CA2535120A1 - Hydroxylamine substituted imidazo-containing compounds - Google Patents

Info

Publication number

CA2535120A1

CA2535120A1 CA002535120A CA2535120A CA2535120A1 CA 2535120 A1 CA2535120 A1 CA 2535120A1 CA 002535120 A CA002535120 A CA 002535120A CA 2535120 A CA2535120 A CA 2535120A CA 2535120 A1 CA2535120 A1 CA 2535120A1

Authority

CA

Canada

Prior art keywords

alkyl

group

aryl

alkylene

compound

Prior art date

2003-08-12

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 326
• AVXURJPOCDRRFD-UHFFFAOYSA-N hydroxylamine group Chemical group NO AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 title abstract description 11
• 238000000034 method Methods 0.000 claims abstract description 34
• 102000004127 Cytokines Human genes 0.000 claims abstract description 25
• 108090000695 Cytokines Proteins 0.000 claims abstract description 25
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 25
• 241001465754 Metazoa Species 0.000 claims abstract description 23
• 201000010099 disease Diseases 0.000 claims abstract description 23
• 230000015572 biosynthetic process Effects 0.000 claims abstract description 16
• 230000003612 virological effect Effects 0.000 claims abstract description 11
• 230000001613 neoplastic effect Effects 0.000 claims abstract description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
• 230000001939 inductive effect Effects 0.000 claims abstract description 5
• 125000000217 alkyl group Chemical group 0.000 claims description 346
• 229910052739 hydrogen Inorganic materials 0.000 claims description 334
• 239000001257 hydrogen Substances 0.000 claims description 334
• -1 heteroarylalkylenyl Chemical group 0.000 claims description 273
• 125000003118 aryl group Chemical group 0.000 claims description 246
• 125000001072 heteroaryl group Chemical group 0.000 claims description 196
• 125000003342 alkenyl group Chemical group 0.000 claims description 191
• 150000003839 salts Chemical class 0.000 claims description 181
• 125000000623 heterocyclic group Chemical group 0.000 claims description 174
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 161
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 147
• 229910052736 halogen Inorganic materials 0.000 claims description 124
• 125000002947 alkylene group Chemical group 0.000 claims description 117
• 150000002367 halogens Chemical class 0.000 claims description 117
• 125000001424 substituent group Chemical group 0.000 claims description 100
• 125000001188 haloalkyl group Chemical group 0.000 claims description 84
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 73
• 125000003545 alkoxy group Chemical group 0.000 claims description 72
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 70
• 125000004450 alkenylene group Chemical group 0.000 claims description 60
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 58
• 125000000304 alkynyl group Chemical group 0.000 claims description 57
• 125000005466 alkylenyl group Chemical group 0.000 claims description 48
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 47
• 125000000732 arylene group Chemical group 0.000 claims description 44
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 43
• 125000005549 heteroarylene group Chemical group 0.000 claims description 43
• 229910052757 nitrogen Inorganic materials 0.000 claims description 43
• 125000004419 alkynylene group Chemical group 0.000 claims description 38
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 38
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 38
• 125000005532 aryl alkyleneoxy group Chemical group 0.000 claims description 33
• 125000004104 aryloxy group Chemical group 0.000 claims description 33
• 229920006395 saturated elastomer Polymers 0.000 claims description 31
• 125000004414 alkyl thio group Chemical group 0.000 claims description 23
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 19
• 125000003282 alkyl amino group Chemical group 0.000 claims description 18
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 18
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
• 125000004043 oxo group Chemical group O=* 0.000 claims description 18
• 125000005529 alkyleneoxy group Chemical group 0.000 claims description 17
• 125000005842 heteroatom Chemical group 0.000 claims description 16
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 14
• 150000002825 nitriles Chemical class 0.000 claims description 14
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
• 230000002452 interceptive effect Effects 0.000 claims description 11
• 125000004076 pyridyl group Chemical group 0.000 claims description 10
• 229910052717 sulfur Inorganic materials 0.000 claims description 10
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 9
• 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 9
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 9
• 125000005275 alkylenearyl group Chemical group 0.000 claims description 5
• 125000005218 alkyleneheteroaryl group Chemical group 0.000 claims description 5
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 2
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 2
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
• 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 78
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 22
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 22
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 14
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical group [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 9
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 7
• 238000011282 treatment Methods 0.000 abstract description 11
• 239000000543 intermediate Substances 0.000 abstract description 8
• VFTLXHXYGQSOEN-UHFFFAOYSA-N 1h-imidazo[4,5-b][1,8]naphthyridine Chemical class C1=CN=C2NC3=NC=NC3=CC2=C1 VFTLXHXYGQSOEN-UHFFFAOYSA-N 0.000 abstract description 5
• 239000002955 immunomodulating agent Substances 0.000 abstract description 5
• 229940121354 immunomodulator Drugs 0.000 abstract description 5
• RHKWIGHJGOEUSM-UHFFFAOYSA-N 3h-imidazo[4,5-h]quinoline Chemical class C1=CN=C2C(N=CN3)=C3C=CC2=C1 RHKWIGHJGOEUSM-UHFFFAOYSA-N 0.000 abstract description 3
• 150000005232 imidazopyridines Chemical class 0.000 abstract description 2
• 238000006243 chemical reaction Methods 0.000 description 198
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 133
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 116
• 239000000243 solution Substances 0.000 description 105
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
• 101100513046 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) eth-1 gene Proteins 0.000 description 90
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 72
• 239000007787 solid Substances 0.000 description 70
• 239000000203 mixture Substances 0.000 description 69
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
• 239000000047 product Substances 0.000 description 54
• 239000002904 solvent Substances 0.000 description 54
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 46
• 238000007796 conventional method Methods 0.000 description 46
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 41
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
• ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 38
• TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 36
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 31
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 23
• 235000019341 magnesium sulphate Nutrition 0.000 description 23
• 238000012360 testing method Methods 0.000 description 22
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 21
• 239000003153 chemical reaction reagent Substances 0.000 description 21
• 238000001914 filtration Methods 0.000 description 21
• 239000010410 layer Substances 0.000 description 21
• 239000012267 brine Substances 0.000 description 20
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
• 239000000741 silica gel Substances 0.000 description 19
• 229910002027 silica gel Inorganic materials 0.000 description 19
• 238000005160 1H NMR spectroscopy Methods 0.000 description 18
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
• 239000000706 filtrate Substances 0.000 description 18
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 18
• 239000012043 crude product Substances 0.000 description 16
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 16
• 238000010828 elution Methods 0.000 description 16
• 239000002244 precipitate Substances 0.000 description 16
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 16
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 15
• 239000000908 ammonium hydroxide Substances 0.000 description 15
• 239000012044 organic layer Substances 0.000 description 15
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
• AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 14
• 238000010992 reflux Methods 0.000 description 14
• 238000003756 stirring Methods 0.000 description 14
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 13
• 239000002585 base Substances 0.000 description 13
• 239000011541 reaction mixture Substances 0.000 description 13
• CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 12
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
• 239000000843 powder Substances 0.000 description 12
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
• 235000017557 sodium bicarbonate Nutrition 0.000 description 12
• 238000010189 synthetic method Methods 0.000 description 12
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 11
• 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 11
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
• 102100040247 Tumor necrosis factor Human genes 0.000 description 10
• 238000004587 chromatography analysis Methods 0.000 description 10
• 150000002923 oximes Chemical class 0.000 description 10
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 10
• 229910052938 sodium sulfate Inorganic materials 0.000 description 10
• 235000011152 sodium sulphate Nutrition 0.000 description 10
• 229910052727 yttrium Inorganic materials 0.000 description 10
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 9
• 125000004122 cyclic group Chemical group 0.000 description 9
• 230000009467 reduction Effects 0.000 description 9
• 125000003396 thiol group Chemical group [H]S* 0.000 description 9
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
• FQYRLEXKXQRZDH-UHFFFAOYSA-N 4-aminoquinoline Chemical class C1=CC=C2C(N)=CC=NC2=C1 FQYRLEXKXQRZDH-UHFFFAOYSA-N 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 238000004458 analytical method Methods 0.000 description 8
• 125000004432 carbon atom Chemical group C* 0.000 description 8
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 8
• 125000005843 halogen group Chemical group 0.000 description 8
• 238000010438 heat treatment Methods 0.000 description 8
• 238000004519 manufacturing process Methods 0.000 description 8
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 8
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
• 229910000029 sodium carbonate Inorganic materials 0.000 description 8
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 8
• 206010028980 Neoplasm Diseases 0.000 description 7
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 7
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• 230000000694 effects Effects 0.000 description 7
• VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 7
• 230000028993 immune response Effects 0.000 description 7
• 239000007858 starting material Substances 0.000 description 7
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 7
• RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 6
• VMLKTERJLVWEJJ-UHFFFAOYSA-N 1,5-naphthyridine Chemical compound C1=CC=NC2=CC=CN=C21 VMLKTERJLVWEJJ-UHFFFAOYSA-N 0.000 description 6
• ITIRVXDSMXFTPW-UHFFFAOYSA-N 1H-imidazo[4,5-c]quinoline Chemical group C1=CC=CC2=C(NC=N3)C3=CN=C21 ITIRVXDSMXFTPW-UHFFFAOYSA-N 0.000 description 6
• HQBUPOAKJGJGCD-UHFFFAOYSA-N 3h-imidazo[4,5-c]quinolin-4-amine Chemical compound NC1=NC2=CC=CC=C2C2=C1N=CN2 HQBUPOAKJGJGCD-UHFFFAOYSA-N 0.000 description 6
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• 238000006751 Mitsunobu reaction Methods 0.000 description 6
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
• IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
• 150000001412 amines Chemical class 0.000 description 6
• 150000008064 anhydrides Chemical class 0.000 description 6
• 239000012298 atmosphere Substances 0.000 description 6
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 6
• 150000001805 chlorine compounds Chemical class 0.000 description 6
• 238000005859 coupling reaction Methods 0.000 description 6
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
• 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 6
• 238000005984 hydrogenation reaction Methods 0.000 description 6
• 230000006698 induction Effects 0.000 description 6
• 150000002576 ketones Chemical class 0.000 description 6
• GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 description 6
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
• WELPXTGIQIVGOG-UHFFFAOYSA-N o-[3-(4-amino-2-propylimidazo[4,5-c]quinolin-1-yl)propyl]hydroxylamine Chemical compound C1=CC=CC2=C(N(C(CCC)=N3)CCCON)C3=C(N)N=C21 WELPXTGIQIVGOG-UHFFFAOYSA-N 0.000 description 6
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 6
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 6
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 6
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• JAFMOTJMRSZOJE-UHFFFAOYSA-N 1,1,1-trimethoxybutane Chemical compound CCCC(OC)(OC)OC JAFMOTJMRSZOJE-UHFFFAOYSA-N 0.000 description 5
• 101150041968 CDC13 gene Proteins 0.000 description 5
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 5
• 239000012346 acetyl chloride Substances 0.000 description 5
• 239000003054 catalyst Substances 0.000 description 5
• 238000005119 centrifugation Methods 0.000 description 5
• 238000004440 column chromatography Methods 0.000 description 5
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 5
• 238000002953 preparative HPLC Methods 0.000 description 5
• 208000026079 recessive X-linked ichthyosis Diseases 0.000 description 5
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