JP2010504323A - Ｉｖ型ホスホジエステラーゼの阻害物質 - Google Patents

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Publication number

JP2010504323A

JP2010504323A JP2009528863A JP2009528863A JP2010504323A JP 2010504323 A JP2010504323 A JP 2010504323A JP 2009528863 A JP2009528863 A JP 2009528863A JP 2009528863 A JP2009528863 A JP 2009528863A JP 2010504323 A JP2010504323 A JP 2010504323A

Authority

JP

Japan

Prior art keywords

compound

formula

azaspiro

dioxa

difluoromethoxy

Prior art date

2006-09-22

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.)

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• 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 title claims abstract description 18
• 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 title claims abstract description 18
• 239000003112 inhibitor Substances 0.000 title claims abstract description 13
• 150000001875 compounds Chemical class 0.000 claims abstract description 1019
• 238000000034 method Methods 0.000 claims abstract description 105
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims abstract description 15
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims abstract description 15
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims abstract description 15
• 201000000028 adult respiratory distress syndrome Diseases 0.000 claims abstract description 15
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 13
• 208000015114 central nervous system disease Diseases 0.000 claims abstract description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
• 206010009900 Colitis ulcerative Diseases 0.000 claims abstract description 8
• 206010010744 Conjunctivitis allergic Diseases 0.000 claims abstract description 8
• 208000011231 Crohn disease Diseases 0.000 claims abstract description 8
• 206010012438 Dermatitis atopic Diseases 0.000 claims abstract description 8
• 201000004681 Psoriasis Diseases 0.000 claims abstract description 8
• 206010039085 Rhinitis allergic Diseases 0.000 claims abstract description 8
• 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract description 8
• 208000002205 allergic conjunctivitis Diseases 0.000 claims abstract description 8
• 201000010105 allergic rhinitis Diseases 0.000 claims abstract description 8
• 206010003246 arthritis Diseases 0.000 claims abstract description 8
• 208000024998 atopic conjunctivitis Diseases 0.000 claims abstract description 8
• 201000008937 atopic dermatitis Diseases 0.000 claims abstract description 8
• 230000035939 shock Effects 0.000 claims abstract description 8
• 208000030507 AIDS Diseases 0.000 claims abstract description 7
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 7
• 208000006673 asthma Diseases 0.000 claims abstract description 7
• 206010006451 bronchitis Diseases 0.000 claims abstract description 7
• 125000000217 alkyl group Chemical group 0.000 claims description 127
• -1 al Reel Chemical group 0.000 claims description 112
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 81
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 71
• 150000003839 salts Chemical class 0.000 claims description 66
• 125000000623 heterocyclic group Chemical group 0.000 claims description 58
• 125000001072 heteroaryl group Chemical group 0.000 claims description 52
• 239000012453 solvate Substances 0.000 claims description 52
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 48
• 150000001204 N-oxides Chemical class 0.000 claims description 46
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 45
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 43
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 43
• 125000003118 aryl group Chemical group 0.000 claims description 42
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 41
• 229910052794 bromium Inorganic materials 0.000 claims description 39
• 229910052801 chlorine Inorganic materials 0.000 claims description 39
• 229910052740 iodine Inorganic materials 0.000 claims description 39
• 229910052736 halogen Inorganic materials 0.000 claims description 36
• 150000002367 halogens Chemical class 0.000 claims description 36
• 125000003342 alkenyl group Chemical group 0.000 claims description 34
• 125000000304 alkynyl group Chemical group 0.000 claims description 34
• 229910052739 hydrogen Inorganic materials 0.000 claims description 33
• 239000001257 hydrogen Substances 0.000 claims description 33
• 238000002360 preparation method Methods 0.000 claims description 32
• 125000003545 alkoxy group Chemical group 0.000 claims description 30
• 230000008569 process Effects 0.000 claims description 29
• 125000001424 substituent group Chemical group 0.000 claims description 28
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 22
• 229910052731 fluorine Inorganic materials 0.000 claims description 21
• 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims description 20
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 19
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 19
• 229910052717 sulfur Inorganic materials 0.000 claims description 19
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 19
• 125000004432 carbon atom Chemical group C* 0.000 claims description 18
• 125000005842 heteroatom Chemical group 0.000 claims description 18
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
• 229960001867 guaiacol Drugs 0.000 claims description 16
• 229910052760 oxygen Inorganic materials 0.000 claims description 16
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 14
• 230000005764 inhibitory process Effects 0.000 claims description 14
• 125000002252 acyl group Chemical group 0.000 claims description 13
• 239000003246 corticosteroid Substances 0.000 claims description 12
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 11
• 125000004043 oxo group Chemical group O=* 0.000 claims description 10
• 229940043355 kinase inhibitor Drugs 0.000 claims description 9
• 239000003757 phosphotransferase inhibitor Substances 0.000 claims description 9
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 8
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• 229940121948 Muscarinic receptor antagonist Drugs 0.000 claims description 7
• 201000008482 osteoarthritis Diseases 0.000 claims description 7
• HJCRSXYVPNDWDX-RBFZIWAESA-N 1-[(2r)-2-[[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]methyl]pyrrolidin-1-yl]propan-1-one Chemical compound CCC(=O)N1CCC[C@@H]1COC1=CC(C=2CC3(COCC3)ON=2)=CC=C1OC(F)F HJCRSXYVPNDWDX-RBFZIWAESA-N 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
• 125000004429 atom Chemical group 0.000 claims description 6
• 229940124748 beta 2 agonist Drugs 0.000 claims description 6
• 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 claims description 6
• 125000002950 monocyclic group Chemical group 0.000 claims description 6
• OJLNTYBVVYDBIR-UHFFFAOYSA-N 3-[4-(difluoromethoxy)-3-methoxyphenyl]-1-oxa-2-azaspiro[4.5]dec-2-en-8-one Chemical compound C1=C(OC(F)F)C(OC)=CC(C=2CC3(ON=2)CCC(=O)CC3)=C1 OJLNTYBVVYDBIR-UHFFFAOYSA-N 0.000 claims description 5
• 239000000043 antiallergic agent Substances 0.000 claims description 5
• 239000003795 chemical substances by application Substances 0.000 claims description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
• 230000009467 reduction Effects 0.000 claims description 5
• KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical group CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 claims description 4
• 102000019034 Chemokines Human genes 0.000 claims description 4
• 108010012236 Chemokines Proteins 0.000 claims description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
• 239000000812 cholinergic antagonist Substances 0.000 claims description 4
• 201000010099 disease Diseases 0.000 claims description 4
• 230000002401 inhibitory effect Effects 0.000 claims description 4
• 239000003199 leukotriene receptor blocking agent Substances 0.000 claims description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
• 239000001301 oxygen Substances 0.000 claims description 4
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
• 125000004434 sulfur atom Chemical group 0.000 claims description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
• VTIRXKHOOLRNDQ-IWPPFLRJSA-N 1-[(2r)-2-[[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]methyl]pyrrolidin-1-yl]ethanone Chemical compound CC(=O)N1CCC[C@@H]1COC1=CC(C=2CC3(COCC3)ON=2)=CC=C1OC(F)F VTIRXKHOOLRNDQ-IWPPFLRJSA-N 0.000 claims description 3
• VTIRXKHOOLRNDQ-OOJLDXBWSA-N 1-[(2s)-2-[[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]methyl]pyrrolidin-1-yl]ethanone Chemical compound CC(=O)N1CCC[C@H]1COC1=CC(C=2CC3(COCC3)ON=2)=CC=C1OC(F)F VTIRXKHOOLRNDQ-OOJLDXBWSA-N 0.000 claims description 3
• HKZFVODVUJOCMP-KTQQKIMGSA-N 1-[(3s)-3-[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]pyrrolidin-1-yl]ethanone Chemical compound C1N(C(=O)C)CC[C@@H]1OC1=CC(C=2CC3(COCC3)ON=2)=CC=C1OC(F)F HKZFVODVUJOCMP-KTQQKIMGSA-N 0.000 claims description 3
• DIQKIPUYXSNLNR-PVCZSOGJSA-N 1-[(3s)-3-[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]pyrrolidin-1-yl]propan-1-one Chemical compound C1N(C(=O)CC)CC[C@@H]1OC1=CC(C=2CC3(COCC3)ON=2)=CC=C1OC(F)F DIQKIPUYXSNLNR-PVCZSOGJSA-N 0.000 claims description 3
• KMFUVVRLBOYMAY-UHFFFAOYSA-N 1-[3-[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]piperidin-1-yl]ethanone Chemical compound C1N(C(=O)C)CCCC1OC1=CC(C=2CC3(COCC3)ON=2)=CC=C1OC(F)F KMFUVVRLBOYMAY-UHFFFAOYSA-N 0.000 claims description 3
• NXTVNOKGNYDNBY-UHFFFAOYSA-N 1-[3-[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]piperidin-1-yl]propan-1-one Chemical compound C1N(C(=O)CC)CCCC1OC1=CC(C=2CC3(COCC3)ON=2)=CC=C1OC(F)F NXTVNOKGNYDNBY-UHFFFAOYSA-N 0.000 claims description 3
• JAJTVVDBPOVKQM-UHFFFAOYSA-N 1-[4-[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1OC1=CC(C=2CC3(COCC3)ON=2)=CC=C1OC(F)F JAJTVVDBPOVKQM-UHFFFAOYSA-N 0.000 claims description 3
• LECHGRBFRSCYPJ-UHFFFAOYSA-N 1-[4-[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]piperidin-1-yl]propan-1-one Chemical compound C1CN(C(=O)CC)CCC1OC1=CC(C=2CC3(COCC3)ON=2)=CC=C1OC(F)F LECHGRBFRSCYPJ-UHFFFAOYSA-N 0.000 claims description 3
• ORABMQSVAJXFTQ-UHFFFAOYSA-N 2-[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]-n-methylacetamide Chemical compound C1=C(OC(F)F)C(OCC(=O)NC)=CC(C=2CC3(COCC3)ON=2)=C1 ORABMQSVAJXFTQ-UHFFFAOYSA-N 0.000 claims description 3
• WSXGQCQWPNRNBR-UHFFFAOYSA-N 2-[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]acetamide Chemical compound C1=C(OC(F)F)C(OCC(=O)N)=CC(C=2CC3(COCC3)ON=2)=C1 WSXGQCQWPNRNBR-UHFFFAOYSA-N 0.000 claims description 3
• MOWKSKDNBFDKRV-UHFFFAOYSA-N 2-[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]acetonitrile Chemical compound C1=C(OCC#N)C(OC(F)F)=CC=C1C(C1)=NOC11COCC1 MOWKSKDNBFDKRV-UHFFFAOYSA-N 0.000 claims description 3
• YMURQVVCUSLYKS-UHFFFAOYSA-N 2-[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]ethanol Chemical compound C1=C(OC(F)F)C(OCCO)=CC(C=2CC3(COCC3)ON=2)=C1 YMURQVVCUSLYKS-UHFFFAOYSA-N 0.000 claims description 3
• YFUKEBPCOQABOU-UHFFFAOYSA-N 2-[2-[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]ethyl]isoindole-1,3-dione Chemical compound C1=C(OCCN2C(C3=CC=CC=C3C2=O)=O)C(OC(F)F)=CC=C1C(C1)=NOC21CCOC2 YFUKEBPCOQABOU-UHFFFAOYSA-N 0.000 claims description 3
• AIXDJDCVSAUVKT-UHFFFAOYSA-N 2-[4-(difluoromethoxy)-3-methoxyphenyl]-4,9,12-trioxa-3-azadispiro[4.2.4^{8}.2^{5}]tetradec-2-ene Chemical compound C1=C(OC(F)F)C(OC)=CC(C=2CC3(ON=2)CCC2(CC3)OCCO2)=C1 AIXDJDCVSAUVKT-UHFFFAOYSA-N 0.000 claims description 3
• BUSSLELEXALTFA-UHFFFAOYSA-N 3-[2-(difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]cyclopentan-1-ol Chemical compound C1C(O)CCC1OC1=CC(C=2CC3(COCC3)ON=2)=CC=C1OC(F)F BUSSLELEXALTFA-UHFFFAOYSA-N 0.000 claims description 3
• COXSONPHLJNWNX-UHFFFAOYSA-N 3-[3-(2,3-dihydro-1h-inden-2-yloxy)-4-(2,2,2-trifluoroethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound C1=C(OC2CC3=CC=CC=C3C2)C(OCC(F)(F)F)=CC=C1C(C1)=NOC21CCOC2 COXSONPHLJNWNX-UHFFFAOYSA-N 0.000 claims description 3
• JGOJHHGLHYSJTJ-UHFFFAOYSA-N 3-[3-(4-chlorophenoxy)-4-(difluoromethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)OC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OC1=CC=C(Cl)C=C1 JGOJHHGLHYSJTJ-UHFFFAOYSA-N 0.000 claims description 3
• MJAYCNQRTRHMHZ-UHFFFAOYSA-N 3-[3-(cyclohexylmethoxy)-4-(2,2,2-trifluoroethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)(F)COC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OCC1CCCCC1 MJAYCNQRTRHMHZ-UHFFFAOYSA-N 0.000 claims description 3
• AKJREIJOXINJHE-UHFFFAOYSA-N 3-[3-(cyclohexylmethoxy)-4-(difluoromethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)OC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OCC1CCCCC1 AKJREIJOXINJHE-UHFFFAOYSA-N 0.000 claims description 3
• YDZAHLCRNIVRAT-UHFFFAOYSA-N 3-[3-(cyclopentylmethoxy)-4-(difluoromethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)OC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OCC1CCCC1 YDZAHLCRNIVRAT-UHFFFAOYSA-N 0.000 claims description 3
• SXJWHNWLHZVCJI-UHFFFAOYSA-N 3-[3-(cyclopropylmethoxy)-4-(2,2,2-trifluoroethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)(F)COC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OCC1CC1 SXJWHNWLHZVCJI-UHFFFAOYSA-N 0.000 claims description 3
• ASEVYHAUDQBLKT-XGLRFROISA-N 3-[3-[(3s)-1-benzylpyrrolidin-3-yl]oxy-4-(difluoromethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound C([C@@H](C1)OC2=CC(=CC=C2OC(F)F)C=2CC3(COCC3)ON=2)CN1CC1=CC=CC=C1 ASEVYHAUDQBLKT-XGLRFROISA-N 0.000 claims description 3
• LYKKKBORLKCYAT-UHFFFAOYSA-N 3-[3-butoxy-4-(2,2,2-trifluoroethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound C1=C(OCC(F)(F)F)C(OCCCC)=CC(C=2CC3(COCC3)ON=2)=C1 LYKKKBORLKCYAT-UHFFFAOYSA-N 0.000 claims description 3
• BQMMOALJHYMYEJ-UHFFFAOYSA-N 3-[3-cyclohexyloxy-4-(2,2,2-trifluoroethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)(F)COC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OC1CCCCC1 BQMMOALJHYMYEJ-UHFFFAOYSA-N 0.000 claims description 3
• KWLYPJFNMTUYLT-UHFFFAOYSA-N 3-[3-cyclohexyloxy-4-(difluoromethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)OC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OC1CCCCC1 KWLYPJFNMTUYLT-UHFFFAOYSA-N 0.000 claims description 3
• PCZCTKMVCGAKPV-UHFFFAOYSA-N 3-[3-cyclopentyloxy-4-(2,2,2-trifluoroethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)(F)COC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OC1CCCC1 PCZCTKMVCGAKPV-UHFFFAOYSA-N 0.000 claims description 3
• IDRVYYBAWQRRNN-UHFFFAOYSA-N 3-[3-ethoxy-4-(2,2,2-trifluoroethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound C1=C(OCC(F)(F)F)C(OCC)=CC(C=2CC3(COCC3)ON=2)=C1 IDRVYYBAWQRRNN-UHFFFAOYSA-N 0.000 claims description 3
• NIRSPKVHULAAOC-UHFFFAOYSA-N 3-[3-methoxy-4-(2,2,2-trifluoroethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound C1=C(OCC(F)(F)F)C(OC)=CC(C=2CC3(COCC3)ON=2)=C1 NIRSPKVHULAAOC-UHFFFAOYSA-N 0.000 claims description 3
• DDFZRKDFRSYTHO-UHFFFAOYSA-N 3-[3-phenylmethoxy-4-(2,2,2-trifluoroethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)(F)COC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OCC1=CC=CC=C1 DDFZRKDFRSYTHO-UHFFFAOYSA-N 0.000 claims description 3
• DUMXCRYVFUZHEO-UHFFFAOYSA-N 3-[3-propan-2-yloxy-4-(2,2,2-trifluoroethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound C1=C(OCC(F)(F)F)C(OC(C)C)=CC(C=2CC3(COCC3)ON=2)=C1 DUMXCRYVFUZHEO-UHFFFAOYSA-N 0.000 claims description 3
• MTPJMZWSBDKCLJ-UHFFFAOYSA-N 3-[3-propoxy-4-(2,2,2-trifluoroethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound C1=C(OCC(F)(F)F)C(OCCC)=CC(C=2CC3(COCC3)ON=2)=C1 MTPJMZWSBDKCLJ-UHFFFAOYSA-N 0.000 claims description 3
• RUMVFKRWVRAANZ-UHFFFAOYSA-N 3-[4-(difluoromethoxy)-3-(1-ethylsulfonylpiperidin-3-yl)oxyphenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound C1N(S(=O)(=O)CC)CCCC1OC1=CC(C=2CC3(COCC3)ON=2)=CC=C1OC(F)F RUMVFKRWVRAANZ-UHFFFAOYSA-N 0.000 claims description 3
• SMKJDVMZHMINMF-UHFFFAOYSA-N 3-[4-(difluoromethoxy)-3-(2-morpholin-4-ylethoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)OC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OCCN1CCOCC1 SMKJDVMZHMINMF-UHFFFAOYSA-N 0.000 claims description 3
• VEYQRTKVRVSCQS-UHFFFAOYSA-N 3-[4-(difluoromethoxy)-3-(4-fluorophenoxy)phenyl]-1,7-dioxa-2-azaspiro[4.4]non-2-ene Chemical compound FC(F)OC1=CC=C(C=2CC3(COCC3)ON=2)C=C1OC1=CC=C(F)C=C1 VEYQRTKVRVSCQS-UHFFFAOYSA-N 0.000 claims description 3
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