ES2308260T3 - Derivados de imidazopiridinas como inhibidores de no-sintasa inducible. - Google Patents
Derivados de imidazopiridinas como inhibidores de no-sintasa inducible. Download PDFInfo
- Publication number
- ES2308260T3 ES2308260T3 ES04787262T ES04787262T ES2308260T3 ES 2308260 T3 ES2308260 T3 ES 2308260T3 ES 04787262 T ES04787262 T ES 04787262T ES 04787262 T ES04787262 T ES 04787262T ES 2308260 T3 ES2308260 T3 ES 2308260T3
- Authority
- ES
- Spain
- Prior art keywords
- quad
- alkyl
- phenyl
- ethyl
- pyridin
- 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 - Lifetime
Links
- 239000003112 inhibitor Substances 0.000 title abstract description 10
- 230000001939 inductive effect Effects 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 161
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 169
- -1 ethylenedioxy group Chemical group 0.000 claims description 157
- 239000001257 hydrogen Substances 0.000 claims description 96
- 229910052739 hydrogen Inorganic materials 0.000 claims description 96
- 125000003545 alkoxy group Chemical group 0.000 claims description 86
- 229910052736 halogen Inorganic materials 0.000 claims description 85
- 150000002367 halogens Chemical group 0.000 claims description 85
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 76
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 76
- 125000000217 alkyl group Chemical group 0.000 claims description 75
- 150000003839 salts Chemical class 0.000 claims description 60
- 239000011737 fluorine Substances 0.000 claims description 51
- 229910052731 fluorine Inorganic materials 0.000 claims description 51
- 239000000460 chlorine Chemical group 0.000 claims description 50
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 49
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 49
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 45
- 125000001153 fluoro group Chemical group F* 0.000 claims description 42
- 150000001204 N-oxides Chemical class 0.000 claims description 41
- 229910052757 nitrogen Inorganic materials 0.000 claims description 40
- 125000000623 heterocyclic group Chemical group 0.000 claims description 35
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 33
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 30
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 27
- 229910052799 carbon Inorganic materials 0.000 claims description 23
- 125000004076 pyridyl group Chemical group 0.000 claims description 23
- 229910052801 chlorine Inorganic materials 0.000 claims description 21
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 19
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 19
- 239000005977 Ethylene Substances 0.000 claims description 19
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 18
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 18
- 150000001721 carbon Chemical group 0.000 claims description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 16
- 229920006395 saturated elastomer Polymers 0.000 claims description 16
- 239000000470 constituent Substances 0.000 claims description 15
- 229910052717 sulfur Chemical group 0.000 claims description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 11
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 11
- 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 11
- 125000003386 piperidinyl group Chemical group 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
- 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 7
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 7
- 125000002393 azetidinyl group Chemical group 0.000 claims description 7
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 125000004043 oxo group Chemical group O=* 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 239000001301 oxygen Chemical group 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 239000011593 sulfur Chemical group 0.000 claims description 6
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 5
- 125000002619 bicyclic group Chemical group 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 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 5
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- CHVLLOYBRQEGEM-UHFFFAOYSA-N 4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]-n-phenylbenzenesulfonamide Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)NC=2C=CC=CC=2)=C1 CHVLLOYBRQEGEM-UHFFFAOYSA-N 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 210000000056 organ Anatomy 0.000 claims description 3
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims description 3
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 2
- LLVLJQGDQPJQDW-UHFFFAOYSA-N 1-[4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]phenyl]sulfonyl-1,4-diazepan-5-one Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCC(=O)NCC2)=C1 LLVLJQGDQPJQDW-UHFFFAOYSA-N 0.000 claims description 2
- IWUWJMDAGHCEGR-UHFFFAOYSA-N 1-[4-[4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]phenyl]sulfonylpiperazin-1-yl]ethanone Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCN(CC2)C(C)=O)=C1 IWUWJMDAGHCEGR-UHFFFAOYSA-N 0.000 claims description 2
- FWRGKKMQLQXOLD-UHFFFAOYSA-N 2-[2-(4-methoxypyridin-2-yl)ethyl]-6-(4-piperidin-1-ylsulfonylphenyl)-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCCCC2)=C1 FWRGKKMQLQXOLD-UHFFFAOYSA-N 0.000 claims description 2
- UQCGBFFEFMDNQP-UHFFFAOYSA-N 2-[2-(4-methoxypyridin-2-yl)ethyl]-6-(4-pyrrolidin-1-ylsulfonylphenyl)-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCCC2)=C1 UQCGBFFEFMDNQP-UHFFFAOYSA-N 0.000 claims description 2
- NCPQIHLSOULRHE-UHFFFAOYSA-N 2-[2-(4-methoxypyridin-2-yl)ethyl]-6-[2-methyl-4-(4-methylpiperazin-1-yl)sulfonylphenyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C(=CC(=CC=2)S(=O)(=O)N2CCN(C)CC2)C)=C1 NCPQIHLSOULRHE-UHFFFAOYSA-N 0.000 claims description 2
- UIXHHDQYIINPBD-UHFFFAOYSA-N 2-[2-(4-methoxypyridin-2-yl)ethyl]-6-[4-(4-methylpiperazin-1-yl)sulfonyl-3-(trifluoromethoxy)phenyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=C(OC(F)(F)F)C(=CC=2)S(=O)(=O)N2CCN(C)CC2)=C1 UIXHHDQYIINPBD-UHFFFAOYSA-N 0.000 claims description 2
- IIWHSJWNULMGNK-UHFFFAOYSA-N 2-[2-(4-methoxypyridin-2-yl)ethyl]-6-[4-(4-methylpiperazin-1-yl)sulfonyl-3-(trifluoromethyl)phenyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=C(C(=CC=2)S(=O)(=O)N2CCN(C)CC2)C(F)(F)F)=C1 IIWHSJWNULMGNK-UHFFFAOYSA-N 0.000 claims description 2
- UQRYDMSZRQQKGV-UHFFFAOYSA-N 2-[2-(4-methoxypyridin-2-yl)ethyl]-6-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCN(C)CC2)=C1 UQRYDMSZRQQKGV-UHFFFAOYSA-N 0.000 claims description 2
- VGENBLARBITTCS-UHFFFAOYSA-N 2-[2-(4-methoxypyridin-2-yl)ethyl]-6-[4-(4-methylpiperidin-1-yl)sulfonylphenyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCC(C)CC2)=C1 VGENBLARBITTCS-UHFFFAOYSA-N 0.000 claims description 2
- KCVMUQHTORHZGX-UHFFFAOYSA-N 2-[2-(4-methoxypyridin-2-yl)ethyl]-6-[4-(4-phenylpiperazin-1-yl)sulfonylphenyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCN(CC2)C=2C=CC=CC=2)=C1 KCVMUQHTORHZGX-UHFFFAOYSA-N 0.000 claims description 2
- UEMAFCQRUKCPOR-UHFFFAOYSA-N 2-[2-(4-methoxypyridin-2-yl)ethyl]-6-[4-[(4-methyl-1,4-diazepan-1-yl)sulfonyl]phenyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCN(C)CCC2)=C1 UEMAFCQRUKCPOR-UHFFFAOYSA-N 0.000 claims description 2
- BJIDRNQMIWZUMQ-UHFFFAOYSA-N 2-[2-(4-methoxypyridin-2-yl)ethyl]-6-[4-[4-(2-methylphenyl)piperazin-1-yl]sulfonylphenyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCN(CC2)C=2C(=CC=CC=2)C)=C1 BJIDRNQMIWZUMQ-UHFFFAOYSA-N 0.000 claims description 2
- UXQFUHBKCGXENA-UHFFFAOYSA-N 2-[2-(4-methoxypyridin-2-yl)ethyl]-6-[4-[4-(2-phenylethyl)piperazin-1-yl]sulfonylphenyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCN(CCC=3C=CC=CC=3)CC2)=C1 UXQFUHBKCGXENA-UHFFFAOYSA-N 0.000 claims description 2
- JJYUUKAFDVDYFK-UHFFFAOYSA-N 2-[2-(4-methoxypyridin-2-yl)ethyl]-6-[4-[4-(4-methylphenyl)piperazin-1-yl]sulfonylphenyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCN(CC2)C=2C=CC(C)=CC=2)=C1 JJYUUKAFDVDYFK-UHFFFAOYSA-N 0.000 claims description 2
- BNZLGOCEWCGPJV-UHFFFAOYSA-N 2-[2-(4-methoxypyridin-2-yl)ethyl]-7-methyl-6-(4-piperidin-1-ylsulfonylphenyl)-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C(C)=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCCCC2)=C1 BNZLGOCEWCGPJV-UHFFFAOYSA-N 0.000 claims description 2
- AAKZNRPYQMZCHN-UHFFFAOYSA-N 2-[2-(4-methoxypyridin-2-yl)ethyl]-7-methyl-6-(4-pyrrolidin-1-ylsulfonylphenyl)-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C(C)=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCCC2)=C1 AAKZNRPYQMZCHN-UHFFFAOYSA-N 0.000 claims description 2
- DEODHXJCWPSXSZ-UHFFFAOYSA-N 4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]-n,n,3-trimethylbenzenesulfonamide Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C(=CC(=CC=2)S(=O)(=O)N(C)C)C)=C1 DEODHXJCWPSXSZ-UHFFFAOYSA-N 0.000 claims description 2
- GLJSKFVMAXSSSM-UHFFFAOYSA-N 4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]-n,n-dimethyl-2-(trifluoromethoxy)benzenesulfonamide Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=C(OC(F)(F)F)C(=CC=2)S(=O)(=O)N(C)C)=C1 GLJSKFVMAXSSSM-UHFFFAOYSA-N 0.000 claims description 2
- ZTVZRODAAUIGDP-UHFFFAOYSA-N 4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]-n-(2-methylphenyl)benzenesulfonamide Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)NC=2C(=CC=CC=2)C)=C1 ZTVZRODAAUIGDP-UHFFFAOYSA-N 0.000 claims description 2
- XHWUMEKWSNEQQH-UHFFFAOYSA-N 4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]-n-(4-methylphenyl)benzenesulfonamide Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)NC=2C=CC(C)=CC=2)=C1 XHWUMEKWSNEQQH-UHFFFAOYSA-N 0.000 claims description 2
- ODVLESNQCLONMS-UHFFFAOYSA-N 4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]-n-methyl-n-(2-methylphenyl)benzenesulfonamide Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N(C)C=2C(=CC=CC=2)C)=C1 ODVLESNQCLONMS-UHFFFAOYSA-N 0.000 claims description 2
- DHAVKGIGNSTUSO-UHFFFAOYSA-N 4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]-n-methyl-n-phenylbenzenesulfonamide Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N(C)C=2C=CC=CC=2)=C1 DHAVKGIGNSTUSO-UHFFFAOYSA-N 0.000 claims description 2
- RLALJVXOXTVMIQ-UHFFFAOYSA-N 4-[4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]phenyl]sulfonylmorpholine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCOCC2)=C1 RLALJVXOXTVMIQ-UHFFFAOYSA-N 0.000 claims description 2
- JUOMGMHCJKNQIL-UHFFFAOYSA-N 4-[4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]phenyl]sulfonylthiomorpholine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCSCC2)=C1 JUOMGMHCJKNQIL-UHFFFAOYSA-N 0.000 claims description 2
- NABULSYQLYJQLW-UHFFFAOYSA-N 4-[4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-7-methyl-1h-imidazo[4,5-b]pyridin-6-yl]phenyl]sulfonylmorpholine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C(C)=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCOCC2)=C1 NABULSYQLYJQLW-UHFFFAOYSA-N 0.000 claims description 2
- LPIKXMRCNLQVRY-UHFFFAOYSA-N 4-[4-[4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]phenyl]sulfonylpiperazin-1-yl]benzonitrile Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCN(CC2)C=2C=CC(=CC=2)C#N)=C1 LPIKXMRCNLQVRY-UHFFFAOYSA-N 0.000 claims description 2
- QIVNJPUJPXAISM-UHFFFAOYSA-N 4-benzyl-1-[4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]phenyl]sulfonyl-1,4-diazepan-5-one Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCC(=O)N(CC=3C=CC=CC=3)CC2)=C1 QIVNJPUJPXAISM-UHFFFAOYSA-N 0.000 claims description 2
- XKNQXNRMXIDQMT-UHFFFAOYSA-N 4-ethyl-1-[4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]phenyl]sulfonyl-1,4-diazepan-5-one Chemical compound C1CC(=O)N(CC)CCN1S(=O)(=O)C1=CC=C(C=2C=C3N=C(CCC=4N=CC=C(OC)C=4)NC3=NC=2)C=C1 XKNQXNRMXIDQMT-UHFFFAOYSA-N 0.000 claims description 2
- RKDSRDVECWGUQK-UHFFFAOYSA-N 6,7-diethoxy-2-[4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]phenyl]sulfonyl-3,4-dihydro-1h-isoquinoline Chemical compound C1C=2C=C(OCC)C(OCC)=CC=2CCN1S(=O)(=O)C(C=C1)=CC=C1C(C=C1N=2)=CN=C1NC=2CCC1=CC(OC)=CC=N1 RKDSRDVECWGUQK-UHFFFAOYSA-N 0.000 claims description 2
- MKDKTQNUBJGNJL-UHFFFAOYSA-N 6,7-dimethoxy-2-[4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]phenyl]sulfonyl-3,4-dihydro-1h-isoquinoline Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CC3=CC(OC)=C(OC)C=C3CC2)=C1 MKDKTQNUBJGNJL-UHFFFAOYSA-N 0.000 claims description 2
- MCAXYBOJVGTFKA-UHFFFAOYSA-N 6-[2-fluoro-4-(4-methylpiperazin-1-yl)sulfonylphenyl]-2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C(=CC(=CC=2)S(=O)(=O)N2CCN(C)CC2)F)=C1 MCAXYBOJVGTFKA-UHFFFAOYSA-N 0.000 claims description 2
- SHFWETIBRNSELW-UHFFFAOYSA-N 6-[3-chloro-4-(4-methylpiperazin-1-yl)sulfonylphenyl]-2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=C(Cl)C(=CC=2)S(=O)(=O)N2CCN(C)CC2)=C1 SHFWETIBRNSELW-UHFFFAOYSA-N 0.000 claims description 2
- XWABNSDCQCRHTN-UHFFFAOYSA-N 6-[3-fluoro-4-(4-methylpiperazin-1-yl)sulfonylphenyl]-2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=C(F)C(=CC=2)S(=O)(=O)N2CCN(C)CC2)=C1 XWABNSDCQCRHTN-UHFFFAOYSA-N 0.000 claims description 2
- JZRXSLZWWJFFGE-UHFFFAOYSA-N 6-[4-(4-benzylpiperazin-1-yl)sulfonylphenyl]-2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCN(CC=3C=CC=CC=3)CC2)=C1 JZRXSLZWWJFFGE-UHFFFAOYSA-N 0.000 claims description 2
- DCLHVGYQJVQKPE-UHFFFAOYSA-N 6-[4-(4-ethylpiperazin-1-yl)sulfonylphenyl]-2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridine Chemical compound C1CN(CC)CCN1S(=O)(=O)C1=CC=C(C=2C=C3N=C(CCC=4N=CC=C(OC)C=4)NC3=NC=2)C=C1 DCLHVGYQJVQKPE-UHFFFAOYSA-N 0.000 claims description 2
- IMPGAKUCBTZIBR-UHFFFAOYSA-N 6-[4-(azetidin-1-ylsulfonyl)phenyl]-2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCC2)=C1 IMPGAKUCBTZIBR-UHFFFAOYSA-N 0.000 claims description 2
- NFQMBGJBDOOKAE-UHFFFAOYSA-N 6-[4-(azetidin-1-ylsulfonyl)phenyl]-2-[2-(4-methoxypyridin-2-yl)ethyl]-7-methyl-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C(C)=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCC2)=C1 NFQMBGJBDOOKAE-UHFFFAOYSA-N 0.000 claims description 2
- MMPFTVHFXNBWIJ-UHFFFAOYSA-N 6-[4-[4-(2,4-dimethylphenyl)piperazin-1-yl]sulfonylphenyl]-2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCN(CC2)C=2C(=CC(C)=CC=2)C)=C1 MMPFTVHFXNBWIJ-UHFFFAOYSA-N 0.000 claims description 2
- GCVOIDGBTSJEFB-UHFFFAOYSA-N 6-[4-[4-(2,6-dimethylphenyl)piperazin-1-yl]sulfonylphenyl]-2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCN(CC2)C=2C(=CC=CC=2C)C)=C1 GCVOIDGBTSJEFB-UHFFFAOYSA-N 0.000 claims description 2
- UBJXMIHDMMDBFI-UHFFFAOYSA-N 6-[4-[4-(2-methoxyethyl)piperazin-1-yl]sulfonylphenyl]-2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridine Chemical compound C1CN(CCOC)CCN1S(=O)(=O)C1=CC=C(C=2C=C3N=C(CCC=4N=CC=C(OC)C=4)NC3=NC=2)C=C1 UBJXMIHDMMDBFI-UHFFFAOYSA-N 0.000 claims description 2
- GXHUCKDJEYQZMB-UHFFFAOYSA-N 6-[4-[4-(3,5-dichlorophenyl)piperazin-1-yl]sulfonylphenyl]-2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCN(CC2)C=2C=C(Cl)C=C(Cl)C=2)=C1 GXHUCKDJEYQZMB-UHFFFAOYSA-N 0.000 claims description 2
- KZYRAAIBSKICOP-UHFFFAOYSA-N 8-[4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]phenyl]sulfonyl-1,4-dioxa-8-azaspiro[4.5]decane Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCC3(CC2)OCCO3)=C1 KZYRAAIBSKICOP-UHFFFAOYSA-N 0.000 claims description 2
- OOUOWDQRDITZMW-UHFFFAOYSA-N [1-[4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]phenyl]sulfonylpiperidin-4-yl]-phenylmethanone Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCC(CC2)C(=O)C=2C=CC=CC=2)=C1 OOUOWDQRDITZMW-UHFFFAOYSA-N 0.000 claims description 2
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 2
- KSIHRNOVEIRMFY-UHFFFAOYSA-N n-(2-methoxyphenyl)-4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]benzenesulfonamide Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)NC=2C(=CC=CC=2)OC)=C1 KSIHRNOVEIRMFY-UHFFFAOYSA-N 0.000 claims description 2
- WGUQSWSQBSSVKW-UHFFFAOYSA-N n-(4-chlorophenyl)-4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]benzenesulfonamide Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)NC=2C=CC(Cl)=CC=2)=C1 WGUQSWSQBSSVKW-UHFFFAOYSA-N 0.000 claims description 2
- QNAAMYZLNNEPMX-UHFFFAOYSA-N n-(4-methoxyphenyl)-4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]benzenesulfonamide Chemical compound C1=CC(OC)=CC=C1NS(=O)(=O)C1=CC=C(C=2C=C3N=C(CCC=4N=CC=C(OC)C=4)NC3=NC=2)C=C1 QNAAMYZLNNEPMX-UHFFFAOYSA-N 0.000 claims description 2
- XUYUZZQHFXLSOU-UHFFFAOYSA-N n-cyclobutyl-4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]benzenesulfonamide Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)NC2CCC2)=C1 XUYUZZQHFXLSOU-UHFFFAOYSA-N 0.000 claims description 2
- GJCUZUJEQRQQON-UHFFFAOYSA-N n-cyclopropyl-4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]benzenesulfonamide Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)NC2CC2)=C1 GJCUZUJEQRQQON-UHFFFAOYSA-N 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 230000002093 peripheral effect Effects 0.000 claims description 2
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 2
- MXTFCVLUVCGKJO-UHFFFAOYSA-N 4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]-n,n-dimethyl-2-(trifluoromethyl)benzenesulfonamide Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=C(C(=CC=2)S(=O)(=O)N(C)C)C(F)(F)F)=C1 MXTFCVLUVCGKJO-UHFFFAOYSA-N 0.000 claims 1
- AHBJXZDULVLWFB-UHFFFAOYSA-N 4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]-n-methyl-n-(4-methylphenyl)benzenesulfonamide Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=CC(=CC=2)S(=O)(=O)N(C)C=2C=CC(C)=CC=2)=C1 AHBJXZDULVLWFB-UHFFFAOYSA-N 0.000 claims 1
- IKPYMPLLJORCLT-UHFFFAOYSA-N n-(4-methoxyphenyl)-4-[2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridin-6-yl]-n-methylbenzenesulfonamide Chemical compound C1=CC(OC)=CC=C1N(C)S(=O)(=O)C1=CC=C(C=2C=C3N=C(CCC=4N=CC=C(OC)C=4)NC3=NC=2)C=C1 IKPYMPLLJORCLT-UHFFFAOYSA-N 0.000 claims 1
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 abstract description 25
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 abstract description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 147
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 109
- 239000000203 mixture Substances 0.000 description 107
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 63
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 59
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 58
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 58
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 56
- 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 description 56
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 56
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 49
- 239000007858 starting material Substances 0.000 description 35
- 239000000243 solution Substances 0.000 description 34
- 239000012074 organic phase Substances 0.000 description 30
- XNZJPDGHSRBBKS-UHFFFAOYSA-N 6-iodo-2-[2-(4-methoxypyridin-2-yl)ethyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(I)C=C3N=2)=C1 XNZJPDGHSRBBKS-UHFFFAOYSA-N 0.000 description 29
- 229910000027 potassium carbonate Inorganic materials 0.000 description 29
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 28
- 238000001816 cooling Methods 0.000 description 28
- 150000002431 hydrogen Chemical class 0.000 description 28
- 235000011056 potassium acetate Nutrition 0.000 description 28
- 229910052938 sodium sulfate Inorganic materials 0.000 description 28
- 235000011152 sodium sulphate Nutrition 0.000 description 28
- 239000007787 solid Substances 0.000 description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- 238000002425 crystallisation Methods 0.000 description 27
- 230000008025 crystallization Effects 0.000 description 27
- 229910052763 palladium Inorganic materials 0.000 description 27
- 239000000499 gel Substances 0.000 description 25
- 239000000377 silicon dioxide Substances 0.000 description 22
- 238000001819 mass spectrum Methods 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 19
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 18
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 18
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 16
- 238000000034 method Methods 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 239000002253 acid Substances 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 11
- 239000002904 solvent Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 108010029485 Protein Isoforms Proteins 0.000 description 8
- 102000001708 Protein Isoforms Human genes 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 239000000443 aerosol Substances 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 230000001537 neural effect Effects 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- 239000004475 Arginine Substances 0.000 description 4
- 206010012289 Dementia Diseases 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
- 150000001642 boronic acid derivatives Chemical class 0.000 description 4
- 125000005620 boronic acid group Chemical class 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 4
- 238000011321 prophylaxis Methods 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 206010040070 Septic Shock Diseases 0.000 description 3
- 238000006069 Suzuki reaction reaction Methods 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 208000037976 chronic inflammation Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 230000003511 endothelial effect Effects 0.000 description 3
- 150000005232 imidazopyridines Chemical class 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 230000001991 pathophysiological effect Effects 0.000 description 3
- 230000007310 pathophysiology Effects 0.000 description 3
- 229920000137 polyphosphoric acid Polymers 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 239000003380 propellant Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 208000017520 skin disease Diseases 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- WPWHSFAFEBZWBB-UHFFFAOYSA-N 1-butyl radical Chemical compound [CH2]CCC WPWHSFAFEBZWBB-UHFFFAOYSA-N 0.000 description 2
- UEVABMBUZNGYQI-UHFFFAOYSA-N 4-methoxypyridine-2-carbaldehyde Chemical compound COC1=CC=NC(C=O)=C1 UEVABMBUZNGYQI-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 102000000584 Calmodulin Human genes 0.000 description 2
- 108010041952 Calmodulin Proteins 0.000 description 2
- 208000031229 Cardiomyopathies Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 206010018364 Glomerulonephritis Diseases 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical class [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 208000009525 Myocarditis Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 239000012752 auxiliary agent Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 235000019162 flavin adenine dinucleotide Nutrition 0.000 description 2
- 239000011714 flavin adenine dinucleotide Substances 0.000 description 2
- VWWQXMAJTJZDQX-UYBVJOGSSA-N flavin adenine dinucleotide Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1CO[P@](O)(=O)O[P@@](O)(=O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C2=NC(=O)NC(=O)C2=NC2=C1C=C(C)C(C)=C2 VWWQXMAJTJZDQX-UYBVJOGSSA-N 0.000 description 2
- 239000011768 flavin mononucleotide Substances 0.000 description 2
- FVTCRASFADXXNN-SCRDCRAPSA-N flavin mononucleotide Chemical compound OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-SCRDCRAPSA-N 0.000 description 2
- 229940013640 flavin mononucleotide Drugs 0.000 description 2
- FVTCRASFADXXNN-UHFFFAOYSA-N flavin mononucleotide Natural products OP(=O)(O)OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-UHFFFAOYSA-N 0.000 description 2
- 229940093632 flavin-adenine dinucleotide Drugs 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 235000019231 riboflavin-5'-phosphate Nutrition 0.000 description 2
- FNKQXYHWGSIFBK-RPDRRWSUSA-N sapropterin Chemical compound N1=C(N)NC(=O)C2=C1NC[C@H]([C@@H](O)[C@@H](O)C)N2 FNKQXYHWGSIFBK-RPDRRWSUSA-N 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 230000036303 septic shock Effects 0.000 description 2
- 239000011734 sodium Chemical class 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- YHIIJNLSGULWAA-UHFFFAOYSA-N 1,4-thiazinane 1-oxide Chemical compound O=S1CCNCC1 YHIIJNLSGULWAA-UHFFFAOYSA-N 0.000 description 1
- SXRIODJVOSFHTK-UHFFFAOYSA-N 1-(4-bromophenyl)sulfonyl-1,4-diazepan-5-one Chemical compound C1=CC(Br)=CC=C1S(=O)(=O)N1CCC(=O)NCC1 SXRIODJVOSFHTK-UHFFFAOYSA-N 0.000 description 1
- VRHINIBUNNLKQF-UHFFFAOYSA-N 1-(4-bromophenyl)sulfonyl-4-(2,4-dimethylphenyl)piperazine Chemical compound CC1=CC(C)=CC=C1N1CCN(S(=O)(=O)C=2C=CC(Br)=CC=2)CC1 VRHINIBUNNLKQF-UHFFFAOYSA-N 0.000 description 1
- FBOSKYPOARCXEJ-UHFFFAOYSA-N 1-(4-bromophenyl)sulfonyl-4-(2-methoxyethyl)piperazine Chemical compound C1CN(CCOC)CCN1S(=O)(=O)C1=CC=C(Br)C=C1 FBOSKYPOARCXEJ-UHFFFAOYSA-N 0.000 description 1
- BHIAOTKZDRWRTA-UHFFFAOYSA-N 1-(4-bromophenyl)sulfonyl-4-(3,5-dichlorophenyl)piperazine Chemical compound ClC1=CC(Cl)=CC(N2CCN(CC2)S(=O)(=O)C=2C=CC(Br)=CC=2)=C1 BHIAOTKZDRWRTA-UHFFFAOYSA-N 0.000 description 1
- OGZAWLINCACFDF-UHFFFAOYSA-N 1-(4-bromophenyl)sulfonyl-4-(4-methylphenyl)piperazine Chemical compound C1=CC(C)=CC=C1N1CCN(S(=O)(=O)C=2C=CC(Br)=CC=2)CC1 OGZAWLINCACFDF-UHFFFAOYSA-N 0.000 description 1
- QCAXTVFTVHQJJQ-UHFFFAOYSA-N 1-(4-bromophenyl)sulfonyl-4-methyl-1,4-diazepane Chemical compound C1CN(C)CCCN1S(=O)(=O)C1=CC=C(Br)C=C1 QCAXTVFTVHQJJQ-UHFFFAOYSA-N 0.000 description 1
- CBNDEXDYZUNXBF-UHFFFAOYSA-N 1-(4-bromophenyl)sulfonyl-4-methylpiperazine Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC=C(Br)C=C1 CBNDEXDYZUNXBF-UHFFFAOYSA-N 0.000 description 1
- GTXWMYDMGGSQOD-UHFFFAOYSA-N 1-(4-bromophenyl)sulfonyl-4-methylpiperidine Chemical compound C1CC(C)CCN1S(=O)(=O)C1=CC=C(Br)C=C1 GTXWMYDMGGSQOD-UHFFFAOYSA-N 0.000 description 1
- QGXNVCFMUCORAL-UHFFFAOYSA-N 1-(4-bromophenyl)sulfonyl-4-phenylpiperazine Chemical compound C1=CC(Br)=CC=C1S(=O)(=O)N1CCN(C=2C=CC=CC=2)CC1 QGXNVCFMUCORAL-UHFFFAOYSA-N 0.000 description 1
- NBKDNKGVTSTVQZ-UHFFFAOYSA-N 1-[4-(4-bromophenyl)sulfonylpiperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1S(=O)(=O)C1=CC=C(Br)C=C1 NBKDNKGVTSTVQZ-UHFFFAOYSA-N 0.000 description 1
- GETTWQGXWARMQE-UHFFFAOYSA-N 1-benzyl-4-(4-bromophenyl)sulfonylpiperazine Chemical compound C1=CC(Br)=CC=C1S(=O)(=O)N1CCN(CC=2C=CC=CC=2)CC1 GETTWQGXWARMQE-UHFFFAOYSA-N 0.000 description 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- BSRDBOLHXNMOKP-UHFFFAOYSA-N 2-(4-bromophenyl)sulfonyl-6,7-dimethoxy-3,4-dihydro-1h-isoquinoline Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1S(=O)(=O)C1=CC=C(Br)C=C1 BSRDBOLHXNMOKP-UHFFFAOYSA-N 0.000 description 1
- YGTUPRIZNBMOFV-UHFFFAOYSA-N 2-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=C(O)C=C1 YGTUPRIZNBMOFV-UHFFFAOYSA-N 0.000 description 1
- ZZBRTAXRIKBTMY-UHFFFAOYSA-N 2-(bromomethyl)-3-chlorobenzonitrile Chemical compound ClC1=CC=CC(C#N)=C1CBr ZZBRTAXRIKBTMY-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- AYYFUKWCLZOHPE-UHFFFAOYSA-N 2-[2-(4-methoxypyridin-2-yl)ethyl]-6-[3-(4-methylpiperazin-1-yl)sulfonylphenyl]-1h-imidazo[4,5-b]pyridine Chemical compound COC1=CC=NC(CCC=2NC3=NC=C(C=C3N=2)C=2C=C(C=CC=2)S(=O)(=O)N2CCN(C)CC2)=C1 AYYFUKWCLZOHPE-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
- YSFGGXNLZUSHHS-UHFFFAOYSA-N 2-bromobenzenesulfonamide Chemical class NS(=O)(=O)C1=CC=CC=C1Br YSFGGXNLZUSHHS-UHFFFAOYSA-N 0.000 description 1
- BMIBJCFFZPYJHF-UHFFFAOYSA-N 2-methoxy-5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical group COC1=NC=C(C)C=C1B1OC(C)(C)C(C)(C)O1 BMIBJCFFZPYJHF-UHFFFAOYSA-N 0.000 description 1
- 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- IZGQSDZAESMUQU-UHFFFAOYSA-N 3-(4-methoxypyridin-2-yl)propanoic acid Chemical compound COC1=CC=NC(CCC(O)=O)=C1 IZGQSDZAESMUQU-UHFFFAOYSA-N 0.000 description 1
- PBVZQAXFSQKDKK-UHFFFAOYSA-N 3-Methoxy-3-oxopropanoic acid Chemical compound COC(=O)CC(O)=O PBVZQAXFSQKDKK-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- 150000005240 3H-imidazo[4,5-b]pyridines Chemical class 0.000 description 1
- JWJRLABLXQZFAR-UHFFFAOYSA-N 4-(4-bromophenyl)sulfonylmorpholine Chemical compound C1=CC(Br)=CC=C1S(=O)(=O)N1CCOCC1 JWJRLABLXQZFAR-UHFFFAOYSA-N 0.000 description 1
- VSTZTWAEAXRFAR-UHFFFAOYSA-N 4-[2-[2-(4-methoxypyridin-2-yl)ethyl]imidazo[4,5-b]pyridin-3-yl]-N,N-dimethyl-2-(trifluoromethyl)benzenesulfonamide Chemical compound COC1=CC(=NC=C1)CCC1=NC=2C(=NC=CC=2)N1C1=CC(=C(C=C1)S(=O)(=O)N(C)C)C(F)(F)F VSTZTWAEAXRFAR-UHFFFAOYSA-N 0.000 description 1
- XWNDGIYRIUEXKB-UHFFFAOYSA-N 4-[4-(4-bromophenyl)sulfonylpiperazin-1-yl]benzonitrile Chemical compound C1=CC(Br)=CC=C1S(=O)(=O)N1CCN(C=2C=CC(=CC=2)C#N)CC1 XWNDGIYRIUEXKB-UHFFFAOYSA-N 0.000 description 1
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
- IWCXIBTWBKTRRB-UHFFFAOYSA-N 4-bromo-n,n,3-trimethylbenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Br)C(C)=C1 IWCXIBTWBKTRRB-UHFFFAOYSA-N 0.000 description 1
- AEMXGMOFDSBCKX-UHFFFAOYSA-N 4-bromo-n,n-bis(2-hydroxyethyl)benzenesulfonamide Chemical compound OCCN(CCO)S(=O)(=O)C1=CC=C(Br)C=C1 AEMXGMOFDSBCKX-UHFFFAOYSA-N 0.000 description 1
- GUDSSQORSKFTQR-UHFFFAOYSA-N 4-bromo-n,n-dimethyl-2-(trifluoromethoxy)benzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Br)C=C1OC(F)(F)F GUDSSQORSKFTQR-UHFFFAOYSA-N 0.000 description 1
- MDRXWOJPKUJFHZ-UHFFFAOYSA-N 4-bromo-n,n-dimethyl-2-(trifluoromethyl)benzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Br)C=C1C(F)(F)F MDRXWOJPKUJFHZ-UHFFFAOYSA-N 0.000 description 1
- SYFKBNOLTPSXPQ-UHFFFAOYSA-N 4-bromo-n-(2-hydroxyethyl)benzenesulfonamide Chemical compound OCCNS(=O)(=O)C1=CC=C(Br)C=C1 SYFKBNOLTPSXPQ-UHFFFAOYSA-N 0.000 description 1
- WZNBBKMKBQJNKL-UHFFFAOYSA-N 4-bromo-n-(2-methoxyphenyl)benzenesulfonamide Chemical compound COC1=CC=CC=C1NS(=O)(=O)C1=CC=C(Br)C=C1 WZNBBKMKBQJNKL-UHFFFAOYSA-N 0.000 description 1
- RADMIBNHYAUTFV-UHFFFAOYSA-N 4-bromo-n-(4-chlorophenyl)-n-methylbenzenesulfonamide Chemical compound C=1C=C(Br)C=CC=1S(=O)(=O)N(C)C1=CC=C(Cl)C=C1 RADMIBNHYAUTFV-UHFFFAOYSA-N 0.000 description 1
- BQGUNVMKKZJGGE-UHFFFAOYSA-N 4-bromo-n-(4-methylphenyl)benzenesulfonamide Chemical compound C1=CC(C)=CC=C1NS(=O)(=O)C1=CC=C(Br)C=C1 BQGUNVMKKZJGGE-UHFFFAOYSA-N 0.000 description 1
- JJYBBKJLHWOVBF-UHFFFAOYSA-N 4-bromo-n-[4-(dimethylamino)phenyl]benzenesulfonamide Chemical compound C1=CC(N(C)C)=CC=C1NS(=O)(=O)C1=CC=C(Br)C=C1 JJYBBKJLHWOVBF-UHFFFAOYSA-N 0.000 description 1
- XATZMSCJHBJRTQ-UHFFFAOYSA-N 4-bromo-n-cyclohexylbenzenesulfonamide Chemical compound C1=CC(Br)=CC=C1S(=O)(=O)NC1CCCCC1 XATZMSCJHBJRTQ-UHFFFAOYSA-N 0.000 description 1
- ZCUJCYISOKHAAW-UHFFFAOYSA-N 4-bromo-n-phenylbenzenesulfonamide Chemical compound C1=CC(Br)=CC=C1S(=O)(=O)NC1=CC=CC=C1 ZCUJCYISOKHAAW-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- AFRXFIAZWJFIBL-UHFFFAOYSA-N 5-iodopyridine-2,3-diamine Chemical compound NC1=CC(I)=CN=C1N AFRXFIAZWJFIBL-UHFFFAOYSA-N 0.000 description 1
- FCQMOCFTFSHYNU-UHFFFAOYSA-N 8-(4-bromophenyl)sulfonyl-1,4-dioxa-8-azaspiro[4.5]decane Chemical compound C1=CC(Br)=CC=C1S(=O)(=O)N1CCC2(OCCO2)CC1 FCQMOCFTFSHYNU-UHFFFAOYSA-N 0.000 description 1
- 206010065040 AIDS dementia complex Diseases 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical class [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 102100029133 DNA damage-induced apoptosis suppressor protein Human genes 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 206010012305 Demyelination Diseases 0.000 description 1
- 206010012435 Dermatitis and eczema Diseases 0.000 description 1
- 206010048768 Dermatosis Diseases 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 208000017189 Gastrointestinal inflammatory disease Diseases 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010018634 Gouty Arthritis Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000032456 Hemorrhagic Shock Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000918646 Homo sapiens DNA damage-induced apoptosis suppressor protein Proteins 0.000 description 1
- 101001124991 Homo sapiens Nitric oxide synthase, inducible Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 101150109636 Inos gene Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108010044467 Isoenzymes Proteins 0.000 description 1
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 208000004852 Lung Injury Diseases 0.000 description 1
- 208000007873 MPTP Poisoning Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical class [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000007920 Neurogenic Inflammation Diseases 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 1
- 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 229910002666 PdCl2 Inorganic materials 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010049771 Shock haemorrhagic Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 description 1
- 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 206010042496 Sunburn Diseases 0.000 description 1
- 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 description 1
- 206010043269 Tension headache Diseases 0.000 description 1
- 208000008548 Tension-Type Headache Diseases 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical class [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 206010069363 Traumatic lung injury Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 208000001407 Vascular Headaches Diseases 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 206010047124 Vasculitis necrotising Diseases 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- QKXGOSLDJQKZKL-UHFFFAOYSA-N [1-(4-bromophenyl)sulfonylpiperidin-4-yl]-phenylmethanone Chemical compound C1=CC(Br)=CC=C1S(=O)(=O)N1CCC(C(=O)C=2C=CC=CC=2)CC1 QKXGOSLDJQKZKL-UHFFFAOYSA-N 0.000 description 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
- ZHDSCPNAZAJOKO-UHFFFAOYSA-N [O]C(F)F Chemical compound [O]C(F)F ZHDSCPNAZAJOKO-UHFFFAOYSA-N 0.000 description 1
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 206010069351 acute lung injury Diseases 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical class [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000011575 calcium Chemical class 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000003684 cardiac depression Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 230000003788 cerebral perfusion Effects 0.000 description 1
- 150000001793 charged compounds Chemical group 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 235000019506 cigar Nutrition 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229950006191 gluconic acid Drugs 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical class NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 231100000515 lung injury Toxicity 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000011777 magnesium Chemical class 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000012740 non-selective inhibitor Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000011049 pearl Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- GRJHONXDTNBDTC-UHFFFAOYSA-N phenyl trifluoromethanesulfonate Chemical class FC(F)(F)S(=O)(=O)OC1=CC=CC=C1 GRJHONXDTNBDTC-UHFFFAOYSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 201000006292 polyarteritis nodosa Diseases 0.000 description 1
- 150000007519 polyprotic acids Polymers 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 208000028173 post-traumatic stress disease Diseases 0.000 description 1
- 239000011591 potassium Chemical class 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- ZZYXNRREDYWPLN-UHFFFAOYSA-N pyridine-2,3-diamine Chemical class NC1=CC=CN=C1N ZZYXNRREDYWPLN-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000007363 regulatory process Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229960004617 sapropterin Drugs 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 206010040400 serum sickness Diseases 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000000050 smooth muscle relaxant Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 150000003462 sulfoxides Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000009121 systemic therapy Methods 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 229910021515 thallium hydroxide Inorganic materials 0.000 description 1
- QGYXCSSUHCHXHB-UHFFFAOYSA-M thallium(i) hydroxide Chemical compound [OH-].[Tl+] QGYXCSSUHCHXHB-UHFFFAOYSA-M 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 239000010936 titanium Chemical class 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 231100000397 ulcer Toxicity 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Psychology (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Ophthalmology & Optometry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Transplantation (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP03022046 | 2003-10-01 | ||
| EP03022046 | 2003-10-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2308260T3 true ES2308260T3 (es) | 2008-12-01 |
Family
ID=34384570
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES04787262T Expired - Lifetime ES2308260T3 (es) | 2003-10-01 | 2004-09-30 | Derivados de imidazopiridinas como inhibidores de no-sintasa inducible. |
Country Status (19)
| Country | Link |
|---|---|
| US (3) | US7279488B2 (https=) |
| EP (1) | EP1670796B1 (https=) |
| JP (1) | JP2007507466A (https=) |
| KR (1) | KR20060092297A (https=) |
| CN (1) | CN100422182C (https=) |
| AT (1) | ATE399168T1 (https=) |
| AU (1) | AU2004276014A1 (https=) |
| BR (1) | BRPI0414933A (https=) |
| CA (1) | CA2540243A1 (https=) |
| DE (1) | DE602004014628D1 (https=) |
| EA (1) | EA200600607A1 (https=) |
| ES (1) | ES2308260T3 (https=) |
| IL (1) | IL173810A0 (https=) |
| MX (1) | MXPA06003351A (https=) |
| NO (1) | NO20061317L (https=) |
| NZ (1) | NZ546435A (https=) |
| RS (1) | RS20060200A (https=) |
| WO (1) | WO2005030770A1 (https=) |
| ZA (1) | ZA200601553B (https=) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RS20060206A (sr) | 2003-10-01 | 2008-08-07 | Altana Pharma Ag., | Derivati aminopiridina kao inhibitori inducibilne no-sintaze |
| DE602004014523D1 (de) | 2003-10-01 | 2008-07-31 | Nycomed Gmbh | Imidazoä4,5-büpyridinderivate als inhibitoren der induzierbaren no-synthase |
| EA200600607A1 (ru) * | 2003-10-01 | 2006-10-27 | Алтана Фарма Аг | Производные имидазопиридина в качестве ингибиторов индуцируемой no-синтазы |
| BRPI0414972A (pt) | 2003-10-01 | 2006-11-07 | Altana Pharma Ag | derivados de imidazopiridinas como inibidores de no-sintase induzìvel |
| ES2309765T3 (es) | 2004-05-28 | 2008-12-16 | 4Sc Ag | Tetrahidropiridotiofenos. |
| US7714134B2 (en) | 2004-06-11 | 2010-05-11 | 4Sc Ag | Compounds and use of tetrahydropyridothiophenes |
| EP1851229A1 (en) | 2005-02-09 | 2007-11-07 | Nycomed GmbH | Tetrahydropyridothiophenes for the treatment of proliferative diseases such as cancer |
| AU2006212179A1 (en) | 2005-02-11 | 2006-08-17 | 4Sc Ag | Tetrahydropyridothiophenes as antripoliferative agents for the treatment of cancer |
| US7763728B2 (en) | 2005-05-25 | 2010-07-27 | 4Sc Ag | Tetrahydropyridothiophenes |
| US7714136B2 (en) | 2005-05-25 | 2010-05-11 | 4Sc Ag | Tetrahydropyridothiophenes |
| UY29823A1 (es) * | 2005-10-03 | 2007-05-31 | Astrazeneca Ab | Derivados sustituidos de 7-cloro-3h-imidazol-(4,5-b) piridina, composiciones farmacéuticas que los contienen, procesos para la preparación de los mismos y aplicaciones |
| AR055669A1 (es) * | 2005-10-03 | 2007-08-29 | Astrazeneca Ab | Derivados de 3h - imidazo[4, 5 -b]piridina como inhibidores selectivos de gsk3, metodos e internediarios para su preparacion, composiciones farmaceuticas que los contienen y su uso para la elaboracion de un medicamento para el tratamiento de enfermedades neurodegenerativas y mentales. |
| WO2007045622A1 (en) * | 2005-10-18 | 2007-04-26 | Nycomed Gmbh | Oxazolo [4 , 5-b] pyridine compounds as nitric oxide synthase inhibitors |
| JP2009519933A (ja) | 2005-12-14 | 2009-05-21 | アムゲン インコーポレイティッド | ジアザ複素環式スルホンアミド誘導体およびそれらの使用法 |
| CN107427514B (zh) * | 2015-03-16 | 2021-07-13 | 豪夫迈·罗氏有限公司 | 使用tlr7激动剂和hbv衣壳装配抑制剂的组合治疗 |
| GB201512635D0 (en) | 2015-07-17 | 2015-08-26 | Ucl Business Plc | Uses of therapeutic compounds |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4045564A (en) | 1974-02-18 | 1977-08-30 | Ab Hassle | Benzimidazole derivatives useful as gastric acid secretion inhibitors |
| SE418966B (sv) | 1974-02-18 | 1981-07-06 | Haessle Ab | Analogiforfarande for framstellning av foreningar med magsyrasekretionsinhiberande verkan |
| GB8307865D0 (en) | 1983-03-22 | 1983-04-27 | Fujisawa Pharmaceutical Co | Benzimidazole derivatives |
| AU650953B2 (en) * | 1991-03-21 | 1994-07-07 | Novartis Ag | Inhaler |
| SE512835C2 (sv) | 1996-01-08 | 2000-05-22 | Astrazeneca Ab | Doseringsform innehållande en mångfald enheter alla inneslutande syralabil H+K+ATPas-hämmare |
| AUPP873799A0 (en) * | 1999-02-17 | 1999-03-11 | Fujisawa Pharmaceutical Co., Ltd. | Pyridine compounds |
| NZ535959A (en) | 2002-03-27 | 2006-05-26 | Altana Pharma Ag | Novel alkoxypyridine-derivatives as selective inhibitors of inducible nitric oxidase synthase NOS |
| EA200600607A1 (ru) * | 2003-10-01 | 2006-10-27 | Алтана Фарма Аг | Производные имидазопиридина в качестве ингибиторов индуцируемой no-синтазы |
| AU2004276013A1 (en) | 2003-10-01 | 2005-04-07 | Altana Pharma Ag | Imidazopyridine-derivatives as inducible no-synthase inhibitors |
| BRPI0414972A (pt) * | 2003-10-01 | 2006-11-07 | Altana Pharma Ag | derivados de imidazopiridinas como inibidores de no-sintase induzìvel |
| DE602004014523D1 (de) | 2003-10-01 | 2008-07-31 | Nycomed Gmbh | Imidazoä4,5-büpyridinderivate als inhibitoren der induzierbaren no-synthase |
| RS20060206A (sr) | 2003-10-01 | 2008-08-07 | Altana Pharma Ag., | Derivati aminopiridina kao inhibitori inducibilne no-sintaze |
-
2004
- 2004-09-30 EA EA200600607A patent/EA200600607A1/ru unknown
- 2004-09-30 ES ES04787262T patent/ES2308260T3/es not_active Expired - Lifetime
- 2004-09-30 RS YUP-2006/0200A patent/RS20060200A/sr unknown
- 2004-09-30 CN CNB2004800278331A patent/CN100422182C/zh not_active Expired - Fee Related
- 2004-09-30 CA CA002540243A patent/CA2540243A1/en not_active Abandoned
- 2004-09-30 KR KR1020067005902A patent/KR20060092297A/ko not_active Withdrawn
- 2004-09-30 US US10/573,202 patent/US7279488B2/en not_active Expired - Fee Related
- 2004-09-30 MX MXPA06003351A patent/MXPA06003351A/es not_active Application Discontinuation
- 2004-09-30 JP JP2006530263A patent/JP2007507466A/ja not_active Withdrawn
- 2004-09-30 AT AT04787262T patent/ATE399168T1/de not_active IP Right Cessation
- 2004-09-30 DE DE602004014628T patent/DE602004014628D1/de not_active Expired - Lifetime
- 2004-09-30 AU AU2004276014A patent/AU2004276014A1/en not_active Abandoned
- 2004-09-30 BR BRPI0414933-5A patent/BRPI0414933A/pt not_active IP Right Cessation
- 2004-09-30 EP EP04787262A patent/EP1670796B1/en not_active Expired - Lifetime
- 2004-09-30 WO PCT/EP2004/052377 patent/WO2005030770A1/en not_active Ceased
- 2004-09-30 NZ NZ546435A patent/NZ546435A/en unknown
-
2006
- 2006-02-19 IL IL173810A patent/IL173810A0/en unknown
- 2006-02-22 ZA ZA200601553A patent/ZA200601553B/en unknown
- 2006-03-23 NO NO20061317A patent/NO20061317L/no not_active Application Discontinuation
-
2007
- 2007-09-27 US US11/905,033 patent/US7709488B2/en not_active Expired - Fee Related
-
2010
- 2010-05-03 US US12/772,455 patent/US20100216790A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2004276014A1 (en) | 2005-04-07 |
| ZA200601553B (en) | 2007-04-25 |
| DE602004014628D1 (de) | 2008-08-07 |
| IL173810A0 (en) | 2006-07-05 |
| MXPA06003351A (es) | 2006-06-08 |
| US7709488B2 (en) | 2010-05-04 |
| BRPI0414933A (pt) | 2006-11-07 |
| ATE399168T1 (de) | 2008-07-15 |
| HK1096549A1 (zh) | 2007-06-01 |
| CN1856495A (zh) | 2006-11-01 |
| KR20060092297A (ko) | 2006-08-22 |
| EP1670796A1 (en) | 2006-06-21 |
| CA2540243A1 (en) | 2005-04-07 |
| EP1670796B1 (en) | 2008-06-25 |
| US7279488B2 (en) | 2007-10-09 |
| CN100422182C (zh) | 2008-10-01 |
| JP2007507466A (ja) | 2007-03-29 |
| NO20061317L (no) | 2006-03-23 |
| NZ546435A (en) | 2009-08-28 |
| US20060293302A1 (en) | 2006-12-28 |
| US20080021039A1 (en) | 2008-01-24 |
| RS20060200A (sr) | 2008-08-07 |
| US20100216790A1 (en) | 2010-08-26 |
| WO2005030770A1 (en) | 2005-04-07 |
| EA200600607A1 (ru) | 2006-10-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7781244B2 (ja) | Ｐａｒｇ阻害剤としての４－置換インドールおよびインダゾールスルホンアミド誘導体 | |
| US7709488B2 (en) | Imidazopyridine-derivatives as inducible no-synthase inhibitors | |
| EP2112150B1 (en) | Improved raf inhibitors | |
| JP2019031549A (ja) | Ｅｒｋの阻害剤および使用方法 | |
| ES2300599T3 (es) | Derivados de alcoxipiridina. | |
| AU2011288876A2 (en) | Phthalazinone ketone derivative, preparation method thereof, and pharmaceutical use thereof | |
| AU2012310168B2 (en) | 6 - substituted 3 - (quinolin- 6 - ylthio) - [1,2,4] triazolo [4, 3 -a] pyradines as tyrosine kinase | |
| AU2007311480A1 (en) | Pyrido [2, 3-d] pyrimidines and their use as kinase inhibitors | |
| WO2013071698A1 (zh) | 三环类PI3K和/或mTOR抑制剂 | |
| CN116262750A (zh) | 一种芳杂环类化合物及其制备方法和用途 | |
| WO2024173514A1 (en) | Amide and ester-substituted imidazopyridine compounds | |
| ES2309567T3 (es) | Derivados de imidazopiridinas como inhibidores de no-sintasa inducible. | |
| EP1673371B1 (en) | Imidazopyridine-derivatives as inducible no-synthase inhibitors | |
| WO2007039580A1 (en) | Imidazolyl-substituted benzophenone compounds | |
| ES2273225T3 (es) | Derivados de imidazo (4,5-b) quinolina y su uso como inhibidores de la no-sintasa. | |
| ES2328626T3 (es) | Derivados de imidazopiridina utiles como inhibidores de inos. | |
| HK1096549B (en) | Imidazopyridine-derivatives as inducible no-synthase inhibitors | |
| WO2007039581A1 (en) | Imidazolyl-substituted diazabenzophenone compounds | |
| HK1137985B (en) | Improved raf inhibitors | |
| HK1078850B (en) | Novel alkoxypyridine-derivatives |