JP3157165B2 - 抗腫瘍化合物、医薬組成物、それらの調製方法及び治療方法 - Google Patents
抗腫瘍化合物、医薬組成物、それらの調製方法及び治療方法Info
- Publication number
- JP3157165B2 JP3157165B2 JP52219294A JP52219294A JP3157165B2 JP 3157165 B2 JP3157165 B2 JP 3157165B2 JP 52219294 A JP52219294 A JP 52219294A JP 52219294 A JP52219294 A JP 52219294A JP 3157165 B2 JP3157165 B2 JP 3157165B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- hydrogen
- carbon atoms
- phenyl
- tert
- 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
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 62
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 3
- 238000002360 preparation method Methods 0.000 title description 25
- 230000000259 anti-tumor effect Effects 0.000 title description 9
- 229940123237 Taxane Drugs 0.000 claims abstract description 39
- 238000000034 method Methods 0.000 claims abstract description 37
- 229930190007 Baccatin Natural products 0.000 claims abstract description 4
- -1 isooctyl Chemical group 0.000 claims description 525
- 229910052739 hydrogen Inorganic materials 0.000 claims description 110
- 239000001257 hydrogen Substances 0.000 claims description 109
- 125000004432 carbon atom Chemical group C* 0.000 claims description 94
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 76
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 74
- 125000001072 heteroaryl group Chemical group 0.000 claims description 54
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 52
- 125000000217 alkyl group Chemical group 0.000 claims description 50
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 49
- 125000003342 alkenyl group Chemical group 0.000 claims description 46
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 44
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 42
- 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 42
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 42
- 125000003118 aryl group Chemical group 0.000 claims description 41
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 39
- 150000003952 β-lactams Chemical class 0.000 claims description 38
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 37
- 125000004122 cyclic group Chemical group 0.000 claims description 36
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 35
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 35
- 150000002431 hydrogen Chemical class 0.000 claims description 34
- 125000000304 alkynyl group Chemical group 0.000 claims description 32
- 125000002252 acyl group Chemical group 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 29
- 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 29
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 29
- 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 29
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 28
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 26
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 claims description 26
- 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 26
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 26
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 25
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 claims description 24
- 125000003944 tolyl group Chemical group 0.000 claims description 24
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 22
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 22
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 21
- UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 claims description 20
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 20
- 125000002541 furyl group Chemical group 0.000 claims description 20
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 20
- 125000004076 pyridyl group Chemical group 0.000 claims description 20
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 20
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 19
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 19
- 125000000286 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 19
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 18
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
- 125000003107 substituted aryl group Chemical group 0.000 claims description 18
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 18
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 17
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 16
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 16
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 15
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 15
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 15
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 claims description 15
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000003386 piperidinyl group Chemical group 0.000 claims description 15
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 15
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 15
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 15
- 229920002554 vinyl polymer Polymers 0.000 claims description 15
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 14
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 14
- 125000005110 aryl thio group Chemical group 0.000 claims description 14
- 239000004305 biphenyl Substances 0.000 claims description 14
- 235000010290 biphenyl Nutrition 0.000 claims description 14
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 14
- 125000001624 naphthyl group Chemical group 0.000 claims description 14
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 14
- 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 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000003282 alkyl amino group Chemical group 0.000 claims description 13
- NKLCHDQGUHMCGL-UHFFFAOYSA-N cyclohexylidenemethanone Chemical group O=C=C1CCCCC1 NKLCHDQGUHMCGL-UHFFFAOYSA-N 0.000 claims description 13
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 claims description 12
- 125000003277 amino group Chemical group 0.000 claims description 12
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 12
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical group C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 claims description 12
- 230000002194 synthesizing effect Effects 0.000 claims description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims description 11
- 125000004104 aryloxy group Chemical group 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 claims description 11
- 125000003229 2-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 10
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 10
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 10
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 claims description 10
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 10
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 10
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 10
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 10
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 10
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims description 10
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 claims description 10
- 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 claims description 10
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
- 125000000466 oxiranyl group Chemical group 0.000 claims description 10
- 239000011734 sodium Substances 0.000 claims description 10
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 10
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 claims description 8
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 7
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 7
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 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
- ZMJJCODMIXQWCQ-UHFFFAOYSA-N potassium;di(propan-2-yl)azanide Chemical compound [K+].CC(C)[N-]C(C)C ZMJJCODMIXQWCQ-UHFFFAOYSA-N 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- YHOBGCSGTGDMLF-UHFFFAOYSA-N sodium;di(propan-2-yl)azanide Chemical compound [Na+].CC(C)[N-]C(C)C YHOBGCSGTGDMLF-UHFFFAOYSA-N 0.000 claims description 6
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 5
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 5
- 125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 5
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000003074 decanoyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 claims description 5
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 5
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 5
- 125000000268 heptanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[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 5
- 125000000400 lauroyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
- QQZOPKMRPOGIEB-UHFFFAOYSA-N n-butyl methyl ketone Natural products CCCCC(C)=O QQZOPKMRPOGIEB-UHFFFAOYSA-N 0.000 claims description 5
- 125000001402 nonanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 125000005592 polycycloalkyl group Polymers 0.000 claims description 5
- 125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 5
- 239000012312 sodium hydride Substances 0.000 claims description 5
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 5
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 5
- 125000000297 undecanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 4
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 claims description 3
- 229910000105 potassium hydride Inorganic materials 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims 11
- 125000003396 thiol group Chemical group [H]S* 0.000 claims 11
- 125000005368 heteroarylthio group Chemical group 0.000 claims 10
- 238000001308 synthesis method Methods 0.000 claims 8
- 125000005587 carbonate group Chemical group 0.000 claims 4
- SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 claims 4
- 229910000103 lithium hydride Inorganic materials 0.000 claims 4
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 claims 4
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 claims 4
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 4
- PYFHBOKDODRNSV-UHFFFAOYSA-N C1(=CC=CC=C1)C=C(CCC)C(C(OC=C=C=C=COC=C)=C(CCC)CCC)C(C(C(C(C)C)=C)(CC)CC)=C Chemical group C1(=CC=CC=C1)C=C(CCC)C(C(OC=C=C=C=COC=C)=C(CCC)CCC)C(C(C(C(C)C)=C)(CC)CC)=C PYFHBOKDODRNSV-UHFFFAOYSA-N 0.000 claims 3
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 claims 2
- 125000003963 dichloro group Chemical group Cl* 0.000 claims 2
- RSHAOIXHUHAZPM-UHFFFAOYSA-N magnesium hydride Chemical compound [MgH2] RSHAOIXHUHAZPM-UHFFFAOYSA-N 0.000 claims 2
- 229910012375 magnesium hydride Inorganic materials 0.000 claims 2
- 239000011591 potassium Substances 0.000 claims 2
- 229910052700 potassium Inorganic materials 0.000 claims 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims 1
- 235000014676 Phragmites communis Nutrition 0.000 claims 1
- 239000003610 charcoal Substances 0.000 claims 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
- 125000005553 heteroaryloxy group Chemical group 0.000 claims 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims 1
- 238000010189 synthetic method Methods 0.000 claims 1
- 238000005859 coupling reaction Methods 0.000 abstract description 10
- 206010028980 Neoplasm Diseases 0.000 abstract description 9
- 239000002246 antineoplastic agent Substances 0.000 abstract description 8
- 239000002243 precursor Substances 0.000 abstract description 5
- 229940127089 cytotoxic agent Drugs 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 101
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- 239000007787 solid Substances 0.000 description 38
- 239000000243 solution Substances 0.000 description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 238000004458 analytical method Methods 0.000 description 33
- 239000011541 reaction mixture Substances 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 235000019439 ethyl acetate Nutrition 0.000 description 25
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- CJCYABFPESVRKC-VIMPDCIZSA-N taxane ia Chemical compound O([C@H]1[C@H]2[C@@](C(C(=O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)C=4C=CC=CC=4)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 CJCYABFPESVRKC-VIMPDCIZSA-N 0.000 description 1
- QRCRZVITFSCZAR-PXWJKWRZSA-N tert-butyl (2s,3r)-2-(cyclohexylmethyl)-3-(1-ethoxyethoxy)-4-oxoazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(=O)[C@H](OC(C)OCC)[C@@H]1CC1CCCCC1 QRCRZVITFSCZAR-PXWJKWRZSA-N 0.000 description 1
- PLAUIGSDHJXQIK-JQXSQYPDSA-N tert-butyl (2s,3r)-2-cyclohexyl-3-(1-ethoxyethoxy)-4-oxoazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(=O)[C@H](OC(C)OCC)[C@@H]1C1CCCCC1 PLAUIGSDHJXQIK-JQXSQYPDSA-N 0.000 description 1
- PVKINVVDOGIDEK-LWNNLKQOSA-N tert-butyl (2s,3r)-3-(1-ethoxyethoxy)-2-(2-methylpropyl)-4-oxoazetidine-1-carboxylate Chemical compound CCOC(C)O[C@@H]1[C@H](CC(C)C)N(C(=O)OC(C)(C)C)C1=O PVKINVVDOGIDEK-LWNNLKQOSA-N 0.000 description 1
- WBVQQBOHJVFBFQ-MWSTZMHHSA-N tert-butyl (3r,4s)-3-(1-ethoxyethoxy)-2-oxo-4-(2-phenylethenyl)azetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(=O)[C@H](OC(C)OCC)[C@@H]1C=CC1=CC=CC=C1 WBVQQBOHJVFBFQ-MWSTZMHHSA-N 0.000 description 1
- CZTZICYNMYGUNU-JQXSQYPDSA-N tert-butyl (3r,4s)-3-(1-ethoxyethoxy)-2-oxo-4-phenylazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(=O)[C@H](OC(C)OCC)[C@@H]1C1=CC=CC=C1 CZTZICYNMYGUNU-JQXSQYPDSA-N 0.000 description 1
- PDBCRPKYNWQALZ-QWHCGFSZSA-N tert-butyl (3r,4s)-3-acetyl-2-oxo-4-phenylazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(=O)[C@@H](C(=O)C)[C@H]1C1=CC=CC=C1 PDBCRPKYNWQALZ-QWHCGFSZSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epoxy Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US040,189 | 1993-03-26 | ||
| US08/040,189 | 1993-03-26 | ||
| US08/040,189 US5475011A (en) | 1993-03-26 | 1993-03-26 | Anti-tumor compounds, pharmaceutical compositions, methods for preparation thereof and for treatment |
| PCT/US1994/003215 WO1994022856A1 (en) | 1993-03-26 | 1994-03-24 | Anti-tumor compounds, pharmaceutical compositions, methods for preparation thereof and for treatment |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10293599A Division JP3145993B2 (ja) | 1993-03-26 | 1999-04-09 | 抗腫瘍化合物及びその調製方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH08508497A JPH08508497A (ja) | 1996-09-10 |
| JP3157165B2 true JP3157165B2 (ja) | 2001-04-16 |
Family
ID=21909617
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP52219294A Expired - Fee Related JP3157165B2 (ja) | 1993-03-26 | 1994-03-24 | 抗腫瘍化合物、医薬組成物、それらの調製方法及び治療方法 |
| JP10293599A Expired - Fee Related JP3145993B2 (ja) | 1993-03-26 | 1999-04-09 | 抗腫瘍化合物及びその調製方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10293599A Expired - Fee Related JP3145993B2 (ja) | 1993-03-26 | 1999-04-09 | 抗腫瘍化合物及びその調製方法 |
Country Status (19)
| Country | Link |
|---|---|
| US (3) | US5475011A (enExample) |
| EP (1) | EP0690856B1 (enExample) |
| JP (2) | JP3157165B2 (enExample) |
| KR (1) | KR100223720B1 (enExample) |
| CN (1) | CN1067682C (enExample) |
| AT (1) | ATE229018T1 (enExample) |
| AU (1) | AU676041B2 (enExample) |
| CA (1) | CA2158147C (enExample) |
| CZ (1) | CZ288924B6 (enExample) |
| DE (1) | DE69431833T2 (enExample) |
| DK (1) | DK0690856T3 (enExample) |
| ES (1) | ES2190440T3 (enExample) |
| HU (1) | HUT73848A (enExample) |
| NO (1) | NO311722B1 (enExample) |
| PL (2) | PL179587B1 (enExample) |
| PT (1) | PT690856E (enExample) |
| RU (1) | RU2137764C1 (enExample) |
| SK (1) | SK282317B6 (enExample) |
| WO (1) | WO1994022856A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015004022A (ja) * | 2013-06-24 | 2015-01-08 | 株式会社パイロットコーポレーション | 熱消色性筆記具インキ組成物及びそれを内蔵した筆記具 |
Families Citing this family (80)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6335362B1 (en) * | 1991-09-23 | 2002-01-01 | Florida State University | Taxanes having an alkyl substituted side-chain and pharmaceutical compositions containing them |
| US5475011A (en) * | 1993-03-26 | 1995-12-12 | The Research Foundation Of State University Of New York | Anti-tumor compounds, pharmaceutical compositions, methods for preparation thereof and for treatment |
| US6005120A (en) | 1993-07-20 | 1999-12-21 | Florida State University | Tricyclic and tetracyclic taxanes |
| FR2718137B1 (fr) * | 1994-04-05 | 1996-04-26 | Rhone Poulenc Rorer Sa | Procédé de préparation de trialcoylsilyl-7 baccatine III. |
| US5763477A (en) * | 1994-07-22 | 1998-06-09 | Dr. Reddy's Research Foundation | Taxane derivatives from 14-β-hydroxy-10 deacetylbaccatin III |
| IT1275936B1 (it) * | 1995-03-17 | 1997-10-24 | Indena Spa | Derivati della 10-deacetilbaccatina iii e della 10-deacetil-14b- idrossibaccatina iii loro metodo di preparazione e formulazioni |
| BR9608040B1 (pt) | 1995-04-28 | 2010-02-23 | composto taxàide pentacÍclico. | |
| IT1275435B (it) * | 1995-05-19 | 1997-08-07 | Indena Spa | Derivati della 10-desacetil-14beta-idrossibaccatina iii,loro metodo di preparazione e formulazioni che li contengono |
| EP0747372A1 (en) * | 1995-06-06 | 1996-12-11 | Dr. Reddy's Research Foundation | Taxane derivatives from 14-beta-hydroxy-10 deacetybaccatin III |
| US5654448A (en) * | 1995-10-02 | 1997-08-05 | Xechem International, Inc. | Isolation and purification of paclitaxel from organic matter containing paclitaxel, cephalomannine and other related taxanes |
| US5840748A (en) * | 1995-10-02 | 1998-11-24 | Xechem International, Inc. | Dihalocephalomannine and methods of use therefor |
| US5807888A (en) * | 1995-12-13 | 1998-09-15 | Xechem International, Inc. | Preparation of brominated paclitaxel analogues and their use as effective antitumor agents |
| US6177456B1 (en) | 1995-10-02 | 2001-01-23 | Xechem International, Inc. | Monohalocephalomannines having anticancer and antileukemic activity and method of preparation therefor |
| US5854278A (en) * | 1995-12-13 | 1998-12-29 | Xechem International, Inc. | Preparation of chlorinated paclitaxel analogues and use thereof as antitumor agents |
| US5688977A (en) * | 1996-02-29 | 1997-11-18 | Napro Biotherapeutics, Inc. | Method for docetaxel synthesis |
| KR20040097250A (ko) | 1996-05-24 | 2004-11-17 | 유니버시티 오브 브리티시 콜롬비아 | 신체 통로의 질병을 치료 또는 예방하기 위한 조성물 및방법 |
| AU3572397A (en) * | 1996-07-02 | 1998-01-21 | Bristol-Myers Squibb Company | Ortho-ester analogs of paclitaxel |
| KR100225535B1 (ko) * | 1996-08-27 | 1999-10-15 | 정지석 | 파클리탁셀의 제조방법 |
| EP0868422A1 (de) * | 1996-09-24 | 1998-10-07 | Marigen S.A. | Ultramikroemulsionen aus spontan dispergierbaren konzentraten mit antitumoral und antiviral wirksamen estern von baccatin-iii-verbindungen |
| US6515016B2 (en) * | 1996-12-02 | 2003-02-04 | Angiotech Pharmaceuticals, Inc. | Composition and methods of paclitaxel for treating psoriasis |
| US5811452A (en) * | 1997-01-08 | 1998-09-22 | The Research Foundation Of State University Of New York | Taxoid reversal agents for drug-resistance in cancer chemotherapy and pharmaceutical compositions thereof |
| US7288665B1 (en) | 1997-08-18 | 2007-10-30 | Florida State University | Process for selective derivatization of taxanes |
| DK1019347T3 (da) | 1997-08-21 | 2003-07-21 | Univ Florida State | Fremgangsmåde til syntesen af taxaner |
| US6235782B1 (en) | 1998-11-12 | 2001-05-22 | Rifat Pamukcu | Method for treating a patient with neoplasia by treatment with a platinum coordination complex |
| US6235776B1 (en) | 1998-11-12 | 2001-05-22 | Cell Pathways, Inc. | Method for treating a patient with neoplasia by treatment with a paclitaxel derivative |
| ITMI991483A1 (it) * | 1999-07-06 | 2001-01-06 | Indena Spa | Derivati tassanici e procedimenti per la loro preparazione |
| AU775373B2 (en) | 1999-10-01 | 2004-07-29 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
| CA2386772C (en) * | 1999-10-15 | 2009-01-13 | Daiichi Pharmaceutical Co., Ltd. | Pentacyclic taxane compound |
| EP1242401B1 (en) * | 1999-11-24 | 2006-12-27 | Immunogen, Inc. | Cytotoxic agents comprising taxanes and their therapeutic use |
| HUP0200756A3 (en) * | 2000-02-02 | 2005-02-28 | Univ Florida State Res Found | C7 carbonate substituted taxanes as antitumor agents and pharmaceutical compositions containing them |
| US6649632B2 (en) | 2000-02-02 | 2003-11-18 | Fsu Research Foundation, Inc. | C10 ester substituted taxanes |
| EP1165550A1 (en) | 2000-02-02 | 2002-01-02 | Florida State University Research Foundation, Inc. | C10 carbonate substituted taxanes as antitumor agents |
| JP2003522172A (ja) * | 2000-02-02 | 2003-07-22 | フロリダ・ステイト・ユニバーシティ・リサーチ・ファウンデイション・インコーポレイテッド | 抗腫瘍剤としてのｃ１０エステル置換タキサン |
| US6916942B2 (en) * | 2000-02-03 | 2005-07-12 | Bristol-Myers Squibb Company | Process for the preparation of C-4 carbonate taxanes |
| US6750246B1 (en) * | 2000-02-03 | 2004-06-15 | Bristol-Myers Squibb Company | C-4 carbonate taxanes |
| IT1318678B1 (it) * | 2000-08-10 | 2003-08-27 | Indena Spa | Procedimento per la preparazione di derivati della baccatina iii. |
| IT1320107B1 (it) * | 2000-11-28 | 2003-11-18 | Indena Spa | Procedimento per la preparazione di derivati tassanici. |
| US6449899B1 (en) * | 2001-03-08 | 2002-09-17 | Council Of Scientific And Industrial Research | Method for inducing improved seed germination in Podophyllum hexandrum Royle |
| ITMI20012185A1 (it) * | 2001-10-19 | 2003-04-19 | Indena Spa | Procedimento per la preparazione della 14beta-idrossi-baccatina iii-1,14-carbonato |
| ITMI20012186A1 (it) * | 2001-10-19 | 2003-04-19 | Indena Spa | Procedimento per la preparazione della 14-beta-idrossi-baccatina iii-1,14-carbonato |
| TWI333856B (en) * | 2001-11-29 | 2010-12-01 | Daiichi Seiyaku Co | Crystals of taxane and process for their production |
| US7390898B2 (en) * | 2002-08-02 | 2008-06-24 | Immunogen Inc. | Cytotoxic agents containing novel potent taxanes and their therapeutic use |
| BR0313197A (pt) | 2002-08-02 | 2005-08-09 | Immunogen Inc | Agentes citotóxicos contendo potentes taxanos e seu uso terapêutico |
| ITMI20021921A1 (it) | 2002-09-10 | 2004-03-11 | Indena Spa | Funzionalizzazione della posizione 14 dei nuclei tassanici e sintesi di nuovi derivati antitumorali. |
| CA2501805C (en) * | 2002-10-09 | 2012-05-22 | Phytogen Life Sciences, Inc. | Novel taxanes and methods related to use and preparation thereof |
| US7064980B2 (en) * | 2003-09-17 | 2006-06-20 | Sandisk Corporation | Non-volatile memory and method with bit line coupled compensation |
| US7202370B2 (en) * | 2003-10-27 | 2007-04-10 | Conor Medsystems, Inc. | Semi-synthesis of taxane intermediates from 9-dihydro-13-acetylbaccatin III |
| PE20050693A1 (es) * | 2004-02-13 | 2005-09-27 | Univ Florida State Res Found | Taxanos sustituidos con esteres de ciclopentilo en c10 |
| TW200533339A (en) * | 2004-03-16 | 2005-10-16 | Bristol Myers Squibb Co | Therapeutic synergy of anti-cancer compounds |
| AU2004224925C1 (en) * | 2004-08-30 | 2011-07-21 | Biotest Ag | Immunoconjugates targeting syndecan-1 expressing cells and use thereof |
| US7446126B2 (en) * | 2004-10-08 | 2008-11-04 | Indena S.P.A. | Semisynthesis process for the preparation of 10-deacetyl-N-debenzoyl-paclitaxel |
| MX2007009748A (es) * | 2005-02-14 | 2007-09-26 | Univ Florida State Res Found | Composiciones de taxano sustituidas con esteres ciclopropilicos en c10. |
| EP2428510A3 (en) * | 2005-03-31 | 2012-06-13 | Accord Healthcare Inc. | Preparation of taxanes from 9-dihydro-13-acetylbaccatin III |
| US8207358B2 (en) * | 2005-11-04 | 2012-06-26 | Accord Healthcare Ltd. | Methods for the preparation of taxanes using chiral auxiliaries |
| CN100516067C (zh) * | 2006-01-10 | 2009-07-22 | 上海恒瑞医药有限公司 | 具有抗肿瘤活性的紫杉酚衍生物 |
| US7615653B2 (en) * | 2006-03-15 | 2009-11-10 | The Research Foundation Of State University Of New York | Anti-tuberculosis taxane compounds |
| US20100137221A1 (en) * | 2007-02-27 | 2010-06-03 | University Utah Research Foundation | Peptides that interact with topoisomerase i and methods thereof |
| RU2370261C2 (ru) * | 2007-08-03 | 2009-10-20 | Закрытое Акционерное Общество "Биокад" | Стабильная эмульсия для парентерального введения плохо растворимых в воде соединений, обладающих противоопухолевой активностью, и способ ее получения |
| ES2526433T3 (es) * | 2007-12-26 | 2015-01-12 | Biotest Ag | Inmunoconjugados dirigidos a CD138 y usos de los mismos |
| JP2011507933A (ja) * | 2007-12-26 | 2011-03-10 | バイオテスト・アクチエンゲゼルシヤフト | 免疫複合体の細胞傷害性副作用の低減及び有効性の改善方法 |
| AR069981A1 (es) * | 2007-12-26 | 2010-03-03 | Biotest Ag | Los "anticuerpo modificado geneticamente que reconocen cd138". |
| AU2008339913B2 (en) * | 2007-12-26 | 2014-03-20 | Biotest Ag | Methods and agents for improving targeting of CD138 expressing tumor cells |
| DK2080764T3 (da) | 2008-01-18 | 2012-09-24 | Indena Spa | Faste former af ortataxel |
| EP2080763A1 (en) * | 2008-01-18 | 2009-07-22 | INDENA S.p.A. | Crystalline form I of ortataxel |
| US8242166B2 (en) * | 2008-03-31 | 2012-08-14 | Florida State University Research Foundation, Inc. | C(10) ethyl ester and C(10) cyclopropyl ester substituted taxanes |
| KR101764927B1 (ko) | 2008-04-30 | 2017-08-03 | 이뮤노젠 아이엔씨 | 가교제 및 그 용도 |
| US8790691B2 (en) | 2008-05-23 | 2014-07-29 | The University Of British Columbia | Modified drugs for use in liposomal nanoparticles |
| CN101838281B (zh) * | 2010-05-20 | 2015-02-18 | 上海博速医药科技有限公司 | 一种多西他赛手性侧链中间体的制备方法 |
| JP5605511B2 (ja) | 2011-08-02 | 2014-10-15 | アステラス製薬株式会社 | 薬剤の併用による癌治療方法 |
| KR20140100571A (ko) | 2011-12-08 | 2014-08-14 | 바이오테스트 아게 | Ｃｄ１３８을 타겟팅하는 면역접합체의 용도 |
| US10131682B2 (en) | 2012-11-24 | 2018-11-20 | Hangzhou Dac Biotech Co., Ltd. | Hydrophilic linkers and their uses for conjugation of drugs to a cell binding molecules |
| CN104650109B (zh) * | 2013-11-22 | 2019-01-01 | 江苏天士力帝益药业有限公司 | 紫杉烷类化合物 |
| CN106414465B (zh) | 2014-02-28 | 2021-11-16 | 杭州多禧生物科技有限公司 | 带电荷链接体及其在共轭反应上的应用 |
| US9557445B2 (en) | 2015-02-24 | 2017-01-31 | Arkema France | Optical diffusion blend materials for LED lighting |
| EP4678240A2 (en) | 2015-07-12 | 2026-01-14 | Hangzhou Dac Biotech Co., Ltd. | Bridge linkers for conjugation of cell-binding molecules |
| US9839687B2 (en) | 2015-07-15 | 2017-12-12 | Suzhou M-Conj Biotech Co., Ltd. | Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule |
| KR20220150408A (ko) | 2016-11-14 | 2022-11-10 | 항저우 디에이씨 바이오테크 씨오, 엘티디 | 결합 링커, 그러한 결합 링커를 함유하는 세포 결합 분자-약물 결합체, 링커를 갖는 그러한 결합체의 제조 및 사용 |
| AU2019223076A1 (en) | 2018-02-21 | 2020-10-08 | Celgene Corporation | BCMA-binding antibodies and uses thereof |
| CN109485593A (zh) * | 2018-12-12 | 2019-03-19 | 福建紫杉园生物有限公司 | 一种拉洛他赛手性侧链的合成工艺 |
| JP2024541058A (ja) | 2021-11-03 | 2024-11-06 | ハンジョウ ディーエーシー バイオテック シーオー．，エルティディ． | 抗体の特異的共役 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4876399A (en) * | 1987-11-02 | 1989-10-24 | Research Corporation Technologies, Inc. | Taxols, their preparation and intermediates thereof |
| FR2629819B1 (fr) * | 1988-04-06 | 1990-11-16 | Rhone Poulenc Sante | Procede de preparation de derives de la baccatine iii et de la desacetyl-10 baccatine iii |
| US4857683A (en) * | 1988-12-28 | 1989-08-15 | W. H. Brady Co. | Membrane switchcores with key cell contact elements connected together for continuous path testing |
| US4960790A (en) * | 1989-03-09 | 1990-10-02 | University Of Kansas | Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof |
| US5175315A (en) * | 1989-05-31 | 1992-12-29 | Florida State University | Method for preparation of taxol using β-lactam |
| US5015744A (en) * | 1989-11-14 | 1991-05-14 | Florida State University | Method for preparation of taxol using an oxazinone |
| US5015722A (en) * | 1990-04-04 | 1991-05-14 | Hoechst Celanese Corporation | Melt-processable polyester capable of forming an anisotropic melt which exhibits a highly attractive balance between its molding and heat deflection temperatures |
| MX9102128A (es) * | 1990-11-23 | 1992-07-08 | Rhone Poulenc Rorer Sa | Derivados de taxano,procedimiento para su preparacion y composicion farmaceutica que los contiene |
| IT1254517B (it) * | 1992-03-06 | 1995-09-25 | Indena Spa | 14-beta idrossi-10-deacetil-baccatina iii, suoi derivati, loro prepazione ed impiego terapeutico |
| FR2698363B1 (fr) * | 1992-11-23 | 1994-12-30 | Rhone Poulenc Rorer Sa | Nouveaux dérivés du taxane, leur préparation et les compositions qui les contiennent. |
| US5475011A (en) * | 1993-03-26 | 1995-12-12 | The Research Foundation Of State University Of New York | Anti-tumor compounds, pharmaceutical compositions, methods for preparation thereof and for treatment |
-
1993
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-
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Non-Patent Citations (2)
| Title |
|---|
| Ｊ．Ｃｈｅｍ．Ｓｏｃ．，Ｐｅｒｋｉｎ Ｔｒａｎｓ．１，Ｎｏ．１４，ｐ．１５６３−１５６６（１９９３） |
| Ｊ．Ｍｅｄ．Ｃｈｅｍ．，Ｖｏｌ．３７，Ｎｏ．１０，ｐ．１４０８−１４１０（１９９４） |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015004022A (ja) * | 2013-06-24 | 2015-01-08 | 株式会社パイロットコーポレーション | 熱消色性筆記具インキ組成物及びそれを内蔵した筆記具 |
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