000000126 substance Substances 0.000 description 41
• 230000000394 mitotic effect Effects 0.000 description 40
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
• 239000000047 product Substances 0.000 description 36
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
• 125000003118 aryl group Chemical group 0.000 description 31
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• YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 description 12
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