WO2008156701A3 - Hydroxamate inhibitors of insulin-degrading enzyme and uses thereof - Google Patents

Hydroxamate inhibitors of insulin-degrading enzyme and uses thereof Download PDF

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Publication number
WO2008156701A3
WO2008156701A3 PCT/US2008/007447 US2008007447W WO2008156701A3 WO 2008156701 A3 WO2008156701 A3 WO 2008156701A3 US 2008007447 W US2008007447 W US 2008007447W WO 2008156701 A3 WO2008156701 A3 WO 2008156701A3
Authority
WO
WIPO (PCT)
Prior art keywords
insulin
degrading enzyme
hydroxamate inhibitors
hydroxamate
inhibitors
Prior art date
Application number
PCT/US2008/007447
Other languages
French (fr)
Other versions
WO2008156701A2 (en
Inventor
Malcolm A Leissring
Dennis Selkoe
Gregory D Cuny
Sungwoon Choi
Ross L Stein
Benjamin Turk
Lewis C Cantley
Original Assignee
Brigham & Womens Hospital
Harvard College
Univ Yale
Malcolm A Leissring
Dennis Selkoe
Gregory D Cuny
Sungwoon Choi
Ross L Stein
Benjamin Turk
Lewis C Cantley
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 Brigham & Womens Hospital, Harvard College, Univ Yale, Malcolm A Leissring, Dennis Selkoe, Gregory D Cuny, Sungwoon Choi, Ross L Stein, Benjamin Turk, Lewis C Cantley filed Critical Brigham & Womens Hospital
Publication of WO2008156701A2 publication Critical patent/WO2008156701A2/en
Publication of WO2008156701A3 publication Critical patent/WO2008156701A3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
    • C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
    • C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
    • C07C279/04—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton
    • C07C279/14—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D209/20—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals substituted additionally by nitrogen atoms, e.g. tryptophane
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0815—Tripeptides with the first amino acid being basic
    • C07K5/0817—Tripeptides with the first amino acid being basic the first amino acid being Arg

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biophysics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention provides a novel therapeutic approach for the prevention and treatment of infections and for the treatment of diabetes wherein the degradation of insulin is reduced through inhibition of insulin-degrading enzyme (IDE) by hydroxamate inhibitors.
PCT/US2008/007447 2007-06-13 2008-06-13 Hydroxamate inhibitors of insulin-degrading enzyme and uses thereof WO2008156701A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US93458707P 2007-06-13 2007-06-13
US60/934,587 2007-06-13

Publications (2)

Publication Number Publication Date
WO2008156701A2 WO2008156701A2 (en) 2008-12-24
WO2008156701A3 true WO2008156701A3 (en) 2009-02-26

Family

ID=40156847

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/007447 WO2008156701A2 (en) 2007-06-13 2008-06-13 Hydroxamate inhibitors of insulin-degrading enzyme and uses thereof

Country Status (1)

Country Link
WO (1) WO2008156701A2 (en)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8691760B2 (en) 2009-02-02 2014-04-08 Ramot At Tel-Aviv University Peptides, pharmaceutical compositions comprising same and uses thereof
EP2371421A1 (en) 2010-03-04 2011-10-05 Université de Lille 2 Droit et Santé Ligands of insulin degrading enzyme and their uses
US8975232B2 (en) 2010-07-29 2015-03-10 President And Fellows Of Harvard College Macrocyclic kinase inhibitors and uses thereof
US8901074B2 (en) 2010-08-04 2014-12-02 Ramot At Tel-Aviv University Methods of treating autoimmune diseases of the central nervous system (CNS) and neurodegenerative diseases
FR2968560A1 (en) 2010-12-13 2012-06-15 Oreal USE OF THE IDE AS A BIOMARKER OF A CONDITION OF THE SCALP
WO2013006451A2 (en) 2011-07-01 2013-01-10 President And Fellows Of Harvard College Macrocyclic insulin-degrading enzyme (ide) inhibitors and uses thereof
US11040976B2 (en) 2015-04-24 2021-06-22 President And Fellows Of Harvard College Substrate selective inhibitors of insulin-degrading enzyme (IDE) and uses thereof
CN111032628A (en) 2017-08-21 2020-04-17 细胞基因公司 Process for preparing tert-butyl (S) -4, 5-diamino-5-oxovalerate
WO2019168654A2 (en) 2018-02-09 2019-09-06 President And Fellows Of Harvard College Dna-templated macrocycle library
FR3132644A1 (en) 2022-02-11 2023-08-18 L'oreal Method for screening active ingredients making it possible to prevent the reduction and/or to reinforce the defenses of the skin comprising measuring the level of expression or activity of the IDE

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1038864A1 (en) * 1997-12-12 2000-09-27 Fuji Yakuhin Kogyo Kabushiki Kaisha Novel metalloproteinase inhibitors
EP1101492A1 (en) * 1998-07-17 2001-05-23 Fuji Yakuhin Kogyo Kabushiki Kaisha Novel remedies for allergic diseases

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1038864A1 (en) * 1997-12-12 2000-09-27 Fuji Yakuhin Kogyo Kabushiki Kaisha Novel metalloproteinase inhibitors
EP1101492A1 (en) * 1998-07-17 2001-05-23 Fuji Yakuhin Kogyo Kabushiki Kaisha Novel remedies for allergic diseases

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
MORENO, M . ET AL.: "Stereochemically pure a-trifluoromethyl-malic hydroxamates: synthesis and evaluation as inhibitors of matrix metalloproteinases", TETRAHEDRON, vol. 62, no. 43, 2006, pages 10171 - 10181, XP005649828, ISSN: 0040-4020 *
SANI, M. ET AL.: "Synthesis and evaluation of stereopure a-trifluoromethyl-malic hydroxamates as inhibitors of matrix metalloproteinases", TETRAHEDRON LETTERS, vol. 45, no. 8, 2004, pages 1611 - 1615, XP004487111, ISSN: 0040-4039 *

Also Published As

Publication number Publication date
WO2008156701A2 (en) 2008-12-24

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