Isoxazole o-linked carbamoyl cyclohexyl acids as LPA antagonists
The present invention provides compounds of Formula (Ia) or (Ib) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein X1, X2, X3, and X4 are each independently CR6 or N; provided that no more than two of X1, X2, X3, or X4 are N; L is C1-4 alkylene substituted...
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creator | Kaltenbach, III, Robert F Zhang, Hao Shi, Yan Li, Jun Cheng, Peter Tai Wah |
description | The present invention provides compounds of Formula (Ia) or (Ib) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein X1, X2, X3, and X4 are each independently CR6 or N; provided that no more than two of X1, X2, X3, or X4 are N; L is C1-4 alkylene substituted with 0 to 4 R7; R1 is (-CH2)aR9; a is an integer of 0 or 1; R2 is each independently halo, cyano, hydroxyl, amino, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxy, alkoxyalkyl, haloalkoxyallcyl, or haloalkoxy; n is an integer of 0, 1, or 2; R3 is hydrogen, C1-6 alkyl, C1-6 deuterated alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy, and the alkyl, by itself or as part of other moiety, is optionally substituted with deuterium partially or fully; R4 is C1-10 alkyl, C1-10 deuterated alkyl, C1-10 haloalkyl, C1-10 alkenyl, C3-8 cycloalkyl, 6 to 10-membered aryl, 3 to 8-membered heterocyclyl, -(C1-6 alkylene)-(C3-8 cycloalkyl), -(C1-6 alkylene)-(6 to 10-membered aryl), -(C1-6 alkylene)-(3 to 8-membered heterocyclyl), or -(C1-6 alkylene)-(5 to 6-membered heteroaryl); wherein each of the alkyl, alkylene, alkenyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, by itself or as part of other moiety, is independently substituted with 0 to 3 R8; or alternatively, R3 and R4, taken together with the N atom to which they are attached, form a 4 to 9-membered heterocyclic ring moiety which is substituted with 0 to 3 R; R5 and R6 are each independently hydrogen, halo, cyano, hydroxyl, amino, C1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R7 is halo, oxo, cyano, hydroxyl, amino, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R8 are each independently deuterium, halo, hydroxyl, amino, cyano, C1-6 alkyl, C1-6 deuterated alkyl, C2-6 alkenyl, C2-6 alkynyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl; or alternatively, two R8, taken together with the atoms to which they are attached, form a 3 to 6-membered carbocyclic ring or a 3 to 6-membered heterocyclic ring each of which is independently substituted with 0 to 3 R12; R9 is selected from -CN, -C(O)OR10, -C(O)NR11aR11b, -CO-NH-CO-Re, -CO-NH-SO2-Re, -CO-NH-SO-Re, -SO2-OH, -SO2 |
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fullrecord | <record><control><sourceid>epo_EVB</sourceid><recordid>TN_cdi_epo_espacenet_US11180488B2</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>US11180488B2</sourcerecordid><originalsourceid>FETCH-epo_espacenet_US11180488B23</originalsourceid><addsrcrecordid>eNrjZHDwLM6vSKzKz0lVyNfNyczLTk1RSE4sSkrMza_MUUiuTM7Jz0itADITkzNTihUSixV8AhwVEvNKEtPz8zKLS4p5GFjTEnOKU3mhNDeDoptriLOHbmpBfnxqcUFicmpeakl8aLChoaGFgYmFhZORMTFqAMyWMWg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>patent</recordtype></control><display><type>patent</type><title>Isoxazole o-linked carbamoyl cyclohexyl acids as LPA antagonists</title><source>esp@cenet</source><creator>Kaltenbach, III, Robert F ; Zhang, Hao ; Shi, Yan ; Li, Jun ; Cheng, Peter Tai Wah</creator><creatorcontrib>Kaltenbach, III, Robert F ; Zhang, Hao ; Shi, Yan ; Li, Jun ; Cheng, Peter Tai Wah</creatorcontrib><description>The present invention provides compounds of Formula (Ia) or (Ib) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein X1, X2, X3, and X4 are each independently CR6 or N; provided that no more than two of X1, X2, X3, or X4 are N; L is C1-4 alkylene substituted with 0 to 4 R7; R1 is (-CH2)aR9; a is an integer of 0 or 1; R2 is each independently halo, cyano, hydroxyl, amino, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxy, alkoxyalkyl, haloalkoxyallcyl, or haloalkoxy; n is an integer of 0, 1, or 2; R3 is hydrogen, C1-6 alkyl, C1-6 deuterated alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy, and the alkyl, by itself or as part of other moiety, is optionally substituted with deuterium partially or fully; R4 is C1-10 alkyl, C1-10 deuterated alkyl, C1-10 haloalkyl, C1-10 alkenyl, C3-8 cycloalkyl, 6 to 10-membered aryl, 3 to 8-membered heterocyclyl, -(C1-6 alkylene)-(C3-8 cycloalkyl), -(C1-6 alkylene)-(6 to 10-membered aryl), -(C1-6 alkylene)-(3 to 8-membered heterocyclyl), or -(C1-6 alkylene)-(5 to 6-membered heteroaryl); wherein each of the alkyl, alkylene, alkenyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, by itself or as part of other moiety, is independently substituted with 0 to 3 R8; or alternatively, R3 and R4, taken together with the N atom to which they are attached, form a 4 to 9-membered heterocyclic ring moiety which is substituted with 0 to 3 R; R5 and R6 are each independently hydrogen, halo, cyano, hydroxyl, amino, C1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R7 is halo, oxo, cyano, hydroxyl, amino, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R8 are each independently deuterium, halo, hydroxyl, amino, cyano, C1-6 alkyl, C1-6 deuterated alkyl, C2-6 alkenyl, C2-6 alkynyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl; or alternatively, two R8, taken together with the atoms to which they are attached, form a 3 to 6-membered carbocyclic ring or a 3 to 6-membered heterocyclic ring each of which is independently substituted with 0 to 3 R12; R9 is selected from -CN, -C(O)OR10, -C(O)NR11aR11b, -CO-NH-CO-Re, -CO-NH-SO2-Re, -CO-NH-SO-Re, -SO2-OH, -SO2-NH-CO-Re, -P(O)(OH)2, tetrazol-5-yl, -CH2-CO-NH-CO-Re, -CH2-CO-NH-SO2-Re, CH2-CO-NH-SO-Re, -CH2-SO2-OH, -CH2-SO2-NH-CO-Re, -CH2-P(O)(OH)2, tetrazol-5-ylmethylene; Re is C1-6 alkyl, C3-6 cycloalkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, or haloalkoxyalkyl; R10 is hydrogen or C1-10 alkyl; and R11a and R11b are each independently hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; and R12 is halo, cyano, hydroxyl, amino, C1-6alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl. These compounds are selective LPA receptor inhibitors.</description><language>eng</language><subject>CHEMISTRY ; HETEROCYCLIC COMPOUNDS ; METALLURGY ; ORGANIC CHEMISTRY</subject><creationdate>2021</creationdate><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20211123&DB=EPODOC&CC=US&NR=11180488B2$$EHTML$$P50$$Gepo$$Hfree_for_read</linktohtml><link.rule.ids>230,308,776,881,25542,76289</link.rule.ids><linktorsrc>$$Uhttps://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20211123&DB=EPODOC&CC=US&NR=11180488B2$$EView_record_in_European_Patent_Office$$FView_record_in_$$GEuropean_Patent_Office$$Hfree_for_read</linktorsrc></links><search><creatorcontrib>Kaltenbach, III, Robert F</creatorcontrib><creatorcontrib>Zhang, Hao</creatorcontrib><creatorcontrib>Shi, Yan</creatorcontrib><creatorcontrib>Li, Jun</creatorcontrib><creatorcontrib>Cheng, Peter Tai Wah</creatorcontrib><title>Isoxazole o-linked carbamoyl cyclohexyl acids as LPA antagonists</title><description>The present invention provides compounds of Formula (Ia) or (Ib) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein X1, X2, X3, and X4 are each independently CR6 or N; provided that no more than two of X1, X2, X3, or X4 are N; L is C1-4 alkylene substituted with 0 to 4 R7; R1 is (-CH2)aR9; a is an integer of 0 or 1; R2 is each independently halo, cyano, hydroxyl, amino, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxy, alkoxyalkyl, haloalkoxyallcyl, or haloalkoxy; n is an integer of 0, 1, or 2; R3 is hydrogen, C1-6 alkyl, C1-6 deuterated alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy, and the alkyl, by itself or as part of other moiety, is optionally substituted with deuterium partially or fully; R4 is C1-10 alkyl, C1-10 deuterated alkyl, C1-10 haloalkyl, C1-10 alkenyl, C3-8 cycloalkyl, 6 to 10-membered aryl, 3 to 8-membered heterocyclyl, -(C1-6 alkylene)-(C3-8 cycloalkyl), -(C1-6 alkylene)-(6 to 10-membered aryl), -(C1-6 alkylene)-(3 to 8-membered heterocyclyl), or -(C1-6 alkylene)-(5 to 6-membered heteroaryl); wherein each of the alkyl, alkylene, alkenyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, by itself or as part of other moiety, is independently substituted with 0 to 3 R8; or alternatively, R3 and R4, taken together with the N atom to which they are attached, form a 4 to 9-membered heterocyclic ring moiety which is substituted with 0 to 3 R; R5 and R6 are each independently hydrogen, halo, cyano, hydroxyl, amino, C1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R7 is halo, oxo, cyano, hydroxyl, amino, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R8 are each independently deuterium, halo, hydroxyl, amino, cyano, C1-6 alkyl, C1-6 deuterated alkyl, C2-6 alkenyl, C2-6 alkynyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl; or alternatively, two R8, taken together with the atoms to which they are attached, form a 3 to 6-membered carbocyclic ring or a 3 to 6-membered heterocyclic ring each of which is independently substituted with 0 to 3 R12; R9 is selected from -CN, -C(O)OR10, -C(O)NR11aR11b, -CO-NH-CO-Re, -CO-NH-SO2-Re, -CO-NH-SO-Re, -SO2-OH, -SO2-NH-CO-Re, -P(O)(OH)2, tetrazol-5-yl, -CH2-CO-NH-CO-Re, -CH2-CO-NH-SO2-Re, CH2-CO-NH-SO-Re, -CH2-SO2-OH, -CH2-SO2-NH-CO-Re, -CH2-P(O)(OH)2, tetrazol-5-ylmethylene; Re is C1-6 alkyl, C3-6 cycloalkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, or haloalkoxyalkyl; R10 is hydrogen or C1-10 alkyl; and R11a and R11b are each independently hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; and R12 is halo, cyano, hydroxyl, amino, C1-6alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl. These compounds are selective LPA receptor inhibitors.</description><subject>CHEMISTRY</subject><subject>HETEROCYCLIC COMPOUNDS</subject><subject>METALLURGY</subject><subject>ORGANIC CHEMISTRY</subject><fulltext>true</fulltext><rsrctype>patent</rsrctype><creationdate>2021</creationdate><recordtype>patent</recordtype><sourceid>EVB</sourceid><recordid>eNrjZHDwLM6vSKzKz0lVyNfNyczLTk1RSE4sSkrMza_MUUiuTM7Jz0itADITkzNTihUSixV8AhwVEvNKEtPz8zKLS4p5GFjTEnOKU3mhNDeDoptriLOHbmpBfnxqcUFicmpeakl8aLChoaGFgYmFhZORMTFqAMyWMWg</recordid><startdate>20211123</startdate><enddate>20211123</enddate><creator>Kaltenbach, III, Robert F</creator><creator>Zhang, Hao</creator><creator>Shi, Yan</creator><creator>Li, Jun</creator><creator>Cheng, Peter Tai Wah</creator><scope>EVB</scope></search><sort><creationdate>20211123</creationdate><title>Isoxazole o-linked carbamoyl cyclohexyl acids as LPA antagonists</title><author>Kaltenbach, III, Robert F ; Zhang, Hao ; Shi, Yan ; Li, Jun ; Cheng, Peter Tai Wah</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-epo_espacenet_US11180488B23</frbrgroupid><rsrctype>patents</rsrctype><prefilter>patents</prefilter><language>eng</language><creationdate>2021</creationdate><topic>CHEMISTRY</topic><topic>HETEROCYCLIC COMPOUNDS</topic><topic>METALLURGY</topic><topic>ORGANIC CHEMISTRY</topic><toplevel>online_resources</toplevel><creatorcontrib>Kaltenbach, III, Robert F</creatorcontrib><creatorcontrib>Zhang, Hao</creatorcontrib><creatorcontrib>Shi, Yan</creatorcontrib><creatorcontrib>Li, Jun</creatorcontrib><creatorcontrib>Cheng, Peter Tai Wah</creatorcontrib><collection>esp@cenet</collection></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Kaltenbach, III, Robert F</au><au>Zhang, Hao</au><au>Shi, Yan</au><au>Li, Jun</au><au>Cheng, Peter Tai Wah</au><format>patent</format><genre>patent</genre><ristype>GEN</ristype><title>Isoxazole o-linked carbamoyl cyclohexyl acids as LPA antagonists</title><date>2021-11-23</date><risdate>2021</risdate><abstract>The present invention provides compounds of Formula (Ia) or (Ib) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein X1, X2, X3, and X4 are each independently CR6 or N; provided that no more than two of X1, X2, X3, or X4 are N; L is C1-4 alkylene substituted with 0 to 4 R7; R1 is (-CH2)aR9; a is an integer of 0 or 1; R2 is each independently halo, cyano, hydroxyl, amino, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxy, alkoxyalkyl, haloalkoxyallcyl, or haloalkoxy; n is an integer of 0, 1, or 2; R3 is hydrogen, C1-6 alkyl, C1-6 deuterated alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy, and the alkyl, by itself or as part of other moiety, is optionally substituted with deuterium partially or fully; R4 is C1-10 alkyl, C1-10 deuterated alkyl, C1-10 haloalkyl, C1-10 alkenyl, C3-8 cycloalkyl, 6 to 10-membered aryl, 3 to 8-membered heterocyclyl, -(C1-6 alkylene)-(C3-8 cycloalkyl), -(C1-6 alkylene)-(6 to 10-membered aryl), -(C1-6 alkylene)-(3 to 8-membered heterocyclyl), or -(C1-6 alkylene)-(5 to 6-membered heteroaryl); wherein each of the alkyl, alkylene, alkenyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, by itself or as part of other moiety, is independently substituted with 0 to 3 R8; or alternatively, R3 and R4, taken together with the N atom to which they are attached, form a 4 to 9-membered heterocyclic ring moiety which is substituted with 0 to 3 R; R5 and R6 are each independently hydrogen, halo, cyano, hydroxyl, amino, C1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R7 is halo, oxo, cyano, hydroxyl, amino, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R8 are each independently deuterium, halo, hydroxyl, amino, cyano, C1-6 alkyl, C1-6 deuterated alkyl, C2-6 alkenyl, C2-6 alkynyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl; or alternatively, two R8, taken together with the atoms to which they are attached, form a 3 to 6-membered carbocyclic ring or a 3 to 6-membered heterocyclic ring each of which is independently substituted with 0 to 3 R12; R9 is selected from -CN, -C(O)OR10, -C(O)NR11aR11b, -CO-NH-CO-Re, -CO-NH-SO2-Re, -CO-NH-SO-Re, -SO2-OH, -SO2-NH-CO-Re, -P(O)(OH)2, tetrazol-5-yl, -CH2-CO-NH-CO-Re, -CH2-CO-NH-SO2-Re, CH2-CO-NH-SO-Re, -CH2-SO2-OH, -CH2-SO2-NH-CO-Re, -CH2-P(O)(OH)2, tetrazol-5-ylmethylene; Re is C1-6 alkyl, C3-6 cycloalkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, or haloalkoxyalkyl; R10 is hydrogen or C1-10 alkyl; and R11a and R11b are each independently hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; and R12 is halo, cyano, hydroxyl, amino, C1-6alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl. These compounds are selective LPA receptor inhibitors.</abstract><oa>free_for_read</oa></addata></record> |
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title | Isoxazole o-linked carbamoyl cyclohexyl acids as LPA antagonists |
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