CA1289137C - Imidazoquinolinylether derivatives - Google Patents
Imidazoquinolinylether derivativesInfo
- Publication number
- CA1289137C CA1289137C CA000537720A CA537720A CA1289137C CA 1289137 C CA1289137 C CA 1289137C CA 000537720 A CA000537720 A CA 000537720A CA 537720 A CA537720 A CA 537720A CA 1289137 C CA1289137 C CA 1289137C
- Authority
- CA
- Canada
- Prior art keywords
- compound
- imidazo
- dihydro
- quinolin
- oxo
- 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
- MOJBIJPADSWXCM-UHFFFAOYSA-N 2-(3h-imidazo[4,5-h]quinolin-2-yloxy)-3h-imidazo[4,5-h]quinoline Chemical class C1=CC=NC2=C(NC(OC=3NC4=C5N=CC=CC5=CC=C4N=3)=N3)C3=CC=C21 MOJBIJPADSWXCM-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 158
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 69
- -1 oxo ketone Chemical class 0.000 claims abstract description 57
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 30
- 239000001257 hydrogen Substances 0.000 claims abstract description 30
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 25
- 150000002148 esters Chemical class 0.000 claims abstract description 25
- 210000001772 blood platelet Anatomy 0.000 claims abstract description 19
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 13
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 13
- 150000002367 halogens Chemical group 0.000 claims abstract description 13
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims abstract description 12
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 75
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 70
- 150000003839 salts Chemical class 0.000 claims description 67
- 239000002253 acid Substances 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 43
- 125000004432 carbon atom Chemical group C* 0.000 claims description 34
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 19
- 229910052740 iodine Inorganic materials 0.000 claims description 19
- 239000011630 iodine Substances 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 229940091173 hydantoin Drugs 0.000 claims description 13
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 13
- 239000000463 material Substances 0.000 claims description 12
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims description 10
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 9
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 claims description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
- 150000001469 hydantoins Chemical class 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 150000002576 ketones Chemical class 0.000 claims description 8
- 150000001408 amides Chemical class 0.000 claims 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 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical group CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 230000002829 reductive effect Effects 0.000 claims description 6
- XNHZEJRZFBXTOB-UHFFFAOYSA-N 4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanoic acid Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCCC(=O)O)=CC=C21 XNHZEJRZFBXTOB-UHFFFAOYSA-N 0.000 claims description 5
- 230000000297 inotrophic effect Effects 0.000 claims description 5
- 239000007800 oxidant agent Substances 0.000 claims description 5
- 230000001590 oxidative effect Effects 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 239000012458 free base Substances 0.000 claims description 4
- 230000003301 hydrolyzing effect Effects 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- ZKPTVJPUVOPSSN-UHFFFAOYSA-N 7-(3-hydroxypropoxy)-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCCO)=CC=C21 ZKPTVJPUVOPSSN-UHFFFAOYSA-N 0.000 claims description 3
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 claims description 3
- 229940095074 cyclic amp Drugs 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- WORHBDQKZCWBBV-UHFFFAOYSA-N 4-[(1-methyl-2-oxo-3h-imidazo[4,5-b]quinolin-7-yl)oxy]butanoic acid Chemical compound OC(=O)CCCOC1=CC=C2N=C(NC(N3C)=O)C3=CC2=C1 WORHBDQKZCWBBV-UHFFFAOYSA-N 0.000 claims description 2
- VUHFMTBOSKAVGD-UHFFFAOYSA-N 5-[(1-methyl-2-oxo-3h-imidazo[4,5-b]quinolin-7-yl)oxy]pentanoic acid Chemical compound OC(=O)CCCCOC1=CC=C2N=C(NC(N3C)=O)C3=CC2=C1 VUHFMTBOSKAVGD-UHFFFAOYSA-N 0.000 claims description 2
- BJHINFNFMZFKMO-UHFFFAOYSA-N 7-(2-ethoxyethoxy)-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCOCC)=CC=C21 BJHINFNFMZFKMO-UHFFFAOYSA-N 0.000 claims description 2
- AOAQFGRPXBJZPI-UHFFFAOYSA-N 7-(4-hydroxypentoxy)-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCCC(O)C)=CC=C21 AOAQFGRPXBJZPI-UHFFFAOYSA-N 0.000 claims description 2
- IIRDWOWRQLOSDT-UHFFFAOYSA-N 7-[2-hydroxy-3-(propan-2-ylamino)propoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCC(O)CNC(C)C)=CC=C21 IIRDWOWRQLOSDT-UHFFFAOYSA-N 0.000 claims description 2
- CXKZVQGXPZXMLT-UHFFFAOYSA-N 7-[3-(benzenesulfonyl)propoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound C=1C=C2N=C3NC(=O)NC3=CC2=CC=1OCCCS(=O)(=O)C1=CC=CC=C1 CXKZVQGXPZXMLT-UHFFFAOYSA-N 0.000 claims description 2
- 150000001414 amino alcohols Chemical class 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- QJCPQIHEKQJMJL-UHFFFAOYSA-N methyl 4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanoate Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCCC(=O)OC)=CC=C21 QJCPQIHEKQJMJL-UHFFFAOYSA-N 0.000 claims description 2
- HWFONEMQJJUUCU-UHFFFAOYSA-N n-cycloheptyl-n-methyl-4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanamide Chemical compound C=1C=C2N=C3NC(=O)NC3=CC2=CC=1OCCCC(=O)N(C)C1CCCCCC1 HWFONEMQJJUUCU-UHFFFAOYSA-N 0.000 claims description 2
- RBJPQMVNZAIYKC-UHFFFAOYSA-N n-cyclohexyl-n-methyl-4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanamide Chemical compound C=1C=C2N=C3NC(=O)NC3=CC2=CC=1OCCCC(=O)N(C)C1CCCCC1 RBJPQMVNZAIYKC-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- XZOWIJDBQIHMFC-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O.CCCC(N)=O XZOWIJDBQIHMFC-UHFFFAOYSA-N 0.000 claims 2
- NEXQSNFNHKOAMU-UHFFFAOYSA-N 1-methyl-7-(4-oxo-4-piperidin-1-ylbutoxy)-3h-imidazo[4,5-b]quinolin-2-one Chemical compound C=1C=C2N=C3NC(=O)N(C)C3=CC2=CC=1OCCCC(=O)N1CCCCC1 NEXQSNFNHKOAMU-UHFFFAOYSA-N 0.000 claims 1
- ANBLGOPBKUCVNY-UHFFFAOYSA-N 2-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]acetic acid Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCC(=O)O)=CC=C21 ANBLGOPBKUCVNY-UHFFFAOYSA-N 0.000 claims 1
- IYFJFKYCOWHMMW-UHFFFAOYSA-N 2-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]ethyl acetate Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCOC(=O)C)=CC=C21 IYFJFKYCOWHMMW-UHFFFAOYSA-N 0.000 claims 1
- QCGGKODVYQZPLC-UHFFFAOYSA-N 3-(2,3-dihydro-1h-imidazo[4,5-b]quinolin-7-yloxy)propyl acetate Chemical compound N1=C2NCNC2=CC2=CC(OCCCOC(=O)C)=CC=C21 QCGGKODVYQZPLC-UHFFFAOYSA-N 0.000 claims 1
- YVEQUTSPFYJJAS-UHFFFAOYSA-N 3-tert-butyl-5-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxymethyl]-1,3-oxazolidin-2-one Chemical compound O1C(=O)N(C(C)(C)C)CC1COC1=CC=C(N=C2C(NC(=O)N2)=C2)C2=C1 YVEQUTSPFYJJAS-UHFFFAOYSA-N 0.000 claims 1
- VDJBMWZCELLWPP-UHFFFAOYSA-N 4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]-n-pentan-3-ylbutanamide Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCCC(=O)NC(CC)CC)=CC=C21 VDJBMWZCELLWPP-UHFFFAOYSA-N 0.000 claims 1
- AHNFHVODVZRNNS-UHFFFAOYSA-N 5-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]pentanoic acid Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCCCC(=O)O)=CC=C21 AHNFHVODVZRNNS-UHFFFAOYSA-N 0.000 claims 1
- OGIFXNGAJSAHFH-UHFFFAOYSA-N 5-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxymethyl]-3-propan-2-yl-1,3-oxazolidin-2-one Chemical compound O1C(=O)N(C(C)C)CC1COC1=CC=C(N=C2C(NC(=O)N2)=C2)C2=C1 OGIFXNGAJSAHFH-UHFFFAOYSA-N 0.000 claims 1
- HCLMLIZWYIZMGK-UHFFFAOYSA-N 7-(4-oxo-4-piperidin-1-ylbutoxy)-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound C=1C=C2NC3=NC(O)=NC3=CC2=CC=1OCCCC(=O)N1CCCCC1 HCLMLIZWYIZMGK-UHFFFAOYSA-N 0.000 claims 1
- CZDOWLCKYCPNMU-UHFFFAOYSA-N 7-(4-oxopentoxy)-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCCC(=O)C)=CC=C21 CZDOWLCKYCPNMU-UHFFFAOYSA-N 0.000 claims 1
- NHSCJGOJCUSYKC-UHFFFAOYSA-N 7-[3-(benzenesulfonyl)propoxy]-1-methyl-3h-imidazo[4,5-b]quinolin-2-one Chemical compound C=1C=C2N=C3NC(=O)N(C)C3=CC2=CC=1OCCCS(=O)(=O)C1=CC=CC=C1 NHSCJGOJCUSYKC-UHFFFAOYSA-N 0.000 claims 1
- JAODEWCDRHAJPF-UHFFFAOYSA-N 7-[4-(1-cyclohexyltetrazol-5-yl)butoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound C=1C=C2N=C3NC(=O)NC3=CC2=CC=1OCCCCC1=NN=NN1C1CCCCC1 JAODEWCDRHAJPF-UHFFFAOYSA-N 0.000 claims 1
- WAEGLNICSZBTBF-UHFFFAOYSA-N 7-[4-oxo-4-(4-phenylpiperazin-1-yl)butoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound C=1C=C2N=C3NC(=O)NC3=CC2=CC=1OCCCC(=O)N(CC1)CCN1C1=CC=CC=C1 WAEGLNICSZBTBF-UHFFFAOYSA-N 0.000 claims 1
- FYTROBAKOHFNCC-UHFFFAOYSA-N ethyl 1-[4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanoyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(=O)CCCOC1=CC=C(N=C2C(NC(=O)N2)=C2)C2=C1 FYTROBAKOHFNCC-UHFFFAOYSA-N 0.000 claims 1
- GRGAAYMCHPTCLG-UHFFFAOYSA-N ethyl 2-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]acetate Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCC(=O)OCC)=CC=C21 GRGAAYMCHPTCLG-UHFFFAOYSA-N 0.000 claims 1
- IMWBJZZHCMTYMG-UHFFFAOYSA-N ethyl 2-[4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanoylamino]acetate Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCCC(=O)NCC(=O)OCC)=CC=C21 IMWBJZZHCMTYMG-UHFFFAOYSA-N 0.000 claims 1
- QUDPEUROOLGXHA-UHFFFAOYSA-N methyl 2-[cyclohexyl-[4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanoyl]amino]acetate Chemical compound C=1C=C2N=C3NC(=O)NC3=CC2=CC=1OCCCC(=O)N(CC(=O)OC)C1CCCCC1 QUDPEUROOLGXHA-UHFFFAOYSA-N 0.000 claims 1
- MNUCPNWZRLQCDI-UHFFFAOYSA-N methyl 4-[(1-methyl-2-oxo-3h-imidazo[4,5-b]quinolin-7-yl)oxy]butanoate Chemical compound N1=C2NC(=O)N(C)C2=CC2=CC(OCCCC(=O)OC)=CC=C21 MNUCPNWZRLQCDI-UHFFFAOYSA-N 0.000 claims 1
- DHHNFBRHDIGAHC-UHFFFAOYSA-N methyl 5-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]pentanoate Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCCCC(=O)OC)=CC=C21 DHHNFBRHDIGAHC-UHFFFAOYSA-N 0.000 claims 1
- 125000005322 morpholin-1-yl group Chemical group 0.000 claims 1
- QTNSXEDSNVXNDG-UHFFFAOYSA-N n-cycloheptyl-4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanamide Chemical compound C=1C=C2NC3=NC(O)=NC3=CC2=CC=1OCCCC(=O)NC1CCCCCC1 QTNSXEDSNVXNDG-UHFFFAOYSA-N 0.000 claims 1
- CVZAAYRCMFKBOJ-UHFFFAOYSA-N n-cycloheptyl-n-methyl-4-[(1-methyl-2-oxo-3h-imidazo[4,5-b]quinolin-7-yl)oxy]butanamide Chemical compound C=1C=C2N=C3NC(=O)N(C)C3=CC2=CC=1OCCCC(=O)N(C)C1CCCCCC1 CVZAAYRCMFKBOJ-UHFFFAOYSA-N 0.000 claims 1
- PTEGEICPLYKICS-UHFFFAOYSA-N n-cycloheptyl-n-methyl-5-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]pentanamide Chemical compound C=1C=C2N=C3NC(=O)NC3=CC2=CC=1OCCCCC(=O)N(C)C1CCCCCC1 PTEGEICPLYKICS-UHFFFAOYSA-N 0.000 claims 1
- AUZJVEDTLNZEHH-UHFFFAOYSA-N n-cyclohexyl-4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanamide Chemical compound C=1C=C2N=C3NC(=O)NC3=CC2=CC=1OCCCC(=O)NC1CCCCC1 AUZJVEDTLNZEHH-UHFFFAOYSA-N 0.000 claims 1
- SFVRSCDYQRBUBX-UHFFFAOYSA-N n-cyclohexyl-n-methyl-5-[(1-methyl-2-oxo-3h-imidazo[4,5-b]quinolin-7-yl)oxy]pentanamide Chemical compound C=1C=C2N=C3NC(=O)N(C)C3=CC2=CC=1OCCCCC(=O)N(C)C1CCCCC1 SFVRSCDYQRBUBX-UHFFFAOYSA-N 0.000 claims 1
- LBNMGMHTMGRWNZ-UHFFFAOYSA-N n-cyclopentyl-4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanamide Chemical compound C=1C=C2NC3=NC(O)=NC3=CC2=CC=1OCCCC(=O)NC1CCCC1 LBNMGMHTMGRWNZ-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 abstract description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 abstract description 4
- 239000000496 cardiotonic agent Substances 0.000 abstract description 3
- 239000003112 inhibitor Substances 0.000 abstract description 3
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 abstract description 3
- REFKNIQUQMRNSW-UHFFFAOYSA-N 1-[(2-oxo-3h-imidazo[4,5-b]quinolin-1-yl)oxy]-3h-imidazo[4,5-b]quinolin-2-one Chemical class C1=CC=C2N=C(NC(N3ON4C5=CC6=CC=CC=C6N=C5NC4=O)=O)C3=CC2=C1 REFKNIQUQMRNSW-UHFFFAOYSA-N 0.000 abstract 1
- 150000003857 carboxamides Chemical class 0.000 abstract 1
- 125000004663 dialkyl amino group Chemical group 0.000 abstract 1
- 150000002169 ethanolamines Chemical class 0.000 abstract 1
- 125000003831 tetrazolyl group Chemical group 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 description 160
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 154
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 115
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 91
- 239000000203 mixture Substances 0.000 description 88
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 70
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- 239000000243 solution Substances 0.000 description 57
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
- 239000000460 chlorine Substances 0.000 description 43
- 238000005481 NMR spectroscopy Methods 0.000 description 36
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 32
- 239000007787 solid Substances 0.000 description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 22
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 19
- 238000010992 reflux Methods 0.000 description 18
- 230000036961 partial effect Effects 0.000 description 16
- 239000000538 analytical sample Substances 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- 238000002425 crystallisation Methods 0.000 description 14
- 230000008025 crystallization Effects 0.000 description 14
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 14
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 14
- 150000003254 radicals Chemical class 0.000 description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
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- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
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- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
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- 239000000314 lubricant Substances 0.000 description 1
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- VZXMZMJSGLFKQI-ABVWVHJUSA-N midafotel Chemical compound OC(=O)[C@H]1CN(C\C=C\P(O)(O)=O)CCN1 VZXMZMJSGLFKQI-ABVWVHJUSA-N 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
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- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
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- NAPKHDRXTZVUOK-UHFFFAOYSA-N n-cycloheptyl-n-methyl-5-[(1-methyl-2-oxo-3h-imidazo[4,5-b]quinolin-7-yl)oxy]pentanamide Chemical compound C=1C=C2N=C3NC(=O)N(C)C3=CC2=CC=1OCCCCC(=O)N(C)C1CCCCCC1 NAPKHDRXTZVUOK-UHFFFAOYSA-N 0.000 description 1
- DREARSDKHPADMU-UHFFFAOYSA-N n-cyclohexyl-4-(3-formyl-4-nitrophenoxy)-n-methylpentanamide Chemical compound C=1C=C([N+]([O-])=O)C(C=O)=CC=1OC(C)CCC(=O)N(C)C1CCCCC1 DREARSDKHPADMU-UHFFFAOYSA-N 0.000 description 1
- ICAYDZWGWKWMMB-UHFFFAOYSA-N n-cyclohexyl-n-methyl-4-[(1-methyl-2-oxo-3h-imidazo[4,5-b]quinolin-7-yl)oxy]butanamide Chemical compound C=1C=C2N=C3NC(=O)N(C)C3=CC2=CC=1OCCCC(=O)N(C)C1CCCCC1 ICAYDZWGWKWMMB-UHFFFAOYSA-N 0.000 description 1
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- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 1
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- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
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- 125000006225 propoxyethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- JCXAWTMMACYASJ-UHFFFAOYSA-N propyl butanoate Chemical compound [CH2]CCC(=O)OCCC JCXAWTMMACYASJ-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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- 150000003624 transition metals Chemical class 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/866,813 US4775674A (en) | 1986-05-23 | 1986-05-23 | Imidazoquinolinylether derivatives useful as phosphodiesterase and blood aggregation inhibitors |
| US866,813 | 1992-04-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1289137C true CA1289137C (en) | 1991-09-17 |
Family
ID=25348473
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000537720A Expired - Fee Related CA1289137C (en) | 1986-05-23 | 1987-05-22 | Imidazoquinolinylether derivatives |
Country Status (24)
Families Citing this family (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1306260C (en) * | 1985-10-18 | 1992-08-11 | Shionogi & Co., Ltd. | Condensed imidazopyridine derivatives |
| JPH01189791A (ja) * | 1988-01-26 | 1989-07-28 | New Japan Radio Co Ltd | 非接触ｉｄカード |
| US4943573A (en) * | 1989-11-01 | 1990-07-24 | Bristol-Myers Squibb Company | Imidazo[4,5-b]quinolinyloxyalkanoic acid amides with enhanced water solubility |
| US5262540A (en) * | 1989-12-20 | 1993-11-16 | Bristol-Myers Squibb Company | [2(4,5-diaryl-2 oxazoyl substituted phenoxy alkanoic acid and esters |
| PH31245A (en) * | 1991-10-30 | 1998-06-18 | Janssen Pharmaceutica Nv | 1,3-Dihydro-2H-imidazoÄ4,5-BÜ-quinolin-2-one derivatives. |
| US5196428A (en) * | 1992-04-03 | 1993-03-23 | Bristol-Myers Squibb Company | Imidazo[4,5-b]qinolinyl oxy alkyl ureas |
| US5348960A (en) * | 1992-04-03 | 1994-09-20 | Bristol-Myers Squibb Company | Imidazo[4,5-b]quinolinyl oxy alkyl tetrazolyl piperidine derivatives |
| US5208237A (en) * | 1992-04-03 | 1993-05-04 | Bristol-Meyers Squibb Company | 7-oxypropylsulfonamido-imidazo[4,5-b]quinolin-2-ones |
| US5158958A (en) * | 1992-04-03 | 1992-10-27 | Bristol-Myers Squibb Company | Imidazo[4,5-b]quinolinyl oxy alkyl sulfonyl piperidine derivatives |
| US5552267A (en) * | 1992-04-03 | 1996-09-03 | The Trustees Of Columbia University In The City Of New York | Solution for prolonged organ preservation |
| US5187188A (en) * | 1992-04-03 | 1993-02-16 | Bristol-Myers Squibb Company | Oxazole carboxylic acid derivatives |
| TW593317B (en) | 1993-06-21 | 2004-06-21 | Janssen Pharmaceutica Nv | Positive cardiac inotropic and lusitropic pyrroloquinolinone derivatives |
| US6573273B1 (en) | 1999-06-10 | 2003-06-03 | 3M Innovative Properties Company | Urea substituted imidazoquinolines |
| US6541485B1 (en) | 1999-06-10 | 2003-04-01 | 3M Innovative Properties Company | Urea substituted imidazoquinolines |
| US6331539B1 (en) * | 1999-06-10 | 2001-12-18 | 3M Innovative Properties Company | Sulfonamide and sulfamide substituted imidazoquinolines |
| US6756382B2 (en) * | 1999-06-10 | 2004-06-29 | 3M Innovative Properties Company | Amide substituted imidazoquinolines |
| JP4767429B2 (ja) * | 2001-03-02 | 2011-09-07 | 株式会社クラレ | 架橋剤および架橋性重合体 |
| WO2004050657A2 (en) * | 2002-11-27 | 2004-06-17 | Artesian Therapeutics, Inc. | COMPOUNDS WITH MIXED PDE-INHIBITORY AND β-ADRENERGIC ANTAGONIST OR PARTIAL AGONIST ACTIVITY FOR TREATMENT OF HEART FAILURE |
| US8673932B2 (en) | 2003-08-12 | 2014-03-18 | 3M Innovative Properties Company | Oxime substituted imidazo-containing compounds |
| JP5128815B2 (ja) | 2003-08-27 | 2013-01-23 | スリーエム イノベイティブ プロパティズ カンパニー | アリールオキシ置換およびアリールアルキレンオキシ置換イミダゾキノリン |
| WO2005023190A2 (en) | 2003-09-05 | 2005-03-17 | 3M Innovative Properties Company | Treatment for cd5+ b cell lymphoma |
| US7544697B2 (en) | 2003-10-03 | 2009-06-09 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridines and analogs thereof |
| ES2544477T3 (es) | 2003-10-03 | 2015-08-31 | 3M Innovative Properties Company | Imidazoquinolinas sustituidas con alcoxi |
| EP1682544A4 (en) | 2003-11-14 | 2009-05-06 | 3M Innovative Properties Co | HYDROXYLAMINE SUBSTITUTED IMIDAZO RING COMPOUNDS |
| CN1906193A (zh) | 2003-11-14 | 2007-01-31 | 3M创新有限公司 | 肟取代的咪唑环化合物 |
| MXPA06005910A (es) | 2003-11-25 | 2006-08-23 | 3M Innovative Properties Co | Sistemas de anillo imidazo sustituido y metodos. |
| EP1701955A1 (en) | 2003-12-29 | 2006-09-20 | 3M Innovative Properties Company | Arylalkenyl and arylalkynyl substituted imidazoquinolines |
| JP2007517044A (ja) | 2003-12-30 | 2007-06-28 | スリーエム イノベイティブ プロパティズ カンパニー | イミダゾキノリニル、イミダゾピリジニル、およびイミダゾナフチリジニルスルホンアミド |
| CA2559863A1 (en) | 2004-03-24 | 2005-10-13 | 3M Innovative Properties Company | Amide substituted imidazopyridines, imidazoquinolines, and imidazonaphthyridines |
| WO2005123080A2 (en) | 2004-06-15 | 2005-12-29 | 3M Innovative Properties Company | Nitrogen-containing heterocyclyl substituted imidazoquinolines and imidazonaphthyridines |
| US7915281B2 (en) | 2004-06-18 | 2011-03-29 | 3M Innovative Properties Company | Isoxazole, dihydroisoxazole, and oxadiazole substituted imidazo ring compounds and method |
| WO2006038923A2 (en) | 2004-06-18 | 2006-04-13 | 3M Innovative Properties Company | Aryl substituted imidazonaphthyridines |
| WO2006009826A1 (en) | 2004-06-18 | 2006-01-26 | 3M Innovative Properties Company | Aryloxy and arylalkyleneoxy substituted thiazoloquinolines and thiazolonaphthyridines |
| EP1831221B1 (en) | 2004-12-30 | 2012-08-08 | 3M Innovative Properties Company | Substituted chiral fused 1,2 imidazo 4,5-c ring compounds |
| ES2392647T3 (es) | 2004-12-30 | 2012-12-12 | 3M Innovative Properties Company | Compuestos tetracíclicos quirales que inducen la biosíntesis de interferón |
| JP2008530022A (ja) | 2005-02-04 | 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 | 免疫反応調節物質を含む水性ゲル処方物 |
| WO2006086634A2 (en) | 2005-02-11 | 2006-08-17 | Coley Pharmaceutical Group, Inc. | Oxime and hydroxylamine substituted imidazo[4,5-c] ring compounds and methods |
| AU2006232377A1 (en) | 2005-04-01 | 2006-10-12 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridine-1,4-diamines and analogs thereof |
| JP2008538550A (ja) | 2005-04-01 | 2008-10-30 | 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 | ウイルス感染および腫瘍性疾患を処置するためのサイトカイン生合成の調節因子としての１−置換ピラゾロ（３，４−ｃ）環状化合物 |
| EP2258359A3 (en) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation with sabcomelin |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3932407A (en) * | 1973-11-19 | 1976-01-13 | Bristol-Myers Company | Optionally substituted 1,2,3,5-tetrahydroimidezo(2,1-b)-quinazolin-2-ones and 6(H)-1,2,3,4-tetrahydropyimido(2,1-b)quinazolin-2-ones |
| NL7807507A (nl) * | 1977-07-25 | 1979-01-29 | Hoffmann La Roche | Tricyclische verbindingen. |
| IL62402A0 (en) * | 1980-03-24 | 1981-05-20 | Sterling Drug Inc | Imidazo(4,5-b)pyridines,their preparation and pharmaceutical compositions containing them |
| US4490371A (en) * | 1983-02-16 | 1984-12-25 | Syntex (U.S.A.) Inc. | N,N-Disubstituted-(2-oxo-1,2,3,5-tetrahydroimidazo-[2,1-B]quinazolinyl)oxyalkylamides |
| JPS604186A (ja) * | 1983-06-21 | 1985-01-10 | Dai Ichi Seiyaku Co Ltd | イミダゾキナゾリン化合物 |
| JPS6028979A (ja) * | 1983-07-14 | 1985-02-14 | Dai Ichi Seiyaku Co Ltd | イミダゾキナゾリン類化合物 |
| NZ211117A (en) * | 1984-02-15 | 1987-10-30 | Syntex Inc | Fused tetrahydroimidazo-(2,1-b)quinazoline derivatives and pharmaceutical compositions |
| US4668686A (en) * | 1985-04-25 | 1987-05-26 | Bristol-Myers Company | Imidazoquinoline antithrombrogenic cardiotonic agents |
-
1986
- 1986-05-23 US US06/866,813 patent/US4775674A/en not_active Expired - Fee Related
-
1987
- 1987-05-15 AU AU72993/87A patent/AU603577B2/en not_active Ceased
- 1987-05-18 NZ NZ220345A patent/NZ220345A/xx unknown
- 1987-05-19 GB GB8711839A patent/GB2190676B/en not_active Expired - Fee Related
- 1987-05-19 ZA ZA873583A patent/ZA873583B/xx unknown
- 1987-05-20 FI FI872220A patent/FI86723C/fi not_active IP Right Cessation
- 1987-05-21 GR GR870803A patent/GR870803B/el unknown
- 1987-05-21 IL IL82612A patent/IL82612A0/xx not_active IP Right Cessation
- 1987-05-22 PT PT84938A patent/PT84938B/pt unknown
- 1987-05-22 AT AT1320/87A patent/AT392790B/de not_active IP Right Cessation
- 1987-05-22 FR FR878707252A patent/FR2603586B1/fr not_active Expired - Fee Related
- 1987-05-22 DK DK263587A patent/DK166084C/da active
- 1987-05-22 KR KR1019870005066A patent/KR900008567B1/ko not_active Expired
- 1987-05-22 DE DE19873717291 patent/DE3717291A1/de not_active Withdrawn
- 1987-05-22 ES ES8701506A patent/ES2005588A6/es not_active Expired
- 1987-05-22 BE BE8700581A patent/BE1002033A4/fr not_active IP Right Cessation
- 1987-05-22 HU HU872295A patent/HU197570B/hu not_active IP Right Cessation
- 1987-05-22 NL NL8701226A patent/NL8701226A/nl not_active Application Discontinuation
- 1987-05-22 SE SE8702158A patent/SE465163B/sv not_active IP Right Cessation
- 1987-05-22 JP JP62125642A patent/JPS62283972A/ja active Pending
- 1987-05-22 LU LU86896A patent/LU86896A1/fr unknown
- 1987-05-22 CA CA000537720A patent/CA1289137C/en not_active Expired - Fee Related
- 1987-05-22 IT IT20650/87A patent/IT1205031B/it active
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