SK88399A3 - Farnesyl transferase inhibitors - Google Patents

Info

Publication number

SK88399A3

SK88399A3 SK883-99A SK88399A SK88399A3 SK 88399 A3 SK88399 A3 SK 88399A3 SK 88399 A SK88399 A SK 88399A SK 88399 A3 SK88399 A3 SK 88399A3

Authority

SK

Slovakia

Prior art keywords

methoxyphenyl

3ars

hexahydro

isoindole

ethano

Prior art date

1996-12-30

Links

• Espacenet
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• 239000003528 protein farnesyltransferase inhibitor Substances 0.000 title description 5
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 128
• 238000002360 preparation method Methods 0.000 claims abstract description 96
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 53
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 53
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 52
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 49
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 46
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 43
• 239000001257 hydrogen Substances 0.000 claims abstract description 41
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 37
• 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 35
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 34
• 230000003287 optical effect Effects 0.000 claims abstract description 34
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 28
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 22
• 150000003839 salts Chemical class 0.000 claims abstract description 22
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
• 102000007317 Farnesyltranstransferase Human genes 0.000 claims abstract description 11
• 108010007508 Farnesyltranstransferase Proteins 0.000 claims abstract description 11
• 229910052736 halogen Chemical group 0.000 claims abstract description 11
• 150000002367 halogens Chemical group 0.000 claims abstract description 9
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims abstract description 6
• CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims abstract description 4
• 125000003367 polycyclic group Chemical group 0.000 claims abstract description 4
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 378
• 150000001875 compounds Chemical class 0.000 claims description 256
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 254
• -1 cyanomethyl Chemical group 0.000 claims description 220
• 125000003118 aryl group Chemical group 0.000 claims description 142
• 238000000034 method Methods 0.000 claims description 136
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 123
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 90
• 125000004432 carbon atom Chemical group C* 0.000 claims description 81
• 238000006243 chemical reaction Methods 0.000 claims description 75
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 68
• 239000011541 reaction mixture Substances 0.000 claims description 62
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 59
• 238000009835 boiling Methods 0.000 claims description 55
• 239000002253 acid Substances 0.000 claims description 48
• 239000003960 organic solvent Substances 0.000 claims description 42
• 239000001301 oxygen Substances 0.000 claims description 40
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 39
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 37
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 36
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 36
• 238000011282 treatment Methods 0.000 claims description 36
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 35
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 34
• 229910052757 nitrogen Inorganic materials 0.000 claims description 31
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 30
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 28
• 229920006395 saturated elastomer Polymers 0.000 claims description 28
• 125000003282 alkyl amino group Chemical group 0.000 claims description 26
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 25
• 150000003254 radicals Chemical class 0.000 claims description 25
• 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 24
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 24
• 125000005843 halogen group Chemical group 0.000 claims description 24
• 239000011593 sulfur Chemical group 0.000 claims description 24
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 22
• 125000006239 protecting group Chemical group 0.000 claims description 22
• 125000004434 sulfur atom Chemical group 0.000 claims description 22
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 21
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 21
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 20
• 125000003396 thiol group Chemical class [H]S* 0.000 claims description 20
• 125000003277 amino group Chemical group 0.000 claims description 19
• 230000008569 process Effects 0.000 claims description 19
• 125000005117 dialkylcarbamoyl group Chemical group 0.000 claims description 18
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 18
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 17
• 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 17
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 16
• 201000010099 disease Diseases 0.000 claims description 16
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 16
• WIXCPASTLDMTDB-UHFFFAOYSA-N isoindole-3a-carboxylic acid Chemical compound C1=CC=CC2(C(=O)O)C1=CN=C2 WIXCPASTLDMTDB-UHFFFAOYSA-N 0.000 claims description 16
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 15
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 14
• 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 14
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 13
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 13
• 125000004429 atom Chemical group 0.000 claims description 13
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 13
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 13
• 206010028980 Neoplasm Diseases 0.000 claims description 12
• 150000008064 anhydrides Chemical class 0.000 claims description 12
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 11
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 11
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 11
• 229910052763 palladium Inorganic materials 0.000 claims description 11
• 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 11
• 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 10
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 10
• 230000002401 inhibitory effect Effects 0.000 claims description 10
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 9
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 9
• 125000003342 alkenyl group Chemical group 0.000 claims description 9
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 9
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 9
• 238000007327 hydrogenolysis reaction Methods 0.000 claims description 9
• 238000003402 intramolecular cyclocondensation reaction Methods 0.000 claims description 9
• 230000004663 cell proliferation Effects 0.000 claims description 8
• 150000004820 halides Chemical class 0.000 claims description 8
• 150000002431 hydrogen Chemical class 0.000 claims description 8
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 7
• 238000005727 Friedel-Crafts reaction Methods 0.000 claims description 7
• 201000011510 cancer Diseases 0.000 claims description 7
• 150000004702 methyl esters Chemical class 0.000 claims description 7
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 7
• 239000002841 Lewis acid Substances 0.000 claims description 6
• 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 6
• 210000004556 brain Anatomy 0.000 claims description 6
• 210000000481 breast Anatomy 0.000 claims description 6
• 210000004027 cell Anatomy 0.000 claims description 6
• 150000007517 lewis acids Chemical class 0.000 claims description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 5
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 5
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 5
• 150000001412 amines Chemical group 0.000 claims description 5
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 5
• 210000001072 colon Anatomy 0.000 claims description 5
• 208000029742 colonic neoplasm Diseases 0.000 claims description 5
• GHXZPUGJZVBLGC-UHFFFAOYSA-N iodoethene Chemical group IC=C GHXZPUGJZVBLGC-UHFFFAOYSA-N 0.000 claims description 5
• 239000012948 isocyanate Substances 0.000 claims description 5
• 150000002513 isocyanates Chemical class 0.000 claims description 5
• 210000004072 lung Anatomy 0.000 claims description 5
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
• 230000001225 therapeutic effect Effects 0.000 claims description 5
• VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 claims description 4
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 4
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 4
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 4
• 206010009944 Colon cancer Diseases 0.000 claims description 4
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 4
• 150000001543 aryl boronic acids Chemical class 0.000 claims description 4
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
• 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 4
• 238000006482 condensation reaction Methods 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 210000004185 liver Anatomy 0.000 claims description 4
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
• 125000002950 monocyclic group Chemical group 0.000 claims description 4
• 201000002528 pancreatic cancer Diseases 0.000 claims description 4
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 3
• 208000007766 Kaposi sarcoma Diseases 0.000 claims description 3
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 3
• 201000004681 Psoriasis Diseases 0.000 claims description 3
• 238000006619 Stille reaction Methods 0.000 claims description 3
• 238000006069 Suzuki reaction reaction Methods 0.000 claims description 3
• 150000001450 anions Chemical class 0.000 claims description 3
• 210000000988 bone and bone Anatomy 0.000 claims description 3
• 230000001684 chronic effect Effects 0.000 claims description 3
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 3
• 150000002540 isothiocyanates Chemical class 0.000 claims description 3
• 125000001979 organolithium group Chemical group 0.000 claims description 3
• 125000002734 organomagnesium group Chemical group 0.000 claims description 3
• 208000037803 restenosis Diseases 0.000 claims description 3
• 238000007363 ring formation reaction Methods 0.000 claims description 3
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
• LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 claims description 2
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 2
• 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 2
• 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 2
• AOIQHOHWYAJBGN-UHFFFAOYSA-N COC1=C(C=CC=C1)C(C(=O)N1CC2(C3C4=C(C(C2C1)(CC3)C1=CC(=CC=C1)C)C=CC=C4)C(=O)OC)=C Chemical compound COC1=C(C=CC=C1)C(C(=O)N1CC2(C3C4=C(C(C2C1)(CC3)C1=CC(=CC=C1)C)C=CC=C4)C(=O)OC)=C AOIQHOHWYAJBGN-UHFFFAOYSA-N 0.000 claims description 2
• NICKMCPMZJATNT-UHFFFAOYSA-N COC1=CC=CC=2C3(C4CN(CC4(C(C=21)CC3)C(=O)OC)C(C(=C)C1=C(C=CC=C1)OC)=O)C1=CC=C(C=C1)C Chemical compound COC1=CC=CC=2C3(C4CN(CC4(C(C=21)CC3)C(=O)OC)C(C(=C)C1=C(C=CC=C1)OC)=O)C1=CC=C(C=C1)C NICKMCPMZJATNT-UHFFFAOYSA-N 0.000 claims description 2
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 2
• 201000009030 Carcinoma Diseases 0.000 claims description 2
• 208000006332 Choriocarcinoma Diseases 0.000 claims description 2
• 206010018338 Glioma Diseases 0.000 claims description 2
• 208000017604 Hodgkin disease Diseases 0.000 claims description 2
• 206010025323 Lymphomas Diseases 0.000 claims description 2
• 208000008383 Wilms tumor Diseases 0.000 claims description 2
• 210000004100 adrenal gland Anatomy 0.000 claims description 2
• 125000004849 alkoxymethyl group Chemical group 0.000 claims description 2
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 claims description 2
• WLJVXDMOQOGPHL-UHFFFAOYSA-N benzyl-alpha-carboxylic acid Natural products OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 claims description 2
• 210000000601 blood cell Anatomy 0.000 claims description 2
• 208000006990 cholangiocarcinoma Diseases 0.000 claims description 2
• 210000002808 connective tissue Anatomy 0.000 claims description 2
• FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohex-2-enone Chemical class O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 claims description 2
• 210000002249 digestive system Anatomy 0.000 claims description 2
• 230000005764 inhibitory process Effects 0.000 claims description 2
• 210000000936 intestine Anatomy 0.000 claims description 2
• 230000001926 lymphatic effect Effects 0.000 claims description 2
• 210000004324 lymphatic system Anatomy 0.000 claims description 2
• 230000003211 malignant effect Effects 0.000 claims description 2
• 201000001441 melanoma Diseases 0.000 claims description 2
• 210000003205 muscle Anatomy 0.000 claims description 2
• 210000000056 organ Anatomy 0.000 claims description 2
• 230000002611 ovarian Effects 0.000 claims description 2
• 210000000496 pancreas Anatomy 0.000 claims description 2
• 229960003424 phenylacetic acid Drugs 0.000 claims description 2
• 239000003279 phenylacetic acid Substances 0.000 claims description 2
• ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical group [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 claims description 2
• 230000003439 radiotherapeutic effect Effects 0.000 claims description 2
• 210000005227 renal system Anatomy 0.000 claims description 2
• 210000003491 skin Anatomy 0.000 claims description 2
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 claims description 2
• 238000012360 testing method Methods 0.000 claims description 2
• 210000001550 testis Anatomy 0.000 claims description 2
• 210000001685 thyroid gland Anatomy 0.000 claims description 2
• 210000001519 tissue Anatomy 0.000 claims description 2
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 2
• URZSOMZSASLCGC-UHFFFAOYSA-N 1-(4-chlorophenyl)-11-[2-(2-methoxyphenyl)prop-2-enoyl]-11-azatetracyclo[6.5.2.02,7.09,13]pentadeca-2,4,6-triene-9-carboxylic acid Chemical compound COC1=CC=CC=C1C(=C)C(=O)N1CC(C(O)=O)(C2C3=CC=CC=C3C3(C=4C=CC(Cl)=CC=4)CC2)C3C1 URZSOMZSASLCGC-UHFFFAOYSA-N 0.000 claims 1
• YOUFEADCSHUSQK-UHFFFAOYSA-N 1-(4-methoxyphenyl)-11-[2-(2-methoxyphenyl)prop-2-enoyl]-8-methyl-11-azatetracyclo[6.5.2.02,7.09,13]pentadeca-2,4,6-triene-9-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1(C2CN(CC22C(O)=O)C(=O)C(=C)C=3C(=CC=CC=3)OC)C3=CC=CC=C3C2(C)CC1 YOUFEADCSHUSQK-UHFFFAOYSA-N 0.000 claims 1
• ASMYOVNRBKBQHA-UHFFFAOYSA-N 11-[2-(2-methoxyphenyl)prop-2-enoyl]-1-(4-propan-2-ylphenyl)-11-azatetracyclo[6.5.2.02,7.09,13]pentadeca-2,4,6-triene-9-carboxylic acid Chemical compound COC1=CC=CC=C1C(=C)C(=O)N1CC(C(O)=O)(C2C3=CC=CC=C3C3(C=4C=CC(=CC=4)C(C)C)CC2)C3C1 ASMYOVNRBKBQHA-UHFFFAOYSA-N 0.000 claims 1
• SWLNLVQJRDCTNA-UHFFFAOYSA-N 2,3,8,8a,9,9a-hexahydro-1h-benzo[f]isoindole Chemical compound C1=CCC2CC3CNCC3=CC2=C1 SWLNLVQJRDCTNA-UHFFFAOYSA-N 0.000 claims 1
• YDHIMEXEGOCNHU-UHFFFAOYSA-N 2-pyridin-3-ylacetamide Chemical compound NC(=O)CC1=CC=CN=C1 YDHIMEXEGOCNHU-UHFFFAOYSA-N 0.000 claims 1
• 238000006584 Barton reaction Methods 0.000 claims 1
• 208000034578 Multiple myelomas Diseases 0.000 claims 1
• VPQDJSGQSNLEJE-UHFFFAOYSA-L [Cl-].[Cl-].[Ce+2] Chemical compound [Cl-].[Cl-].[Ce+2] VPQDJSGQSNLEJE-UHFFFAOYSA-L 0.000 claims 1
• 230000001154 acute effect Effects 0.000 claims 1
• 125000000129 anionic group Chemical group 0.000 claims 1
• 210000003714 granulocyte Anatomy 0.000 claims 1
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• 239000000546 pharmaceutical excipient Substances 0.000 claims 1
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• 208000001608 teratocarcinoma Diseases 0.000 claims 1
• 239000003814 drug Substances 0.000 abstract description 7
• 230000000719 anti-leukaemic effect Effects 0.000 abstract description 2
• 239000003112 inhibitor Substances 0.000 abstract description 2
• 125000002947 alkylene group Chemical group 0.000 abstract 1
• 229940079593 drug Drugs 0.000 abstract 1
• 150000002391 heterocyclic compounds Chemical class 0.000 abstract 1
• 230000002476 tumorcidal effect Effects 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 447
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 191
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 180
• 239000000243 solution Substances 0.000 description 139
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 117
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 114
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 112
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 99
• 239000000741 silica gel Substances 0.000 description 86
• 229910002027 silica gel Inorganic materials 0.000 description 86
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 74
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 74
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 65
• 238000003818 flash chromatography Methods 0.000 description 63
• 238000001819 mass spectrum Methods 0.000 description 61
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