Indolyamides as modulators for an EP2 receptor

Substituted indole compounds (I) and their isomers, diastereomers, enantiomers, salts or cyclodextrin clathrate, are new. Substituted indole compounds of formula (I) and their isomers, diastereomers, enantiomers, salts or cyclodextrin clathrate, are new. X : CH or N; Y 1>O, N, S, NH,-CH=N-, -N=CH...

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Hauptverfasser: KOPPITZ, MARCUS, LANGER, GERNOT DR, LINDENTHAL, BERNHARD, WINTERMANTER, TIM, BUCHMANN, BERND, TER LAAK, ANTONIUS, BRAEUER, NICO
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creator KOPPITZ, MARCUS
LANGER, GERNOT DR
LINDENTHAL, BERNHARD
WINTERMANTER, TIM
BUCHMANN, BERND
TER LAAK, ANTONIUS
BRAEUER, NICO
description Substituted indole compounds (I) and their isomers, diastereomers, enantiomers, salts or cyclodextrin clathrate, are new. Substituted indole compounds of formula (I) and their isomers, diastereomers, enantiomers, salts or cyclodextrin clathrate, are new. X : CH or N; Y 1>O, N, S, NH,-CH=N-, -N=CH-, -N=N- or -CH=CH- (when X is N); R 1>H or 1-6C alkyl (optionally substituted); R 2>1-4C alkoxy or 1-6C alkyl (both can be arbitrarily substituted), H, halo, CN or -S(O) q-CH 3; q : 0-2; R 3>H, 1-4C alkoxy or halo; R 4>H or F; R 5>H or halo; R 6>, R 9>H, F or Cl; R 7>H or R 10>, provided that when R 7>is H, then R 8>is R 10>, and when R 8>is H, then R 7>is R 10>; R 10>-CONH-R 11>or CO-NR 11>R 12>; R 11>, R 12>1-6C alkyl (which is substituted with one or more -S(O) p-R 13>, OH, CN, COOH, CO-NH 2, SO 2NH 2, SO 2NH-R 13>, CO-NH-SO 2-R 13>, SO 2-NH-CO-R 13>, 1-6C acyl, OR 13>, CO 2-R 13>,-NR 13>R 14>, NH-R 13>, CO-NHR 13>, CO-NR 13>R 14>, NH-COR 13>, NH-SO 2R 13>, NR 15>-COR 13>, NH-CONH 2, NH-CO-NHR 13>, NH-CO-NR 13>R 14>, NR 15>-CO-NH-R 13>or NR 15>-CO-N(1-6C alkyl)-R 13>, or 6-12C aryl, 5-12C heteroaryl or 3-6C cycloalkyl (all substituted with 1 or 2 substituents of T)), or 3-6C cycloalkyl, 6-12C aryl or 5-12C heteroaryl (all substituted with 1-3 substituents of T, NH-(3-6C cycloalkyl), CO-NH(1-6C-alkyl) or CON(1-6C-alkyl) 2); T : CONH 2, SO 2NH 2, CONHCH 3, CON(CH 3) 2, SO 2NHCH 3, CO-NH-SO 2CH 3or 1-6C acyl; either R 13>-R 15>1-6C-alkyl, 3-6C-cycloalkyl, 6-12C-aryl, 5-12C-heteroaryl, CH 2-6-12C-aryl or CH 2-5-12C-heteroaryl; or R 13>R 15>together with N-CO-N-CO-NH group : 5 or 6 membered ring, which optionally contains additional heteroatoms and substituted one, two or three times, by halo, amino, OH, CN or 1-6C-alkyl that optionally substituted; and p : 0-2. Independent claims are included for: (1) the preparation of (I); and (2) a medicament comprising (I) in combination with a cyclooxygenase inhibitor, which are aspirin, naproxen, indomethacin, meloxicam, ibuprofen, celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide), parecoxib (N-[4-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonylpropionamide), rofecoxib (4-(4-mesylphenyl)-3-phenylfuran-2(5H)-one), valdecoxib (4-[5-methyl-3-phenyl-4-isoxazoyl)] benzenesulfonamide, NS-398 (N-methyl-2-cyclohexanoxy-4-nitrobenzenesulfonamide), lumiracoxib [2-(2'-chloro-6'-fluorophenyl)]-amino-5-methylbenzeneacetic acid, ceracoxib and etoricoxib. [Image] ACTIVITY : Antiinfertility; Gynecologic
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fullrecord <record><control><sourceid>epo_EVB</sourceid><recordid>TN_cdi_epo_espacenet_EP2149554A1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>EP2149554A1</sourcerecordid><originalsourceid>FETCH-epo_espacenet_EP2149554A13</originalsourceid><addsrcrecordid>eNrjZNDzzEvJz6lMzM1MSS1WSCxWyM1PKc1JLMkvKlZIyy9SSMxTcA0wUihKTU4tAAryMLCmJeYUp_JCaW4GBTfXEGcP3dSC_PjU4oLE5NS81JJ4oBZDE0tTUxNHQ2MilAAAgKopug</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>patent</recordtype></control><display><type>patent</type><title>Indolyamides as modulators for an EP2 receptor</title><source>esp@cenet</source><creator>KOPPITZ, MARCUS ; LANGER, GERNOT DR ; LINDENTHAL, BERNHARD ; WINTERMANTER, TIM ; BUCHMANN, BERND ; TER LAAK, ANTONIUS ; BRAEUER, NICO</creator><creatorcontrib>KOPPITZ, MARCUS ; LANGER, GERNOT DR ; LINDENTHAL, BERNHARD ; WINTERMANTER, TIM ; BUCHMANN, BERND ; TER LAAK, ANTONIUS ; BRAEUER, NICO</creatorcontrib><description>Substituted indole compounds (I) and their isomers, diastereomers, enantiomers, salts or cyclodextrin clathrate, are new. Substituted indole compounds of formula (I) and their isomers, diastereomers, enantiomers, salts or cyclodextrin clathrate, are new. X : CH or N; Y 1&gt;O, N, S, NH,-CH=N-, -N=CH-, -N=N- or -CH=CH- (when X is N); R 1&gt;H or 1-6C alkyl (optionally substituted); R 2&gt;1-4C alkoxy or 1-6C alkyl (both can be arbitrarily substituted), H, halo, CN or -S(O) q-CH 3; q : 0-2; R 3&gt;H, 1-4C alkoxy or halo; R 4&gt;H or F; R 5&gt;H or halo; R 6&gt;, R 9&gt;H, F or Cl; R 7&gt;H or R 10&gt;, provided that when R 7&gt;is H, then R 8&gt;is R 10&gt;, and when R 8&gt;is H, then R 7&gt;is R 10&gt;; R 10&gt;-CONH-R 11&gt;or CO-NR 11&gt;R 12&gt;; R 11&gt;, R 12&gt;1-6C alkyl (which is substituted with one or more -S(O) p-R 13&gt;, OH, CN, COOH, CO-NH 2, SO 2NH 2, SO 2NH-R 13&gt;, CO-NH-SO 2-R 13&gt;, SO 2-NH-CO-R 13&gt;, 1-6C acyl, OR 13&gt;, CO 2-R 13&gt;,-NR 13&gt;R 14&gt;, NH-R 13&gt;, CO-NHR 13&gt;, CO-NR 13&gt;R 14&gt;, NH-COR 13&gt;, NH-SO 2R 13&gt;, NR 15&gt;-COR 13&gt;, NH-CONH 2, NH-CO-NHR 13&gt;, NH-CO-NR 13&gt;R 14&gt;, NR 15&gt;-CO-NH-R 13&gt;or NR 15&gt;-CO-N(1-6C alkyl)-R 13&gt;, or 6-12C aryl, 5-12C heteroaryl or 3-6C cycloalkyl (all substituted with 1 or 2 substituents of T)), or 3-6C cycloalkyl, 6-12C aryl or 5-12C heteroaryl (all substituted with 1-3 substituents of T, NH-(3-6C cycloalkyl), CO-NH(1-6C-alkyl) or CON(1-6C-alkyl) 2); T : CONH 2, SO 2NH 2, CONHCH 3, CON(CH 3) 2, SO 2NHCH 3, CO-NH-SO 2CH 3or 1-6C acyl; either R 13&gt;-R 15&gt;1-6C-alkyl, 3-6C-cycloalkyl, 6-12C-aryl, 5-12C-heteroaryl, CH 2-6-12C-aryl or CH 2-5-12C-heteroaryl; or R 13&gt;R 15&gt;together with N-CO-N-CO-NH group : 5 or 6 membered ring, which optionally contains additional heteroatoms and substituted one, two or three times, by halo, amino, OH, CN or 1-6C-alkyl that optionally substituted; and p : 0-2. Independent claims are included for: (1) the preparation of (I); and (2) a medicament comprising (I) in combination with a cyclooxygenase inhibitor, which are aspirin, naproxen, indomethacin, meloxicam, ibuprofen, celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide), parecoxib (N-[4-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonylpropionamide), rofecoxib (4-(4-mesylphenyl)-3-phenylfuran-2(5H)-one), valdecoxib (4-[5-methyl-3-phenyl-4-isoxazoyl)] benzenesulfonamide, NS-398 (N-methyl-2-cyclohexanoxy-4-nitrobenzenesulfonamide), lumiracoxib [2-(2'-chloro-6'-fluorophenyl)]-amino-5-methylbenzeneacetic acid, ceracoxib and etoricoxib. [Image] ACTIVITY : Antiinfertility; Gynecological; Analgesic; Contraceptive; Osteopathic; Cytostatic; Neuroprotective; Nootropic; Antiparkinsonian; Antiinflammatory; Gastrointestinal-Gen.; Antiulcer; Nephrotropic; Antiarteriosclerotic; Respiratory-Gen.; Antimicrobial. MECHANISM OF ACTION : Prostaglandin E2 (subtype EP2) receptor modulator. The prostaglandin E2 (subtype EP2) receptor antagonistic activity of (I) was tested using an in vitro method. The result showed that 1H-indol-2,6-dicarboxylic acid 6-carbamoylmethyl-amide 2-{[2-(7-fluoro-2,4-dimethyl-1H-indol-3-yl)-ethyl]-amide} exhibited an IC 50value of 0.022 mu M. Die vorliegende Erfindung betrifft Indolylamid-Derivate der allgemeinen Formel (I), Verfahren zu ihrer Herstellung sowie deren Verwendung zur Herstellung von pharmazeutischen Mitteln zur Behandlung von Erkrankungen und Indikationen, die im Zusammenhang stehen mit dem EP 2 Rezeptor.</description><language>eng ; fre ; ger</language><subject>CHEMISTRY ; HETEROCYCLIC COMPOUNDS ; HUMAN NECESSITIES ; HYGIENE ; MEDICAL OR VETERINARY SCIENCE ; METALLURGY ; ORGANIC CHEMISTRY ; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES ; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS</subject><creationdate>2010</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&amp;date=20100203&amp;DB=EPODOC&amp;CC=EP&amp;NR=2149554A1$$EHTML$$P50$$Gepo$$Hfree_for_read</linktohtml><link.rule.ids>230,308,780,885,25564,76419</link.rule.ids><linktorsrc>$$Uhttps://worldwide.espacenet.com/publicationDetails/biblio?FT=D&amp;date=20100203&amp;DB=EPODOC&amp;CC=EP&amp;NR=2149554A1$$EView_record_in_European_Patent_Office$$FView_record_in_$$GEuropean_Patent_Office$$Hfree_for_read</linktorsrc></links><search><creatorcontrib>KOPPITZ, MARCUS</creatorcontrib><creatorcontrib>LANGER, GERNOT DR</creatorcontrib><creatorcontrib>LINDENTHAL, BERNHARD</creatorcontrib><creatorcontrib>WINTERMANTER, TIM</creatorcontrib><creatorcontrib>BUCHMANN, BERND</creatorcontrib><creatorcontrib>TER LAAK, ANTONIUS</creatorcontrib><creatorcontrib>BRAEUER, NICO</creatorcontrib><title>Indolyamides as modulators for an EP2 receptor</title><description>Substituted indole compounds (I) and their isomers, diastereomers, enantiomers, salts or cyclodextrin clathrate, are new. Substituted indole compounds of formula (I) and their isomers, diastereomers, enantiomers, salts or cyclodextrin clathrate, are new. X : CH or N; Y 1&gt;O, N, S, NH,-CH=N-, -N=CH-, -N=N- or -CH=CH- (when X is N); R 1&gt;H or 1-6C alkyl (optionally substituted); R 2&gt;1-4C alkoxy or 1-6C alkyl (both can be arbitrarily substituted), H, halo, CN or -S(O) q-CH 3; q : 0-2; R 3&gt;H, 1-4C alkoxy or halo; R 4&gt;H or F; R 5&gt;H or halo; R 6&gt;, R 9&gt;H, F or Cl; R 7&gt;H or R 10&gt;, provided that when R 7&gt;is H, then R 8&gt;is R 10&gt;, and when R 8&gt;is H, then R 7&gt;is R 10&gt;; R 10&gt;-CONH-R 11&gt;or CO-NR 11&gt;R 12&gt;; R 11&gt;, R 12&gt;1-6C alkyl (which is substituted with one or more -S(O) p-R 13&gt;, OH, CN, COOH, CO-NH 2, SO 2NH 2, SO 2NH-R 13&gt;, CO-NH-SO 2-R 13&gt;, SO 2-NH-CO-R 13&gt;, 1-6C acyl, OR 13&gt;, CO 2-R 13&gt;,-NR 13&gt;R 14&gt;, NH-R 13&gt;, CO-NHR 13&gt;, CO-NR 13&gt;R 14&gt;, NH-COR 13&gt;, NH-SO 2R 13&gt;, NR 15&gt;-COR 13&gt;, NH-CONH 2, NH-CO-NHR 13&gt;, NH-CO-NR 13&gt;R 14&gt;, NR 15&gt;-CO-NH-R 13&gt;or NR 15&gt;-CO-N(1-6C alkyl)-R 13&gt;, or 6-12C aryl, 5-12C heteroaryl or 3-6C cycloalkyl (all substituted with 1 or 2 substituents of T)), or 3-6C cycloalkyl, 6-12C aryl or 5-12C heteroaryl (all substituted with 1-3 substituents of T, NH-(3-6C cycloalkyl), CO-NH(1-6C-alkyl) or CON(1-6C-alkyl) 2); T : CONH 2, SO 2NH 2, CONHCH 3, CON(CH 3) 2, SO 2NHCH 3, CO-NH-SO 2CH 3or 1-6C acyl; either R 13&gt;-R 15&gt;1-6C-alkyl, 3-6C-cycloalkyl, 6-12C-aryl, 5-12C-heteroaryl, CH 2-6-12C-aryl or CH 2-5-12C-heteroaryl; or R 13&gt;R 15&gt;together with N-CO-N-CO-NH group : 5 or 6 membered ring, which optionally contains additional heteroatoms and substituted one, two or three times, by halo, amino, OH, CN or 1-6C-alkyl that optionally substituted; and p : 0-2. Independent claims are included for: (1) the preparation of (I); and (2) a medicament comprising (I) in combination with a cyclooxygenase inhibitor, which are aspirin, naproxen, indomethacin, meloxicam, ibuprofen, celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide), parecoxib (N-[4-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonylpropionamide), rofecoxib (4-(4-mesylphenyl)-3-phenylfuran-2(5H)-one), valdecoxib (4-[5-methyl-3-phenyl-4-isoxazoyl)] benzenesulfonamide, NS-398 (N-methyl-2-cyclohexanoxy-4-nitrobenzenesulfonamide), lumiracoxib [2-(2'-chloro-6'-fluorophenyl)]-amino-5-methylbenzeneacetic acid, ceracoxib and etoricoxib. [Image] ACTIVITY : Antiinfertility; Gynecological; Analgesic; Contraceptive; Osteopathic; Cytostatic; Neuroprotective; Nootropic; Antiparkinsonian; Antiinflammatory; Gastrointestinal-Gen.; Antiulcer; Nephrotropic; Antiarteriosclerotic; Respiratory-Gen.; Antimicrobial. MECHANISM OF ACTION : Prostaglandin E2 (subtype EP2) receptor modulator. The prostaglandin E2 (subtype EP2) receptor antagonistic activity of (I) was tested using an in vitro method. The result showed that 1H-indol-2,6-dicarboxylic acid 6-carbamoylmethyl-amide 2-{[2-(7-fluoro-2,4-dimethyl-1H-indol-3-yl)-ethyl]-amide} exhibited an IC 50value of 0.022 mu M. Die vorliegende Erfindung betrifft Indolylamid-Derivate der allgemeinen Formel (I), Verfahren zu ihrer Herstellung sowie deren Verwendung zur Herstellung von pharmazeutischen Mitteln zur Behandlung von Erkrankungen und Indikationen, die im Zusammenhang stehen mit dem EP 2 Rezeptor.</description><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><subject>SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS</subject><fulltext>true</fulltext><rsrctype>patent</rsrctype><creationdate>2010</creationdate><recordtype>patent</recordtype><sourceid>EVB</sourceid><recordid>eNrjZNDzzEvJz6lMzM1MSS1WSCxWyM1PKc1JLMkvKlZIyy9SSMxTcA0wUihKTU4tAAryMLCmJeYUp_JCaW4GBTfXEGcP3dSC_PjU4oLE5NS81JJ4oBZDE0tTUxNHQ2MilAAAgKopug</recordid><startdate>20100203</startdate><enddate>20100203</enddate><creator>KOPPITZ, MARCUS</creator><creator>LANGER, GERNOT DR</creator><creator>LINDENTHAL, BERNHARD</creator><creator>WINTERMANTER, TIM</creator><creator>BUCHMANN, BERND</creator><creator>TER LAAK, ANTONIUS</creator><creator>BRAEUER, NICO</creator><scope>EVB</scope></search><sort><creationdate>20100203</creationdate><title>Indolyamides as modulators for an EP2 receptor</title><author>KOPPITZ, MARCUS ; LANGER, GERNOT DR ; LINDENTHAL, BERNHARD ; WINTERMANTER, TIM ; BUCHMANN, BERND ; TER LAAK, ANTONIUS ; BRAEUER, NICO</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-epo_espacenet_EP2149554A13</frbrgroupid><rsrctype>patents</rsrctype><prefilter>patents</prefilter><language>eng ; fre ; ger</language><creationdate>2010</creationdate><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><topic>SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS</topic><toplevel>online_resources</toplevel><creatorcontrib>KOPPITZ, MARCUS</creatorcontrib><creatorcontrib>LANGER, GERNOT DR</creatorcontrib><creatorcontrib>LINDENTHAL, BERNHARD</creatorcontrib><creatorcontrib>WINTERMANTER, TIM</creatorcontrib><creatorcontrib>BUCHMANN, BERND</creatorcontrib><creatorcontrib>TER LAAK, ANTONIUS</creatorcontrib><creatorcontrib>BRAEUER, NICO</creatorcontrib><collection>esp@cenet</collection></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>KOPPITZ, MARCUS</au><au>LANGER, GERNOT DR</au><au>LINDENTHAL, BERNHARD</au><au>WINTERMANTER, TIM</au><au>BUCHMANN, BERND</au><au>TER LAAK, ANTONIUS</au><au>BRAEUER, NICO</au><format>patent</format><genre>patent</genre><ristype>GEN</ristype><title>Indolyamides as modulators for an EP2 receptor</title><date>2010-02-03</date><risdate>2010</risdate><abstract>Substituted indole compounds (I) and their isomers, diastereomers, enantiomers, salts or cyclodextrin clathrate, are new. Substituted indole compounds of formula (I) and their isomers, diastereomers, enantiomers, salts or cyclodextrin clathrate, are new. X : CH or N; Y 1&gt;O, N, S, NH,-CH=N-, -N=CH-, -N=N- or -CH=CH- (when X is N); R 1&gt;H or 1-6C alkyl (optionally substituted); R 2&gt;1-4C alkoxy or 1-6C alkyl (both can be arbitrarily substituted), H, halo, CN or -S(O) q-CH 3; q : 0-2; R 3&gt;H, 1-4C alkoxy or halo; R 4&gt;H or F; R 5&gt;H or halo; R 6&gt;, R 9&gt;H, F or Cl; R 7&gt;H or R 10&gt;, provided that when R 7&gt;is H, then R 8&gt;is R 10&gt;, and when R 8&gt;is H, then R 7&gt;is R 10&gt;; R 10&gt;-CONH-R 11&gt;or CO-NR 11&gt;R 12&gt;; R 11&gt;, R 12&gt;1-6C alkyl (which is substituted with one or more -S(O) p-R 13&gt;, OH, CN, COOH, CO-NH 2, SO 2NH 2, SO 2NH-R 13&gt;, CO-NH-SO 2-R 13&gt;, SO 2-NH-CO-R 13&gt;, 1-6C acyl, OR 13&gt;, CO 2-R 13&gt;,-NR 13&gt;R 14&gt;, NH-R 13&gt;, CO-NHR 13&gt;, CO-NR 13&gt;R 14&gt;, NH-COR 13&gt;, NH-SO 2R 13&gt;, NR 15&gt;-COR 13&gt;, NH-CONH 2, NH-CO-NHR 13&gt;, NH-CO-NR 13&gt;R 14&gt;, NR 15&gt;-CO-NH-R 13&gt;or NR 15&gt;-CO-N(1-6C alkyl)-R 13&gt;, or 6-12C aryl, 5-12C heteroaryl or 3-6C cycloalkyl (all substituted with 1 or 2 substituents of T)), or 3-6C cycloalkyl, 6-12C aryl or 5-12C heteroaryl (all substituted with 1-3 substituents of T, NH-(3-6C cycloalkyl), CO-NH(1-6C-alkyl) or CON(1-6C-alkyl) 2); T : CONH 2, SO 2NH 2, CONHCH 3, CON(CH 3) 2, SO 2NHCH 3, CO-NH-SO 2CH 3or 1-6C acyl; either R 13&gt;-R 15&gt;1-6C-alkyl, 3-6C-cycloalkyl, 6-12C-aryl, 5-12C-heteroaryl, CH 2-6-12C-aryl or CH 2-5-12C-heteroaryl; or R 13&gt;R 15&gt;together with N-CO-N-CO-NH group : 5 or 6 membered ring, which optionally contains additional heteroatoms and substituted one, two or three times, by halo, amino, OH, CN or 1-6C-alkyl that optionally substituted; and p : 0-2. Independent claims are included for: (1) the preparation of (I); and (2) a medicament comprising (I) in combination with a cyclooxygenase inhibitor, which are aspirin, naproxen, indomethacin, meloxicam, ibuprofen, celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide), parecoxib (N-[4-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonylpropionamide), rofecoxib (4-(4-mesylphenyl)-3-phenylfuran-2(5H)-one), valdecoxib (4-[5-methyl-3-phenyl-4-isoxazoyl)] benzenesulfonamide, NS-398 (N-methyl-2-cyclohexanoxy-4-nitrobenzenesulfonamide), lumiracoxib [2-(2'-chloro-6'-fluorophenyl)]-amino-5-methylbenzeneacetic acid, ceracoxib and etoricoxib. [Image] ACTIVITY : Antiinfertility; Gynecological; Analgesic; Contraceptive; Osteopathic; Cytostatic; Neuroprotective; Nootropic; Antiparkinsonian; Antiinflammatory; Gastrointestinal-Gen.; Antiulcer; Nephrotropic; Antiarteriosclerotic; Respiratory-Gen.; Antimicrobial. MECHANISM OF ACTION : Prostaglandin E2 (subtype EP2) receptor modulator. The prostaglandin E2 (subtype EP2) receptor antagonistic activity of (I) was tested using an in vitro method. The result showed that 1H-indol-2,6-dicarboxylic acid 6-carbamoylmethyl-amide 2-{[2-(7-fluoro-2,4-dimethyl-1H-indol-3-yl)-ethyl]-amide} exhibited an IC 50value of 0.022 mu M. Die vorliegende Erfindung betrifft Indolylamid-Derivate der allgemeinen Formel (I), Verfahren zu ihrer Herstellung sowie deren Verwendung zur Herstellung von pharmazeutischen Mitteln zur Behandlung von Erkrankungen und Indikationen, die im Zusammenhang stehen mit dem EP 2 Rezeptor.</abstract><oa>free_for_read</oa></addata></record>
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subjects CHEMISTRY
HETEROCYCLIC COMPOUNDS
HUMAN NECESSITIES
HYGIENE
MEDICAL OR VETERINARY SCIENCE
METALLURGY
ORGANIC CHEMISTRY
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS
title Indolyamides as modulators for an EP2 receptor
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