SK287833B6 - Antitumour compound, pharmaceutical composition containing it and its use - Google Patents

Info

Publication number

SK287833B6

SK287833B6 SK1601-2002A SK16012002A SK287833B6 SK 287833 B6 SK287833 B6 SK 287833B6 SK 16012002 A SK16012002 A SK 16012002A SK 287833 B6 SK287833 B6 SK 287833B6

Authority

SK

Slovakia

Prior art keywords

compound

alkyl

formula

alkenyl

carbon atoms

Prior art date

2000-05-15

Links

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 494
• 230000000259 anti-tumor effect Effects 0.000 title abstract description 6
• 239000008194 pharmaceutical composition Substances 0.000 title description 6
• -1 hydroxymethylene group Chemical group 0.000 claims abstract description 138
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 136
• 125000004432 carbon atom Chemical group C* 0.000 claims description 95
• 125000000217 alkyl group Chemical group 0.000 claims description 51
• 229910052739 hydrogen Inorganic materials 0.000 claims description 43
• 125000003342 alkenyl group Chemical group 0.000 claims description 39
• 235000001014 amino acid Nutrition 0.000 claims description 31
• 125000003118 aryl group Chemical group 0.000 claims description 31
• 239000001257 hydrogen Substances 0.000 claims description 31
• 125000006239 protecting group Chemical group 0.000 claims description 30
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
• 229910052760 oxygen Inorganic materials 0.000 claims description 19
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 16
• 150000001944 cysteine derivatives Chemical class 0.000 claims description 16
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 15
• 229910052757 nitrogen Inorganic materials 0.000 claims description 14
• 125000004442 acylamino group Chemical group 0.000 claims description 13
• 150000001413 amino acids Chemical class 0.000 claims description 13
• 239000001301 oxygen Substances 0.000 claims description 12
• 125000001072 heteroaryl group Chemical group 0.000 claims description 11
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 10
• 125000005842 heteroatom Chemical group 0.000 claims description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
• LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 claims description 9
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 9
• 125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims description 9
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 9
• 125000005018 aryl alkenyl group Chemical group 0.000 claims description 9
• 229910052799 carbon Inorganic materials 0.000 claims description 9
• 235000018417 cysteine Nutrition 0.000 claims description 9
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 9
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
• 229910052717 sulfur Inorganic materials 0.000 claims description 8
• 239000011593 sulfur Substances 0.000 claims description 8
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 7
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 7
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
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• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
• 239000004474 valine Substances 0.000 claims description 7
• 239000004475 Arginine Substances 0.000 claims description 6
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 6
• 235000004279 alanine Nutrition 0.000 claims description 6
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 6
• 239000004305 biphenyl Substances 0.000 claims description 6
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 5
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 5
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 5
• 235000010290 biphenyl Nutrition 0.000 claims description 5
• 150000002431 hydrogen Chemical class 0.000 claims description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
• 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 125000001624 naphthyl group Chemical group 0.000 claims description 4
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• 125000005843 halogen group Chemical group 0.000 claims description 3
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 3
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• 150000003839 salts Chemical class 0.000 claims description 2
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• 125000004404 heteroalkyl group Chemical group 0.000 claims 1
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• 125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 abstract description 6
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• 238000004440 column chromatography Methods 0.000 description 139
• 239000012044 organic layer Substances 0.000 description 138
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 126
• 229910004298 SiO 2 Inorganic materials 0.000 description 113
• 238000006243 chemical reaction Methods 0.000 description 105
• 239000002904 solvent Substances 0.000 description 103
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• 239000011734 sodium Substances 0.000 description 79
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• 150000003462 sulfoxides Chemical class 0.000 description 75
• 239000000543 intermediate Substances 0.000 description 68
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• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 64
• 229910052938 sodium sulfate Inorganic materials 0.000 description 63
• 235000011152 sodium sulphate Nutrition 0.000 description 63
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 60
• 238000000034 method Methods 0.000 description 53
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 51
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 50
• 229920006395 saturated elastomer Polymers 0.000 description 47
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• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 36
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• 125000002252 acyl group Chemical group 0.000 description 23
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• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 23
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• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 18
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