MX2007006205A - Compuestos de cromanilurea que inhiben al receptor del receptor vanilloide subtipo 1 (vr1), y usos de los mismos. - Google Patents

Info

Publication number

MX2007006205A

MX2007006205A MX2007006205A MX2007006205A MX2007006205A MX 2007006205 A MX2007006205 A MX 2007006205A MX 2007006205 A MX2007006205 A MX 2007006205A MX 2007006205 A MX2007006205 A MX 2007006205A MX 2007006205 A MX2007006205 A MX 2007006205A

Authority

MX

Mexico

Prior art keywords

alkyl

indazol

dihydro

chromen

methyl

Prior art date

2004-11-24

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 342
• 108010025083 TRPV1 receptor Proteins 0.000 title claims abstract description 24
• 102100029613 Transient receptor potential cation channel subfamily V member 1 Human genes 0.000 title description 13
• 102000005962 receptors Human genes 0.000 title description 4
• 150000003839 salts Chemical class 0.000 claims abstract description 7
• 239000000651 prodrug Substances 0.000 claims abstract description 6
• 229940002612 prodrug Drugs 0.000 claims abstract description 6
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 4
• 125000000217 alkyl group Chemical group 0.000 claims description 168
• -1 -ORc Chemical group 0.000 claims description 159
• 238000000034 method Methods 0.000 claims description 128
• 229910052739 hydrogen Inorganic materials 0.000 claims description 60
• 239000001257 hydrogen Substances 0.000 claims description 58
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 51
• 239000004202 carbamide Substances 0.000 claims description 42
• 125000001188 haloalkyl group Chemical group 0.000 claims description 36
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 34
• 125000003342 alkenyl group Chemical group 0.000 claims description 33
• 125000003118 aryl group Chemical group 0.000 claims description 27
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 27
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 26
• 125000001072 heteroaryl group Chemical group 0.000 claims description 24
• 125000001424 substituent group Chemical group 0.000 claims description 24
• 208000002193 Pain Diseases 0.000 claims description 23
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 19
• 125000002950 monocyclic group Chemical group 0.000 claims description 19
• 238000011282 treatment Methods 0.000 claims description 19
• 125000003545 alkoxy group Chemical group 0.000 claims description 16
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 16
• 230000036407 pain Effects 0.000 claims description 15
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 14
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 14
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
• 229910052736 halogen Inorganic materials 0.000 claims description 13
• 150000002367 halogens Chemical class 0.000 claims description 13
• 125000000623 heterocyclic group Chemical group 0.000 claims description 12
• 125000002619 bicyclic group Chemical group 0.000 claims description 9
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 9
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
• 206010046543 Urinary incontinence Diseases 0.000 claims description 7
• 229910052760 oxygen Inorganic materials 0.000 claims description 7
• 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
• 206010065390 Inflammatory pain Diseases 0.000 claims description 5
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 5
• 125000000304 alkynyl group Chemical group 0.000 claims description 5
• 230000003349 osteoarthritic effect Effects 0.000 claims description 5
• 208000008035 Back Pain Diseases 0.000 claims description 4
• 208000000094 Chronic Pain Diseases 0.000 claims description 4
• 208000008930 Low Back Pain Diseases 0.000 claims description 4
• 206010037211 Psychomotor hyperactivity Diseases 0.000 claims description 4
• 208000005298 acute pain Diseases 0.000 claims description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
• 239000002464 receptor antagonist Substances 0.000 claims description 4
• 229940044551 receptor antagonist Drugs 0.000 claims description 4
• 241001465754 Metazoa Species 0.000 claims description 3
• 206010028980 Neoplasm Diseases 0.000 claims description 3
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
• 201000011510 cancer Diseases 0.000 claims description 3
• 230000003247 decreasing effect Effects 0.000 claims description 3
• 125000004043 oxo group Chemical group O=* 0.000 claims description 3
• 239000008194 pharmaceutical composition Substances 0.000 claims description 3
• IHTTUOYEOCHAHS-UHFFFAOYSA-N 1-(2,2-diethyl-7-fluoro-3,4-dihydrochromen-4-yl)-3-(1h-indazol-4-yl)urea Chemical compound C12=CC=C(F)C=C2OC(CC)(CC)CC1NC(=O)NC1=CC=CC2=C1C=NN2 IHTTUOYEOCHAHS-UHFFFAOYSA-N 0.000 claims description 2
• YIDXTTBTOVGXQW-UHFFFAOYSA-N 1-(6-fluoro-3,4-dihydro-2h-chromen-4-yl)-3-isoquinolin-5-ylurea Chemical compound N1=CC=C2C(NC(=O)NC3CCOC4=CC=C(C=C43)F)=CC=CC2=C1 YIDXTTBTOVGXQW-UHFFFAOYSA-N 0.000 claims description 2
• NOYNBCYZPDMZCJ-UHFFFAOYSA-N 1-(6-fluoro-3,4-dihydro-2h-chromen-4-yl)-3-quinolin-8-ylurea Chemical compound C1=CN=C2C(NC(=O)NC3CCOC4=CC=C(C=C43)F)=CC=CC2=C1 NOYNBCYZPDMZCJ-UHFFFAOYSA-N 0.000 claims description 2
• CJHZOBWTVLHNPM-UHFFFAOYSA-N 1-(7-tert-butyl-3,4-dihydro-2h-chromen-4-yl)-3-quinolin-8-ylurea Chemical compound C1=CN=C2C(NC(=O)NC3C4=CC=C(C=C4OCC3)C(C)(C)C)=CC=CC2=C1 CJHZOBWTVLHNPM-UHFFFAOYSA-N 0.000 claims description 2
• SOFXDHKUELFSQW-UHFFFAOYSA-N methyl indazole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC)N=CC2=C1 SOFXDHKUELFSQW-UHFFFAOYSA-N 0.000 claims description 2
• FDAPTCFAZHVYLK-UHFFFAOYSA-N 1-isoquinolin-5-yl-3-[7-(trifluoromethyl)-3,4-dihydro-2h-chromen-4-yl]urea Chemical compound N1=CC=C2C(NC(=O)NC3C4=CC=C(C=C4OCC3)C(F)(F)F)=CC=CC2=C1 FDAPTCFAZHVYLK-UHFFFAOYSA-N 0.000 claims 3
• LNRLQTQYVBBJBO-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[7-(trifluoromethyl)-3,4-dihydro-2h-chromen-4-yl]urea Chemical compound C1COC2=CC(C(F)(F)F)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 LNRLQTQYVBBJBO-UHFFFAOYSA-N 0.000 claims 2
• MASAFVZAJXRZCN-UHFFFAOYSA-N 1-(7-tert-butyl-3,4-dihydro-2h-chromen-4-yl)-3-(3-methylisoquinolin-5-yl)urea Chemical compound C1COC2=CC(C(C)(C)C)=CC=C2C1NC(=O)NC1=C2C=C(C)N=CC2=CC=C1 MASAFVZAJXRZCN-UHFFFAOYSA-N 0.000 claims 2
• FGVFFUSBPJFGCF-UHFFFAOYSA-N 1-(8-tert-butyl-3,4-dihydro-2h-chromen-4-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1COC=2C(C(C)(C)C)=CC=CC=2C1NC(=O)NC1=CC=CC2=C1C=NN2 FGVFFUSBPJFGCF-UHFFFAOYSA-N 0.000 claims 2
• FGXCGGVCKKUACY-UHFFFAOYSA-N 1-(1-benzyl-2,3,4,5-tetrahydro-1-benzazepin-5-yl)-3-(1h-indazol-4-yl)urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NC(C1=CC=CC=C11)CCCN1CC1=CC=CC=C1 FGXCGGVCKKUACY-UHFFFAOYSA-N 0.000 claims 1
• CVNOORHKMWKCEI-UHFFFAOYSA-N 1-(1-benzyl-3,4-dihydro-2h-quinolin-4-yl)-3-(1h-indazol-4-yl)urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NC(C1=CC=CC=C11)CCN1CC1=CC=CC=C1 CVNOORHKMWKCEI-UHFFFAOYSA-N 0.000 claims 1
• FCWIBYQHRCBDSA-UHFFFAOYSA-N 1-(1-benzyl-6-fluoro-3,4-dihydro-2h-quinolin-4-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1CC(NC(=O)NC=2C=3C=NNC=3C=CC=2)C2=CC(F)=CC=C2N1CC1=CC=CC=C1 FCWIBYQHRCBDSA-UHFFFAOYSA-N 0.000 claims 1
• BTIBLCUSSWNUOC-UHFFFAOYSA-N 1-(1-benzyl-7-fluoro-3,4-dihydro-2h-quinolin-3-yl)-3-(1h-indazol-4-yl)urea Chemical compound C12=CC(F)=CC=C2CC(NC(=O)NC=2C=3C=NNC=3C=CC=2)CN1CC1=CC=CC=C1 BTIBLCUSSWNUOC-UHFFFAOYSA-N 0.000 claims 1
• JTXYTPNMHVUMPB-UHFFFAOYSA-N 1-(1-ethylindazol-4-yl)-3-(7-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)urea Chemical compound C1C(C)(C)OC2=CC(F)=CC=C2C1NC(=O)NC1=C2C=NN(CC)C2=CC=C1 JTXYTPNMHVUMPB-UHFFFAOYSA-N 0.000 claims 1
• BWUZDTXKQFBCBM-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-(8-piperidin-1-yl-3,4-dihydro-2h-chromen-4-yl)urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NC1CCOC2=C1C=CC=C2N1CCCCC1 BWUZDTXKQFBCBM-UHFFFAOYSA-N 0.000 claims 1
• OSMLRKGCJFBTSO-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[(1-propyl-3,4-dihydro-2h-quinolin-2-yl)methyl]urea Chemical compound C1CC2=CC=CC=C2N(CCC)C1CNC(=O)NC1=CC=CC2=C1C=NN2 OSMLRKGCJFBTSO-UHFFFAOYSA-N 0.000 claims 1
• HFGWYTFSRSOIGC-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[(6-methyl-3,4-dihydro-2h-chromen-2-yl)methyl]urea Chemical compound C1CC2=CC(C)=CC=C2OC1CNC(=O)NC1=CC=CC2=C1C=NN2 HFGWYTFSRSOIGC-UHFFFAOYSA-N 0.000 claims 1
• AKROQEYMEYIQLL-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[1-(3-phenylpropyl)-7-(trifluoromethoxy)-3,4-dihydro-2h-quinolin-3-yl]urea Chemical compound C12=CC(OC(F)(F)F)=CC=C2CC(NC(=O)NC=2C=3C=NNC=3C=CC=2)CN1CCCC1=CC=CC=C1 AKROQEYMEYIQLL-UHFFFAOYSA-N 0.000 claims 1
• POLTYCBJHGMTBT-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[1-(3-phenylpropyl)-7-(trifluoromethyl)-3,4-dihydro-2h-quinolin-3-yl]urea Chemical compound C12=CC(C(F)(F)F)=CC=C2CC(NC(=O)NC=2C=3C=NNC=3C=CC=2)CN1CCCC1=CC=CC=C1 POLTYCBJHGMTBT-UHFFFAOYSA-N 0.000 claims 1
• CHVBTEZXWRYVOG-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[7-(trifluoromethoxy)-3,4-dihydro-2h-chromen-4-yl]urea Chemical compound C1COC2=CC(OC(F)(F)F)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 CHVBTEZXWRYVOG-UHFFFAOYSA-N 0.000 claims 1
• XKXJVTYDGSUSKI-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[8-(trifluoromethoxy)-3,4-dihydro-2h-chromen-4-yl]urea Chemical compound C1COC=2C(OC(F)(F)F)=CC=CC=2C1NC(=O)NC1=CC=CC2=C1C=NN2 XKXJVTYDGSUSKI-UHFFFAOYSA-N 0.000 claims 1
• NHWCANILDANDRT-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[[1-[[2-(trifluoromethyl)phenyl]methyl]-3,4-dihydro-2h-quinolin-2-yl]methyl]urea Chemical compound FC(F)(F)C1=CC=CC=C1CN1C2=CC=CC=C2CCC1CNC(=O)NC1=CC=CC2=C1C=NN2 NHWCANILDANDRT-UHFFFAOYSA-N 0.000 claims 1
• JUSPWOFSXJZIOC-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[[1-[[3-(trifluoromethyl)phenyl]methyl]-3,4-dihydro-2h-quinolin-2-yl]methyl]urea Chemical compound FC(F)(F)C1=CC=CC(CN2C3=CC=CC=C3CCC2CNC(=O)NC=2C=3C=NNC=3C=CC=2)=C1 JUSPWOFSXJZIOC-UHFFFAOYSA-N 0.000 claims 1
• UBUYYVLKHWWBOU-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[[1-[[4-(trifluoromethyl)phenyl]methyl]-3,4-dihydro-2h-quinolin-2-yl]methyl]urea Chemical compound C1=CC(C(F)(F)F)=CC=C1CN1C2=CC=CC=C2CCC1CNC(=O)NC1=CC=CC2=C1C=NN2 UBUYYVLKHWWBOU-UHFFFAOYSA-N 0.000 claims 1
• HMFVETJDTOLOJD-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-methylurea Chemical compound CNC(=O)NC1=CC=CC2=C1C=NN2 HMFVETJDTOLOJD-UHFFFAOYSA-N 0.000 claims 1
• MMSMTMQGZFFWET-UHFFFAOYSA-N 1-(2,2-diethyl-7-fluoro-3,4-dihydrochromen-4-yl)-3-(1-methylindazol-4-yl)urea Chemical compound C12=CC=C(F)C=C2OC(CC)(CC)CC1NC(=O)NC1=CC=CC2=C1C=NN2C MMSMTMQGZFFWET-UHFFFAOYSA-N 0.000 claims 1
• HNYUSGJGGMMXFW-UHFFFAOYSA-N 1-(2-ethylindazol-4-yl)-3-(7-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)urea Chemical compound C1C(C)(C)OC2=CC(F)=CC=C2C1NC(=O)NC1=CC=CC2=NN(CC)C=C21 HNYUSGJGGMMXFW-UHFFFAOYSA-N 0.000 claims 1
• BUGPFPKBJAUVIJ-UHFFFAOYSA-N 1-(2-tert-butyl-7-fluoro-3,4-dihydro-2h-chromen-4-yl)-3-(1-methylindazol-4-yl)urea Chemical compound C1C(C(C)(C)C)OC2=CC(F)=CC=C2C1NC(=O)NC1=C2C=NN(C)C2=CC=C1 BUGPFPKBJAUVIJ-UHFFFAOYSA-N 0.000 claims 1
• LRSVHBILTQOERP-UHFFFAOYSA-N 1-(6-chloro-7-methyl-3,4-dihydro-2h-chromen-4-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1=2C=C(Cl)C(C)=CC=2OCCC1NC(=O)NC1=CC=CC2=C1C=NN2 LRSVHBILTQOERP-UHFFFAOYSA-N 0.000 claims 1
• VQJCSJIAIWNJSO-UHFFFAOYSA-N 1-(6-chloro-7-methyl-3,4-dihydro-2h-chromen-4-yl)-3-isoquinolin-5-ylurea Chemical compound N1=CC=C2C(NC(=O)NC3CCOC=4C=C(C(=CC=43)Cl)C)=CC=CC2=C1 VQJCSJIAIWNJSO-UHFFFAOYSA-N 0.000 claims 1
• GMGYJBTXGBSQGB-UHFFFAOYSA-N 1-(6-fluoro-2-methyl-3,4-dihydro-2h-chromen-4-yl)-3-(1h-indazol-4-yl)urea Chemical compound C12=CC(F)=CC=C2OC(C)CC1NC(=O)NC1=CC=CC2=C1C=NN2 GMGYJBTXGBSQGB-UHFFFAOYSA-N 0.000 claims 1
• WDXRHDBNVFLNOA-UHFFFAOYSA-N 1-(6-fluoro-3,4-dihydro-2h-chromen-4-yl)-3-(1h-indazol-4-yl)urea Chemical compound C12=CC(F)=CC=C2OCCC1NC(=O)NC1=CC=CC2=C1C=NN2 WDXRHDBNVFLNOA-UHFFFAOYSA-N 0.000 claims 1
• QWWCSSSULKYTLF-UHFFFAOYSA-N 1-(6-fluoro-3,4-dihydro-2h-chromen-4-yl)-3-quinolin-5-ylurea Chemical compound C1=CC=C2C(NC(=O)NC3CCOC4=CC=C(C=C43)F)=CC=CC2=N1 QWWCSSSULKYTLF-UHFFFAOYSA-N 0.000 claims 1
• JJAHUIPYJLEKHW-UHFFFAOYSA-N 1-(6-methyl-3,4-dihydro-2h-chromen-4-yl)-3-(3-methylisoquinolin-5-yl)urea Chemical compound N1=C(C)C=C2C(NC(=O)NC3CCOC4=CC=C(C=C43)C)=CC=CC2=C1 JJAHUIPYJLEKHW-UHFFFAOYSA-N 0.000 claims 1
• AAKPNNJMZRMCHW-UHFFFAOYSA-N 1-(6-methyl-3,4-dihydro-2h-chromen-4-yl)-3-quinolin-8-ylurea Chemical compound C1=CN=C2C(NC(=O)NC3CCOC4=CC=C(C=C43)C)=CC=CC2=C1 AAKPNNJMZRMCHW-UHFFFAOYSA-N 0.000 claims 1
• QKGZZEPGSFJYIP-UHFFFAOYSA-N 1-(7,8-difluoro-3,4-dihydro-2h-chromen-4-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1COC2=C(F)C(F)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 QKGZZEPGSFJYIP-UHFFFAOYSA-N 0.000 claims 1
• FFCWGBYAHCCERO-UHFFFAOYSA-N 1-(7-fluoro-1-methyl-3,4-dihydro-2h-quinolin-4-yl)-3-(1h-indazol-4-yl)urea Chemical compound C12=CC=C(F)C=C2N(C)CCC1NC(=O)NC1=CC=CC2=C1C=NN2 FFCWGBYAHCCERO-UHFFFAOYSA-N 0.000 claims 1
• OMIRFNXDMYBLLF-UHFFFAOYSA-N 1-(7-tert-butyl-3,4-dihydro-2h-chromen-4-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1COC2=CC(C(C)(C)C)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 OMIRFNXDMYBLLF-UHFFFAOYSA-N 0.000 claims 1
• PFLVWBBMCOHXBI-UHFFFAOYSA-N 1-(7-tert-butyl-3,4-dihydro-2h-chromen-4-yl)-3-quinolin-5-ylurea Chemical compound C1=CC=C2C(NC(=O)NC3C4=CC=C(C=C4OCC3)C(C)(C)C)=CC=CC2=N1 PFLVWBBMCOHXBI-UHFFFAOYSA-N 0.000 claims 1
• NVMRZBHUMZFLEI-UHFFFAOYSA-N 1-(8-cyclohexyl-3,4-dihydro-2h-chromen-4-yl)-3-(1h-indazol-4-yl)urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NC(C1=CC=C2)CCOC1=C2C1CCCCC1 NVMRZBHUMZFLEI-UHFFFAOYSA-N 0.000 claims 1
• FAWFVJIDGASJLP-UHFFFAOYSA-N 1-[(1-benzyl-3,4-dihydro-2h-quinolin-2-yl)methyl]-3-(1h-indazol-4-yl)urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NCC1CCC2=CC=CC=C2N1CC1=CC=CC=C1 FAWFVJIDGASJLP-UHFFFAOYSA-N 0.000 claims 1
• VJGKAUKWFSBMMV-UHFFFAOYSA-N 1-[(1-benzyl-3,4-dihydro-2h-quinolin-2-yl)methyl]-3-isoquinolin-5-ylurea Chemical compound C=1C=CC2=CN=CC=C2C=1NC(=O)NCC1CCC2=CC=CC=C2N1CC1=CC=CC=C1 VJGKAUKWFSBMMV-UHFFFAOYSA-N 0.000 claims 1
• YBHFLNPHBYUHSF-UHFFFAOYSA-N 1-[(1-benzyl-6-fluoro-3,4-dihydro-2h-quinolin-2-yl)methyl]-3-(1h-indazol-4-yl)urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NCC1CCC2=CC(F)=CC=C2N1CC1=CC=CC=C1 YBHFLNPHBYUHSF-UHFFFAOYSA-N 0.000 claims 1
• RMURSGKDSRERHP-UHFFFAOYSA-N 1-[7-(3,3-dimethylbutyl)-1-methyl-3,4-dihydro-2h-quinolin-4-yl]-3-(1h-indazol-4-yl)urea Chemical compound C12=CC=C(CCC(C)(C)C)C=C2N(C)CCC1NC(=O)NC1=CC=CC2=C1C=NN2 RMURSGKDSRERHP-UHFFFAOYSA-N 0.000 claims 1
• ILZMLSPSCRIAII-UHFFFAOYSA-N 1-[8-chloro-1-(3-methylbutyl)-3,4-dihydro-2h-quinolin-4-yl]-3-(1h-indazol-4-yl)urea Chemical compound C12=CC=CC(Cl)=C2N(CCC(C)C)CCC1NC(=O)NC1=CC=CC2=C1C=NN2 ILZMLSPSCRIAII-UHFFFAOYSA-N 0.000 claims 1
• DDMMMYOZYVTAEO-UHFFFAOYSA-N 1-[8-chloro-7-(trifluoromethyl)-3,4-dihydro-2h-chromen-4-yl]-3-(1h-indazol-4-yl)urea Chemical compound C1COC2=C(Cl)C(C(F)(F)F)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 DDMMMYOZYVTAEO-UHFFFAOYSA-N 0.000 claims 1
• WWNNLZBHVPFHOE-UHFFFAOYSA-N 1-[8-fluoro-7-(trifluoromethyl)-3,4-dihydro-2h-chromen-4-yl]-3-(1h-indazol-4-yl)urea Chemical compound C12=CC=C(C(F)(F)F)C(F)=C2OCCC1NC(=O)NC1=CC=CC2=C1C=NN2 WWNNLZBHVPFHOE-UHFFFAOYSA-N 0.000 claims 1
• PHHRDEAESPQCIV-UHFFFAOYSA-N 1-isoquinolin-5-yl-3-(6-methyl-3,4-dihydro-2h-chromen-4-yl)urea Chemical compound N1=CC=C2C(NC(=O)NC3CCOC4=CC=C(C=C43)C)=CC=CC2=C1 PHHRDEAESPQCIV-UHFFFAOYSA-N 0.000 claims 1
• HQUQCIBCUMNQAA-UHFFFAOYSA-N 1-isoquinolin-5-yl-3-(8-piperidin-1-yl-3,4-dihydro-2h-chromen-4-yl)urea Chemical compound C=1C=CC2=CN=CC=C2C=1NC(=O)NC1CCOC2=C1C=CC=C2N1CCCCC1 HQUQCIBCUMNQAA-UHFFFAOYSA-N 0.000 claims 1
• MTVMLXMUFHTONP-UHFFFAOYSA-N 1-quinolin-5-yl-3-[7-(trifluoromethyl)-3,4-dihydro-2h-chromen-4-yl]urea Chemical compound C1=CC=C2C(NC(=O)NC3C4=CC=C(C=C4OCC3)C(F)(F)F)=CC=CC2=N1 MTVMLXMUFHTONP-UHFFFAOYSA-N 0.000 claims 1
• 125000002947 alkylene group Chemical group 0.000 claims 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
• 239000005557 antagonist Substances 0.000 abstract description 3
• 230000001668 ameliorated effect Effects 0.000 abstract 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 402
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 366
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 294
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 269
• 238000005481 NMR spectroscopy Methods 0.000 description 268
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