CA2550717A1 - Bicycloheteroarylamine compounds as ion channel ligands and uses thereof - Google Patents

Info

Publication number

CA2550717A1

CA2550717A1 CA002550717A CA2550717A CA2550717A1 CA 2550717 A1 CA2550717 A1 CA 2550717A1 CA 002550717 A CA002550717 A CA 002550717A CA 2550717 A CA2550717 A CA 2550717A CA 2550717 A1 CA2550717 A1 CA 2550717A1

Authority

CA

Canada

Prior art keywords

substituted

unsubstituted

amine

pyrimidin

compound according

Prior art date

2003-12-24

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

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• Global Dossier
• CIPO
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• 150000001875 compounds Chemical class 0.000 title claims abstract description 293
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• 239000003446 ligand Substances 0.000 title description 6
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• 208000014674 injury Diseases 0.000 claims abstract 2
• 125000003118 aryl group Chemical group 0.000 claims description 159
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 109
• 125000001072 heteroaryl group Chemical group 0.000 claims description 98
• 125000000217 alkyl group Chemical group 0.000 claims description 92
• 238000000034 method Methods 0.000 claims description 80
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 75
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 66
• 125000002252 acyl group Chemical group 0.000 claims description 60
• 229910052739 hydrogen Inorganic materials 0.000 claims description 60
• 239000001257 hydrogen Substances 0.000 claims description 59
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 59
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 55
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 47
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 43
• 125000003545 alkoxy group Chemical group 0.000 claims description 40
• YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 claims description 38
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• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 29
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• 125000004663 dialkyl amino group Chemical group 0.000 claims description 28
• 125000005843 halogen group Chemical group 0.000 claims description 28
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 28
• 125000003107 substituted aryl group Chemical group 0.000 claims description 28
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 28
• 125000004442 acylamino group Chemical group 0.000 claims description 27
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 27
• 229910052727 yttrium Inorganic materials 0.000 claims description 26
• 125000001931 aliphatic group Chemical group 0.000 claims description 25
• 150000003839 salts Chemical class 0.000 claims description 25
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• 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 17
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• 125000001309 chloro group Chemical group Cl* 0.000 claims description 16
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 15
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• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 14
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 14
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• LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims description 10
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• RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 8
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• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
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• 125000001188 haloalkyl group Chemical group 0.000 claims description 6
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 6
• 125000005864 sulfonamidyl group Chemical group 0.000 claims description 6
• UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical group C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 claims description 5
• ZYNPVMNVSYTWEV-UHFFFAOYSA-N 7-(3-chloropyridin-2-yl)-2-methylsulfonyl-n-[4-(trifluoromethyl)phenyl]-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-amine Chemical compound N=1C(S(=O)(=O)C)=NC=2CN(C=3C(=CC=CN=3)Cl)CCC=2C=1NC1=CC=C(C(F)(F)F)C=C1 ZYNPVMNVSYTWEV-UHFFFAOYSA-N 0.000 claims description 5
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• HNKYHTDVORHWCX-UHFFFAOYSA-N 1-[7-[[7-(3-chloropyridin-2-yl)-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl]amino]-4,4-dimethyl-1,3-dihydroisoquinolin-2-yl]ethanone Chemical compound C=1C=C2C(C)(C)CN(C(=O)C)CC2=CC=1NC(C=1CC2)=NC=NC=1CN2C1=NC=CC=C1Cl HNKYHTDVORHWCX-UHFFFAOYSA-N 0.000 claims description 4
• PFDDJTBRVZXBCT-UHFFFAOYSA-N 6-(3-chloropyridin-2-yl)-n-[4-(trifluoromethyl)phenyl]-7,8-dihydro-5h-2,6-naphthyridin-1-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=NC=CC2=C1CCN(C=1C(=CC=CN=1)Cl)C2 PFDDJTBRVZXBCT-UHFFFAOYSA-N 0.000 claims description 4
• DOJYBNFARUEVSY-UHFFFAOYSA-N 7-(3-chloropyridin-2-yl)-2-methylsulfanyl-n-[4-(trifluoromethyl)phenyl]-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-amine Chemical compound N=1C(SC)=NC=2CN(C=3C(=CC=CN=3)Cl)CCC=2C=1NC1=CC=C(C(F)(F)F)C=C1 DOJYBNFARUEVSY-UHFFFAOYSA-N 0.000 claims description 4
• GWVCAQXKSBTCQB-UHFFFAOYSA-N 7-(3-chloropyridin-2-yl)-n-[4-(trifluoromethyl)phenyl]-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=NC=NC2=C1CCN(C=1C(=CC=CN=1)Cl)C2 GWVCAQXKSBTCQB-UHFFFAOYSA-N 0.000 claims description 4
• BXBJWPAXYVRDEA-UHFFFAOYSA-N 7-(3-ethylsulfonylpyridin-2-yl)-n-[4-(trifluoromethyl)phenyl]-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-amine Chemical compound CCS(=O)(=O)C1=CC=CN=C1N1CC(N=CN=C2NC=3C=CC(=CC=3)C(F)(F)F)=C2CC1 BXBJWPAXYVRDEA-UHFFFAOYSA-N 0.000 claims description 4
• SJTKMHMPUXYMDD-UHFFFAOYSA-N 7-benzyl-n-(2,3-dihydro-1,4-benzodioxin-6-yl)-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-amine Chemical compound C1CC(C(=NC=N2)NC=3C=C4OCCOC4=CC=3)=C2CN1CC1=CC=CC=C1 SJTKMHMPUXYMDD-UHFFFAOYSA-N 0.000 claims description 4
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• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 4
• RLELOYZWELMJCR-UHFFFAOYSA-N 7-(3-chloropyridin-2-yl)-2-(methoxymethyl)-n-[4-(trifluoromethyl)phenyl]-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-amine Chemical compound N=1C(COC)=NC=2CN(C=3C(=CC=CN=3)Cl)CCC=2C=1NC1=CC=C(C(F)(F)F)C=C1 RLELOYZWELMJCR-UHFFFAOYSA-N 0.000 claims description 3
• IKBBIUPOCDMVFV-UHFFFAOYSA-N 7-(3-chloropyridin-2-yl)-2-ethoxy-n-[4-(trifluoromethyl)phenyl]-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-amine Chemical compound N=1C(OCC)=NC=2CN(C=3C(=CC=CN=3)Cl)CCC=2C=1NC1=CC=C(C(F)(F)F)C=C1 IKBBIUPOCDMVFV-UHFFFAOYSA-N 0.000 claims description 3
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• UREVHCLUOWTTIG-UHFFFAOYSA-N 7-(3-chloropyridin-2-yl)-n-(4,4-dimethyl-2,3-dihydro-1h-quinolin-7-yl)-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-amine Chemical compound C=1C=C2C(C)(C)CCNC2=CC=1NC(C=1CC2)=NC=NC=1CN2C1=NC=CC=C1Cl UREVHCLUOWTTIG-UHFFFAOYSA-N 0.000 claims description 3
• GWZDYZSZWHSLRQ-UHFFFAOYSA-N 7-(3-chloropyridin-2-yl)-n-[4-(trifluoromethylsulfonyl)phenyl]-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-amine Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1NC1=NC=NC2=C1CCN(C=1C(=CC=CN=1)Cl)C2 GWZDYZSZWHSLRQ-UHFFFAOYSA-N 0.000 claims description 3
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• XCTIHQWCBDHNQI-UHFFFAOYSA-N 7-(3-methylphenyl)-n-[4-(trifluoromethyl)phenyl]-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-amine Chemical compound CC1=CC=CC(N2CC3=C(C(=NC=N3)NC=3C=CC(=CC=3)C(F)(F)F)CC2)=C1 XCTIHQWCBDHNQI-UHFFFAOYSA-N 0.000 claims description 3
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