Nothing Special   »   [go: up one dir, main page]

BRPI0209249B8 - agonista de receptor de pgi2, inibidor de agregacao de plaqueta, agentes terapeuticos e derivados de composto heterociclico - Google Patents

agonista de receptor de pgi2, inibidor de agregacao de plaqueta, agentes terapeuticos e derivados de composto heterociclico

Info

Publication number
BRPI0209249B8
BRPI0209249B8 BRPI0209249A BR0209249A BRPI0209249B8 BR PI0209249 B8 BRPI0209249 B8 BR PI0209249B8 BR PI0209249 A BRPI0209249 A BR PI0209249A BR 0209249 A BR0209249 A BR 0209249A BR PI0209249 B8 BRPI0209249 B8 BR PI0209249B8
Authority
BR
Brazil
Prior art keywords
receptor agonist
heterocyclic compound
therapeutic agents
platelet aggregation
compound derivatives
Prior art date
Application number
BRPI0209249A
Other languages
English (en)
Other versions
BR0209249A (pt
BRPI0209249B1 (pt
Inventor
Kuwano Keiichi
Hamamoto Taisuke
Asaki Tetsuo
Original Assignee
Nippon Shinyaku Co Ltd
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=18978246&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=BRPI0209249(B8) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Nippon Shinyaku Co Ltd filed Critical Nippon Shinyaku Co Ltd
Publication of BR0209249A publication Critical patent/BR0209249A/pt
Publication of BRPI0209249B1 publication Critical patent/BRPI0209249B1/pt
Publication of BRPI0209249B8 publication Critical patent/BRPI0209249B8/pt

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4418Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965Non-condensed pyrazines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965Non-condensed pyrazines
    • A61K31/497Non-condensed pyrazines containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/53Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/08Bronchodilators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/08Antiallergic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/08Vasodilators for multiple indications
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72Nitrogen atoms
    • C07D213/74Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32One oxygen, sulfur or nitrogen atom
    • C07D239/42One nitrogen atom
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D241/00Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/12Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D241/00Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/18Oxygen or sulfur atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D241/00Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/20Nitrogen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D253/00Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
    • C07D253/02Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
    • C07D253/061,2,4-Triazines
    • C07D253/0651,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
    • C07D253/071,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members with hetero atoms, or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Pulmonology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Dermatology (AREA)
  • Vascular Medicine (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Obesity (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyridine Compounds (AREA)

Abstract

"derivados de composto heterocíclico e medicamentos". a presente invenção provê um composto que é útil como um agonista de receptor de pgi~ 2~, e uma composição farmacêutica. a presente invenção é direcionada a uma composição farmacêutica compreendendo um composto representado pela seguinte fórmula [1]: -conh-so~ 2~-r^ 910^ (22 z) (r^ 1^ e r^ 2^ são idênticos ou diferentes e cada um representa arila opcionalmente substituída, y representa n ou ch, z representa n ou ch, a representa nh, nr^ 5^, o, s, ou etileno, r^ 5^ representa alquila, d representa alquileno ou alquenilono, e representa fenileno ou ligação simples, g representa o, s, ou ch~ 2~, r^ 3^ e r^ 4^ são idênticos ou diferentes e cada um representa hidrogênio ou alquil, q representa carbóxi, alcóxi carbonila, tetrazolila, carbamoíla, ou n-(alquil sulfonil) carbamoíla, ou um seu sal farmaceuticamente aceitável como um ingrediente ativo.
BRPI0209249A 2001-04-26 2002-04-25 agonista de receptor de pgi2, inibidor de agregacao de plaqueta, agentes terapeuticos e derivados de composto heterociclico BRPI0209249B8 (pt)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2001129765 2001-04-26
PCT/JP2002/004118 WO2002088084A1 (fr) 2001-04-26 2002-04-25 Derives de composes heterocycliques et medicaments

Publications (3)

Publication Number Publication Date
BR0209249A BR0209249A (pt) 2004-06-08
BRPI0209249B1 BRPI0209249B1 (pt) 2016-04-26
BRPI0209249B8 true BRPI0209249B8 (pt) 2021-05-25

Family

ID=18978246

Family Applications (1)

Application Number Title Priority Date Filing Date
BRPI0209249A BRPI0209249B8 (pt) 2001-04-26 2002-04-25 agonista de receptor de pgi2, inibidor de agregacao de plaqueta, agentes terapeuticos e derivados de composto heterociclico

Country Status (19)

Country Link
US (1) US7205302B2 (pt)
EP (1) EP1400518B1 (pt)
JP (1) JP4479152B2 (pt)
KR (1) KR100921760B1 (pt)
CN (1) CN1301973C (pt)
BE (1) BE2016C051I2 (pt)
BR (1) BRPI0209249B8 (pt)
CA (1) CA2445344C (pt)
DE (1) DE60217674T2 (pt)
DK (1) DK1400518T3 (pt)
ES (1) ES2276931T3 (pt)
FR (1) FR16C0042I2 (pt)
LU (1) LU93266I2 (pt)
MX (1) MXPA03009800A (pt)
NL (1) NL300836I2 (pt)
PT (1) PT1400518E (pt)
RU (1) RU2283835C3 (pt)
TW (1) TWI316055B (pt)
WO (1) WO2002088084A1 (pt)

Families Citing this family (85)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7326706B2 (en) 2003-08-15 2008-02-05 Bristol-Myers Squibb Company Pyrazine modulators of cannabinoid receptors
WO2005037199A2 (en) 2003-10-10 2005-04-28 Bristol-Myers Squibb Company Pyrazole derivatives as cannabinoid receptor modulators
EP1763382A1 (fr) * 2004-04-22 2007-03-21 L'oreal Compose 2-oxy-acetamide ses utilisations et compositions pour stimuler ou induire la pousse des fibres keratiniques et/ou freiner leur chute
FR2869224B1 (fr) * 2004-04-22 2006-06-09 Oreal Compose 2-oxy-acetamide, ses utilisations et compositions pour stimuler ou induire la pousse des fibres keratiniques et/ou freiner leur chute
AU2006236387A1 (en) * 2005-04-18 2006-10-26 Neurogen Corporation Subtituted heteroaryl CB1 antagonists
CN104761509A (zh) 2008-02-28 2015-07-08 日本新药株式会社 纤维化抑制剂
KR20220031743A (ko) * 2008-03-18 2022-03-11 아레나 파마슈티칼스, 인크. 프로스타시클린 (pgi2) 수용체와 관련된 장애의 치료에 유용한 상기 수용체의 조절제
WO2009154246A1 (ja) * 2008-06-19 2009-12-23 日本新薬株式会社 勃起不全治療剤
WO2009157397A1 (ja) * 2008-06-23 2009-12-30 日本新薬株式会社 非ステロイド性抗炎症剤投与に伴う腸管傷害治療剤
JP5527206B2 (ja) 2008-06-23 2014-06-18 日本新薬株式会社 炎症性腸疾患治療剤
DK2292231T3 (en) * 2008-06-23 2015-12-14 Nippon Shinyaku Co Ltd THERAPEUTIC AGENT FOR SPINAL CHANNEL STENOSIS
EP2305653B9 (en) 2008-07-23 2015-06-24 Toray Industries, Inc. Therapeutic agent for chronic renal failure
AR073031A1 (es) 2008-08-13 2010-10-06 Actelion Pharmaceuticals Ltd Composiciones terapeuticas que contienen macitentan
EP3275871B1 (en) * 2009-06-26 2020-01-15 Nippon Shinyaku Co., Ltd. Crystals
WO2011024874A1 (ja) * 2009-08-26 2011-03-03 日本新薬株式会社 塩基付加塩
CN102655866B (zh) 2009-11-13 2013-11-13 东丽株式会社 糖尿病的治疗或预防药
WO2011095625A1 (en) 2010-02-05 2011-08-11 Heptares Therapeutics Limited 1,2,4-triazine-4-amine derivatives
BR112013000946B1 (pt) * 2010-07-14 2020-09-08 Novartis Ag Compostos heterocíclicos agonistas de receptor de ip, seus usos, composição e combinação farmacêuticas
CN104053659B (zh) 2012-01-13 2016-11-09 诺华股份有限公司 用于治疗肺动脉高压(pah)及相关病症的作为ip 受体激动剂的稠合的吡咯类
US9181186B2 (en) 2012-02-13 2015-11-10 Takeda Pharmaceutical Company Limited Aromatic ring compound
JP6095580B2 (ja) 2012-02-13 2017-03-15 武田薬品工業株式会社 芳香環化合物
EP2913047B1 (en) 2012-10-29 2019-05-08 Cardio Incorporated Pulmonary disease-specific therapeutic agent
US9604981B2 (en) 2013-02-13 2017-03-28 Novartis Ag IP receptor agonist heterocyclic compounds
JP6449166B2 (ja) 2013-10-15 2019-01-09 小野薬品工業株式会社 薬剤溶出性ステントグラフト
CN103588598B (zh) * 2013-11-20 2015-06-17 苏州大学 一种制备2-烯醛衍生物的方法
CN104829465B (zh) * 2015-02-13 2018-04-27 普济生物科技(台州)有限公司 一种4-异丙氨基-1-丁醇的制备方法
CN106279047B (zh) 2015-05-13 2019-05-03 普济生物科技(台州)有限公司 一种前列环素受体激动剂的制备方法
WO2016193994A1 (en) 2015-05-29 2016-12-08 Megafine Pharma (P) Ltd. Amorphous selexipag and process for preparation thereof
CN106467496B (zh) * 2015-08-14 2020-12-08 苏州国匡医药科技有限公司 4-[(5,6-二苯基哌嗪-2-基)(异丙基)胺基]-1-丁醇的制备方法
ES2762943T3 (es) 2015-09-03 2020-05-26 Teva Pharmaceuticals Int Gmbh Formas de Selexipag en estado sólido
WO2017042731A1 (en) 2015-09-10 2017-03-16 Lupin Limited Amorphous form of selexipag and solid dispersion thereof
WO2017042828A2 (en) 2015-09-10 2017-03-16 Megafine Pharma (P) Ltd. Process for the preparation of selexipag and intermediates thereof
WO2017060827A1 (en) 2015-10-07 2017-04-13 Lupin Limited An imrpoved process for the preparation of selexipag or its pharmaceutically acceptable salts
AU2016366073B2 (en) 2015-12-02 2021-08-26 Nippon Shinyaku Co., Ltd. Pharmaceutical composition containing 2-{4-[N-(5,6- diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N- (methylsulfonyl)acetamide
WO2017109772A1 (en) * 2015-12-20 2017-06-29 Mapi Pharma Ltd. Amorphous form of selexipag
JP7149073B2 (ja) * 2015-12-23 2022-10-06 コモンウェルス サイエンティフィック アンド インダストリアル リサーチ オーガナイゼーション 化合物
EP3192502A1 (en) 2016-01-15 2017-07-19 Sandoz Ag Pharmaceutical composition of selexipag
US10815204B2 (en) * 2016-04-01 2020-10-27 Honour (R&D) Process for the preparation of diphenylpyrazine derivatives
CN107286104A (zh) * 2016-04-12 2017-10-24 常州方楠医药技术有限公司 一种赛乐西帕与药用辅料的固体分散体及其制备方法
CN105949135A (zh) * 2016-05-10 2016-09-21 湖南欧亚生物有限公司 一种赛乐西帕的合成方法
WO2018008042A1 (en) * 2016-07-05 2018-01-11 Maithri Drugs Private Limited Novel process for the preparation of 2-{4-[(5,6-diphenyl pyrazin-2-yl)(isopropyl)amino]butoxy}-n-(methylsulfonyl)acetamide and novel polymorphs thereof
WO2018015974A1 (en) 2016-07-20 2018-01-25 Mylan Laboratories Limited Polymorphic forms and amorphous solid dispersion of selexipag
WO2018015975A1 (en) * 2016-07-22 2018-01-25 Sun Pharmaceutical Industries Limited Amorphous solid dispersion of selexipag
WO2018022704A1 (en) 2016-07-26 2018-02-01 Teva Pharmaceuticals International Gmbh Crystalline form vi of selexipag
WO2018021520A1 (ja) 2016-07-29 2018-02-01 東レ株式会社 グアニジン誘導体及びその医薬用途
CN109563055B (zh) * 2016-07-29 2021-12-24 成都苑东生物制药股份有限公司 氨基吡嗪类化合物或盐、异构体、其制备方法及用途
CN106316967B (zh) * 2016-08-19 2019-02-05 上海艾康睿医药科技有限公司 西里帕格中间体及西里帕格的制备方法
WO2018078383A1 (en) 2016-10-27 2018-05-03 Cipla Limited Pharmaceutical composition comprising amorphous selexipag
US10912778B2 (en) 2016-12-14 2021-02-09 Respira Therapeutics, Inc. Methods for treatment of pulmonary hypertension
EP3977985B1 (en) 2017-03-01 2023-09-06 Arena Pharmaceuticals, Inc. Compositions comprising pgi2-receptor agonists and processes for the preparation thereof
JOP20190204A1 (ar) 2017-03-08 2019-09-05 Actelion Pharmaceuticals Ltd تركيبة صيدلانية تشتمل على سيليكسيباغ
CN107365275B (zh) * 2017-06-14 2020-07-03 杭州华东医药集团新药研究院有限公司 高纯度的赛乐西帕
EP3658187A1 (en) 2017-07-27 2020-06-03 Allergan, Inc. Prostacyclin receptor agonists for reduction of body fat
JP7160043B2 (ja) 2017-09-28 2022-10-25 日本新薬株式会社 結晶
US10407396B2 (en) * 2017-11-16 2019-09-10 Apotex Inc. Crystalline form of selexipag
CA3082009A1 (en) 2017-11-16 2019-05-23 Nippon Shinyaku Co., Ltd. Controlled-release preparation
JP2021512902A (ja) * 2018-02-07 2021-05-20 メッドシャイン ディスカバリー インコーポレイテッド プロスタサイクリン受容体アゴニスト
RU2020130411A (ru) 2018-02-21 2022-03-21 Ниппон Синяку Ко., Лтд. Гранулярная композиция, способ получения гранулярной композиции и способ улучшения свойств растворения для гранулярной композиции
CN108558653A (zh) * 2018-05-14 2018-09-21 湖南华腾制药有限公司 赛乐西帕中间体及赛乐西帕的制备方法
CN108774183A (zh) * 2018-08-03 2018-11-09 成都苑东生物制药股份有限公司 一种乙二醇类化合物的制备方法
CN108863955B (zh) * 2018-08-03 2021-08-13 成都苑东生物制药股份有限公司 二苯基吡嗪类化合物或其药学上可接受的盐、异构体及其制备方法和用途
CN109125325B (zh) * 2018-09-25 2021-05-25 中国人民解放军总医院 前列环素受体激动剂的医药用途
JP2022532076A (ja) 2019-05-06 2022-07-13 アクテリオン ファーマシューティカルズ リミテッド サルコイドーシス関連肺高血圧症の治療方法
JP2022533394A (ja) 2019-05-21 2022-07-22 アクテリオン ファーマシューティカルズ リミテッド 肺動脈性肺高血圧症の治療を受けている患者のセレキシパグへの移行方法
JP2022536623A (ja) 2019-06-11 2022-08-18 アクテリオン ファーマシューティカルズ リミテッド 肺動脈性肺高血圧症の治療方法
CN114206842A (zh) * 2019-08-19 2022-03-18 日本新药株式会社
JOP20220093A1 (ar) 2019-10-23 2023-01-30 Actelion Pharmaceuticals Ltd تركيبة صيدلانية تشتمل على سيليكسيباغ
BR112022010311A2 (pt) 2019-11-29 2022-08-16 Actelion Pharmaceuticals Ltd Métodos de tratamento de hipertensão arterial pulmonar
JP2023507626A (ja) 2019-12-16 2023-02-24 テナックス・セラピューティクス,インコーポレイテッド 駆出率が保たれた心不全を伴う肺高血圧症(PH-HF-pEF)を治療するためのレボシメンダン
EP4096643A1 (en) 2020-01-31 2022-12-07 Actelion Pharmaceuticals Ltd Controlled release selexipag composition
WO2021156227A1 (en) 2020-02-03 2021-08-12 Actelion Pharmaceuticals Ltd Methods of treating and assessing pulmonary arterial hypertension with selexipag
WO2022106621A1 (en) 2020-11-20 2022-05-27 Actelion Pharmaceuticals Ltd Selexipag for use via intracolonic administration
TW202239408A (zh) 2021-01-29 2022-10-16 瑞士商艾克泰聯製藥有限公司 包含二苯基吡𠯤衍生物的醫藥組成物
TW202241425A (zh) 2021-01-29 2022-11-01 瑞士商艾克泰聯製藥有限公司 用於製造二苯基吡𠯤衍生物之程序
KR20230165247A (ko) 2021-03-31 2023-12-05 니뽄 신야쿠 가부시키가이샤 보행 장애 치료제
JP7010404B1 (ja) 2021-03-31 2022-02-10 日本新薬株式会社 歩行障害治療剤
WO2022238375A1 (en) 2021-05-11 2022-11-17 Actelion Pharmaceuticals Ltd Methods of treating pulmonary hypertension
CN118206499A (zh) * 2021-11-29 2024-06-18 郑州大学 一种2,3,5-三取代吡嗪类化合物及其制备方法和应用
WO2023131608A1 (en) 2022-01-04 2023-07-13 Actelion Pharmaceuticals Ltd Controlled release compositions
IL314717A (en) 2022-02-15 2024-10-01 United Therapeutics Corp Crystalline prostacyclin (IP) receptor agonist and uses thereof
WO2023214059A1 (en) 2022-05-06 2023-11-09 Actelion Pharmaceuticals Ltd Diphenylpyrazine compounds as prodrugs
WO2024017964A1 (en) 2022-07-20 2024-01-25 Actelion Pharmaceuticals Ltd Injectable pharmaceutical composition comprising a diphenylpyrazine derivative
TW202426428A (zh) * 2022-12-20 2024-07-01 大陸商長風藥業股份有限公司 二苯基吡嗪類衍生物、其製備方法及應用
WO2024133620A1 (en) 2022-12-22 2024-06-27 Actelion Pharmaceuticals Ltd In vitro dissolution test
WO2024194449A1 (en) 2023-03-23 2024-09-26 Actelion Pharmaceuticals Ltd Pharmaceutical composition comprising a diphenylpyrazine derivative

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5416491A (en) 1977-05-17 1979-02-07 Diamond Shamrock Corp Substituted 1*2*44triazines having pharmacological action
US4513135A (en) * 1982-03-05 1985-04-23 Eli Lilly And Company Diaryl-pyrazine derivatives affecting GABA binding
FR2665159B1 (fr) 1990-07-24 1992-11-13 Rhone Poulenc Sante Nouveaux derives de la pyridine et de la quinoleine, leur preparation et les compositions pharmaceutiques qui les contiennent.
JPH06501926A (ja) * 1990-08-06 1994-03-03 藤沢薬品工業株式会社 複素環式化合物
US5219510A (en) * 1990-09-26 1993-06-15 Eastman Kodak Company Method of manufacture of cellulose ester film
JP3169413B2 (ja) * 1992-01-31 2001-05-28 エーザイ株式会社 イミダゾール誘導体
JPH0733752A (ja) * 1993-07-16 1995-02-03 Sankyo Co Ltd ジフェニルピラジン誘導体及び除草剤
AUPP003297A0 (en) * 1997-10-27 1997-11-20 Fujisawa Pharmaceutical Co., Ltd. 4,5-diaryloxazole compounds
AUPQ253199A0 (en) * 1999-08-30 1999-09-23 Fujisawa Pharmaceutical Co., Ltd. Non-prostanoid prostaglandin I2-agonist

Also Published As

Publication number Publication date
RU2283835C2 (ru) 2006-09-20
BE2016C051I2 (pt) 2021-07-19
DE60217674D1 (de) 2007-03-08
ES2276931T3 (es) 2007-07-01
PT1400518E (pt) 2007-03-30
CN1301973C (zh) 2007-02-28
EP1400518B1 (en) 2007-01-17
CA2445344C (en) 2011-07-26
KR20040015174A (ko) 2004-02-18
US7205302B2 (en) 2007-04-17
FR16C0042I1 (fr) 2016-12-09
MXPA03009800A (es) 2004-01-29
KR100921760B1 (ko) 2009-10-15
CA2445344A1 (en) 2002-11-07
RU2003134190A (ru) 2005-06-10
DK1400518T3 (da) 2007-03-26
JPWO2002088084A1 (ja) 2004-09-09
LU93266I2 (fr) 2016-12-19
BR0209249A (pt) 2004-06-08
TWI316055B (pt) 2009-10-21
JP4479152B2 (ja) 2010-06-09
NL300836I2 (pt) 2016-11-16
US20040102436A1 (en) 2004-05-27
EP1400518A1 (en) 2004-03-24
EP1400518A4 (en) 2005-04-20
WO2002088084A1 (fr) 2002-11-07
CN1516690A (zh) 2004-07-28
RU2283835C3 (ru) 2021-02-15
DE60217674T2 (de) 2007-10-11
FR16C0042I2 (fr) 2017-03-17
BRPI0209249B1 (pt) 2016-04-26

Similar Documents

Publication Publication Date Title
BRPI0209249B8 (pt) agonista de receptor de pgi2, inibidor de agregacao de plaqueta, agentes terapeuticos e derivados de composto heterociclico
BR9907040A (pt) Composto, composição farmacêutica, e, processos para tratar ou prevenir condições causadas pela adesão de células mediada por alfa4 em um paciente e para preparar o composto
DE60043349D1 (de) Chinazolin-derivate und ihre verwendung als arzneimittel
EA200301306A1 (ru) Производные 1-фенилсульфонил-1,3-дигидро-2h-индол-2-она, их получение и их терапевтическое применение
AR056215A1 (es) Derivados de indol como inhibidores de la proteina activadora de 5-lipoxigenasa (flap), composiciones farmaceuticas que los comprenden y su uso en el tratamiento de trastornos respiratorios e inflamatorios
DE69118082D1 (de) Imidazolderivate, starke und selektive Angiotensin-II-Rezeptor-Antagonisten
PT719253E (pt) Piperidinas 3-amino-5-carboxi-substituidas e pirrolidinas 3-amino-4-carboxi-substituidas como antagonistas de taquicinina
DK0976748T3 (da) Pyrrolidinderivater med phospholispase A2-hæmmende aktivitet
HK1126216A1 (en) 2,4,5-triphenyl imidazoline derivatives as inhibitors of the interaction between p53 and mdm2 proteins for use as anticancer agents
EP1939175A4 (en) SULFONAMIDE DERIVATIVITY WITH PGD2 RECEPTOR ANTAGONISTIC EFFECT
BR0012697A (pt) Inibidores da diferenciação de th2
FR2838439B1 (fr) Derives de terphenyle, leur preparation, les compositions pharmaceutqiues en contenant
BR0306150A (pt) Composto, uso de um composto, e, composição farmacêutica
EP1302458A4 (en) ESTERDERIVATE
NO20072515L (no) 2-amido-4-fenyltnazolderivater, fremstilling og terapeutsik anvendelse derav
TW200732309A (en) Fused heterocyclic derivative, medicinal composition containing the same, and medicinal use thereof
ATE132140T1 (de) Benzo-annellierte-n-enthaltende heterocyclische derivate
DE69524246D1 (de) 1,2,3,4-Tetrahydroquinoxalindion Derivate und ihre Verwendung als Glutamat Rezeptor Antagonisten
BR0213464A (pt) Derivados de 3-azabiciclo[3.1.0]hexano como antagonistas receptores de opióide
ATE377602T1 (de) Morphinanderivate und ihre medizinische anwendung
TR200002481T2 (tr) Muskarinik Reseptör antegonistleri olarak 2-ariletil-(piperidin-4-ilmetil) amin türevleri
AR040126A1 (es) Compuesto de fenilsulfonilo, composicion farmaceutica que lo comprende y su uso para la elaboracion de un medicamento
SE0201194D0 (sv) New compounds
BR0309558A (pt) Derivados de quinazolina e medicamentos
NO20070157L (no) Substituerte diketopiperaziner som oksytocinantagonister

Legal Events

Date Code Title Description
B06F Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]
B07D Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]
B08F Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette]

Free format text: PAGAR RESTAURACAO.

B08H Application fees: decision cancelled [chapter 8.8 patent gazette]

Free format text: REFERENTE AO DESPACHO 8.6 PUBLICADO NA RPI 2260 DE 29/04/2014.

B07E Notification of approval relating to section 229 industrial property law [chapter 7.5 patent gazette]

Free format text: NOTIFICACAO DE ANUENCIA RELACIONADA COM O ART 229 DA LPI

B07A Application suspended after technical examination (opinion) [chapter 7.1 patent gazette]
B06A Patent application procedure suspended [chapter 6.1 patent gazette]
B09A Decision: intention to grant [chapter 9.1 patent gazette]
B16A Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]

Free format text: PRAZO DE VALIDADE: 10 (DEZ) ANOS CONTADOS A PARTIR DE 26/04/2016, OBSERVADAS AS CONDICOES LEGAIS.

B16C Correction of notification of the grant [chapter 16.3 patent gazette]

Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 25/04/2002 OBSERVADAS AS CONDICOES LEGAIS. PATENTE CONCEDIDA CONFORME ADI 5.529/DF

B22O Other matters related to patents and certificates of addition of invention: legal action concerning patent

Free format text: INPI NO 52402.001484/2022-07 ORIGEM: 2A VARA FEDERAL CIVEL DA SJDF (TRF1) PROCESSO NO: 52400.129576/2014-52 SUBJUDICE COM PEDIDO DE ANTECIPACAO DE TUTELA AUTOR: NIPPON SHINYAKU CO., LTD. REU(S): INSTITUTO NACIONAL DA PROPRIEDADE INDUSTRIAL ? INPI

B19A Notification of judicial decision: notification of judicial decision

Free format text: PROCESSO INPI NO 52402.001484/2022-07 PROCESSO JUDICIAL: 1004522-04.2022.4.01.3400 NUP: 00424.030538/2022-81 (REF. 1004522-04.2022.4.01.3400) POLO ATIVO: NIPPON SHINYAKU CO., LTD. POLO PASSIVO:INSTITUTO NACIONAL DA PROPRIEDADE INDUSTRIAL - INPI E OUTROS. DECISAO: "PELO EXPOSTO, AD CAUTELAM, DEFIRO O PEDIDO DE TUTELA DE URGENCIA PARA DETERMINAR QUE A REQUERIDA SUSPENDA OS EFEITOS DO DESPACHO 16.3 DO INPI, PUBLICADO NA RPI DE 25.05.2021, QUE NOTICIOU O TERMINO DO PRAZO DA PATENTE PI0209249-2 PARA O DIA 25.04.2022.

B16B Notification of grant cancelled [chapter 16.2 patent gazette]

Free format text: ANULADA A PUBLICACAO CODIGO 16.3 NA RPI NO 2629 DE 25/05/2021 POR MOTIVO DO PROCESSO INPI NO 52402.001484/2022-07 PROCESSO JUDICIAL: 1004522-04.2022.4.01.3400 NUP: 00424.030538/2022-81 (REF. 1004522-04.2022.4.01.3400) POLO ATIVO: NIPPON SHINYAKU CO., LTD. POLO PASSIVO:INSTITUTO NACIONAL DA PROPRIEDADE INDUSTRIAL - INPI E OUTROS. DECISAO: PELO EXPOSTO, AD CAUTELAM, DEFIRO O PEDIDO DE TUTELA DE URGENCIA PARA DETERMINAR QUE A REQUERIDA SUSPENDA OS EFEITOS DO DESPACHO 16.3 DO INPI, PUBLICADO NA RPI DE 25.05.2021, QUE NOTICIOU O TERMINO DO PRAZO DA PATENTE PI0209249-2 PARA O DIA 25.04.2022.

B16B Notification of grant cancelled [chapter 16.2 patent gazette]

Free format text: ANULADA A PUBLICACAO CODIGO 16.2 NA RPI NO 2680 DE 17/05/2022 POR TER SIDO INDEVIDA.

B19A Notification of judicial decision: notification of judicial decision

Free format text: PROCESSO INPI NO 52402.001484/2022-07 SECAO JUDICIARIA DO DISTRITO FEDERAL 2A VARA FEDERAL CIVEL DA SJDF SENTENCA TIPO "A" PROCESSO: 1004522-04.2022.4.01.3400 PROCEDIMENTO COMUM CIVEL (7) POLO ATIVO: AUTOR: NIPPON SHINYAKU CO., LTD. POLO PASSIVO: REU: INSTITUTO NACIONAL DA PROPRIEDADE INDUSTRIAL ? INPI SENTENCA: REVOGO A DECISAO LIMINAR QUE DEFERIU A TUTELA DE URGENCIA PELAS RAZOES PRECEDENTES, E JULGO IMPROCEDENTES OS PEDIDOS APRESENTADOS. PELO EXPOSTO, JULGO IMPROCEDENTES OS PEDIDOS, NOS TERMOS DO ART. 487, I, DO CPC, E DETERMINO O TERMINO DO PRAZO DA PATENTE PI 0209249-2.