SPIRO-CYCLIC AMINE DERIVATIVES AS S1P MODULATORS
The present invention relates spiro-cyclic amine derivatives of the formula ( I ) wherein R1 is selected from cyano, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkyl each optionally substituted with CN or one or more fluoro atoms, (3-6C)cycloalkyl, (4-6C)cycloalkenyl or a (8-10C)bicyclic group, each option...
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| creator | Leflemme, Nicolas J.-L.D Stoit, Axel Iwema Bakker, Wouter I van Dongen, Maria J.P Hobson, Adrian Coolen, Hein K.A.C |
| description | The present invention relates spiro-cyclic amine derivatives of the formula ( I )
wherein
R1 is selected from
cyano,
(2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkyl each optionally substituted with CN or one or more fluoro atoms,
(3-6C)cycloalkyl, (4-6C)cycloalkenyl or a (8-10C)bicyclic group, each optionally substituted with halogen or (1-4C)alkyl,
phenyl, biphenyl, naphthyl, each optionally substituted with one or more substituents independently selected from halogen, cyano, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (1-6C)alkoxy optionally substituted with one or more fluoro atoms, amino, di(1-4C)alkylamino and (3-6C)cycloalkyl optionally substituted with phenyl which may be substituted with (1-4C)alkyl or halogen,
phenyl substituted with phenoxy, benzyl, benzyloxy, phenylethyl or monocyclic heterocycle, each optionally substituted with (1-4C)alkyl optionally substituted with one or more fluoro atoms,
monocyclic heterocycle optionally independently substituted with halogen, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (3-6C)cycloalkyl, or phenyl optionally substituted with (1-4C)alkyl or halogen,
and
bicyclic heterocycle optionally substituted with halogen or (1-4C)alkyl optionally substituted with one or more fluoro atoms;
-Y-(C n -alkylene)-X- is a linking group wherein
Y is attached to R1 and selected from a bond, -O-, -CO-, -S-, -SO-, -SO 2 -, -NH-, -CH=CH-, -C(CF 3 )=CH-, -C¡C-, -CH 2 -O-, -O-CO-, -CO-O-, -CO-NH-, -NH-CO-, and trans-cyclopropylene;
n is an integer from 0 to 10; and
X is attached to the phenylene/pyridyl moiety and selected from a bond, -O-, -S-, -SO-, -SO 2 -, -NH-, -CO-, -CH=CH-, and trans-cyclopropylene;
R2 is H or independently selected from one or more substituents selected from halogen, (1-4C)alkoxy and (1-4C)alkyl optionally substituted with one or more fluor atoms; and
R3 is (1-4C)alkylene-R4 wherein the alkylene group may be substituted with one or more halogen atoms or with (CH 2 ) 2 to form a cyclopropyl moiety, or R3 is (3-6C)cycloalkylene-R4, -CH 2 -(3-6C)cycloalkylene-R4, (3-6C)cycloalkylene-CH 2 -R4 or -CO-CH 2 -R4, wherein R4 is -OH, -PO 3 H 2 , -OPO 3 H 2 , -COOH, -COO(1-4C)alkyl or tetrazol-5-yl;
Q is a bond or -O-;
-W-T- is selected from -CH=CH-, -CH 2 -CH 2 -, -CH 2 -O-, -O-CH 2 -, -O-CH 2 -CH 2 -, and -CO-O-;
R5 is H or independently selected from one or more halogens;
Z is CH, CR2 or N; and
A represents a morpholine ring structure or a 5-, 6- or 7-membered cyclic amine;
or |
| format | Patent |
| fullrecord | <record><control><sourceid>epo_EVB</sourceid><recordid>TN_cdi_epo_espacenet_US2021130364A1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>US2021130364A1</sourcerecordid><originalsourceid>FETCH-epo_espacenet_US2021130364A13</originalsourceid><addsrcrecordid>eNrjZDAIDvAM8td1jnT28XRWcPT19HNVcHEN8gxzDPEMcw1WcAxWCDYMUPD1dwn1cQzxDwrmYWBNS8wpTuWF0twMym6uIc4euqkF-fGpxQWJyal5qSXxocFGBkaGhsYGxmYmjobGxKkCAMaWJyo</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>patent</recordtype></control><display><type>patent</type><title>SPIRO-CYCLIC AMINE DERIVATIVES AS S1P MODULATORS</title><source>esp@cenet</source><creator>Leflemme, Nicolas J.-L.D ; Stoit, Axel ; Iwema Bakker, Wouter I ; van Dongen, Maria J.P ; Hobson, Adrian ; Coolen, Hein K.A.C</creator><creatorcontrib>Leflemme, Nicolas J.-L.D ; Stoit, Axel ; Iwema Bakker, Wouter I ; van Dongen, Maria J.P ; Hobson, Adrian ; Coolen, Hein K.A.C</creatorcontrib><description>The present invention relates spiro-cyclic amine derivatives of the formula ( I )
wherein
R1 is selected from
cyano,
(2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkyl each optionally substituted with CN or one or more fluoro atoms,
(3-6C)cycloalkyl, (4-6C)cycloalkenyl or a (8-10C)bicyclic group, each optionally substituted with halogen or (1-4C)alkyl,
phenyl, biphenyl, naphthyl, each optionally substituted with one or more substituents independently selected from halogen, cyano, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (1-6C)alkoxy optionally substituted with one or more fluoro atoms, amino, di(1-4C)alkylamino and (3-6C)cycloalkyl optionally substituted with phenyl which may be substituted with (1-4C)alkyl or halogen,
phenyl substituted with phenoxy, benzyl, benzyloxy, phenylethyl or monocyclic heterocycle, each optionally substituted with (1-4C)alkyl optionally substituted with one or more fluoro atoms,
monocyclic heterocycle optionally independently substituted with halogen, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (3-6C)cycloalkyl, or phenyl optionally substituted with (1-4C)alkyl or halogen,
and
bicyclic heterocycle optionally substituted with halogen or (1-4C)alkyl optionally substituted with one or more fluoro atoms;
-Y-(C n -alkylene)-X- is a linking group wherein
Y is attached to R1 and selected from a bond, -O-, -CO-, -S-, -SO-, -SO 2 -, -NH-, -CH=CH-, -C(CF 3 )=CH-, -C¡C-, -CH 2 -O-, -O-CO-, -CO-O-, -CO-NH-, -NH-CO-, and trans-cyclopropylene;
n is an integer from 0 to 10; and
X is attached to the phenylene/pyridyl moiety and selected from a bond, -O-, -S-, -SO-, -SO 2 -, -NH-, -CO-, -CH=CH-, and trans-cyclopropylene;
R2 is H or independently selected from one or more substituents selected from halogen, (1-4C)alkoxy and (1-4C)alkyl optionally substituted with one or more fluor atoms; and
R3 is (1-4C)alkylene-R4 wherein the alkylene group may be substituted with one or more halogen atoms or with (CH 2 ) 2 to form a cyclopropyl moiety, or R3 is (3-6C)cycloalkylene-R4, -CH 2 -(3-6C)cycloalkylene-R4, (3-6C)cycloalkylene-CH 2 -R4 or -CO-CH 2 -R4, wherein R4 is -OH, -PO 3 H 2 , -OPO 3 H 2 , -COOH, -COO(1-4C)alkyl or tetrazol-5-yl;
Q is a bond or -O-;
-W-T- is selected from -CH=CH-, -CH 2 -CH 2 -, -CH 2 -O-, -O-CH 2 -, -O-CH 2 -CH 2 -, and -CO-O-;
R5 is H or independently selected from one or more halogens;
Z is CH, CR2 or N; and
A represents a morpholine ring structure or a 5-, 6- or 7-membered cyclic amine;
or a pharmaceutically acceptable salt, a solvate or hydrate thereof or one or more N-oxides thereof. The compounds of the invention have affinity to S1P receptors and may be used in the treatment, alleviation or prevention of diseases and conditions in which (a) S1P receptor(s) is (are) involved.</description><language>eng</language><subject>ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM ; CHEMISTRY ; HETEROCYCLIC COMPOUNDS ; HUMAN NECESSITIES ; HYGIENE ; MEDICAL OR VETERINARY SCIENCE ; METALLURGY ; ORGANIC CHEMISTRY ; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES</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=20210506&DB=EPODOC&CC=US&NR=2021130364A1$$EHTML$$P50$$Gepo$$Hfree_for_read</linktohtml><link.rule.ids>230,308,780,885,25564,76547</link.rule.ids><linktorsrc>$$Uhttps://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20210506&DB=EPODOC&CC=US&NR=2021130364A1$$EView_record_in_European_Patent_Office$$FView_record_in_$$GEuropean_Patent_Office$$Hfree_for_read</linktorsrc></links><search><creatorcontrib>Leflemme, Nicolas J.-L.D</creatorcontrib><creatorcontrib>Stoit, Axel</creatorcontrib><creatorcontrib>Iwema Bakker, Wouter I</creatorcontrib><creatorcontrib>van Dongen, Maria J.P</creatorcontrib><creatorcontrib>Hobson, Adrian</creatorcontrib><creatorcontrib>Coolen, Hein K.A.C</creatorcontrib><title>SPIRO-CYCLIC AMINE DERIVATIVES AS S1P MODULATORS</title><description>The present invention relates spiro-cyclic amine derivatives of the formula ( I )
wherein
R1 is selected from
cyano,
(2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkyl each optionally substituted with CN or one or more fluoro atoms,
(3-6C)cycloalkyl, (4-6C)cycloalkenyl or a (8-10C)bicyclic group, each optionally substituted with halogen or (1-4C)alkyl,
phenyl, biphenyl, naphthyl, each optionally substituted with one or more substituents independently selected from halogen, cyano, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (1-6C)alkoxy optionally substituted with one or more fluoro atoms, amino, di(1-4C)alkylamino and (3-6C)cycloalkyl optionally substituted with phenyl which may be substituted with (1-4C)alkyl or halogen,
phenyl substituted with phenoxy, benzyl, benzyloxy, phenylethyl or monocyclic heterocycle, each optionally substituted with (1-4C)alkyl optionally substituted with one or more fluoro atoms,
monocyclic heterocycle optionally independently substituted with halogen, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (3-6C)cycloalkyl, or phenyl optionally substituted with (1-4C)alkyl or halogen,
and
bicyclic heterocycle optionally substituted with halogen or (1-4C)alkyl optionally substituted with one or more fluoro atoms;
-Y-(C n -alkylene)-X- is a linking group wherein
Y is attached to R1 and selected from a bond, -O-, -CO-, -S-, -SO-, -SO 2 -, -NH-, -CH=CH-, -C(CF 3 )=CH-, -C¡C-, -CH 2 -O-, -O-CO-, -CO-O-, -CO-NH-, -NH-CO-, and trans-cyclopropylene;
n is an integer from 0 to 10; and
X is attached to the phenylene/pyridyl moiety and selected from a bond, -O-, -S-, -SO-, -SO 2 -, -NH-, -CO-, -CH=CH-, and trans-cyclopropylene;
R2 is H or independently selected from one or more substituents selected from halogen, (1-4C)alkoxy and (1-4C)alkyl optionally substituted with one or more fluor atoms; and
R3 is (1-4C)alkylene-R4 wherein the alkylene group may be substituted with one or more halogen atoms or with (CH 2 ) 2 to form a cyclopropyl moiety, or R3 is (3-6C)cycloalkylene-R4, -CH 2 -(3-6C)cycloalkylene-R4, (3-6C)cycloalkylene-CH 2 -R4 or -CO-CH 2 -R4, wherein R4 is -OH, -PO 3 H 2 , -OPO 3 H 2 , -COOH, -COO(1-4C)alkyl or tetrazol-5-yl;
Q is a bond or -O-;
-W-T- is selected from -CH=CH-, -CH 2 -CH 2 -, -CH 2 -O-, -O-CH 2 -, -O-CH 2 -CH 2 -, and -CO-O-;
R5 is H or independently selected from one or more halogens;
Z is CH, CR2 or N; and
A represents a morpholine ring structure or a 5-, 6- or 7-membered cyclic amine;
or a pharmaceutically acceptable salt, a solvate or hydrate thereof or one or more N-oxides thereof. The compounds of the invention have affinity to S1P receptors and may be used in the treatment, alleviation or prevention of diseases and conditions in which (a) S1P receptor(s) is (are) involved.</description><subject>ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM</subject><subject>CHEMISTRY</subject><subject>HETEROCYCLIC COMPOUNDS</subject><subject>HUMAN NECESSITIES</subject><subject>HYGIENE</subject><subject>MEDICAL OR VETERINARY SCIENCE</subject><subject>METALLURGY</subject><subject>ORGANIC CHEMISTRY</subject><subject>PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES</subject><fulltext>true</fulltext><rsrctype>patent</rsrctype><creationdate>2021</creationdate><recordtype>patent</recordtype><sourceid>EVB</sourceid><recordid>eNrjZDAIDvAM8td1jnT28XRWcPT19HNVcHEN8gxzDPEMcw1WcAxWCDYMUPD1dwn1cQzxDwrmYWBNS8wpTuWF0twMym6uIc4euqkF-fGpxQWJyal5qSXxocFGBkaGhsYGxmYmjobGxKkCAMaWJyo</recordid><startdate>20210506</startdate><enddate>20210506</enddate><creator>Leflemme, Nicolas J.-L.D</creator><creator>Stoit, Axel</creator><creator>Iwema Bakker, Wouter I</creator><creator>van Dongen, Maria J.P</creator><creator>Hobson, Adrian</creator><creator>Coolen, Hein K.A.C</creator><scope>EVB</scope></search><sort><creationdate>20210506</creationdate><title>SPIRO-CYCLIC AMINE DERIVATIVES AS S1P MODULATORS</title><author>Leflemme, Nicolas J.-L.D ; Stoit, Axel ; Iwema Bakker, Wouter I ; van Dongen, Maria J.P ; Hobson, Adrian ; Coolen, Hein K.A.C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-epo_espacenet_US2021130364A13</frbrgroupid><rsrctype>patents</rsrctype><prefilter>patents</prefilter><language>eng</language><creationdate>2021</creationdate><topic>ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM</topic><topic>CHEMISTRY</topic><topic>HETEROCYCLIC COMPOUNDS</topic><topic>HUMAN NECESSITIES</topic><topic>HYGIENE</topic><topic>MEDICAL OR VETERINARY SCIENCE</topic><topic>METALLURGY</topic><topic>ORGANIC CHEMISTRY</topic><topic>PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES</topic><toplevel>online_resources</toplevel><creatorcontrib>Leflemme, Nicolas J.-L.D</creatorcontrib><creatorcontrib>Stoit, Axel</creatorcontrib><creatorcontrib>Iwema Bakker, Wouter I</creatorcontrib><creatorcontrib>van Dongen, Maria J.P</creatorcontrib><creatorcontrib>Hobson, Adrian</creatorcontrib><creatorcontrib>Coolen, Hein K.A.C</creatorcontrib><collection>esp@cenet</collection></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Leflemme, Nicolas J.-L.D</au><au>Stoit, Axel</au><au>Iwema Bakker, Wouter I</au><au>van Dongen, Maria J.P</au><au>Hobson, Adrian</au><au>Coolen, Hein K.A.C</au><format>patent</format><genre>patent</genre><ristype>GEN</ristype><title>SPIRO-CYCLIC AMINE DERIVATIVES AS S1P MODULATORS</title><date>2021-05-06</date><risdate>2021</risdate><abstract>The present invention relates spiro-cyclic amine derivatives of the formula ( I )
wherein
R1 is selected from
cyano,
(2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkyl each optionally substituted with CN or one or more fluoro atoms,
(3-6C)cycloalkyl, (4-6C)cycloalkenyl or a (8-10C)bicyclic group, each optionally substituted with halogen or (1-4C)alkyl,
phenyl, biphenyl, naphthyl, each optionally substituted with one or more substituents independently selected from halogen, cyano, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (1-6C)alkoxy optionally substituted with one or more fluoro atoms, amino, di(1-4C)alkylamino and (3-6C)cycloalkyl optionally substituted with phenyl which may be substituted with (1-4C)alkyl or halogen,
phenyl substituted with phenoxy, benzyl, benzyloxy, phenylethyl or monocyclic heterocycle, each optionally substituted with (1-4C)alkyl optionally substituted with one or more fluoro atoms,
monocyclic heterocycle optionally independently substituted with halogen, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (3-6C)cycloalkyl, or phenyl optionally substituted with (1-4C)alkyl or halogen,
and
bicyclic heterocycle optionally substituted with halogen or (1-4C)alkyl optionally substituted with one or more fluoro atoms;
-Y-(C n -alkylene)-X- is a linking group wherein
Y is attached to R1 and selected from a bond, -O-, -CO-, -S-, -SO-, -SO 2 -, -NH-, -CH=CH-, -C(CF 3 )=CH-, -C¡C-, -CH 2 -O-, -O-CO-, -CO-O-, -CO-NH-, -NH-CO-, and trans-cyclopropylene;
n is an integer from 0 to 10; and
X is attached to the phenylene/pyridyl moiety and selected from a bond, -O-, -S-, -SO-, -SO 2 -, -NH-, -CO-, -CH=CH-, and trans-cyclopropylene;
R2 is H or independently selected from one or more substituents selected from halogen, (1-4C)alkoxy and (1-4C)alkyl optionally substituted with one or more fluor atoms; and
R3 is (1-4C)alkylene-R4 wherein the alkylene group may be substituted with one or more halogen atoms or with (CH 2 ) 2 to form a cyclopropyl moiety, or R3 is (3-6C)cycloalkylene-R4, -CH 2 -(3-6C)cycloalkylene-R4, (3-6C)cycloalkylene-CH 2 -R4 or -CO-CH 2 -R4, wherein R4 is -OH, -PO 3 H 2 , -OPO 3 H 2 , -COOH, -COO(1-4C)alkyl or tetrazol-5-yl;
Q is a bond or -O-;
-W-T- is selected from -CH=CH-, -CH 2 -CH 2 -, -CH 2 -O-, -O-CH 2 -, -O-CH 2 -CH 2 -, and -CO-O-;
R5 is H or independently selected from one or more halogens;
Z is CH, CR2 or N; and
A represents a morpholine ring structure or a 5-, 6- or 7-membered cyclic amine;
or a pharmaceutically acceptable salt, a solvate or hydrate thereof or one or more N-oxides thereof. The compounds of the invention have affinity to S1P receptors and may be used in the treatment, alleviation or prevention of diseases and conditions in which (a) S1P receptor(s) is (are) involved.</abstract><oa>free_for_read</oa></addata></record> |
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| subjects | ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM CHEMISTRY HETEROCYCLIC COMPOUNDS HUMAN NECESSITIES HYGIENE MEDICAL OR VETERINARY SCIENCE METALLURGY ORGANIC CHEMISTRY PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES |
| title | SPIRO-CYCLIC AMINE DERIVATIVES AS S1P MODULATORS |
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