WO2010027431A1 - Substituted tricyclic acid derivatives as s1p1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders - Google Patents

Substituted tricyclic acid derivatives as s1p1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders Download PDF

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Publication number
WO2010027431A1
WO2010027431A1 PCT/US2009/004851 US2009004851W WO2010027431A1 WO 2010027431 A1 WO2010027431 A1 WO 2010027431A1 US 2009004851 W US2009004851 W US 2009004851W WO 2010027431 A1 WO2010027431 A1 WO 2010027431A1
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WO
WIPO (PCT)
Prior art keywords
indol
dihydro
pyrrolo
acetic acid
benzyloxy
Prior art date
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.)
Ceased
Application number
PCT/US2009/004851
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English (en)
French (fr)
Inventor
Robert M. Jones
Daniel J. Buzard
Andrew M. Kawasaki
Sun Hee Kim
Lars Thoresen
Juerg Lehmann
Xiuwen Zhu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Arena Pharmaceuticals Inc
Original Assignee
Arena Pharmaceuticals Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority to RS20160577A priority Critical patent/RS54970B1/sr
Priority to MX2011002199A priority patent/MX2011002199A/es
Priority to EP09789210.3A priority patent/EP2342205B1/en
Priority to ES09789210.3T priority patent/ES2583630T3/es
Priority to KR1020177014649A priority patent/KR101800595B1/ko
Priority to HK11112888.7A priority patent/HK1158624B/en
Priority to JP2011524992A priority patent/JP5726737B2/ja
Priority to CA2733671A priority patent/CA2733671C/en
Priority to EA201170374A priority patent/EA036955B1/ru
Priority to NZ591001A priority patent/NZ591001A/xx
Priority to HRP20160890TT priority patent/HRP20160890T1/hr
Priority to AU2009288738A priority patent/AU2009288738B9/en
Priority to CN200980142790.4A priority patent/CN102197038B/zh
Application filed by Arena Pharmaceuticals Inc filed Critical Arena Pharmaceuticals Inc
Priority to BRPI0917923-2A priority patent/BRPI0917923B1/pt
Priority to SI200931475A priority patent/SI2342205T1/sl
Priority to US13/060,477 priority patent/US8415484B2/en
Publication of WO2010027431A1 publication Critical patent/WO2010027431A1/en
Priority to IL211107A priority patent/IL211107A0/en
Priority to ZA2011/01524A priority patent/ZA201101524B/en
Anticipated expiration legal-status Critical
Priority to US13/787,233 priority patent/US9108969B2/en
Priority to IL233869A priority patent/IL233869A/en
Priority to US14/817,954 priority patent/US20150336966A1/en
Priority to CY20161100713T priority patent/CY1117830T1/el
Priority to SM201600318T priority patent/SMT201600318B/it
Ceased legal-status Critical Current

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    • C07—ORGANIC CHEMISTRY
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    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
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    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Definitions

  • One aspect of the present invention pertains to the use of compounds of the present invention in the manufacture of a medicament for the treatment of an SlPl receptor-associated disorder.
  • One aspect of the present invention pertains to the use of compounds of the present invention in the manufacture of a medicament for the treatment of cancer.
  • One aspect of the present invention pertains to compounds of the present invention for use in a method for the treatment of myocardial ischemia-reperfusion injury.
  • Figure 3 shows a general synthetic scheme for the preparation of 2-(6-hydroxy-2,3- dihydro-lH-benzo[d]pyrrolo[l,2-a]imidazol-3-yl)acetate derivatives, as intermediates useful in the preparation of compounds of Formula (I), by alkylation of tert-buty ⁇ 2-oxopyrrolidine-l- carboxylate, followed by N-arylation, reduction / deprotection and cyclization.
  • Figure 4 shows a general synthetic scheme for the preparation of tricyclic acid derivatives, via coupling of the aryl methyl halides or alcohols with 2,3-dihydro-lH-pyrrolo acetate derivatives. Subsequent deprotection and/or halogenation afford compounds of Formula (I), by alkylation of tert-buty ⁇ 2-oxopyrrolidine-l- carboxylate, followed by N-arylation, reduction / deprotection and cyclization.
  • Figure 4 shows a general synthetic scheme for the preparation of
  • n 2
  • compounds of the present invention are represented by Formula (Ig) as illustrated below:
  • Y is N. In some embodiments, Y is CR 1 . In some embodiments, Z is N. In some embodiments, Z is CR 4 . In some embodiments, W is N. In some embodiments, W is CR 5 .
  • R 3 is selected from the group consisting of H, chloro, carboxamide, cyano, cyclohexyl, cyclohexylmethyl, cyclopentyloxy, cyclopentyl, cyclopropylmethoxy, l,3-difluoropropan-2-yloxy, ethoxy, fluoromethoxy, isobutyl, isopropoxy, methoxy, and methylsulfonyl.
  • R 3 is cyclopropylmethoxy.
  • Step A Preparation of tert-Butyl 2-(7-(4-(MethyIsulfonyl)benzyloxy)-2,3-dihydro- lH-pyrrolo[l,2-a]indol-l-yl)acetate.
  • Step C Preparation of 7-Methoxy-8-methyl-2,3-dihydro-lH-pyrrolo[l,2-a]indol-l- one.
  • Step A Preparation of 5-(Chloromethyi)-2-cyclopentylbenzonitriIe.
  • 2-Cyclopentylbenzonitrile 1.3 g, 7.59 mmol was transferred into a 2-necked RB flask, fitted with an addition funnel and dry nitrogen inlet. The starting material was stirred and cooled to -22 0 C (dry ice/IPA bath). Sulfuric acid(3.25 mL, 61.0 mmol) was added in drops. 1,3,5- Trioxane (0.877 mL, 11.39 mmol) was added in 3 batches (The batches were added fairly quickly, one after another).
  • Example 1.53 Preparation of 1 st Enantiomer of 2-(9-Chloro-7-(3-cyano-4- methoxybenzyloxy)-2,3-dihydro-l//-pyrrolo[l,2-a]indol-l-yl)acetic Acid (Compound 34).
  • No or substantially no increase of intracellular calcium in response to a test compound is indicative of the test compound exhibiting no or substantially no agonist activity on the S1P3 receptor.
  • Such an assay can be performed commercially, e.g. by Caliper LifeSciences (Hopkinton, MA).
  • FIG. 1 in which peripheral blood lymphocyte (PBL) count is shown for the 5 hour group.
  • PBL peripheral blood lymphocyte
  • Drug treatment Mice are dosed orally, with vehicle or a test compound, once a day from day 3 until day 21. Dosing volume is 5 mL/kg. The test compound is dosed at, e.g., 1 mg/kg, 3 mg/kg, 10 mg/kg or 30 mg/kg. Mice are weighed daily. Mice are monitored daily from day 7 onward for disease symptoms. After the last dose on day 21, disease progression is monitored daily for 2 more weeks. Reduction of the severity of disease symptoms by the test compound in comparison with vehicle is indicative of the test compound exhibiting therapeutic efficacy in EAE. B. PLP-induced EAE in Mice.
  • mice Male Lewis rats (325-375 g at start of study) (Harlan, San Diego, CA) are housed two per cage and maintained in a humidity-controlled (30-70%) and temperature- controlled (20-22 0 C) facility on a 12 h: 12 h light/dark cycle (lights on at 6:30 A.M.) with free access to food (Harlan-Teklad Western Res., Orange, CA, Rodent Diet 8604) and water. Rats are allowed one week of habituation to the animal facility before testing. During the study, rats are weighed daily prior to clinical scoring at 11 am.
  • Example 7 Allograft Survival.
  • a compound of the invention can be shown to have therapeutic efficacy in prolonging allograft survival by showing it to have therapeutic efficacy in prolonging, e.g. , survival of a skin allograft in an animal model.
  • mice are euthanized with CO 2 and colon is removed from anus to cecum.
  • Excised colon is measured for entire length, length from anus to end of inflamed area and length of inflamed (affected) area. After measurements, colon is cleared of excrement by flushing with saline and then cut open to clear more thoroughly. Colon is then weighed and preserved in neutral buffered formalin (NBF; 10% formalin, pH 6.7-7.0). The colon tissue is embedded in paraffin and processed for hematoxylin and eosin (H & E)-stained sections.
  • NNF neutral buffered formalin

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PCT/US2009/004851 2008-08-27 2009-08-26 Substituted tricyclic acid derivatives as s1p1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders Ceased WO2010027431A1 (en)

Priority Applications (23)

Application Number Priority Date Filing Date Title
CN200980142790.4A CN102197038B (zh) 2008-08-27 2009-08-26 用于治疗自身免疫性病症和炎性病症的作为s1p1受体激动剂的经取代的三环酸衍生物
EP09789210.3A EP2342205B1 (en) 2008-08-27 2009-08-26 Substituted tricyclic acid derivatives as s1p1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
ES09789210.3T ES2583630T3 (es) 2008-08-27 2009-08-26 Derivados de ácido tricíclico sustituido como agonistas del receptor S1P1 útiles en el tratamiento de trastornos autoinmunes e inflamatorios
KR1020177014649A KR101800595B1 (ko) 2008-08-27 2009-08-26 자가면역 및 염증성 장애의 치료에 유용한, ｓ1ｐ1 수용체 효능제로서의 치환된 트리시클릭 산 유도체
HK11112888.7A HK1158624B (en) 2008-08-27 2009-08-26 Substituted tricyclic acid derivatives as s1p1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
JP2011524992A JP5726737B2 (ja) 2008-08-27 2009-08-26 自己免疫障害および免疫性障害の治療において有用なｓ１ｐ１受容体のアゴニストとしての置換三環式酸誘導体
CA2733671A CA2733671C (en) 2008-08-27 2009-08-26 Substituted tricyclic acid derivatives as s1p1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
EA201170374A EA036955B1 (ru) 2008-08-27 2009-08-26 Производные замещенных трициклических кислот в качестве агонистов рецептора s1p1, применимые при лечении аутоиммунных и воспалительных заболеваний
MX2011002199A MX2011002199A (es) 2008-08-27 2009-08-26 Derivados de acidos triciclicos substituidos como agonistas del receptor s1p1 utiles en el tratamiento de trastornos autoinmunes e inflamatorios.
HRP20160890TT HRP20160890T1 (hr) 2008-08-27 2009-08-26 Derivati supstituirane tricikličke kiseline kao agonisti s1p1-receptora korisni u liječenju autoimunih i upalnih poremećaja
BRPI0917923-2A BRPI0917923B1 (pt) 2008-08-27 2009-08-26 Derivado de ácido tricíclico substituído, sua composição, seu uso e processo para preparar a referida composição
RS20160577A RS54970B1 (sr) 2008-08-27 2009-08-26 Supstituisani triciklični derivati kiselina kao s1p1 receptor agonisti korisni pri lečenju autoimunih i upalnih poremećaja
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AU2009288738A AU2009288738B9 (en) 2008-08-27 2009-08-26 Substituted tricyclic acid derivatives as S1P1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
SI200931475A SI2342205T1 (sl) 2008-08-27 2009-08-26 Substituirani triciklični kislinski derivati kot agonisti S1P1 receptorja, uporabni v zdravljenju avtoimunskih in vnetnih obolenj
US13/060,477 US8415484B2 (en) 2008-08-27 2009-08-26 Substituted tricyclic acid derivatives as S1P1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
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IL233869A IL233869A (en) 2008-08-27 2014-07-30 Trichelic acid derivatives are conserved as p1 s 1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011005295A1 (en) * 2009-06-24 2011-01-13 Arena Pharmaceuticals, Inc. Modulators of the sphingosine-1-phosphate (s1p) receptor useful for the treatment of disorders related thereto
WO2011109471A1 (en) * 2010-03-03 2011-09-09 Arena Pharmaceuticals, Inc. Processes for the preparation of s1p1 receptor modulators and crystalline forms thereof
US8415484B2 (en) 2008-08-27 2013-04-09 Arena Pharmaceuticals, Inc. Substituted tricyclic acid derivatives as S1P1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
US8580841B2 (en) 2008-07-23 2013-11-12 Arena Pharmaceuticals, Inc. Substituted 1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid derivatives useful in the treatment of autoimmune and inflammatory disorders
US8853419B2 (en) 2010-01-27 2014-10-07 Arena Pharmaceuticals, Inc. Processes for the preparation of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid and salts thereof
US10301262B2 (en) 2015-06-22 2019-05-28 Arena Pharmaceuticals, Inc. Crystalline L-arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta [b]indol-3-yl)acetic acid(Compund1) for use in SIPI receptor-associated disorders
WO2020140957A1 (en) * 2019-01-04 2020-07-09 Ascentage Pharma (Suzhou) Co., Ltd. Method for preparing sulfonamides drugs
US11007175B2 (en) 2015-01-06 2021-05-18 Arena Pharmaceuticals, Inc. Methods of treating conditions related to the S1P1 receptor
US11478448B2 (en) 2017-02-16 2022-10-25 Arena Pharmaceuticals, Inc. Compounds and methods for treatment of inflammatory bowel disease with extra-intestinal manifestations
US11534424B2 (en) 2017-02-16 2022-12-27 Arena Pharmaceuticals, Inc. Compounds and methods for treatment of primary biliary cholangitis
US11555015B2 (en) 2018-09-06 2023-01-17 Arena Pharmaceuticals, Inc. Compounds useful in the treatment of autoimmune and inflammatory disorders
US12156866B2 (en) 2018-06-06 2024-12-03 Arena Pharmaceuticals, Inc. Methods of treating conditions related to the S1P1 receptor

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HUE033168T2 (en) 2008-03-17 2017-11-28 Actelion Pharmaceuticals Ltd Dosage regimen for selective SIP1 receptor agonist
CN104478885B (zh) * 2014-12-12 2017-08-01 常州大学 9‑氨基‑9a‑烯丙基苯并吡咯里西啶生物碱的制备方法
CN104710426B (zh) * 2014-12-12 2017-08-01 常州大学 苯并吡咯里西啶生物碱及其制备方法和用途
EP3892616A4 (en) * 2018-12-06 2022-07-27 Shanghai Jemincare Pharmaceuticals Co., Ltd. AROMATIC RING DERIVATIVE AS IMMUNOREGULATION AND MANUFACTURING METHOD AND APPLICATION OF AN AROMATIC RING DERIVATIVE
US20220142977A1 (en) * 2019-01-08 2022-05-12 Arena Pharmaceuticals, Inc. Methods of treating conditions related to the s1p1 receptor
WO2021213393A1 (en) * 2020-04-20 2021-10-28 Zebrapeutics Inc. Method of treating ship1-mediated diseases using pelorol derivatives
CN112812052B (zh) * 2021-02-02 2023-12-01 成都阿奇生物医药科技有限公司 一种治疗溃疡性结肠炎的化合物及其制备方法和用途

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050033055A1 (en) * 2002-01-18 2005-02-10 Bugianesi Robert L. Edg receptor agonists
WO2008074821A1 (en) * 2006-12-21 2008-06-26 Glaxo Group Limited Indole derivatives as s1p1 receptor agonists

Family Cites Families (147)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL293572A (https=) 1962-06-07
DE2226703A1 (de) 1972-05-25 1973-12-13 Schering Ag Neue tetrahydrocarbazolderivate und verfahren zu ihrer herstellung
US4057559A (en) * 1973-10-01 1977-11-08 American Home Products Corporation Carbazole acetic acid derivatives
US4810699A (en) * 1987-02-20 1989-03-07 American Home Products Corporation Substituted 1,3,4,9-tetrahydropyrano[3,4,-b]indole-1-acetic acids, pharmaceutical compositions containing them, and methods for treating inflammatory conditions and for analgesic purposes using them
US4782076A (en) * 1988-03-01 1988-11-01 American Home Products Corporation Substituted 2,3,4,9-tetrahydro-1H-carbazole-1-acetic acid derivatives, composition and use
PT95692A (pt) 1989-10-27 1991-09-13 American Home Prod Processo para a preparacao de derivados de acidos indole-,indeno-,piranoindole- e tetra-hidrocarbazole-alcanoicos, ou quais sao uteis como inibidores de pla2 e da lipoxigenase
US5221678A (en) 1990-07-26 1993-06-22 Merck Frosst Canada, Inc. (quinolin-2-ylmethoxy)tetrahydrocarbazoles as inhibitors of the biosynthesis of leukotrienes
US5998499A (en) 1994-03-25 1999-12-07 Dentsply G.M.B.H. Liquid crystalline (meth)acrylate compounds, composition and method
US5776967A (en) * 1996-07-26 1998-07-07 American Home Products Corporation Pyranoindole inhibitors of COX--2
US5830911A (en) * 1996-08-14 1998-11-03 American Home Products Corporation Pyranoindole and tetrahydrocarbazole inhibitors of COX-2
US6861448B2 (en) * 1998-01-14 2005-03-01 Virtual Drug Development, Inc. NAD synthetase inhibitors and uses thereof
NZ515086A (en) 1999-04-28 2003-10-31 Aventis Pharma Gmbh Di-aryl acid derivatives as PPAR receptor ligands
US6410583B1 (en) * 2000-07-25 2002-06-25 Merck Frosst Canada & Co. Cyclopentanoindoles, compositions containing such compounds and methods of treatment
WO2002039987A2 (en) 2000-11-14 2002-05-23 Neurosearch A/S Use of malaria parasite anion channel blockers for treating malaria
US7064217B2 (en) 2001-01-30 2006-06-20 University Of Virginia Patent Foundation Agonists and antagonists of sphingosine-1-phosphate receptors
EP1375463A4 (en) * 2001-03-29 2009-09-02 Osaka Gas Co Ltd OPTICALLY ACTIVE COMPOUND AND PHOTOSENSITIVE RESIN COMPOSITION
WO2002092068A1 (en) 2001-05-10 2002-11-21 Ono Pharmaceutical Co., Ltd. Carboxylic acid derivatives and drugs containing the same as the active ingredient
MXPA04002679A (es) 2001-09-27 2004-07-30 Kyorin Seiyaku Kk Derivados de sulfuro de diarilo, sales de los mismos y agentes inmunosupresores que utilizan los mismos.
WO2003059346A1 (en) * 2002-01-18 2003-07-24 The Genetics Company Inc. Beta-secretase inhibitors
US20050070506A1 (en) 2002-01-18 2005-03-31 Doherty George A. Selective s1p1/edg1 receptor agonists
US7309721B2 (en) 2002-03-01 2007-12-18 Merck + Co., Inc. Aminoalkylphosphonates and related compounds as Edg receptor agonists
AU2003218056A1 (en) 2002-03-01 2003-09-16 Merck & Co., Inc. Aminoalkylphosphonates and related compounds as edg receptor agonists
JP2005533058A (ja) 2002-06-17 2005-11-04 メルク　エンド　カムパニー　インコーポレーテッド Ｅｄｇ受容体アゴニストとしての１−（（５−アリール−１，２，４−オキサジアゾール−３−イル）ベンジル）アゼチジン−３−カルボキシラートおよび１−（（５−アリール−１，２，４−オキサジアゾール−３−イル）ベンジル）ピロリジン−３−カルボキシラート
US20060004010A1 (en) * 2002-07-10 2006-01-05 Hiromu Habashita Ccr4 antagonist and medical use thereof
CA2533587A1 (en) 2002-07-30 2004-02-05 University Of Virginia Patent Foundation Compounds active in sphingosine 1-phosphate signaling
AU2003277576A1 (en) * 2002-11-08 2004-06-07 Takeda Pharmaceutical Company Limited Receptor function controlling agent
JP4516430B2 (ja) 2002-12-20 2010-08-04 メルク・シャープ・エンド・ドーム・コーポレイション １−（アミノ）インダン並びに（１，２−ジヒドロ−３−アミノ）−ベンゾフラン、ベンゾチオフェン及びインドール
MXPA05008531A (es) 2003-02-11 2005-11-17 Irm Llc Compuestos biciclicos novedosos y composiciones.
US7456157B2 (en) 2003-02-18 2008-11-25 Kyorin Pharmaceutical Co., Ltd. Aminophosphonic acid derivatives, addition salts thereof and S1P receptor modulators
MXPA05011539A (es) * 2003-04-30 2006-01-23 Inst For Pharm Discovery Inc Acidos carboxilicos sustituidos con heterociclo como inhibidores de la proteina tirosina-fosfatasa-1b.
CA2523677A1 (en) 2003-04-30 2004-11-11 Novartis Ag Aminopropanol derivatives as sphingosine-1-phosphate receptor modulators
EP1622860B1 (en) 2003-04-30 2012-02-29 Novartis AG AMINO-PROPANOL DERIVATIVES AS SPHINGOSINE-1-PHOSPHATE RECEPTOR MODULATORs
US20060252741A1 (en) 2003-05-15 2006-11-09 Colandrea Vincent J 3-(2-amino-1-azacyclyl)-5-aryl-1,2,4-oxadiazoles as s1p receptor agonists
WO2004104205A2 (en) 2003-05-16 2004-12-02 Merck & Co., Inc. Enzymatic preparation of chiral indole esters
CN1791592B (zh) * 2003-05-19 2012-07-04 Irm责任有限公司 免疫抑制剂化合物和组合物
ES2558761T3 (es) 2003-05-19 2016-02-08 Novartis Ag Compuestos y composiciones inmunosupresores
BRPI0410439A (pt) 2003-05-19 2006-06-06 Irm Llc compostos e composições imunossupressoras
MY150088A (en) 2003-05-19 2013-11-29 Irm Llc Immunosuppressant compounds and compositions
GB0313612D0 (en) 2003-06-12 2003-07-16 Novartis Ag Organic compounds
EP1661879A4 (en) * 2003-08-04 2006-11-29 Ono Pharmaceutical Co A DIPHENYL ETHER COMPOUND, PROCESS FOR THE PRODUCTION AND USE THEREOF
CN1874996B (zh) 2003-08-28 2011-05-18 诺瓦提斯公司 氨基丙醇衍生物
EP1661881B1 (en) 2003-08-29 2014-12-17 Ono Pharmaceutical Co., Ltd. Compound capable of binding s1p receptor and pharmaceutical use thereof
CN1874991A (zh) * 2003-08-29 2006-12-06 小野药品工业株式会社 能够结合s1p受体的化合物及其药物用途
EP1661889A4 (en) * 2003-09-05 2009-08-05 Ono Pharmaceutical Co ANTAGONIST OF THE CHEMOKINE RECEPTOR AND ITS USE FOR MEDICAL PURPOSES
CN1859908A (zh) * 2003-10-01 2006-11-08 默克公司 作为s1p受体激动剂的3,5－芳基、杂芳基或环烷基取代的－1,2,4－噁二唑类化合物
WO2005041899A2 (en) 2003-11-03 2005-05-12 University Of Virginia Patent Foundation Orally available sphingosine 1-phosphate receptor agonists and antagonists
WO2005044780A1 (ja) 2003-11-10 2005-05-19 Kyorin Pharmaceutical Co., Ltd. アミノカルボン酸誘導体とその付加塩及びｓ１ｐ受容体調節剤
US7605171B2 (en) 2003-12-17 2009-10-20 Merck & Co., Inc. (3,4-disubstituted)propanoic carboxylates as S1P (Edg) receptor agonists
ATE528276T1 (de) * 2003-12-19 2011-10-15 Ono Pharmaceutical Co Lysophosphatidylsäurerezeptor-antagonistische verbindungen und ihre anwendungen
GB0329498D0 (en) 2003-12-19 2004-01-28 Novartis Ag Organic compounds
GB0401332D0 (en) 2004-01-21 2004-02-25 Novartis Ag Organic compounds
JP2005272453A (ja) * 2004-02-24 2005-10-06 Sankyo Co Ltd アミノアルコール化合物
TW200538433A (en) 2004-02-24 2005-12-01 Irm Llc Immunosuppressant compounds and compositiions
JP4740884B2 (ja) 2004-02-24 2011-08-03 アイアールエム・リミテッド・ライアビリティ・カンパニー 免疫抑制性化合物および組成物
WO2005085214A1 (ja) * 2004-03-05 2005-09-15 Banyu Pharmaceutical Co., Ltd ジアリール置換複素５員環誘導体
GB0405289D0 (en) 2004-03-09 2004-04-21 Novartis Ag Organic compounds
TWI344954B (en) 2004-04-02 2011-07-11 Merck Sharp & Dohme Asymmetric hydrogenation process
WO2005123677A1 (en) 2004-06-16 2005-12-29 Actelion Pharmaceuticals Ltd 4-carbonyl substituted 1,1,2-trimethyl-1a,4,5,5a-tetrahydro-1h-4-aza-cyclopropa'a!pentalene derivatives as agonists for the g-protein-coupled receptor s1p1/edg1 and immunosuppressive agents
EP1760071A4 (en) 2004-06-23 2008-03-05 Ono Pharmaceutical Co COMPOUND WITH S1P RECEPTOR BINDING ABILITY AND USE THEREOF
CN101014329B (zh) 2004-07-16 2010-09-08 杏林制药株式会社 用于对器官或组织的移植的排异反应或骨髓移植的移植物抗宿主反应预防或治疗的药物组合物
JP2007284350A (ja) * 2004-07-27 2007-11-01 Takeda Chem Ind Ltd 糖尿病治療剤
TW200611687A (en) 2004-07-29 2006-04-16 Sankyo Co Pharmaceutical compositions used for immunosuppressant
WO2006010379A1 (en) 2004-07-29 2006-02-02 Actelion Pharmaceuticals Ltd. Novel thiophene derivatives as immunosuppressive agents
US8022225B2 (en) * 2004-08-04 2011-09-20 Taisho Pharmaceutical Co., Ltd Triazole derivative
US20060223866A1 (en) 2004-08-13 2006-10-05 Praecis Pharmaceuticals, Inc. Methods and compositions for modulating sphingosine-1-phosphate (S1P) receptor activity
MX2007001661A (es) 2004-08-13 2007-04-23 Praecis Pharm Inc Metodos y composiciones para modular la actividad del receptor de esfingosina -1 fosfato (sip).
MX2007003371A (es) 2004-09-23 2007-05-07 Wyeth Corp Derivados de carbazol y ciclopentaindol para tratar infeccion con virus de hepatitis c.
MX2007004262A (es) * 2004-10-12 2008-03-04 Forbes Medi Tech Res Inc Compuestos y metodos para tratar resistencia a la insulina y cardiomiopatia.
AU2005299851B2 (en) 2004-10-22 2011-03-17 Merck Sharp & Dohme Corp. 2-(aryl)azacyclylmethyl carboxylates, sulfonates, phosphonates, phosphinates and heterocycles as S1P receptor agonists
ATE397582T1 (de) 2004-10-22 2008-06-15 Bioprojet Soc Civ Neue dicarbonsäurederivate
AU2005307718A1 (en) * 2004-11-18 2006-05-26 The Institutes For Pharmaceutical Discovery, Llc Heterocycle substituted carboxylic acids for the treatment of diabetes
US20080051418A1 (en) * 2004-11-26 2008-02-28 Tsuyoshi Maekawa Arylalkanoic Acid Derivative
JP2008522977A (ja) 2004-12-06 2008-07-03 ユニバーシティ オブ バージニア パテント ファンデーション スフィンゴシン＝１−リン酸のアリールアミドアナログ
EP2592066B1 (en) 2004-12-13 2014-12-03 Ono Pharmaceutical Co., Ltd. Aminocarboxylic acid derivative and medical use thereof
WO2006079406A1 (en) 2005-01-25 2006-08-03 Merck Patent Gmbh Mesogenic compounds, liquid crystal medium and liquid crystal display
AU2006214314B2 (en) 2005-02-14 2012-02-09 University Of Virginia Patent Foundation Sphingosine 1- phos phate agonists comprising cycloalkanes and 5 -membered heterocycles substituted by amino and phenyl groups
KR20080002850A (ko) 2005-03-23 2008-01-04 액테리온 파마슈티칼 리미티드 신규한 티오펜 유도체
BRPI0609668A2 (pt) 2005-03-23 2011-10-18 Actelion Pharmaceuticals Ltd composto, composição farmacêutica, e, uso de um composto
US7723378B2 (en) 2005-03-23 2010-05-25 Actelion Pharmaceuticals Ltd. Hydrogenated benzo (C) thiophene derivatives as immunomodulators
BRPI0612028A2 (pt) 2005-06-08 2010-10-13 Novartis Ag oxadiazóis ou isodiazóis policìclicos e uso dos mesmos como ligantes de receptor s1p
TWI418350B (zh) 2005-06-24 2013-12-11 Sankyo Co 含有ｐｐａｒ調節劑之醫藥組成物的用途
EP1896446A1 (en) 2005-06-24 2008-03-12 Actelion Pharmaceuticals Ltd. Novel thiophene derivatives
US20070060573A1 (en) * 2005-08-10 2007-03-15 Lars Wortmann Acyltryptophanols
WO2007024922A1 (en) 2005-08-23 2007-03-01 Irm Llc Immunosuppressant compounds and compositions
JPWO2007037196A1 (ja) 2005-09-29 2009-04-09 山本化成株式会社 インドリン系化合物及びその製造方法
EP1965807A4 (en) * 2005-11-23 2010-10-27 Epix Delaware Inc S1P RECEPTOR MODULATING COMPOUNDS AND THEIR USE
AR057894A1 (es) 2005-11-23 2007-12-26 Actelion Pharmaceuticals Ltd Derivados de tiofeno
TWI404706B (zh) 2006-01-11 2013-08-11 Actelion Pharmaceuticals Ltd 新穎噻吩衍生物
TW200736234A (en) 2006-01-17 2007-10-01 Astrazeneca Ab Chemical compounds
ATE447568T1 (de) 2006-01-24 2009-11-15 Actelion Pharmaceuticals Ltd Neue pyrinderivate
GB0601744D0 (en) 2006-01-27 2006-03-08 Novartis Ag Organic compounds
TWI389683B (zh) * 2006-02-06 2013-03-21 Kyorin Seiyaku Kk A therapeutic agent for an inflammatory bowel disease or an inflammatory bowel disease treatment using a 2-amino-1,3-propanediol derivative as an active ingredient
AU2007212193A1 (en) 2006-02-09 2007-08-16 University Of Virginia Patent Foundation Bicyclic sphingosine 1-phosphate analogs
TW200806611A (en) 2006-02-09 2008-02-01 Daiichi Seiyaku Co Novel amidopropionic acid derivatives and medicine containing the same
US20070191371A1 (en) * 2006-02-14 2007-08-16 Kalypsys, Inc. Heterocyclic modulators of ppar
BRPI0707873A2 (pt) 2006-02-15 2011-05-10 Allergan Inc compostos amida, Éster, tioamida e tiol Éster do Ácido indol-3-carboxÍlico carregando grupos arila ou heteroarila tendo atividade biolàgica antagonista de recptor de esfingosina-1-fosfato (s1p)
CN101460458A (zh) * 2006-02-15 2009-06-17 阿勒根公司 具有1－磷酸－鞘氨醇(s1p)受体拮抗剂生物活性的带芳基或者杂芳基基团的吲哚－3－羧酸的酰胺、酯、硫代酰胺和硫羟酸酯化合物
BRPI0707957A2 (pt) 2006-02-21 2011-05-17 Univ Virginia Patent Found composto, e, método para prevenção ou tratamento de uma condição ou sintoma patológico em um mamìfero
US7649098B2 (en) 2006-02-24 2010-01-19 Lexicon Pharmaceuticals, Inc. Imidazole-based compounds, compositions comprising them and methods of their use
CA2646430A1 (en) * 2006-03-14 2007-09-20 Amgen Inc. Bicyclic carboxylic acid derivatives useful for treating metabolic disorders
JP2009530389A (ja) 2006-03-21 2009-08-27 エピックス デラウェア， インコーポレイテッド Ｓ１ｐ受容体調節化合物及びその使用
JP2007262009A (ja) 2006-03-29 2007-10-11 Dai Ichi Seiyaku Co Ltd ヘテロアリール低級カルボン酸誘導体
MX2008012738A (es) 2006-04-03 2009-02-06 Astellas Pharma Inc Heterocompuesto.
GB0607389D0 (en) 2006-04-12 2006-05-24 Novartis Ag Organic compounds
JPWO2007129745A1 (ja) 2006-05-09 2009-09-17 第一三共株式会社 ヘテロアリールアミド低級カルボン酸誘導体
EA200802058A1 (ru) 2006-05-09 2009-06-30 Пфайзер Продактс Инк. Производные циклоалкиламинокислот и их фармацевтические композиции
WO2007129473A1 (ja) 2006-05-09 2007-11-15 Daiichi Sankyo Company, Limited 二環性アリール誘導体
TW200823182A (en) 2006-08-01 2008-06-01 Praecis Pharm Inc Chemical compounds
US20080070866A1 (en) 2006-08-01 2008-03-20 Praecis Pharmaceuticals Incorporated Chemical compounds
JP2009545630A (ja) 2006-08-04 2009-12-24 プリーシス・ファーマシューティカルズ・インコーポレイテッド 化合物
JP5188972B2 (ja) * 2006-08-08 2013-04-24 杏林製薬株式会社 アミノリン酸エステル誘導体及びそれらを有効成分とするｓ１ｐ受容体調節剤
WO2008024196A1 (en) 2006-08-24 2008-02-28 Praecis Pharmaceuticals Incorporated Chemical compounds
JP2009269819A (ja) 2006-08-25 2009-11-19 Asahi Kasei Pharma Kk アミン化合物
TWI392671B (zh) 2006-09-07 2013-04-11 Actelion Pharmaceuticals Ltd 吡啶-４-基衍生物
TWI408139B (zh) 2006-09-07 2013-09-11 Actelion Pharmaceuticals Ltd 新穎噻吩衍生物
AU2007292347A1 (en) 2006-09-07 2008-03-13 Allergan, Inc. Heteroaromatic compounds having sphingosine-1-phosphate (S1P) receptor agonist and/or antagonist biological activity
PE20080769A1 (es) 2006-09-08 2008-08-14 Novartis Ag Derivados de biaril-sulfonamida
MX2009002915A (es) 2006-09-21 2009-03-31 Actelion Pharmaceuticals Ltd Derivados de fenilo y su uso como inmunomoduladores.
SG177221A1 (en) 2006-12-15 2012-01-30 Abbott Lab Novel oxadiazole compounds
GB0625648D0 (en) 2006-12-21 2007-01-31 Glaxo Group Ltd Compounds
CL2007003784A1 (es) 2006-12-21 2008-06-27 Abbott Lab Compuestos derivados de 1-amino-3-fenilciclopentano, que son agonistas o antagonistas de uno o mas receptores de la familia s1p; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar la esclerosis multiple, artritis reumato
JP2010515750A (ja) 2007-01-11 2010-05-13 アラーガン インコーポレイテッド スフィンゴシン−１−ホスフェート（ｓ１ｐ）受容体アンタゴニスト生物活性を有する６−置換インドール−３−カルボン酸アミド化合物
WO2008091967A1 (en) 2007-01-26 2008-07-31 Smithkline Beecham Corporation Chemical compounds
WO2008097819A2 (en) 2007-02-05 2008-08-14 Smithkline Beecham Corporation Chemical compounds
PT2125797E (pt) 2007-03-16 2014-03-11 Actelion Pharmaceuticals Ltd Derivados aminopiridina como agonistas do receptor s1p1/edg1
MX2009010060A (es) 2007-03-21 2010-01-20 Epix Pharm Inc Compuestos moduladores del receptor de esfingosin-1-fosfato y uso de los mismos.
KR20090130062A (ko) 2007-04-19 2009-12-17 글락소 그룹 리미티드 스핑고신 １―포스페이트 (ｓ１ｐ) 효능제로서 사용하기 위한 옥사디아졸 치환된 인다졸 유도체
EP2014653A1 (en) 2007-06-15 2009-01-14 Bioprojet Novel dicarboxylic acid derivatives as S1P1 receptor agonists
US20090069288A1 (en) 2007-07-16 2009-03-12 Breinlinger Eric C Novel therapeutic compounds
WO2009019506A1 (en) 2007-08-03 2009-02-12 Astrazeneca Ab Heterocyclyc sulfonamides having edg-1 antagonistic activity
MX2010001446A (es) 2007-08-08 2010-03-01 Merck Serono Sa Derivados de 6-amino-pirimidina-4-carboxamida y compuestos relacionados que se enlazan a los receptores para esfingosina 1-fosfato (s1p) para el tratamiento de esclerosis multiple.
UY31468A1 (es) 2007-11-15 2009-07-17 Derivados bis-(sulfonilamino) en terapia 065
EP2222668B1 (en) 2007-12-18 2011-11-02 Arena Pharmaceuticals, Inc. Tetrahydrocyclopenta[b]indol-3-yl carboxylic acid derivatives useful in the treatment of autoimmune and inflammatory disorders
AU2009206733A1 (en) * 2008-01-25 2009-07-30 Arena Pharmaceuticals, Inc. Dihydro- 1H- pyrrolo [1,2-a] indol-1-yl carboxylic derivatives which act as S1P1 agonists
AR070398A1 (es) 2008-02-22 2010-03-31 Gruenenthal Chemie Derivados sustituidos de indol
SI2291080T1 (sl) 2008-05-14 2015-11-30 The Scripps Research Institute Novi modulatorji sfingosinskih fosfatnih receptorjev
WO2009151621A1 (en) 2008-06-13 2009-12-17 Arena Pharmaceuticals, Inc. Substituted (1, 2, 4-0xadiaz0l-3-yl) indolin-1-yl carboxylic acid derivatives useful as s1p1 agonists
WO2009151626A1 (en) 2008-06-13 2009-12-17 Arena Pharmaceuticals, Inc. Substituted (1, 2, 4-0xadiaz0l-3-yl) indolin-1-yl carboxylic acid derivatives useful as s1p1 agonists
EA019252B1 (ru) * 2008-07-23 2014-02-28 Арена Фармасьютикалз, Инк. ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ (1,2,3,4-ТЕТРАГИДРОЦИКЛОПЕНТА[b]ИНДОЛ-3-ИЛ)УКСУСНОЙ КИСЛОТЫ, ПРИМЕНИМЫЕ В ЛЕЧЕНИИ АУТОИММУННЫХ И ВОСПАЛИТЕЛЬНЫХ РАССТРОЙСТВ
SI2342205T1 (sl) 2008-08-27 2016-09-30 Arena Pharmaceuticals, Inc. Substituirani triciklični kislinski derivati kot agonisti S1P1 receptorja, uporabni v zdravljenju avtoimunskih in vnetnih obolenj
MX2011008450A (es) 2009-02-10 2011-09-01 Abbott Lab Agonistas y antagonistas del receptor s1p5, y metodos de uso de los mismos.
WO2011005290A1 (en) 2009-06-23 2011-01-13 Arena Pharmaceuticals, Inc. Disubstituted oxadiazole derivatives useful in the treatment of autoimmune and inflammatory disorders
WO2011005295A1 (en) 2009-06-24 2011-01-13 Arena Pharmaceuticals, Inc. Modulators of the sphingosine-1-phosphate (s1p) receptor useful for the treatment of disorders related thereto
JP5728487B2 (ja) 2009-10-29 2015-06-03 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ 三環式ヘテロ環化合物
SG10201906876PA (en) 2010-01-27 2019-09-27 Arena Pharm Inc Processes for the preparation of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid and salts thereof
SG183416A1 (en) 2010-03-03 2012-09-27 Arena Pharm Inc Processes for the preparation of s1p1 receptor modulators and crystalline forms thereof
EP2598126A2 (en) 2010-07-30 2013-06-05 Saint Louis University Methods of treating pain

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050033055A1 (en) * 2002-01-18 2005-02-10 Bugianesi Robert L. Edg receptor agonists
WO2008074821A1 (en) * 2006-12-21 2008-06-26 Glaxo Group Limited Indole derivatives as s1p1 receptor agonists

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
CHUN ET AL., PHARMACOLOGICAL REVIEWS, vol. 54, 2002, pages 265 - 269
COLLIER, T. L.: "B. Ortho 125Iodination of phenols: This procedure allows for the incorporation of 125I at the ortho position of a phenol", J. LABELLED COMPD. RADIOPHARM., vol. 42, 1999, pages S264 - S266
LE BAS, M.-D., J. LABELLED COMPD. RADIOPHARM., vol. 44, 2001, pages S280 - S282
VACHAL PETR ET AL: "Highly selective and potent agonists of sphingosine-1-phosphate 1 (S1P1) receptor", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, PERGAMON, ELSEVIER SCIENCE, GB, vol. 16, no. 14, 15 July 2006 (2006-07-15), pages 3684 - 3687, XP002515397, ISSN: 0960-894X, [retrieved on 20060506] *
ZHU, G-D., J. ORG. CHEM., vol. 67, 2002, pages 943 - 948

Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8580841B2 (en) 2008-07-23 2013-11-12 Arena Pharmaceuticals, Inc. Substituted 1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid derivatives useful in the treatment of autoimmune and inflammatory disorders
US9522133B2 (en) 2008-07-23 2016-12-20 Arena Pharmaceuticals, Inc. Substituted 1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid derivatives useful in the treatment of autoimmune and inflammatory disorders
US9126932B2 (en) 2008-07-23 2015-09-08 Arena Pharmaceuticals, Inc. Substituted 1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid derivatives useful in the treatment of autoimmune and inflammatory disorders
US9108969B2 (en) 2008-08-27 2015-08-18 Arena Pharmaceuticals, Inc. Substituted tricyclic acid derivatives as S1P1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
US8415484B2 (en) 2008-08-27 2013-04-09 Arena Pharmaceuticals, Inc. Substituted tricyclic acid derivatives as S1P1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
WO2011005295A1 (en) * 2009-06-24 2011-01-13 Arena Pharmaceuticals, Inc. Modulators of the sphingosine-1-phosphate (s1p) receptor useful for the treatment of disorders related thereto
US8853419B2 (en) 2010-01-27 2014-10-07 Arena Pharmaceuticals, Inc. Processes for the preparation of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid and salts thereof
US11149292B2 (en) 2010-01-27 2021-10-19 Arena Pharmaceuticals, Inc. Processes for the preparation of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[B]indol-3-yl)acetic acid and salts thereof
US9175320B2 (en) 2010-01-27 2015-11-03 Arena Pharmaceuticals, Inc. Processes for the preparation of (R)-2-(7-4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[B]indol-3-yl)acetic acid and salts thereof
US9447041B2 (en) 2010-01-27 2016-09-20 Arena Pharmaceuticals, Inc. Processes for the preparation of (R)-2-(7-4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[B]indol-3-yl)acetic acid and salts thereof
US11674163B2 (en) 2010-01-27 2023-06-13 Arena Pharmaceuticals, Inc. Processes for the preparation of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid and salts thereof
US9085581B2 (en) 2010-03-03 2015-07-21 Arena Pharmaceuticals, Inc. Processes for the preparation of S1P1 receptor modulators and crystalline forms thereof
WO2011109471A1 (en) * 2010-03-03 2011-09-09 Arena Pharmaceuticals, Inc. Processes for the preparation of s1p1 receptor modulators and crystalline forms thereof
US11896578B2 (en) 2015-01-06 2024-02-13 Arena Pharmaceuticals, Inc. Methods of treating conditions related to the S1P1 receptor
US11007175B2 (en) 2015-01-06 2021-05-18 Arena Pharmaceuticals, Inc. Methods of treating conditions related to the S1P1 receptor
US10676435B2 (en) 2015-06-22 2020-06-09 Arena Pharmaceuticals, Inc. Crystalline L-arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta [b]indol-3-yl)acetic acid(Compound 1) for use in SIPI receptor-associated disorders
US11091435B2 (en) 2015-06-22 2021-08-17 Arena Pharmaceuticals, Inc. Crystalline L-arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3, 4-tetrahydrocyclo-penta [b]indol-3-yl)acetic acid(compound1) for use in S1P1 receptor-associated disorders
US11884626B2 (en) 2015-06-22 2024-01-30 Arena Pharmaceuticals, Inc. Crystalline L-arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta [b]indol-3-yl)acetic acid(Compound1) for use in S1P1 receptor-associated disorders
US10301262B2 (en) 2015-06-22 2019-05-28 Arena Pharmaceuticals, Inc. Crystalline L-arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta [b]indol-3-yl)acetic acid(Compund1) for use in SIPI receptor-associated disorders
US11478448B2 (en) 2017-02-16 2022-10-25 Arena Pharmaceuticals, Inc. Compounds and methods for treatment of inflammatory bowel disease with extra-intestinal manifestations
US11534424B2 (en) 2017-02-16 2022-12-27 Arena Pharmaceuticals, Inc. Compounds and methods for treatment of primary biliary cholangitis
US12097182B2 (en) 2017-02-16 2024-09-24 Arena Pharmaceuticals, Inc. Compounds and methods for treatment of inflammatory bowel disease with extra-intestinal manifestations
US12156866B2 (en) 2018-06-06 2024-12-03 Arena Pharmaceuticals, Inc. Methods of treating conditions related to the S1P1 receptor
US11555015B2 (en) 2018-09-06 2023-01-17 Arena Pharmaceuticals, Inc. Compounds useful in the treatment of autoimmune and inflammatory disorders
US11414400B2 (en) 2019-01-04 2022-08-16 Ascentage Pharma (Suzhou) Co., Ltd. Method for preparing sulfonamides drugs
WO2020140957A1 (en) * 2019-01-04 2020-07-09 Ascentage Pharma (Suzhou) Co., Ltd. Method for preparing sulfonamides drugs

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