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

Info

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 JP2008515697A priority Critical patent/JP5122446B2/en
Priority to CA002583345A priority patent/CA2583345A1/en
Priority to EP06751414A priority patent/EP1891090A2/en
Priority to US11/577,922 priority patent/US20090275648A1/en
Publication of WO2006137974A2 publication Critical patent/WO2006137974A2/en
Publication of WO2006137974A3 publication Critical patent/WO2006137974A3/en

Links

Classifications

    • 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)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Pain & Pain Management (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Nutrition Science (AREA)
  • Rheumatology (AREA)
  • Emergency Medicine (AREA)
  • Cardiology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (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
JP2008515697A JP5122446B2 (en) 2005-06-13 2006-04-26 Macrocyclic ghrelin receptor antagonists and inverse agonists and methods of use thereof
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
US11/577,922 US20090275648A1 (en) 2005-06-13 2006-04-26 Macrocyclic ghrelin receptor antagonists and inverse agonists and methods of using the same

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
CA2677045C (en) 2007-01-31 2016-10-18 Dana-Farber Cancer Institute, Inc. Stabilized p53 peptides and uses thereof
ES2602789T3 (en) 2007-02-09 2017-02-22 Ocera Therapeutics, Inc. Connector intermediates for the synthesis of macrocyclic modulators of the ghrelin receptor
CA2682174C (en) 2007-03-28 2021-04-06 President And Fellows Of Harvard College 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
WO2012021876A2 (en) 2010-08-13 2012-02-16 Aileron Therapeutics, Inc. Peptidomimetic macrocycles
CN108929375A (en) 2011-10-18 2018-12-04 爱勒让治疗公司 Peptidomimetic macrocyclic compound
WO2013123267A1 (en) 2012-02-15 2013-08-22 Aileron Therapeutics, Inc. Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles
ES2817877T3 (en) 2012-02-15 2021-04-08 Aileron Therapeutics Inc Peptidomimetic macrocycles
JP6526563B2 (en) 2012-11-01 2019-06-05 エイルロン セラピューティクス，インコーポレイテッド Disubstituted amino acids and methods for their preparation and use
BR112017005736A2 (en) 2014-09-24 2017-12-12 Aileron Therapeutics Inc peptidomimetic macrocycles and formulations thereof
SG10201902594QA (en) 2014-09-24 2019-04-29 Aileron Therapeutics Inc Peptidomimetic macrocycles and uses thereof
CA2979847A1 (en) 2015-03-20 2016-09-29 Aileron Therapeutics, Inc. Peptidomimetic macrocycles and uses thereof
CN108368161A (en) 2015-09-10 2018-08-03 艾瑞朗医疗公司 Peptidomimetic macrocyclic compound as MCL-1 conditioning agents

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
WO2005012331A1 (en) * 2003-07-31 2005-02-10 Tranzyme Pharma Spatially-defined macrocyclic compounds useful for drug discovery
WO2005012332A1 (en) * 2003-07-31 2005-02-10 Tranzyme Pharma Spatially-defined macrocycles incorporating peptide bond surrogates
WO2006009674A1 (en) * 2004-06-18 2006-01-26 Tranzyme Pharma, Inc. Macrocyclic modulators of the ghrelin receptor
WO2006009645A1 (en) * 2004-06-18 2006-01-26 Tranzyme Pharma, Inc. Methods of using 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
WO2005012331A1 (en) * 2003-07-31 2005-02-10 Tranzyme Pharma Spatially-defined macrocyclic compounds useful for drug discovery
WO2005012332A1 (en) * 2003-07-31 2005-02-10 Tranzyme Pharma Spatially-defined macrocycles incorporating peptide bond surrogates
WO2006009674A1 (en) * 2004-06-18 2006-01-26 Tranzyme Pharma, Inc. Macrocyclic modulators of the ghrelin receptor
WO2006009645A1 (en) * 2004-06-18 2006-01-26 Tranzyme Pharma, Inc. Methods of using 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
CA2583345A1 (en) 2006-12-28
EP1891090A2 (en) 2008-02-27
JP5122446B2 (en) 2013-01-16
JP2009508805A (en) 2009-03-05
WO2006137974A2 (en) 2006-12-28

Similar Documents

Publication Publication Date Title
WO2006137974A3 (en) Macrocyclic ghrelin receptor antagonists and inverse agonists and methods of using the same
WO2006009645A8 (en) Methods of using macrocyclic modulators of the ghrelin receptor
WO2006009674A8 (en) Macrocyclic modulators of the ghrelin receptor
MX2009008574A (en) Macrocyclic ghrelin receptor modulators and methods of using the same.
WO2007127457A3 (en) Ghrelin/growth hormone releasing peptide/growth hormone secretatogue receptor antagonists and uses thereof
WO2007111864A3 (en) Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
WO2007136577A3 (en) Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
WO2006104826A3 (en) Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
WO2006014618A3 (en) Substituted pyrazoles, compositions containing such compounds and methods of use
WO2011159917A3 (en) Growth hormone secretatogue receptor antagonists and uses thereof
WO2007110868A3 (en) Heterocyclic compounds and uses thereof in the treatment of sexual disorders
UA96308C2 (en) Glucagon receptor antagonist compounds, composition comprising such compounds and use thereof
HK1047580A1 (en) Dibenzopyrans as glucocorticoid receptor antagonists for treatment of diabetes.
WO2005086656A3 (en) Heteroarylaminopyrazole derivatives useful for the treatment of diabetes
WO2010123930A3 (en) Chemosensory receptor ligand-based therapies
TW200745031A (en) Acyl indoles, compositions containing such compounds and methods of use
WO2006105442A3 (en) Spirocyclic heterocyclic derivatives and methods of their use
WO2006074428A3 (en) Cxcr4 antagonists for the treatment of medical disorders
WO2006020959A3 (en) Substituted benzofused heterocycles
WO2007076260A3 (en) Farnesoid x receptor agonists
WO2008008286A3 (en) Substituted pyrazoles as ghrelin receptor antagonists
WO2008097428A3 (en) Compounds and compositions as modulators of gpr119 activity
WO2005033073A3 (en) Spirocyclic heterocyclic derivatives and methods of their use
WO2007106721A3 (en) Cannabinoid receptor antagonists/inverse agonists useful for treating obesity
WO2008070111A3 (en) Processes for preparing (r)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1h-3-benzazepine and intermediates thereof

Legal Events

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

Ref document number: 2583345

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2006751414

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 3011/DELNP/2007

Country of ref document: IN

ENP Entry into the national phase

Ref document number: 2008515697

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 11577922

Country of ref document: US