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

Info

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
Authority
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
Other languages
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 SI200931475A priority Critical patent/SI2342205T1/sl
Priority to NZ591001A priority patent/NZ591001A/xx
Priority to AU2009288738A priority patent/AU2009288738B9/en
Priority to HRP20160890TT priority patent/HRP20160890T1/hr
Priority to RS20160577A priority patent/RS54970B1/sr
Priority to US13/060,477 priority patent/US8415484B2/en
Priority to JP2011524992A priority patent/JP5726737B2/ja
Priority to EA201170374A priority patent/EA036955B1/ru
Priority to KR1020177014649A priority patent/KR101800595B1/ko
Priority to MX2011002199A priority patent/MX2011002199A/es
Priority to BRPI0917923-2A priority patent/BRPI0917923B1/pt
Priority to EP09789210.3A priority patent/EP2342205B1/en
Priority to CN200980142790.4A priority patent/CN102197038B/zh
Application filed by Arena Pharmaceuticals Inc filed Critical Arena Pharmaceuticals Inc
Priority to ES09789210.3T priority patent/ES2583630T3/es
Priority to CA2733671A priority patent/CA2733671C/en
Priority to HK11112888.7A priority patent/HK1158624B/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

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • 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
    • C07D487/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • 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
    • A61K31/415—1,2-Diazoles
    • A61K31/4162—1,2-Diazoles condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • 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
    • A61K31/44—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
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—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
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Neurology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Pulmonology (AREA)
  • Dermatology (AREA)
  • Neurosurgery (AREA)
  • Diabetes (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Cardiology (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Emergency Medicine (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Vascular Medicine (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Psychiatry (AREA)
  • Ophthalmology & Optometry (AREA)
  • Endocrinology (AREA)
  • Pain & Pain Management (AREA)
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
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
HRP20160890TT HRP20160890T1 (hr) 2008-08-27 2009-08-26 Derivati supstituirane tricikličke kiseline kao agonisti s1p1-receptora korisni u liječenju autoimunih i upalnih poremećaja
RS20160577A RS54970B1 (sr) 2008-08-27 2009-08-26 Supstituisani triciklični derivati kiselina kao s1p1 receptor agonisti korisni pri lečenju autoimunih i upalnih poremećaja
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
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
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
KR1020177014649A KR101800595B1 (ko) 2008-08-27 2009-08-26 자가면역 및 염증성 장애의 치료에 유용한, ｓ1ｐ1 수용체 효능제로서의 치환된 트리시클릭 산 유도체
NZ591001A NZ591001A (en) 2008-08-27 2009-08-26 Substituted tricyclic acid derivatives as s1p1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
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
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
SI200931475A SI2342205T1 (sl) 2008-08-27 2009-08-26 Substituirani triciklični kislinski derivati kot agonisti S1P1 receptorja, uporabni v zdravljenju avtoimunskih in vnetnih obolenj
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.
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
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
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
IL211107A IL211107A0 (en) 2008-08-27 2011-02-07 Substituted tricyclic acid derivatives as s1p1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
ZA2011/01524A ZA201101524B (en) 2008-08-27 2011-02-25 Substituted tricyclic acid derivatives as s1p1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
US13/787,233 US9108969B2 (en) 2008-08-27 2013-03-06 Substituted tricyclic acid derivatives as S1P1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
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
US14/817,954 US20150336966A1 (en) 2008-08-27 2015-08-04 Substituted tricyclic acid derivatives as s1p1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
CY20161100713T CY1117830T1 (el) 2008-08-27 2016-07-20 Υποκατεστημενα παραγωγα τρικυκλικων οξεων ως αγωνιστες του υποδοχεα s1p1 χρησιμα στην αγωγη αυτοανοσων και φλεγμονοδων διαταραχων
SM201600318T SMT201600318B (it) 2008-08-27 2016-09-14 Derivati dell'acido triciclico sostituiti come agonisti del recettore s1p1 utili nel trattamento di malattie autoimmuni e infiammatorie

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US19031108P 2008-08-27 2008-08-27
US61/190,311 2008-08-27
US26951909P 2009-06-24 2009-06-24
US61/269,519 2009-06-24

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US13/060,477 A-371-Of-International 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
US13/787,233 Continuation US9108969B2 (en) 2008-08-27 2013-03-06 Substituted tricyclic acid derivatives as S1P1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders

Publications (1)

Publication Number Publication Date
WO2010027431A1 true WO2010027431A1 (en) 2010-03-11

Family

ID=41491524

Family Applications (1)

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

Country Status (23)

Country Link
US (3) US8415484B2 (https=)
EP (1) EP2342205B1 (https=)
JP (2) JP5726737B2 (https=)
KR (2) KR101800595B1 (https=)
CN (2) CN105816453B (https=)
AU (1) AU2009288738B9 (https=)
BR (1) BRPI0917923B1 (https=)
CA (1) CA2733671C (https=)
CY (1) CY1117830T1 (https=)
EA (1) EA036955B1 (https=)
ES (1) ES2583630T3 (https=)
HR (1) HRP20160890T1 (https=)
HU (1) HUE031479T2 (https=)
IL (2) IL211107A0 (https=)
MX (1) MX2011002199A (https=)
NZ (1) NZ591001A (https=)
PL (1) PL2342205T3 (https=)
PT (1) PT2342205T (https=)
RS (1) RS54970B1 (https=)
SI (1) SI2342205T1 (https=)
SM (1) SMT201600318B (https=)
WO (1) WO2010027431A1 (https=)
ZA (1) ZA201101524B (https=)

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
PL2278960T5 (pl) * 2008-03-17 2020-06-29 Actelion Pharmaceuticals Ltd. Schemat dawkowania dla selektywnego agonisty receptora sip1
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
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
WO2020114475A1 (zh) 2018-12-06 2020-06-11 上海济煜医药科技有限公司 作为免疫调节的芳环衍生物及其制备方法和应用
CN113874009A (zh) * 2019-01-08 2021-12-31 艾尼纳制药公司 治疗与s1p1受体有关的病况的方法
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 (146)

* 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
YU72201A (sh) 1999-04-28 2005-07-19 Aventis Pharma Deutschland Gmbh. Derivati di-aril kiseline kao ppar receptorski ligandi
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
JP2004529100A (ja) 2001-01-30 2004-09-24 ユニバーシティ オブ バージニア パテント ファウンデーション スフィンゴシン−１−ホスフェートレセプターのアゴニストおよびアンタゴニスト
WO2002079131A1 (en) * 2001-03-29 2002-10-10 Kansai Research Institute, Inc. Optically active compound and photosensitive resin composition
ES2316613T3 (es) 2001-05-10 2009-04-16 Ono Pharmaceutical Co., Ltd. Derivados de acido crboxilico y composiciones farmaceuticas que contienen los mismos como ingrediente activo.
CA2461212C (en) 2001-09-27 2010-08-17 Kyorin Pharmaceutical Co., Ltd. Diaryl sulfide derivatives, salts thereof and immunosuppressive agents using the same
WO2003061567A2 (en) 2002-01-18 2003-07-31 Merck & Co., Inc. Selective s1p1/edg1 receptor agonists
JP2005516967A (ja) * 2002-01-18 2005-06-09 ザ ジェネティクス カンパニー インコーポレーティッド β−セクレターゼインヒビター
WO2003074008A2 (en) 2002-03-01 2003-09-12 Merck & Co., Inc. Aminoalkylphosphonates and related compounds as edg receptor agonists
JP2005531506A (ja) 2002-03-01 2005-10-20 メルク　エンド　カムパニー　インコーポレーテッド Ｅｄｇ受容体作動薬としてのアミノアルキルホスホネートおよび関連化合物
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
AU2003252478A1 (en) * 2002-07-10 2004-02-02 Ono Pharmaceutical Co., Ltd. Ccr4 antagonist and medicinal use thereof
US7241790B2 (en) 2002-07-30 2007-07-10 University Of Virginia Patent Foundation Compounds active in spinigosine 1-phosphate signaling
CA2505322A1 (en) * 2002-11-08 2004-05-21 Takeda Pharmaceutical Company Limited Receptor function regulator
DE60335827D1 (de) * 2002-12-20 2011-03-03 Merck Sharp & Dohme 1-(amino)indane als edg-rezeptoragonisten
PL378134A1 (pl) 2003-02-11 2006-03-06 Irm Llc Nowe pochodne bicykliczne i kompozycje farmaceutyczne zawierające pochodne bicykliczne
BRPI0407658A (pt) * 2003-02-18 2006-02-21 Kyorin Seiyaku Kk derivados de ácido aminofosfÈnico, seus sais e hidratos que atuam como moduladores de receptor de s1p e agente farmacêutico
MXPA05011597A (es) * 2003-04-30 2005-12-15 Novartis Ag Derivados de aminopropanol como moduladores del receptor 1-fosfato de esfingosina.
CN1777575B (zh) 2003-04-30 2010-05-12 诺瓦提斯公司 作为1-磷酸-鞘氨醇受体调节剂的氨基-丙醇衍生物
US7329680B2 (en) * 2003-04-30 2008-02-12 The Institute For Pharmaceutical Discovery, Llc Heterocycle substituted carboxylic acids
AU2004240586A1 (en) 2003-05-15 2004-12-02 Merck & Co., Inc. 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
EP1644367B1 (en) 2003-05-19 2015-10-14 Novartis AG Immunosuppressant compounds and compositions
CL2004001120A1 (es) * 2003-05-19 2005-04-15 Irm Llc Compuestos derivados de amina sustituidas con heterociclos, inmunosupresores; composicion farmaceutica; y uso para tratar enfermedades mediadas por interacciones de linfocito, tales como enfermedades autoinmunes, inflamatorias, infecciosas, cancer.
MY150088A (en) 2003-05-19 2013-11-29 Irm Llc Immunosuppressant compounds and compositions
MXPA05012459A (es) * 2003-05-19 2006-02-22 Irm Llc Compuestos y composiciones inmunosupresoras.
GB0313612D0 (en) * 2003-06-12 2003-07-16 Novartis Ag Organic compounds
JPWO2005012221A1 (ja) * 2003-08-04 2006-09-14 小野薬品工業株式会社 ジフェニルエーテル化合物、その製造方法および用途
ATE449069T1 (de) 2003-08-28 2009-12-15 Novartis Pharma Gmbh Aminopropanolderivate
US7825109B2 (en) * 2003-08-29 2010-11-02 Ono Pharmaceutical Co., Ltd. Compound capable of binding S1P receptor and pharmaceutical use thereof
WO2005023771A1 (ja) * 2003-09-05 2005-03-17 Ono Pharmaceutical Co., Ltd. ケモカインレセプターアンタゴニストおよびその医薬用途
US20070043014A1 (en) * 2003-10-01 2007-02-22 Merck & Co., Inc. 3,5-Aryl, heteroaryl or cycloalkyl substituted-1,2,4-oxadiazoles as s1p receptor agonists
US7638637B2 (en) 2003-11-03 2009-12-29 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
EP1697333A4 (en) 2003-12-17 2009-07-08 Merck & Co Inc (3,4-DISUBSTITUTED) PROPANE ACID BOXYLATES AS AGONISTS OF THE S1P (EDG) RECEPTOR
GB0329498D0 (en) 2003-12-19 2004-01-28 Novartis Ag Organic compounds
ATE528276T1 (de) * 2003-12-19 2011-10-15 Ono Pharmaceutical Co Lysophosphatidylsäurerezeptor-antagonistische verbindungen und ihre anwendungen
GB0401332D0 (en) 2004-01-21 2004-02-25 Novartis Ag Organic compounds
NZ549162A (en) 2004-02-24 2009-12-24 Sankyo Co Amino-pyrrol alcohol compounds
US7718704B2 (en) 2004-02-24 2010-05-18 Irm Llc Immunosuppressant compounds and compositions
TW200538433A (en) 2004-02-24 2005-12-01 Irm Llc Immunosuppressant compounds and compositiions
CN1934094A (zh) * 2004-03-05 2007-03-21 万有制药株式会社 二芳基取代杂环5元环衍生物
GB0405289D0 (en) 2004-03-09 2004-04-21 Novartis Ag Organic compounds
JP5239071B2 (ja) 2004-04-02 2013-07-17 メルク・シャープ・アンド・ドーム・コーポレーション シクロアルカノインドール誘導体の調製のために有用な非対称水素化方法
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
JP5315611B2 (ja) * 2004-06-23 2013-10-16 小野薬品工業株式会社 Ｓ１ｐ受容体結合能を有する化合物およびその用途
US7781617B2 (en) 2004-07-16 2010-08-24 Kyorin Pharmaceutical Co., Ltd Effective use method of medicaments and method of preventing expression of side effect
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).
WO2006034337A2 (en) 2004-09-23 2006-03-30 Wyeth Carbazole and cyclopentaindole derivatives to treat infection with hepatitis c virus
CA2583947A1 (en) * 2004-10-12 2006-04-20 Forbes Medi-Tech (Research) Inc. Compounds and methods of treating insulin resistance and cardiomyopathy
CA2583681A1 (en) 2004-10-22 2006-05-04 Merck & Co., Inc. 2-(aryl)azacyclylmethyl carboxylates, sulfonates, phosphonates, phosphinates and heterocycles as s1p receptor agonists
PL1650186T3 (pl) 2004-10-22 2008-11-28 Bioprojet Soc Civ Nowe pochodne kwasów dikarboksylowych
JP2008520692A (ja) * 2004-11-18 2008-06-19 ジ インスチチュート フォー ファーマシューティカル ディスカバリー、エルエルシー 複素環置換カルボン酸
JPWO2006057448A1 (ja) * 2004-11-26 2008-06-05 武田薬品工業株式会社 アリールアルカン酸誘導体
WO2006063033A2 (en) 2004-12-06 2006-06-15 University Of Virginia Patent Foundation Aryl amide sphingosine 1-phosphate analogs
BRPI0519012A2 (pt) 2004-12-13 2008-12-23 Ono Pharmaceutical Co derivado do Ácido aminocarboxÍlico e seu uso medicinal
DE112005003337T5 (de) 2005-01-25 2008-02-21 Merck Patent Gmbh Mesogene Verbindungen, Flüssigkristallmedium und Flüssigkristallanzeige
US7754703B2 (en) 2005-02-14 2010-07-13 University Of Virginia Patent Foundation Cycloalkane-containing sphingosine 1-phosphate agonists
US7605269B2 (en) 2005-03-23 2009-10-20 Actelion Pharmaceuticals Ltd. Thiophene derivatives as Sphingosine-1-phosphate-1 receptor agonists
KR20080002850A (ko) 2005-03-23 2008-01-04 액테리온 파마슈티칼 리미티드 신규한 티오펜 유도체
CA2602474C (en) 2005-03-23 2014-06-10 Actelion Pharmaceuticals Ltd Hydrogenated benzo (c) thiophene derivatives as immunomodulators
WO2006131336A1 (en) 2005-06-08 2006-12-14 Novartis Ag POLYCYCLIC OXADIAZOLES OR I SOXAZOLES AND THEIR USE AS SlP RECEPTOR LIGANDS
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
US7951794B2 (en) 2005-06-24 2011-05-31 Actelion Pharmaceuticals Ltd. Thiophene derivatives
US20070060573A1 (en) * 2005-08-10 2007-03-15 Lars Wortmann Acyltryptophanols
BRPI0615133A2 (pt) 2005-08-23 2011-05-03 Irm Llc compostos imunossupressores, composições farmacêuticas contendo os mesmos assim como referido uso
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
AR057894A1 (es) 2005-11-23 2007-12-26 Actelion Pharmaceuticals Ltd Derivados de tiofeno
EP1965807A4 (en) * 2005-11-23 2010-10-27 Epix Delaware Inc S1P RECEPTOR MODULATING COMPOUNDS AND THEIR USE
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
AU2007209051A1 (en) 2006-01-24 2007-08-02 Actelion Pharmaceuticals Ltd Novel pyridine derivatives
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
JP2009526073A (ja) 2006-02-09 2009-07-16 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 二環式スフィンゴシン−１−リン酸受容体アナログ
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
AU2007214434B2 (en) 2006-02-15 2012-06-14 Allergan, Inc. Indole-3-carboxylic acid amide, ester, thioamide and thiol ester compounds bearing aryl or heteroaryl groups having sphingosine-1-phosphate (S1P) receptor antagonist biological activity
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
KR20080096780A (ko) 2006-02-21 2008-11-03 유니버시티 오브 버지니아 페이턴트 파운데이션 Ｓ１ｐ 수용체 효능제로서의 페닐-시클로알킬 및 페닐-헤테로시클릭 유도체
US7649098B2 (en) 2006-02-24 2010-01-19 Lexicon Pharmaceuticals, Inc. Imidazole-based compounds, compositions comprising them and methods of their use
MX2008011615A (es) * 2006-03-14 2008-09-22 Amgen Inc Derivados de acidos carboxilicos biciclicos utiles para tratar trastornos metabolicos.
AU2007227274A1 (en) 2006-03-21 2007-09-27 Epix Delaware, Inc. S1P receptor modulating compounds
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
PL2003132T3 (pl) * 2006-04-03 2014-10-31 Astellas Pharma Inc Pochodne oksadiazolu jako agoniści S1P1
GB0607389D0 (en) 2006-04-12 2006-05-24 Novartis Ag Organic compounds
WO2007129473A1 (ja) 2006-05-09 2007-11-15 Daiichi Sankyo Company, Limited 二環性アリール誘導体
EP2258700A1 (en) 2006-05-09 2010-12-08 Pfizer Products Inc. Cycloalkylamino acid derivatives and pharmaceutical compositions thereof
WO2007129745A1 (ja) 2006-05-09 2007-11-15 Daiichi Sankyo Company, Limited ヘテロアリールアミド低級カルボン酸誘導体
EP2046766A1 (en) 2006-08-01 2009-04-15 Praecis Pharmaceuticals Incorporated Agonists of the sphingosine- 1- phosphate receptor (slp)
AR062156A1 (es) 2006-08-01 2008-10-22 Praecis Pharm Inc Compuestos agonistas y selectivos del receptor s1p-1
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
CA2659598A1 (en) 2006-08-08 2008-02-14 Kyorin Pharmaceutical Co., Ltd. Amino phosphate derivative and s1p receptor modulator having same as an active ingredient
EP2054377A1 (en) 2006-08-24 2009-05-06 Praecis Pharmaceuticals Incorporated Chemical compounds
JP2009269819A (ja) * 2006-08-25 2009-11-19 Asahi Kasei Pharma Kk アミン化合物
PT2069336E (pt) 2006-09-07 2013-03-07 Actelion Pharmaceuticals Ltd Derivados de piridin-4-ilo como agentes imunomoduladores
AR061841A1 (es) 2006-09-07 2008-09-24 Actelion Pharmaceuticals Ltd Derivados de tiofen-oxadiazoles, agonistas del receptor s1p1/edg1, composiciones farmaceuticas que los contienen y usos como agentes inmunomoduladores.
CA2662852A1 (en) 2006-09-07 2008-03-13 Allergan, Inc. Heteroaromatic compounds having sphingosine-1-phosphate (s1p) receptor agonist and/or antagonist biological activity
KR20090060333A (ko) 2006-09-08 2009-06-11 노파르티스 아게 림프구 상호작용에 의해 매개되는 질환의 치료에 유용한 ｎ-바이아릴 (헤테로)아릴술폰아미드 유도체
ES2393412T3 (es) 2006-09-21 2012-12-21 Actelion Pharmaceuticals Ltd. Derivados de fenilo y su uso como inmunomoduladores
EP2109364A4 (en) 2006-12-15 2010-04-14 Abbott Lab NOVEL OXADIAZONE COMPOUNDS
GB0625648D0 (en) 2006-12-21 2007-01-31 Glaxo Group Ltd Compounds
BRPI0720478A2 (pt) 2006-12-21 2014-01-14 Abbott Laboratoires Compostos agonistas e antagonistas do receptor esfingosina-1-fosfato
MX2009007334A (es) 2007-01-11 2009-07-15 Allergan Inc Compuestos de amida del acido indol-3-carboxilico 6-substituido que tienen actividad antagonista biologica del receptor esfingosina-1-fosfato (s1p).
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
BRPI0808789A2 (pt) 2007-03-16 2014-08-12 Actelion Pharmaceuticals Ltd Compostos e composição farmacêutica de derivados aminopiridina e uso destes
JP5191497B2 (ja) 2007-03-21 2013-05-08 エピックス ファーマシューティカルズ，インコーポレイテッド Ｓ１ｐ受容体調節化合物およびその使用
AU2008240773B2 (en) 2007-04-19 2013-10-03 Glaxo Group Limited Oxadiazole substituted indazole derivatives for use as sphingosine 1-phosphate (S1P) agonists
EP2014653A1 (en) 2007-06-15 2009-01-14 Bioprojet Novel dicarboxylic acid derivatives as S1P1 receptor agonists
WO2009011850A2 (en) 2007-07-16 2009-01-22 Abbott Laboratories Novel therapeutic compounds
WO2009019506A1 (en) 2007-08-03 2009-02-12 Astrazeneca Ab Heterocyclyc sulfonamides having edg-1 antagonistic activity
CN101790519B (zh) 2007-08-08 2013-10-16 默克雪兰诺有限公司 用于治疗多发性硬化症的结合于鞘氨醇1-磷酸(s1p)的6-氨基-嘧啶-4-羧酰胺衍生物及相关化合物
TW200930368A (en) 2007-11-15 2009-07-16 Astrazeneca Ab Bis-(sulfonylamino) derivatives in therapy
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
EP2252615A1 (en) * 2008-01-25 2010-11-24 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
EP3782991A1 (en) 2008-05-14 2021-02-24 The Scripps Research Institute Novel modulators of sphingosine phosphate receptors
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
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
HRP20160890T1 (hr) * 2008-08-27 2016-09-23 Arena Pharmaceuticals, Inc. Derivati supstituirane tricikličke kiseline kao agonisti s1p1-receptora korisni u liječenju autoimunih i upalnih poremećaja
PE20120578A1 (es) 2009-02-10 2012-06-17 Abbott Lab Agonistas y antagonistas del receptor de 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
US9216972B2 (en) 2009-10-29 2015-12-22 Bristol-Myers Squibb Company Tricyclic heterocyclic compounds
JP5856980B2 (ja) 2010-01-27 2016-02-10 アリーナ ファーマシューティカルズ， インコーポレイテッド （Ｒ）−２−（７−（４−シクロペンチル−３−（トリフルオロメチル）ベンジルオキシ）−１，２，３，４−テトラヒドロシクロペンタ［ｂ］インドール−３−イル）酢酸およびその塩の調製のためのプロセス
CN105503882B (zh) * 2010-03-03 2019-07-05 艾尼纳制药公司 制备s1p1受体调节剂及其晶体形式的方法
JP2013533286A (ja) 2010-07-30 2013-08-22 セントルイス ユニバーシティ 疼痛を治療する方法

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

Also Published As

Publication number Publication date
CA2733671A1 (en) 2010-03-11
ES2583630T3 (es) 2016-09-21
JP5726737B2 (ja) 2015-06-03
AU2009288738B9 (en) 2015-04-16
US8415484B2 (en) 2013-04-09
SMT201600318B (it) 2016-11-10
MX2011002199A (es) 2011-05-10
EA201170374A1 (ru) 2011-12-30
JP2012501327A (ja) 2012-01-19
US9108969B2 (en) 2015-08-18
EP2342205A1 (en) 2011-07-13
IL211107A0 (en) 2011-04-28
AU2009288738B2 (en) 2015-04-09
CN105816453B (zh) 2021-03-05
PT2342205T (pt) 2016-07-28
CN102197038A (zh) 2011-09-21
CN102197038B (zh) 2016-04-20
KR20110058849A (ko) 2011-06-01
IL233869A (en) 2015-05-31
BRPI0917923A2 (pt) 2019-09-10
HRP20160890T1 (hr) 2016-09-23
AU2009288738A1 (en) 2010-03-11
KR101800595B1 (ko) 2017-11-22
US20110160243A1 (en) 2011-06-30
BRPI0917923B1 (pt) 2022-04-05
NZ591001A (en) 2012-11-30
CA2733671C (en) 2018-01-02
JP2015110641A (ja) 2015-06-18
ZA201101524B (en) 2012-07-25
CN105816453A (zh) 2016-08-03
IL233869A0 (en) 2014-09-30
EP2342205B1 (en) 2016-04-20
US20150336966A1 (en) 2015-11-26
HK1158624A1 (zh) 2012-07-20
KR20170063992A (ko) 2017-06-08
PL2342205T4 (pl) 2016-12-30
SI2342205T1 (sl) 2016-09-30
US20130184307A1 (en) 2013-07-18
RS54970B1 (sr) 2016-11-30
CY1117830T1 (el) 2017-05-17
HUE031479T2 (en) 2017-07-28
PL2342205T3 (pl) 2016-12-30
EA036955B1 (ru) 2021-01-19

Similar Documents

Publication Publication Date Title
US20250074874A1 (en) SUBSTITUTED (1,2,3,4-TETRAHYDROCYCLOPENTA[b]INDOL-3-YL)ACETIC ACID DERIVATIVES USEFUL IN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISORDERS
EP2342205B1 (en) Substituted tricyclic acid derivatives as s1p1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
WO2009094157A1 (en) Dihydro- 1h- pyrrolo [1,2-a] indol-1-yl carboxylic derivatives which act as s1p1 agonists
WO2011005290A1 (en) Disubstituted oxadiazole derivatives useful in the treatment of autoimmune and inflammatory disorders
WO2009151621A1 (en) Substituted (1, 2, 4-0xadiaz0l-3-yl) indolin-1-yl carboxylic acid derivatives useful as s1p1 agonists
WO2011005295A1 (en) Modulators of the sphingosine-1-phosphate (s1p) receptor useful for the treatment of disorders related thereto
WO2009151626A1 (en) Substituted (1, 2, 4-0xadiaz0l-3-yl) indolin-1-yl carboxylic acid derivatives useful as s1p1 agonists
HK1158624B (en) Substituted tricyclic acid derivatives as s1p1 receptor agonists useful in the treatment of autoimmune and inflammatory disorders
HK1157333B (en) Substituted 1,2,3,4- tetrahydrocyclopenta[b]indol-3-yl) acetic acid derivatives useful in the treatment of autoimmune and inflammatory disorders

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200980142790.4

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09789210

Country of ref document: EP

Kind code of ref document: A1

DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)
WWE Wipo information: entry into national phase

Ref document number: 211107

Country of ref document: IL

WWE Wipo information: entry into national phase

Ref document number: 591001

Country of ref document: NZ

Ref document number: 2009288738

Country of ref document: AU

ENP Entry into the national phase

Ref document number: 2733671

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 13060477

Country of ref document: US

ENP Entry into the national phase

Ref document number: 2011524992

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: MX/A/2011/002199

Country of ref document: MX

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2009288738

Country of ref document: AU

Date of ref document: 20090826

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2106/DELNP/2011

Country of ref document: IN

Ref document number: 2009789210

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 201170374

Country of ref document: EA

ENP Entry into the national phase

Ref document number: 20117006863

Country of ref document: KR

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 233869

Country of ref document: IL

WWE Wipo information: entry into national phase

Ref document number: P-2016/0577

Country of ref document: RS

ENP Entry into the national phase

Ref document number: PI0917923

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20110228

WWW Wipo information: withdrawn in national office

Ref document number: 591001

Country of ref document: NZ