WO2013015661A3 - Novel prodrugs of 5-(2,4-dihydroxy-5-isopropylphenyl)-n-ethyl-4-(5-methyl1-1,2,4-oxadiazol-3-yl)isoxazole-3-carboxamide - Google Patents

Novel prodrugs of 5-(2,4-dihydroxy-5-isopropylphenyl)-n-ethyl-4-(5-methyl1-1,2,4-oxadiazol-3-yl)isoxazole-3-carboxamide Download PDF

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Publication number
WO2013015661A3
WO2013015661A3 PCT/KR2012/006043 KR2012006043W WO2013015661A3 WO 2013015661 A3 WO2013015661 A3 WO 2013015661A3 KR 2012006043 W KR2012006043 W KR 2012006043W WO 2013015661 A3 WO2013015661 A3 WO 2013015661A3
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
methyl1
isopropylphenyl
oxadiazol
Prior art date
Application number
PCT/KR2012/006043
Other languages
French (fr)
Other versions
WO2013015661A2 (en
Inventor
Jae-Hoon Kang
Hong-Sub Lee
Jin-Sun Kwon
Joon-Tae Park
Jin-Ah Jeong
Sung-Wook Kwon
Original Assignee
Ildong Pharm 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
Application filed by Ildong Pharm Co.,Ltd. filed Critical Ildong Pharm Co.,Ltd.
Priority claimed from KR1020120082521A external-priority patent/KR20130018548A/en
Publication of WO2013015661A2 publication Critical patent/WO2013015661A2/en
Publication of WO2013015661A3 publication Critical patent/WO2013015661A3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

The present invention relates to the novel compound of Formula I. The compound of Formula I are used as a prodrug of the parent compound, Formula II, and have valuable pharmacological properties. The compound of Formula I have improved solubility by 1,000~20,000 times or more, and increased bioavailability compared to those of the compound of Formula II. Furthermore, they can be absorbed into the body with increased concentration by improved value of AUC0-120min and Cmax, more by 3~5 times and 10~20 times respectively compared to the compound of Formula II. Thus, those improved pharmacokinetic properties can be used very effectively to treat various diseases by inhibition of HSP90 activity, especially for ovarian and gastric cancer.
PCT/KR2012/006043 2011-07-28 2012-07-27 Novel prodrugs of 5-(2,4-dihydroxy-5-isopropylphenyl)-n-ethyl-4-(5-methyl1-1,2,4-oxadiazol-3-yl)isoxazole-3-carboxamide WO2013015661A2 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20110074867 2011-07-28
KR10-2011-0074867 2011-07-28
KR10-2012-0082521 2012-07-27
KR1020120082521A KR20130018548A (en) 2011-07-28 2012-07-27 Novel prodrugs of 5-(2,4-dihydroxy-5-isopropylphenyl)-n-ethyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)isoxazole-3-carboxamide

Publications (2)

Publication Number Publication Date
WO2013015661A2 WO2013015661A2 (en) 2013-01-31
WO2013015661A3 true WO2013015661A3 (en) 2013-05-02

Family

ID=47601688

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2012/006043 WO2013015661A2 (en) 2011-07-28 2012-07-27 Novel prodrugs of 5-(2,4-dihydroxy-5-isopropylphenyl)-n-ethyl-4-(5-methyl1-1,2,4-oxadiazol-3-yl)isoxazole-3-carboxamide

Country Status (1)

Country Link
WO (1) WO2013015661A2 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20150010793A (en) 2012-05-25 2015-01-28 버그 엘엘씨 Methods of treating a metabolic syndrome by modulating heat shock protein (hsp) 90-beta
WO2015188198A2 (en) 2014-06-06 2015-12-10 Berg Llc Methods of treating a metabolic syndrome by modulating heat shock protein (hsp) 90-beta
EP3686182A4 (en) 2017-09-22 2021-06-09 Sumitomo Dainippon Pharma Co., Ltd. Chemically activated water-soluble prodrug

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004072051A1 (en) * 2003-02-11 2004-08-26 Vernalis (Cambridge) Limited Isoxazole compounds as inhibitors of heat shock proteins
WO2008104595A1 (en) * 2007-03-01 2008-09-04 Novartis Ag Acid addition salts, hydrates and polymorphs of 5-(2,4-dihydroxy-5-isopropyl-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide and formulations comprising these forms
WO2009036012A1 (en) * 2007-09-10 2009-03-19 Curis, Inc. Hsp90 inhibitors containing a zinc binding moiety
WO2011102660A2 (en) * 2010-02-17 2011-08-25 Ildong Pharm Co., Ltd. A novel 5-membered heterocycle derivatives and manufacturing process thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004072051A1 (en) * 2003-02-11 2004-08-26 Vernalis (Cambridge) Limited Isoxazole compounds as inhibitors of heat shock proteins
WO2008104595A1 (en) * 2007-03-01 2008-09-04 Novartis Ag Acid addition salts, hydrates and polymorphs of 5-(2,4-dihydroxy-5-isopropyl-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide and formulations comprising these forms
WO2009036012A1 (en) * 2007-09-10 2009-03-19 Curis, Inc. Hsp90 inhibitors containing a zinc binding moiety
WO2011102660A2 (en) * 2010-02-17 2011-08-25 Ildong Pharm Co., Ltd. A novel 5-membered heterocycle derivatives and manufacturing process thereof

Also Published As

Publication number Publication date
WO2013015661A2 (en) 2013-01-31

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