ATE197158T1 - Verbindungen mit wachstumshormonfreisetzenden eigenschaften - Google Patents

Verbindungen mit wachstumshormonfreisetzenden eigenschaften

Info

Publication number
ATE197158T1
ATE197158T1 AT95903774T AT95903774T ATE197158T1 AT E197158 T1 ATE197158 T1 AT E197158T1 AT 95903774 T AT95903774 T AT 95903774T AT 95903774 T AT95903774 T AT 95903774T AT E197158 T1 ATE197158 T1 AT E197158T1
Authority
AT
Austria
Prior art keywords
growth hormone
compounds
hormone releasing
releasing properties
pct
Prior art date
Application number
AT95903774T
Other languages
English (en)
Inventor
Nils Langeland Johansen
Jesper Lau
Kjeld Madsen
Behrend Friedrich Lundt
Gersen Henning Th
Birgit Sehested Hansen
Bernd Peschke
Original Assignee
Novo Nordisk As
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 DK143993A external-priority patent/DK143993D0/da
Application filed by Novo Nordisk As filed Critical Novo Nordisk As
Application granted granted Critical
Publication of ATE197158T1 publication Critical patent/ATE197158T1/de

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10Tetrapeptides
    • C07K5/1024Tetrapeptides with the first amino acid being heterocyclic
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic 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
    • A61P5/00Drugs for disorders of the endocrine system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/02Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/06Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/10Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575Hormones
    • C07K14/60Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08Tripeptides
    • C07K5/0802Tripeptides with the first amino acid being neutral
    • C07K5/0812Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Endocrinology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Diabetes (AREA)
  • Neurology (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Hospice & Palliative Care (AREA)
  • Communicable Diseases (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Oncology (AREA)
  • Virology (AREA)
  • Psychiatry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
AT95903774T 1993-12-23 1994-12-22 Verbindungen mit wachstumshormonfreisetzenden eigenschaften ATE197158T1 (de)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DK143993A DK143993D0 (de) 1993-12-23 1993-12-23
DK12194 1994-01-28
DK119194 1994-10-14
PCT/DK1994/000485 WO1995017423A1 (en) 1993-12-23 1994-12-22 Compounds with growth hormone releasing properties

Publications (1)

Publication Number Publication Date
ATE197158T1 true ATE197158T1 (de) 2000-11-15

Family

ID=27220421

Family Applications (1)

Application Number Title Priority Date Filing Date
AT95903774T ATE197158T1 (de) 1993-12-23 1994-12-22 Verbindungen mit wachstumshormonfreisetzenden eigenschaften

Country Status (27)

Country Link
US (1) US5767085A (de)
EP (1) EP0736039B1 (de)
JP (1) JP3181918B2 (de)
KR (1) KR100354897B1 (de)
CN (1) CN1052731C (de)
AT (1) ATE197158T1 (de)
AU (1) AU689181B2 (de)
BR (1) BR9408377A (de)
CA (1) CA2179597A1 (de)
CZ (1) CZ293113B6 (de)
DE (1) DE69426206T2 (de)
DK (1) DK0736039T3 (de)
ES (1) ES2153469T3 (de)
FI (1) FI962584L (de)
GR (1) GR3035150T3 (de)
HU (1) HU224345B1 (de)
IL (1) IL112112A (de)
MX (1) MX9500072A (de)
NO (1) NO315561B1 (de)
NZ (1) NZ277486A (de)
PL (1) PL181280B1 (de)
PT (1) PT736039E (de)
RO (1) RO115635B1 (de)
SG (1) SG55069A1 (de)
SK (1) SK281963B6 (de)
UA (1) UA42747C2 (de)
WO (1) WO1995017423A1 (de)

Families Citing this family (57)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU684878B2 (en) * 1993-11-24 1998-01-08 Merck & Co., Inc. Compounds and the use thereof to promote the release of growth hormone(s)
HU221092B1 (en) * 1993-12-23 2002-08-28 Novo Nordisk As Compounds with growth hormone releasing properties
US5798337A (en) * 1994-11-16 1998-08-25 Genentech, Inc. Low molecular weight peptidomimetic growth hormone secretagogues
US20020111461A1 (en) 1999-05-21 2002-08-15 Todd C. Somers Low molecular weight peptidomimetic growth hormone secretagogues
CZ238197A3 (en) * 1995-01-27 1997-12-17 Novo Nordisk As Growth hormone formation stimulating compounds
KR19990028303A (ko) * 1995-06-22 1999-04-15 한센 핀 베네드, 안네 제헤르 성장호르몬 방출 특성을 가지는 화합물
US6531314B1 (en) 1996-12-10 2003-03-11 Merck & Co., Inc. Growth hormone secretagogue receptor family
US6242199B1 (en) 1995-12-13 2001-06-05 Merck & Co., Inc. Assays for growth hormone secretagogue receptors
GB2308362A (en) * 1995-12-19 1997-06-25 Lilly Industries Ltd Pharmaceutical indole derivatives
PL327227A1 (en) * 1995-12-22 1998-12-07 Novo Nordisk As Compounds exhibiting growth hormone liberating properties
US6451970B1 (en) 1996-02-21 2002-09-17 Novo Nordisk A/S Peptide derivatives
US5919777A (en) * 1996-04-24 1999-07-06 Novo Nordisk A/S Compounds with growth hormone releasing properties
CN1127488C (zh) * 1996-04-24 2003-11-12 诺沃挪第克公司 具有生长激素释放特性的化合物
DE69734215T2 (de) 1996-07-22 2006-06-29 Novo Nordisk A/S Verbindungen mit Wachstumshormon-freisetzenden Eigenschaften
AU3938797A (en) * 1996-08-29 1998-03-19 Novo Nordisk A/S Transdermal delivery of peptides
US6420518B1 (en) 1997-04-04 2002-07-16 Genetech, Inc. Insulin-like growth factor agonist molecules
US20030069177A1 (en) 2000-05-16 2003-04-10 Genentech, Inc. Method for treating cartilage disorders
US6121416A (en) 1997-04-04 2000-09-19 Genentech, Inc. Insulin-like growth factor agonist molecules
US6127341A (en) * 1997-06-20 2000-10-03 Novo Nordisk A/S Compounds with growth hormone releasing properties
JP4116097B2 (ja) 1997-06-20 2008-07-09 ノボ ノルディスク アクティーゼルスカブ 成長ホルモン放出特性をもつ化合物
ATE470671T1 (de) 1998-01-16 2010-06-15 Helsinn Therapeutics Us Inc Verbindungen mit wachstumshormon-freisetzender eigenschaft
US6919315B1 (en) 1998-06-30 2005-07-19 Novo Nordisk A/S Compounds with growth hormone releasing properties
US6682908B1 (en) 1998-07-10 2004-01-27 Merck & Co., Inc. Mouse growth hormone secretagogue receptor
WO2000002919A1 (en) 1998-07-13 2000-01-20 Merck & Co., Inc. Growth hormone secretagogue related receptors and nucleic acids
EP1112282A4 (de) 1998-08-10 2002-10-31 Merck & Co Inc Rezeptor des wachstumshormon-sekretionsförderers aus dem hund
US6696063B1 (en) 1998-12-30 2004-02-24 Applied Research Systems Ars Holding N.V. Treatment of HIV-associated dysmorphia/dysmetabolic syndrome (HADDS) with or without lipodystrophy
CA2356109C (en) 1999-01-06 2008-04-22 Genentech, Inc. Insulin-like growth factor (igf) i mutant variants
WO2000048623A1 (en) * 1999-02-18 2000-08-24 Kaken Pharmaceutical Co., Ltd. Novel amide derivatives as growth hormone secretagogues
WO2000074702A1 (en) * 1999-06-04 2000-12-14 Novo Nordisk A/S Compositions for the treatment of the catabolic state of prolonged critical illness
ATE446758T1 (de) 2000-05-31 2009-11-15 Pfizer Prod Inc Verwendung von wachstumshormonsekretagoga zur förderung der beweglichkeit des verdauungstrakts
TWI331922B (en) 2002-08-09 2010-10-21 Ipsen Pharma Sas Growth hormone releasing peptides
EA008572B1 (ru) * 2003-05-19 2007-06-29 Уорнер-Ламберт Компани Ллс Твёрдая желатиновая капсула, содержащая оксид титана с контролируемым размером частиц, и способ её получения
US7476653B2 (en) 2003-06-18 2009-01-13 Tranzyme Pharma, Inc. Macrocyclic modulators of the ghrelin receptor
DK2274978T3 (en) 2003-09-12 2015-06-15 Ipsen Biopharmaceuticals Inc Methods of treating an insulin-like growth factor-I (IGF-I) deficiency
WO2005027913A1 (en) * 2003-09-19 2005-03-31 Pfizer Products Inc. Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and a growth hormone secretagogue
EP1735055A1 (de) * 2004-03-30 2006-12-27 Sapphire Therapeutics, Inc. Verfahren zur verringerung von c-reaktivem protein mit wachstumshormon-sekretagoga
UA87854C2 (en) 2004-06-07 2009-08-25 Мерк Энд Ко., Инк. N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators
AU2005272598B2 (en) * 2004-08-12 2011-11-17 Helsinn Therapeutics (U.S.), Inc. Method of stimulating the motility of the gastrointestinal system using growth hormone secretagogues
CU23558A1 (es) 2006-02-28 2010-07-20 Ct Ingenieria Genetica Biotech Compuestos análogos a los secretagogos peptidicos de la hormona de crecimiento
US8536120B2 (en) * 2006-04-28 2013-09-17 The Administrators Of The Tulane Educational Fund Ghrelin/growth hormone releasing peptide/growth hormone secretatogue receptor antagonists and uses thereof
CA2677399C (en) 2007-02-09 2016-09-13 Tranzyme Pharma, Inc. Macrocyclic ghrelin receptor modulators and methods of using the same
CA2677813A1 (en) * 2007-02-13 2008-08-21 Helsinn Therapeutics (U.S.), Inc. Method of treating cell proliferative disorders using growth hormone secretagogues
TWI429436B (zh) * 2007-04-10 2014-03-11 Helsinn Therapeutics Us Inc 使用生長激素促泌素治療或預防嘔吐之方法
EP2155769B1 (de) 2007-05-04 2012-06-27 Katholieke Universiteit Leuven KU Leuven Research & Development Schutz gegen gewebedegeneration
CA2710039C (en) 2007-12-26 2018-07-03 Critical Outcome Technologies, Inc. Semicarbazones, thiosemicarbazones and related compounds and methods for treatment of cancer
CA2730890C (en) 2008-07-17 2018-05-15 Critical Outcome Technologies Inc. Thiosemicarbazone inhibitor compounds and cancer treatment methods
UA105657C2 (uk) 2009-02-27 2014-06-10 Хелсінн Терапьютікс (Ю.Ес.), Інк. Поліпшені способи лікування мігрені на основі анамореліну
US9724381B2 (en) 2009-05-12 2017-08-08 The Administrators Of The Tulane Educational Fund Methods of inhibiting the ghrelin/growth hormone secretatogue receptor pathway and uses thereof
EA201270011A1 (ru) * 2009-06-12 2012-05-30 ХЕЛСИНН ТЕРАПЬЮТИКС (Ю.Эс.), ИНК. Растворы для инфузии и инъекции ипаморелин диацетата
CA2794952C (en) 2010-04-01 2018-05-15 Critical Outcome Technologies Inc. Compounds and method for treatment of hiv
WO2013190520A2 (en) 2012-06-22 2013-12-27 The General Hospital Corporation Gh-releasing agents in the treatment of vascular stenosis and associated conditions
US9119832B2 (en) 2014-02-05 2015-09-01 The Regents Of The University Of California Methods of treating mild brain injury
ES2864079T3 (es) 2014-05-30 2021-10-13 Pfizer Derivados de carbonitrilo como moduladores selectivos del receptor de andrógenos
WO2017075535A1 (en) 2015-10-28 2017-05-04 Oxeia Biopharmaceuticals, Inc. Methods of treating neurodegenerative conditions
US12012467B2 (en) 2017-03-28 2024-06-18 Regents Of The University Of Michigan Small molecule DCN1 inhibitors and therapeutic methods using the same
WO2023275715A1 (en) 2021-06-30 2023-01-05 Pfizer Inc. Metabolites of selective androgen receptor modulators
CN119930744B (zh) * 2025-01-20 2025-12-19 昆明理工大学 一种发酵马乳源小分子肽及其应用

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4228156A (en) * 1979-03-30 1980-10-14 Beckman Instruments, Inc. Synthetic peptides having pituitary growth hormone releasing activity
US4223019A (en) * 1979-03-30 1980-09-16 Beckman Instruments, Inc. Synthetic peptides having pituitary growth hormone releasing activity
US4223020A (en) * 1979-03-30 1980-09-16 Beckman Instruments, Inc. Synthetic peptides having pituitary growth hormone releasing activity
WO1983002272A1 (en) * 1981-12-28 1983-07-07 Beckman Instruments Inc Synthetic peptides having pituitary growth hormone releasing activity
US4410512A (en) * 1981-12-28 1983-10-18 Beckman Instruments, Inc. Combinations having synergistic pituitary growth hormone releasing activity
US4803261A (en) * 1986-06-27 1989-02-07 The Administrators Of The Tulane Educational Fund Method for synthesizing a peptide containing a non-peptide
IL98910A0 (en) * 1990-07-24 1992-07-15 Polygen Holding Corp Polypeptide compounds having growth hormone releasing activity and pharmaceutical compositions containing them
US5663146A (en) * 1991-08-22 1997-09-02 Administrators Of The Tulane Educational Fund Polypeptide analogues having growth hormone releasing activity
WO1994007519A1 (en) * 1992-09-25 1994-04-14 Smithkline Beecham Corporation Growth hormone releasing peptides
AU684878B2 (en) * 1993-11-24 1998-01-08 Merck & Co., Inc. Compounds and the use thereof to promote the release of growth hormone(s)

Also Published As

Publication number Publication date
FI962584A0 (fi) 1996-06-20
CN1138335A (zh) 1996-12-18
HU9501947D0 (en) 1995-11-28
DE69426206D1 (de) 2000-11-30
GR3035150T3 (en) 2001-04-30
SK82096A3 (en) 1997-01-08
SK281963B6 (sk) 2001-09-11
MX9500072A (es) 1997-05-31
SG55069A1 (en) 1998-12-21
CA2179597A1 (en) 1995-06-29
HU224345B1 (hu) 2005-08-29
NO962665L (no) 1996-08-23
IL112112A (en) 2000-06-29
RO115635B1 (ro) 2000-04-28
CZ183496A3 (en) 1997-02-12
NZ277486A (en) 1997-03-24
NO315561B1 (no) 2003-09-22
KR100354897B1 (ko) 2003-01-06
AU689181B2 (en) 1998-03-26
EP0736039B1 (de) 2000-10-25
NO962665D0 (no) 1996-06-21
UA42747C2 (uk) 2001-11-15
JP3181918B2 (ja) 2001-07-03
IL112112A0 (en) 1995-03-15
CZ293113B6 (cs) 2004-02-18
PL315113A1 (en) 1996-10-14
US5767085A (en) 1998-06-16
DK0736039T3 (da) 2001-02-12
EP0736039A1 (de) 1996-10-09
WO1995017423A1 (en) 1995-06-29
CN1052731C (zh) 2000-05-24
PT736039E (pt) 2001-04-30
BR9408377A (pt) 1997-08-19
FI962584A7 (fi) 1996-06-20
JPH09507217A (ja) 1997-07-22
PL181280B1 (pl) 2001-07-31
DE69426206T2 (de) 2001-05-17
HUT73497A (en) 1996-08-28
AU1272495A (en) 1995-07-10
FI962584L (fi) 1996-06-20
ES2153469T3 (es) 2001-03-01

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