CA2554554A1 - Novel dicationic imidazo[1,2-a]pyridines and 5,6,7,8-tetrahydro-imidazo[1,2a]pyridines as antiprotozoal agents - Google Patents
Novel dicationic imidazo[1,2-a]pyridines and 5,6,7,8-tetrahydro-imidazo[1,2a]pyridines as antiprotozoal agents Download PDFInfo
- Publication number
- CA2554554A1 CA2554554A1 CA002554554A CA2554554A CA2554554A1 CA 2554554 A1 CA2554554 A1 CA 2554554A1 CA 002554554 A CA002554554 A CA 002554554A CA 2554554 A CA2554554 A CA 2554554A CA 2554554 A1 CA2554554 A1 CA 2554554A1
- Authority
- CA
- Canada
- Prior art keywords
- imidazo
- pyridine
- group
- carboxamidine
- alkyl
- 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.)
- Abandoned
Links
- 150000005234 imidazo[1,2-a]pyridines Chemical class 0.000 title claims description 16
- 239000003904 antiprotozoal agent Substances 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 99
- -1 imidazopyridine compound Chemical class 0.000 claims abstract description 53
- 208000015181 infectious disease Diseases 0.000 claims abstract description 29
- 230000000813 microbial effect Effects 0.000 claims abstract description 19
- 241001442397 Trypanosoma brucei rhodesiense Species 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 113
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 64
- 125000000217 alkyl group Chemical group 0.000 claims description 60
- 150000003839 salts Chemical class 0.000 claims description 56
- 125000003118 aryl group Chemical group 0.000 claims description 51
- 239000000203 mixture Substances 0.000 claims description 42
- 239000011541 reaction mixture Substances 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 33
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 32
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 32
- 125000003107 substituted aryl group Chemical group 0.000 claims description 29
- 229920006395 saturated elastomer Polymers 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 16
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 16
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 14
- 125000002947 alkylene group Chemical group 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- JXYYCJXMMMWGJM-UHFFFAOYSA-N 2-[5-(4-carbamimidoylphenyl)furan-2-yl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-6-carboximidamide Chemical compound C=1N2CC(C(=N)N)CCC2=NC=1C(O1)=CC=C1C1=CC=C(C(N)=N)C=C1 JXYYCJXMMMWGJM-UHFFFAOYSA-N 0.000 claims description 12
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- IZEYIAVFSOQZCD-UHFFFAOYSA-N n'-hydroxy-2-[3-[4-(n'-hydroxycarbamimidoyl)phenyl]phenyl]-8-methylimidazo[1,2-a]pyridine-6-carboximidamide Chemical compound N1=C2C(C)=CC(C(=N)NO)=CN2C=C1C(C=1)=CC=CC=1C1=CC=C(C(=N)NO)C=C1 IZEYIAVFSOQZCD-UHFFFAOYSA-N 0.000 claims description 12
- OTQBRWYINPWMAY-UHFFFAOYSA-N 2-[4-(4-carbamimidoylphenyl)phenyl]imidazo[1,2-a]pyridine-6-carboximidamide Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=C(C=2N=C3C=CC(=CN3C=2)C(N)=N)C=C1 OTQBRWYINPWMAY-UHFFFAOYSA-N 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- AKEXDYLCIVUTSU-UHFFFAOYSA-N n'-hydroxy-2-[3-[4-[(e)-n'-hydroxycarbamimidoyl]phenyl]phenyl]imidazo[1,2-a]pyridine-6-carboximidamide Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=CC(C=2N=C3C=CC(=CN3C=2)C(=N)NO)=C1 AKEXDYLCIVUTSU-UHFFFAOYSA-N 0.000 claims description 11
- JBKBGFMARUWNDU-UHFFFAOYSA-N n'-hydroxy-2-[5-[4-[(e)-n'-hydroxycarbamimidoyl]phenyl]furan-2-yl]imidazo[1,2-a]pyridine-6-carboximidamide Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2N=C3C=CC(=CN3C=2)C(=N)NO)O1 JBKBGFMARUWNDU-UHFFFAOYSA-N 0.000 claims description 11
- VQTUZOCVRYCMAL-UHFFFAOYSA-N n'-methoxy-2-[5-[4-[(e)-n'-methoxycarbamimidoyl]phenyl]furan-2-yl]imidazo[1,2-a]pyridine-6-carboximidamide Chemical compound C1=CC(C(=N)NOC)=CC=C1C1=CC=C(C=2N=C3C=CC(=CN3C=2)C(=N)NOC)O1 VQTUZOCVRYCMAL-UHFFFAOYSA-N 0.000 claims description 11
- WTFKIDCAQZPAHP-UHFFFAOYSA-N 2-bromo-1-(5-bromofuran-2-yl)ethanone Chemical compound BrCC(=O)C1=CC=C(Br)O1 WTFKIDCAQZPAHP-UHFFFAOYSA-N 0.000 claims description 10
- 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 claims description 10
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 10
- 125000004104 aryloxy group Chemical group 0.000 claims description 10
- 239000002585 base Substances 0.000 claims description 10
- 239000003054 catalyst Substances 0.000 claims description 10
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- CEBAHYWORUOILU-UHFFFAOYSA-N (4-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=C(C#N)C=C1 CEBAHYWORUOILU-UHFFFAOYSA-N 0.000 claims description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
- SMXXOXWUDRKNFL-UHFFFAOYSA-N n'-hydroxy-2-[4-[4-[(e)-n'-hydroxycarbamimidoyl]phenyl]phenyl]imidazo[1,2-a]pyridine-6-carboximidamide Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2N=C3C=CC(=CN3C=2)C(=N)NO)C=C1 SMXXOXWUDRKNFL-UHFFFAOYSA-N 0.000 claims description 9
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 9
- KMHCTFSFWQRZTR-UHFFFAOYSA-N 3-aminopyridine-2-carbonitrile Chemical compound NC1=CC=CN=C1C#N KMHCTFSFWQRZTR-UHFFFAOYSA-N 0.000 claims description 8
- KDVBYUUGYXUXNL-UHFFFAOYSA-N 6-aminopyridine-3-carbonitrile Chemical compound NC1=CC=C(C#N)C=N1 KDVBYUUGYXUXNL-UHFFFAOYSA-N 0.000 claims description 8
- DUADCMJZEJDULX-UHFFFAOYSA-N C1=CC=CN2C(C(N)=N)=C(C(=N)N)N=C21 Chemical class C1=CC=CN2C(C(N)=N)=C(C(=N)N)N=C21 DUADCMJZEJDULX-UHFFFAOYSA-N 0.000 claims description 8
- 125000004423 acyloxy group Chemical group 0.000 claims description 8
- 229910052783 alkali metal Inorganic materials 0.000 claims description 8
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 8
- 239000003586 protic polar solvent Substances 0.000 claims description 8
- YDTLZSQZMCRIER-UHFFFAOYSA-N 2-[(z)-n'-hydroxycarbamimidoyl]imidazo[1,2-a]pyridine-3-carboxamide Chemical compound C1=CC=CN2C(C(=O)N)=C(C(N)=NO)N=C21 YDTLZSQZMCRIER-UHFFFAOYSA-N 0.000 claims description 7
- 159000000021 acetate salts Chemical class 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- TVIBDWKPVCACMM-UHFFFAOYSA-N n'-methoxy-2-[4-[4-[(e)-n'-methoxycarbamimidoyl]phenyl]phenyl]imidazo[1,2-a]pyridine-6-carboximidamide Chemical compound C1=CC(C(=N)NOC)=CC=C1C1=CC=C(C=2N=C3C=CC(=CN3C=2)C(=N)NOC)C=C1 TVIBDWKPVCACMM-UHFFFAOYSA-N 0.000 claims description 7
- AUDUAIQWVZGFHX-UHFFFAOYSA-N 2-[4-(4-carbamimidoylphenyl)phenyl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-6-carboximidamide Chemical compound C=1N2CC(C(=N)N)CCC2=NC=1C(C=C1)=CC=C1C1=CC=C(C(N)=N)C=C1 AUDUAIQWVZGFHX-UHFFFAOYSA-N 0.000 claims description 6
- FKJSFKCZZIXQIP-UHFFFAOYSA-N 2-bromo-1-(4-bromophenyl)ethanone Chemical compound BrCC(=O)C1=CC=C(Br)C=C1 FKJSFKCZZIXQIP-UHFFFAOYSA-N 0.000 claims description 6
- SLOISJVQLUVVSD-UHFFFAOYSA-N 6-amino-5-methylpyridine-3-carbonitrile Chemical compound CC1=CC(C#N)=CN=C1N SLOISJVQLUVVSD-UHFFFAOYSA-N 0.000 claims description 6
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000005350 hydroxycycloalkyl group Chemical group 0.000 claims description 6
- ONWNNQXNIDRZNB-UHFFFAOYSA-N n'-hydroxy-2-[5-[4-[(e)-n'-hydroxycarbamimidoyl]phenyl]furan-2-yl]-8-methylimidazo[1,2-a]pyridine-6-carboximidamide Chemical compound N1=C2C(C)=CC(C(=N)NO)=CN2C=C1C(O1)=CC=C1C1=CC=C(C(=N)NO)C=C1 ONWNNQXNIDRZNB-UHFFFAOYSA-N 0.000 claims description 6
- QWEUWPVGJHUPTI-UHFFFAOYSA-N 2-[3-(4-carbamimidoylphenyl)phenyl]-8-methylimidazo[1,2-a]pyridine-6-carboximidamide Chemical compound N1=C2C(C)=CC(C(N)=N)=CN2C=C1C(C=1)=CC=CC=1C1=CC=C(C(N)=N)C=C1 QWEUWPVGJHUPTI-UHFFFAOYSA-N 0.000 claims description 5
- UTMXCUWVXRZXPO-UHFFFAOYSA-N 2-[3-(4-carbamimidoylphenyl)phenyl]imidazo[1,2-a]pyridine-6-carboximidamide Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=CC(C=2N=C3C=CC(=CN3C=2)C(N)=N)=C1 UTMXCUWVXRZXPO-UHFFFAOYSA-N 0.000 claims description 5
- SPCAOBGQKXEQHK-UHFFFAOYSA-N 2-[5-(4-carbamimidoylphenyl)furan-2-yl]imidazo[1,2-a]pyridine-6-carboximidamide Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=C(C=2N=C3C=CC(=CN3C=2)C(N)=N)O1 SPCAOBGQKXEQHK-UHFFFAOYSA-N 0.000 claims description 5
- LJANCPRIUMHGJE-UHFFFAOYSA-N 4-(2-bromoacetyl)benzonitrile Chemical compound BrCC(=O)C1=CC=C(C#N)C=C1 LJANCPRIUMHGJE-UHFFFAOYSA-N 0.000 claims description 5
- 125000004802 cyanophenyl group Chemical group 0.000 claims description 5
- 150000004820 halides Chemical class 0.000 claims description 5
- IUXFKUNLXPVYIV-UHFFFAOYSA-N 2-[3-(4-carbamimidoylphenyl)phenyl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-6-carboximidamide Chemical compound C=1N2CC(C(=N)N)CCC2=NC=1C(C=1)=CC=CC=1C1=CC=C(C(N)=N)C=C1 IUXFKUNLXPVYIV-UHFFFAOYSA-N 0.000 claims description 4
- BPRKMPXUHWFKSO-UHFFFAOYSA-N 2-[5-(4-carbamimidoylphenyl)furan-2-yl]-8-methylimidazo[1,2-a]pyridine-6-carboximidamide Chemical compound N1=C2C(C)=CC(C(N)=N)=CN2C=C1C(O1)=CC=C1C1=CC=C(C(N)=N)C=C1 BPRKMPXUHWFKSO-UHFFFAOYSA-N 0.000 claims description 4
- KBLGGRWUEVCNPY-UHFFFAOYSA-N 5-bromo-3-methylpyridin-2-amine Chemical compound CC1=CC(Br)=CN=C1N KBLGGRWUEVCNPY-UHFFFAOYSA-N 0.000 claims description 4
- WGOLHUGPTDEKCF-UHFFFAOYSA-N 5-bromopyridin-2-amine Chemical compound NC1=CC=C(Br)C=N1 WGOLHUGPTDEKCF-UHFFFAOYSA-N 0.000 claims description 4
- 241000224016 Plasmodium Species 0.000 claims description 4
- 125000005907 alkyl ester group Chemical group 0.000 claims description 4
- 125000005233 alkylalcohol group Chemical group 0.000 claims description 4
- 239000002168 alkylating agent Substances 0.000 claims description 4
- 229940100198 alkylating agent Drugs 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- ZXZBMGGWHWRHPS-UHFFFAOYSA-N cyanato(phenyl)borinic acid Chemical compound N#COB(O)C1=CC=CC=C1 ZXZBMGGWHWRHPS-UHFFFAOYSA-N 0.000 claims description 4
- MZBXSQBQPJWECM-UHFFFAOYSA-N 2-bromo-1-(3-bromophenyl)ethanone Chemical compound BrCC(=O)C1=CC=CC(Br)=C1 MZBXSQBQPJWECM-UHFFFAOYSA-N 0.000 claims description 3
- 150000005323 carbonate salts Chemical class 0.000 claims description 3
- 150000008050 dialkyl sulfates Chemical class 0.000 claims description 3
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 2
- 150000003927 aminopyridines Chemical class 0.000 claims description 2
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 3
- 125000001475 halogen functional group Chemical group 0.000 claims 3
- XDBHWPLGGBLUHH-UHFFFAOYSA-N (3-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(C#N)=C1 XDBHWPLGGBLUHH-UHFFFAOYSA-N 0.000 claims 1
- FOCKIYZLSZKVDH-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1h-imidazo[4,5-b]pyridine Chemical class N1C=CC=C2NCNC21 FOCKIYZLSZKVDH-UHFFFAOYSA-N 0.000 abstract description 5
- 241000223960 Plasmodium falciparum Species 0.000 abstract description 5
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- 150000005232 imidazopyridines 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
- 244000079416 protozoan pathogen Species 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 61
- 235000002639 sodium chloride Nutrition 0.000 description 49
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 40
- 239000000243 solution Substances 0.000 description 28
- 229940002612 prodrug Drugs 0.000 description 23
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 16
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- 239000012362 glacial acetic acid Substances 0.000 description 13
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- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 12
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- 125000005647 linker group Chemical group 0.000 description 10
- SMAGPXUIRBDIQY-UHFFFAOYSA-N 2-[5-(4-cyanophenyl)furan-2-yl]imidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CC=C1C1=CC=C(C=2N=C3C=CC(=CN3C=2)C#N)O1 SMAGPXUIRBDIQY-UHFFFAOYSA-N 0.000 description 9
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- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 208000027531 mycobacterial infectious disease Diseases 0.000 description 1
- DWFBZJSKJILQBB-UHFFFAOYSA-N n'-hydroxy-2-[4-[4-[(e)-n'-hydroxycarbamimidoyl]phenyl]phenyl]imidazo[1,2-a]pyridine-6-carboximidamide;hydrochloride Chemical compound Cl.C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2N=C3C=CC(=CN3C=2)C(=N)NO)C=C1 DWFBZJSKJILQBB-UHFFFAOYSA-N 0.000 description 1
- CBGYNDBJLNJLIA-UHFFFAOYSA-N n'-methoxy-2-[4-[4-[(e)-n'-methoxycarbamimidoyl]phenyl]phenyl]imidazo[1,2-a]pyridine-6-carboximidamide;hydrochloride Chemical compound Cl.C1=CC(C(=N)NOC)=CC=C1C1=CC=C(C=2N=C3C=CC(=CN3C=2)C(=N)NOC)C=C1 CBGYNDBJLNJLIA-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 125000005485 noradamantyl group Chemical group 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- UKOQVLAXCBRRGH-UHFFFAOYSA-N pafuramidine Chemical compound C1=CC(C(/N)=N/OC)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(\N)=N\OC)O1 UKOQVLAXCBRRGH-UHFFFAOYSA-N 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 238000009521 phase II clinical trial Methods 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical group CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 201000000317 pneumocystosis Diseases 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 201000002612 sleeping sickness Diseases 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 239000000176 sodium gluconate Substances 0.000 description 1
- 235000012207 sodium gluconate Nutrition 0.000 description 1
- 229940005574 sodium gluconate Drugs 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 230000003335 steric effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229940035024 thioglycerol Drugs 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US55109104P | 2004-03-08 | 2004-03-08 | |
| US60/551,091 | 2004-03-08 | ||
| PCT/US2005/007566 WO2005086808A2 (en) | 2004-03-08 | 2005-03-08 | NOVEL DICATIONIC IMIDAZO[1,2-a]PYRIDINES AND 5,6,7,8-TETRAHYDRO-IMIDAZO[1,2a]PYRIDINES AS ANTIPROTOZOAL AGENTS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2554554A1 true CA2554554A1 (en) | 2005-09-22 |
Family
ID=34976160
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002554554A Abandoned CA2554554A1 (en) | 2004-03-08 | 2005-03-08 | Novel dicationic imidazo[1,2-a]pyridines and 5,6,7,8-tetrahydro-imidazo[1,2a]pyridines as antiprotozoal agents |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US7432278B2 (enExample) |
| EP (1) | EP1745045A4 (enExample) |
| JP (1) | JP2007527908A (enExample) |
| CN (1) | CN1930159A (enExample) |
| AU (1) | AU2005220882A1 (enExample) |
| CA (1) | CA2554554A1 (enExample) |
| WO (1) | WO2005086808A2 (enExample) |
Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2906250B1 (fr) * | 2006-09-22 | 2008-10-31 | Sanofi Aventis Sa | Derives de 2-aryl-6phenyl-imidazo(1,2-a) pyridines, leur preparation et leur application en therapeutique |
| CA2669522A1 (en) * | 2006-11-17 | 2008-05-22 | Nihon Medi-Physics Co., Ltd. | Novel compounds with affinity for amyloid |
| EP1964840A1 (en) | 2007-02-28 | 2008-09-03 | sanofi-aventis | Imidazo[1,2-a]pyridines and their use as pharmaceuticals |
| KR20100101576A (ko) * | 2007-10-30 | 2010-09-17 | 니혼 메디피직스 가부시키가이샤 | 신규 아밀로이드 친화성 화합물의 사용 및 제조 방법 |
| US9186361B2 (en) * | 2013-03-15 | 2015-11-17 | Novartis Ag | Compounds and compositions for the treatment of parasitic diseases |
| US9296754B2 (en) | 2013-03-15 | 2016-03-29 | Novartis Ag | Compounds and compositions for the treatment of parasitic diseases |
| WO2014151630A2 (en) | 2013-03-15 | 2014-09-25 | Irm Llc | Compounds and compositions for the treatment of parasitic diseases |
| PE20160865A1 (es) | 2013-12-19 | 2016-09-03 | Novartis Ag | Derivados de [1,2,4] triazolo [1,5-a]pirimidina como inhibidores de proteasoma para el tratamiento de enfermedades parasitarias tales como leishmaniasis |
| KR20170137165A (ko) | 2015-04-10 | 2017-12-12 | 베이진 엘티디 | 인돌아민 및/또는 트립토판 2,3-디옥시게나아제로서 신규한 5 또는 8-치환된 이미다조[1,5-a]피리딘 |
| ES2928164T3 (es) | 2015-10-19 | 2022-11-15 | Incyte Corp | Compuestos heterocíclicos como inmunomoduladores |
| HUE060680T2 (hu) | 2015-11-19 | 2023-04-28 | Incyte Corp | Heterociklusos vegyületek mint immunmodulátorok |
| DK3394033T3 (da) | 2015-12-22 | 2021-01-04 | Incyte Corp | Heterocykliske forbindelser som immunmodulatorer |
| MA44860A (fr) | 2016-05-06 | 2019-03-13 | Incyte Holdings Corp | Composés hétérocycliques utilisés comme immunomodulateurs |
| WO2017205464A1 (en) | 2016-05-26 | 2017-11-30 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| SG11201811414TA (en) | 2016-06-20 | 2019-01-30 | Incyte Corp | Heterocyclic compounds as immunomodulators |
| ES2930092T3 (es) | 2016-07-14 | 2022-12-07 | Incyte Corp | Compuestos heterocíclicos como inmunomoduladores |
| EP3504198B1 (en) | 2016-08-29 | 2023-01-25 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| EP3515914A4 (en) * | 2016-09-24 | 2020-04-15 | BeiGene, Ltd. | NEW IMIDAZO [1,5-A] PYRIDINES SUBSTITUTED IN POSITION 5 OR 8 AS INDOLEAMINE AND / OR TRYPTOPHANE 2,3-DIOXYGENASES |
| US20180179179A1 (en) | 2016-12-22 | 2018-06-28 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| EP3558989B1 (en) | 2016-12-22 | 2021-04-14 | Incyte Corporation | Triazolo[1,5-a]pyridine derivatives as immunomodulators |
| MD3558990T2 (ro) | 2016-12-22 | 2023-02-28 | Incyte Corp | Derivați tetrahidro imidazo[4,5-c]piridină ca inductori de internalizare a PD-L1 |
| MA47123A (fr) | 2016-12-22 | 2021-03-17 | Incyte Corp | Dérivés de benzooxazole en tant qu'mmunomodulateurs |
| CA3047991A1 (en) | 2016-12-22 | 2018-06-28 | Incyte Corporation | Bicyclic heteroaromatic compounds as immunomodulators |
| US11472788B2 (en) | 2017-11-25 | 2022-10-18 | Beigene, Ltd. | Benzoimidazoles as selective inhibitors of indoleamine 2,3-dioxygenases |
| KR102708681B1 (ko) | 2018-02-13 | 2024-09-26 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
| US10669271B2 (en) | 2018-03-30 | 2020-06-02 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| EP3781556B1 (en) | 2018-04-19 | 2025-06-18 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
| LT3790877T (lt) | 2018-05-11 | 2023-05-10 | Incyte Corporation | Tetrahidro-imidazo[4,5-c]piridino dariniai kaip pd-l1 imunomoduliatoriai |
| CN118221646A (zh) | 2018-07-13 | 2024-06-21 | 吉利德科学公司 | Pd-1/pd-l1抑制剂 |
| KR102635333B1 (ko) | 2018-10-24 | 2024-02-15 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
| AU2019416589B2 (en) * | 2018-12-29 | 2023-04-06 | Wuhan Ll Science And Technology Development Co., Ltd. | Heterocyclic compound intermediate, preparation method therefor and application thereof |
| TW202115059A (zh) | 2019-08-09 | 2021-04-16 | 美商英塞特公司 | Ｐｄ—１／ｐｄ—ｌ１抑制劑之鹽 |
| EP4037773A1 (en) | 2019-09-30 | 2022-08-10 | Incyte Corporation | Pyrido[3,2-d]pyrimidine compounds as immunomodulators |
| PE20230407A1 (es) | 2019-11-11 | 2023-03-07 | Incyte Corp | Sales y formas cristalinas de un inhibidor de pd-1/pd-l1 |
| EP4603484A2 (en) | 2019-12-19 | 2025-08-20 | Georgia State University Research Foundation, Inc. | Compounds for the treatment of bacterial infections and potentiation of antibiotics |
| WO2022099071A1 (en) | 2020-11-06 | 2022-05-12 | Incyte Corporation | Process for making a pd-1/pd-l1 inhibitor and salts and crystalline forms thereof |
| US11780836B2 (en) | 2020-11-06 | 2023-10-10 | Incyte Corporation | Process of preparing a PD-1/PD-L1 inhibitor |
| WO2022099075A1 (en) | 2020-11-06 | 2022-05-12 | Incyte Corporation | Crystalline form of a pd-1/pd-l1 inhibitor |
| CN118440080B (zh) * | 2024-05-08 | 2024-12-20 | 广东省科学院微生物研究所(广东省微生物分析检测中心) | 三苯胺类阳离子化合物及其制备方法和应用 |
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|---|---|---|---|---|
| US5204352A (en) * | 1987-09-29 | 1993-04-20 | The United States Of America As Represented By The Secretary Of The Army | Compounds exhibiting anti-parasitic activity and a method for their use |
| AU6168296A (en) | 1995-06-07 | 1996-12-30 | The Administrators Of The Tulane Eductional Fund | Chloroquine analogs and methods of preventing and treating p lasmodial disease |
| JP4041624B2 (ja) * | 1999-07-21 | 2008-01-30 | 三井化学株式会社 | 有機電界発光素子 |
| ITMI20031754A1 (it) | 2003-09-12 | 2005-03-13 | Fabrizio Marcucci | Composizione microbicida. |
-
2005
- 2005-03-08 AU AU2005220882A patent/AU2005220882A1/en not_active Abandoned
- 2005-03-08 WO PCT/US2005/007566 patent/WO2005086808A2/en not_active Ceased
- 2005-03-08 EP EP05733801A patent/EP1745045A4/en not_active Withdrawn
- 2005-03-08 CN CNA2005800073247A patent/CN1930159A/zh active Pending
- 2005-03-08 CA CA002554554A patent/CA2554554A1/en not_active Abandoned
- 2005-03-08 JP JP2007502926A patent/JP2007527908A/ja active Pending
- 2005-03-08 US US11/074,565 patent/US7432278B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP1745045A4 (en) | 2009-07-22 |
| WO2005086808A3 (en) | 2006-02-23 |
| AU2005220882A1 (en) | 2005-09-22 |
| CN1930159A (zh) | 2007-03-14 |
| EP1745045A2 (en) | 2007-01-24 |
| US20050282853A1 (en) | 2005-12-22 |
| US7432278B2 (en) | 2008-10-07 |
| WO2005086808A2 (en) | 2005-09-22 |
| JP2007527908A (ja) | 2007-10-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |