CA2571360C - Substituted imidazoquinolines, imidazopyridines, and imidazonaphthyridines useful in inducing cytokine biosynthesis in animals - Google Patents
Substituted imidazoquinolines, imidazopyridines, and imidazonaphthyridines useful in inducing cytokine biosynthesis in animals Download PDFInfo
- Publication number
- CA2571360C CA2571360C CA2571360A CA2571360A CA2571360C CA 2571360 C CA2571360 C CA 2571360C CA 2571360 A CA2571360 A CA 2571360A CA 2571360 A CA2571360 A CA 2571360A CA 2571360 C CA2571360 C CA 2571360C
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- Prior art keywords
- group
- alkyl
- hydrogen
- alkylene
- heteroaryl
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- 102000004127 Cytokines Human genes 0.000 title claims abstract description 25
- 108090000695 Cytokines Proteins 0.000 title claims abstract description 25
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 24
- 230000001939 inductive effect Effects 0.000 title claims abstract description 8
- 241001465754 Metazoa Species 0.000 title abstract description 19
- 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 title abstract description 3
- RHKWIGHJGOEUSM-UHFFFAOYSA-N 3h-imidazo[4,5-h]quinoline Chemical class C1=CN=C2C(N=CN3)=C3C=CC2=C1 RHKWIGHJGOEUSM-UHFFFAOYSA-N 0.000 title description 2
- 150000005232 imidazopyridines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 261
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 28
- 201000010099 disease Diseases 0.000 claims abstract description 26
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 230000003612 virological effect Effects 0.000 claims abstract description 12
- 230000001613 neoplastic effect Effects 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 359
- 229910052739 hydrogen Inorganic materials 0.000 claims description 214
- 239000001257 hydrogen Substances 0.000 claims description 214
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 204
- -1 nitro, hydroxy, mercapto Chemical group 0.000 claims description 181
- 125000001072 heteroaryl group Chemical group 0.000 claims description 168
- 150000003839 salts Chemical class 0.000 claims description 148
- 125000003118 aryl group Chemical group 0.000 claims description 144
- 125000000623 heterocyclic group Chemical group 0.000 claims description 137
- 125000003342 alkenyl group Chemical group 0.000 claims description 131
- 125000003545 alkoxy group Chemical group 0.000 claims description 114
- 125000002947 alkylene group Chemical group 0.000 claims description 113
- 229910052736 halogen Inorganic materials 0.000 claims description 105
- 150000002367 halogens Chemical class 0.000 claims description 105
- 125000000304 alkynyl group Chemical group 0.000 claims description 89
- 125000005466 alkylenyl group Chemical group 0.000 claims description 66
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 55
- 125000001188 haloalkyl group Chemical group 0.000 claims description 55
- 229920006395 saturated elastomer Polymers 0.000 claims description 52
- 229910052757 nitrogen Inorganic materials 0.000 claims description 44
- 125000004414 alkyl thio group Chemical group 0.000 claims description 41
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 41
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 36
- 125000005842 heteroatom Chemical group 0.000 claims description 34
- 125000001424 substituent group Chemical group 0.000 claims description 33
- 125000003282 alkyl amino group Chemical group 0.000 claims description 29
- 125000005529 alkyleneoxy group Chemical group 0.000 claims description 28
- 125000005532 aryl alkyleneoxy group Chemical group 0.000 claims description 28
- 125000004104 aryloxy group Chemical group 0.000 claims description 28
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 28
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 28
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 28
- 125000004043 oxo group Chemical group O=* 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 23
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 22
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 22
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 22
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 20
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical class [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 claims description 19
- 125000005962 1,4-oxazepanyl group Chemical class 0.000 claims description 19
- 125000002393 azetidinyl group Chemical class 0.000 claims description 19
- 125000004069 aziridinyl group Chemical class 0.000 claims description 19
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 19
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 19
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 19
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 19
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 19
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 19
- 125000002883 imidazolyl group Chemical group 0.000 claims description 19
- 125000001041 indolyl group Chemical group 0.000 claims description 19
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 19
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 19
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 19
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 19
- 125000002757 morpholinyl group Chemical class 0.000 claims description 19
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 19
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 19
- 125000002971 oxazolyl group Chemical group 0.000 claims description 19
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 19
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 19
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 19
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 19
- 125000004076 pyridyl group Chemical group 0.000 claims description 19
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 19
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 19
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 19
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 19
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 19
- 125000004621 quinuclidinyl group Chemical class N12C(CC(CC1)CC2)* 0.000 claims description 19
- 125000001412 tetrahydropyranyl group Chemical class 0.000 claims description 19
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 claims description 19
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 19
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 19
- 125000000335 thiazolyl group Chemical group 0.000 claims description 19
- 125000001544 thienyl group Chemical group 0.000 claims description 19
- 125000004568 thiomorpholinyl group Chemical class 0.000 claims description 19
- 125000004306 triazinyl group Chemical group 0.000 claims description 19
- 125000001425 triazolyl group Chemical group 0.000 claims description 19
- 125000002541 furyl group Chemical group 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 8
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 7
- 150000008575 L-amino acids Chemical class 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 5
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 150000001413 amino acids Chemical class 0.000 claims description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 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 2
- 125000003396 thiol group Chemical class [H]S* 0.000 claims 9
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 41
- 150000003530 tetrahydroquinolines Chemical class 0.000 abstract description 3
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 abstract description 2
- 229940111121 antirheumatic drug quinolines Drugs 0.000 abstract description 2
- SQQXRXKYTKFFSM-UHFFFAOYSA-N chembl1992147 Chemical compound OC1=C(OC)C(OC)=CC=C1C1=C(C)C(C(O)=O)=NC(C=2N=C3C4=NC(C)(C)N=C4C(OC)=C(O)C3=CC=2)=C1N SQQXRXKYTKFFSM-UHFFFAOYSA-N 0.000 abstract description 2
- 229940124669 imidazoquinoline Drugs 0.000 abstract description 2
- 239000002955 immunomodulating agent Substances 0.000 abstract description 2
- 229940121354 immunomodulator Drugs 0.000 abstract description 2
- 150000003222 pyridines Chemical class 0.000 abstract description 2
- 150000003248 quinolines Chemical class 0.000 abstract description 2
- VMLKTERJLVWEJJ-UHFFFAOYSA-N 1,5-naphthyridine Chemical class C1=CC=NC2=CC=CN=C21 VMLKTERJLVWEJJ-UHFFFAOYSA-N 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 317
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 209
- 238000006243 chemical reaction Methods 0.000 description 197
- 239000000243 solution Substances 0.000 description 136
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 129
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 114
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 109
- 239000000203 mixture Substances 0.000 description 100
- 239000007787 solid Substances 0.000 description 92
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 72
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 72
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 72
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 69
- 239000003921 oil Substances 0.000 description 59
- 235000019198 oils Nutrition 0.000 description 59
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 52
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
- 239000002904 solvent Substances 0.000 description 49
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 47
- 239000012044 organic layer Substances 0.000 description 47
- 239000000047 product Substances 0.000 description 43
- 238000007796 conventional method Methods 0.000 description 38
- 150000001412 amines Chemical class 0.000 description 37
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 36
- 235000019341 magnesium sulphate Nutrition 0.000 description 36
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- 239000000741 silica gel Substances 0.000 description 33
- 229910002027 silica gel Inorganic materials 0.000 description 33
- 239000012267 brine Substances 0.000 description 31
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 239000013078 crystal Substances 0.000 description 29
- 239000010410 layer Substances 0.000 description 28
- 238000003818 flash chromatography Methods 0.000 description 27
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 27
- 239000000706 filtrate Substances 0.000 description 25
- 238000001914 filtration Methods 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 23
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- 125000000732 arylene group Chemical group 0.000 description 22
- 125000004450 alkenylene group Chemical group 0.000 description 21
- 125000004419 alkynylene group Chemical group 0.000 description 21
- 239000003795 chemical substances by application Substances 0.000 description 21
- 125000005549 heteroarylene group Chemical group 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- 238000010992 reflux Methods 0.000 description 21
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 20
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 20
- 239000007832 Na2SO4 Substances 0.000 description 20
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 235000011114 ammonium hydroxide Nutrition 0.000 description 20
- 229910052938 sodium sulfate Inorganic materials 0.000 description 20
- 235000011152 sodium sulphate Nutrition 0.000 description 20
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 19
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 19
- 150000003573 thiols Chemical class 0.000 description 19
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 17
- 239000006260 foam Substances 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- 239000000908 ammonium hydroxide Substances 0.000 description 16
- ZPMWWAIBJJFPPQ-UHFFFAOYSA-N 2-ethoxyacetyl chloride Chemical compound CCOCC(Cl)=O ZPMWWAIBJJFPPQ-UHFFFAOYSA-N 0.000 description 15
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 14
- ZRFUZDDJSQVQBY-UHFFFAOYSA-N 4-chloro-3-nitroquinoline Chemical compound C1=CC=CC2=C(Cl)C([N+](=O)[O-])=CN=C21 ZRFUZDDJSQVQBY-UHFFFAOYSA-N 0.000 description 13
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- 239000007858 starting material Substances 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 238000005984 hydrogenation reaction Methods 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 238000010189 synthetic method Methods 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 11
- 125000004122 cyclic group Chemical group 0.000 description 11
- 238000010828 elution Methods 0.000 description 11
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 11
- 239000000651 prodrug Substances 0.000 description 11
- 229940002612 prodrug Drugs 0.000 description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 230000028993 immune response Effects 0.000 description 10
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 10
- 101150041968 CDC13 gene Proteins 0.000 description 9
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- 235000017550 sodium carbonate Nutrition 0.000 description 9
- 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 8
- 239000002253 acid Substances 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 150000002576 ketones Chemical class 0.000 description 8
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 8
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 8
- 239000003039 volatile agent Substances 0.000 description 8
- 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 7
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 7
- 206010028980 Neoplasm Diseases 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 7
- 125000000524 functional group Chemical group 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 7
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US58127404P | 2004-06-18 | 2004-06-18 | |
| US60/581,274 | 2004-06-18 | ||
| PCT/US2005/021445 WO2006028545A2 (en) | 2004-06-18 | 2005-06-17 | Substituted imidazoquinolines, imidazopyridines, and imidazonaphthyridines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2571360A1 CA2571360A1 (en) | 2006-03-16 |
| CA2571360C true CA2571360C (en) | 2014-11-25 |
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| CA2571360A Expired - Fee Related CA2571360C (en) | 2004-06-18 | 2005-06-17 | Substituted imidazoquinolines, imidazopyridines, and imidazonaphthyridines useful in inducing cytokine biosynthesis in animals |
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| Country | Link |
|---|---|
| US (1) | US7884207B2 (enExample) |
| EP (1) | EP1765348B1 (enExample) |
| JP (1) | JP5128940B2 (enExample) |
| AU (1) | AU2005283085B2 (enExample) |
| CA (1) | CA2571360C (enExample) |
| WO (1) | WO2006028545A2 (enExample) |
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| WO2003103584A2 (en) | 2002-06-07 | 2003-12-18 | 3M Innovative Properties Company | Ether substituted imidazopyridines |
| US20040265351A1 (en) | 2003-04-10 | 2004-12-30 | Miller Richard L. | Methods and compositions for enhancing immune response |
| RU2006105101A (ru) * | 2003-08-27 | 2007-10-10 | 3М Инновейтив Пропертиз Компани (US) | Арилокси и арилалкиленокси замещенные имидазохинолины |
| WO2005023190A2 (en) | 2003-09-05 | 2005-03-17 | 3M Innovative Properties Company | Treatment for cd5+ b cell lymphoma |
| US8871782B2 (en) | 2003-10-03 | 2014-10-28 | 3M Innovative Properties Company | Alkoxy substituted imidazoquinolines |
| US7544697B2 (en) | 2003-10-03 | 2009-06-09 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridines and analogs thereof |
| AR046172A1 (es) | 2003-10-03 | 2005-11-30 | 3M Innovative Properties Co | Pirazolopiridinas y sus analogos; composiciones farmaceuticas que los contienen y su uso en la inhibicion de la biosintesis de citocinas |
| AR046781A1 (es) | 2003-11-25 | 2005-12-21 | 3M Innovative Properties Co | Derivados de imidazoquinolinas. composiciones farmaceuticas. |
| WO2006065280A2 (en) | 2004-06-18 | 2006-06-22 | 3M Innovative Properties Company | Isoxazole, dihydroisoxazole, and oxadiazole substituted imidazo ring compounds and methods |
| US8541438B2 (en) * | 2004-06-18 | 2013-09-24 | 3M Innovative Properties Company | Substituted imidazoquinolines, imidazopyridines, and imidazonaphthyridines |
| WO2006028962A2 (en) | 2004-09-02 | 2006-03-16 | 3M Innovative Properties Company | 1-alkoxy 1h-imidazo ring systems and methods |
| AU2005326708C1 (en) | 2004-12-30 | 2012-08-30 | 3M Innovative Properties Company | Substituted chiral fused [1,2]imidazo[4,5-c] ring compounds |
| EP1831226B1 (en) | 2004-12-30 | 2012-08-08 | 3M Innovative Properties Company | Chiral tetracyclic compounds inducing interferon biosynthesis |
| AU2006210392A1 (en) | 2005-02-04 | 2006-08-10 | Coley Pharmaceutical Group, Inc. | Aqueous gel formulations containing immune response modifiers |
| AU2006212765B2 (en) * | 2005-02-09 | 2012-02-02 | 3M Innovative Properties Company | Alkyloxy substituted thiazoloquinolines and thiazolonaphthyridines |
| JP2008530252A (ja) | 2005-02-09 | 2008-08-07 | コーリー ファーマシューティカル グループ，インコーポレイテッド | オキシムおよびヒドロキシルアミンで置換されたチアゾロ［４，５−ｃ］環化合物ならびに方法 |
| JP2008532933A (ja) * | 2005-02-11 | 2008-08-21 | コーリー ファーマシューティカル グループ，インコーポレイテッド | 置換イミダゾキノリン類および置換イミダゾナフチリジン類 |
| CA2597587A1 (en) | 2005-02-11 | 2006-08-17 | Coley Pharmaceutical Group, Inc. | Oxime and hydroxylamine substituted imidazo[4,5-c] ring compounds and methods |
| US8158794B2 (en) * | 2005-02-23 | 2012-04-17 | 3M Innovative Properties Company | Hydroxyalkyl substituted imidazoquinoline compounds and methods |
| CA2598639A1 (en) | 2005-02-23 | 2006-08-31 | Coley Pharmaceutical Group, Inc. | Hydroxyalkyl substituted imidazonaphthyridines |
| EP1850849A2 (en) * | 2005-02-23 | 2007-11-07 | Coley Pharmaceutical Group, Inc. | Method of preferentially inducing the biosynthesis of interferon |
| EP1851224A2 (en) * | 2005-02-23 | 2007-11-07 | 3M Innovative Properties Company | Hydroxyalkyl substituted imidazoquinolines |
| US7943636B2 (en) * | 2005-04-01 | 2011-05-17 | 3M Innovative Properties Company | 1-substituted pyrazolo (3,4-C) ring compounds as modulators of cytokine biosynthesis for the treatment of viral infections and neoplastic diseases |
| WO2006107853A2 (en) | 2005-04-01 | 2006-10-12 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridine-1,4-diamines and analogs thereof |
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| WO2006028545A2 (en) | 2006-03-16 |
| US7884207B2 (en) | 2011-02-08 |
| EP1765348A2 (en) | 2007-03-28 |
| CA2571360A1 (en) | 2006-03-16 |
| AU2005283085A1 (en) | 2006-03-16 |
| EP1765348B1 (en) | 2016-08-03 |
| AU2005283085B2 (en) | 2012-06-21 |
| EP1765348A4 (en) | 2010-05-26 |
| JP5128940B2 (ja) | 2013-01-23 |
| WO2006028545A3 (en) | 2007-08-23 |
| JP2008503484A (ja) | 2008-02-07 |
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