WO2006137974A3 - Macrocyclic ghrelin receptor antagonists and inverse agonists and methods of using the same - Google Patents

Macrocyclic ghrelin receptor antagonists and inverse agonists and methods of using the same Download PDF

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Publication number
WO2006137974A3
WO2006137974A3 PCT/US2006/015698 US2006015698W WO2006137974A3 WO 2006137974 A3 WO2006137974 A3 WO 2006137974A3 US 2006015698 W US2006015698 W US 2006015698W WO 2006137974 A3 WO2006137974 A3 WO 2006137974A3
Authority
WO
WIPO (PCT)
Prior art keywords
disorders
ghrelin receptor
methods
inverse agonists
same
Prior art date
Application number
PCT/US2006/015698
Other languages
French (fr)
Other versions
WO2006137974A2 (en
Inventor
Graeme Fraser
Hamid Hoveyda
Original Assignee
Tranzyme Pharma Inc
Graeme Fraser
Hamid Hoveyda
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 claimed from PCT/US2005/020887 external-priority patent/WO2006046977A1/en
Application filed by Tranzyme Pharma Inc, Graeme Fraser, Hamid Hoveyda filed Critical Tranzyme Pharma Inc
Priority to US11/577,922 priority Critical patent/US20090275648A1/en
Priority to CA002583345A priority patent/CA2583345A1/en
Priority to EP06751414A priority patent/EP1891090A2/en
Priority to JP2008515697A priority patent/JP5122446B2/en
Publication of WO2006137974A2 publication Critical patent/WO2006137974A2/en
Publication of WO2006137974A3 publication Critical patent/WO2006137974A3/en

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    • 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
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
    • C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
    • 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
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • 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
    • 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
    • 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
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
    • A61P5/08—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH for decreasing, blocking or antagonising the activity of the anterior pituitary hormones
    • 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
    • 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
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Child & Adolescent Psychology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Emergency Medicine (AREA)
  • Cardiology (AREA)
  • Nutrition Science (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention provides novel conformationally-defined macrocyclic compounds that have been demonstrated to be selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and/or variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as antagonists or inverse agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, cardiovascular disorders, obesity and obesity-associated disorders, gastrointestinal disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.
PCT/US2006/015698 2005-06-13 2006-04-26 Macrocyclic ghrelin receptor antagonists and inverse agonists and methods of using the same WO2006137974A2 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US11/577,922 US20090275648A1 (en) 2005-06-13 2006-04-26 Macrocyclic ghrelin receptor antagonists and inverse agonists and methods of using the same
CA002583345A CA2583345A1 (en) 2005-06-13 2006-04-26 Macrocyclic ghrelin receptor antagonists and inverse agonists and methods of using the same
EP06751414A EP1891090A2 (en) 2005-06-13 2006-04-26 Macrocyclic ghrelin receptor antagonists and inverse agonists and methods of using the same
JP2008515697A JP5122446B2 (en) 2005-06-13 2006-04-26 Macrocyclic ghrelin receptor antagonists and inverse agonists and methods of use thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
USPCT/US2005/020887 2005-06-13
PCT/US2005/020887 WO2006046977A1 (en) 2004-10-26 2005-06-13 Macrocyclic ghrelin receptor antagonists and methods of using the same

Publications (2)

Publication Number Publication Date
WO2006137974A2 WO2006137974A2 (en) 2006-12-28
WO2006137974A3 true WO2006137974A3 (en) 2007-04-12

Family

ID=37570927

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2006/015698 WO2006137974A2 (en) 2005-06-13 2006-04-26 Macrocyclic ghrelin receptor antagonists and inverse agonists and methods of using the same

Country Status (4)

Country Link
EP (1) EP1891090A2 (en)
JP (1) JP5122446B2 (en)
CA (1) CA2583345A1 (en)
WO (1) WO2006137974A2 (en)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101528765B (en) 2006-09-11 2015-04-22 欧塞拉治疗有限公司 Macrocyclic antagonists of the motilin receptor for treatment of gastrointestinal dysmotility disorders
CA2939778C (en) 2007-01-31 2019-01-29 Dana-Farber Cancer Institute, Inc. Stabilized p53 peptides and uses thereof
ES2604943T3 (en) 2007-02-09 2017-03-10 Ocera Therapeutics, Inc. Ghrelin receptor macrocyclic modulators and procedures for their use
KR101525754B1 (en) 2007-03-28 2015-06-09 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 Stitched polypeptides
WO2011053821A1 (en) 2009-10-30 2011-05-05 Tranzyme Pharma, Inc. Macrocyclic ghrelin receptor antagonists and inverse agonists and methods of using the same
SI2603600T1 (en) 2010-08-13 2019-04-30 Aileron Therapeutics, Inc. Peptidomimetic macrocycles
KR20140100937A (en) 2011-10-18 2014-08-18 에일러론 테라퓨틱스 인코포레이티드 Peptidomimetic macrocycles
WO2013123267A1 (en) 2012-02-15 2013-08-22 Aileron Therapeutics, Inc. Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles
CN104159595A (en) 2012-02-15 2014-11-19 爱勒让治疗公司 Peptidomimetic macrocycles
BR112015009470A2 (en) 2012-11-01 2019-12-17 Aileron Therapeutics Inc disubstituted amino acids and their methods of preparation and use
KR20170058424A (en) 2014-09-24 2017-05-26 에일러론 테라퓨틱스 인코포레이티드 Peptidomimetic macrocycles and uses thereof
WO2016049355A1 (en) 2014-09-24 2016-03-31 Aileron Therapeutics, Inc. Peptidomimetic macrocycles and formulations thereof
AU2016235424A1 (en) 2015-03-20 2017-10-05 Aileron Therapeutics, Inc. Peptidomimetic macrocycles and uses thereof
EP3347372A4 (en) 2015-09-10 2019-09-04 Aileron Therapeutics, Inc. Peptidomimetic macrocycles as modulators of mcl-1

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001025257A2 (en) * 1999-10-04 2001-04-12 Neokimia, Inc. Combinatorial synthesis of libraries of macrocyclic compounds useful in drug discovery
WO2004111077A1 (en) * 2003-06-18 2004-12-23 Tranzyme Pharma Inc. Macrocyclic antagonists of the motilin receptor
WO2005012332A1 (en) * 2003-07-31 2005-02-10 Tranzyme Pharma Spatially-defined macrocycles incorporating peptide bond surrogates
WO2005012331A1 (en) * 2003-07-31 2005-02-10 Tranzyme Pharma Spatially-defined macrocyclic compounds useful for drug discovery
WO2006009645A1 (en) * 2004-06-18 2006-01-26 Tranzyme Pharma, Inc. Methods of using macrocyclic modulators of the ghrelin receptor
WO2006009674A1 (en) * 2004-06-18 2006-01-26 Tranzyme Pharma, Inc. Macrocyclic modulators of the ghrelin receptor
WO2006046977A1 (en) * 2004-10-26 2006-05-04 Tranzyme Pharma, Inc. Macrocyclic ghrelin receptor antagonists and methods of using the same

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001025257A2 (en) * 1999-10-04 2001-04-12 Neokimia, Inc. Combinatorial synthesis of libraries of macrocyclic compounds useful in drug discovery
WO2004111077A1 (en) * 2003-06-18 2004-12-23 Tranzyme Pharma Inc. Macrocyclic antagonists of the motilin receptor
WO2005012332A1 (en) * 2003-07-31 2005-02-10 Tranzyme Pharma Spatially-defined macrocycles incorporating peptide bond surrogates
WO2005012331A1 (en) * 2003-07-31 2005-02-10 Tranzyme Pharma Spatially-defined macrocyclic compounds useful for drug discovery
WO2006009645A1 (en) * 2004-06-18 2006-01-26 Tranzyme Pharma, Inc. Methods of using macrocyclic modulators of the ghrelin receptor
WO2006009674A1 (en) * 2004-06-18 2006-01-26 Tranzyme Pharma, Inc. Macrocyclic modulators of the ghrelin receptor
WO2006046977A1 (en) * 2004-10-26 2006-05-04 Tranzyme Pharma, Inc. Macrocyclic ghrelin receptor antagonists and methods of using the same

Also Published As

Publication number Publication date
JP2009508805A (en) 2009-03-05
EP1891090A2 (en) 2008-02-27
JP5122446B2 (en) 2013-01-16
WO2006137974A2 (en) 2006-12-28
CA2583345A1 (en) 2006-12-28

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