NO962162L - Dipeptider som bevirker frigjöring av veksthormon - Google Patents

Dipeptider som bevirker frigjöring av veksthormon

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Publication number
NO962162L
NO962162L NO962162A NO962162A NO962162L NO 962162 L NO962162 L NO 962162L NO 962162 A NO962162 A NO 962162A NO 962162 A NO962162 A NO 962162A NO 962162 L NO962162 L NO 962162L
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Norway
Prior art keywords
growth hormone
dipeptides
pct
hormone release
cause growth
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NO962162A
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English (en)
Other versions
NO962162D0 (no
Inventor
Philip A Carpino
Paul A Dasilva Jardine
Bruce A Lefker
John A Ragan
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Pfizer
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Application filed by Pfizer filed Critical Pfizer
Publication of NO962162D0 publication Critical patent/NO962162D0/no
Publication of NO962162L publication Critical patent/NO962162L/no

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    • 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
    • C07D413/06—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 linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/14—Nitrogen atoms not forming part of a nitro radical
    • 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
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/56—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
    • C07D211/64—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4 having an aryl radical as the second substituent in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07K5/0205—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)3-C(=0)-, e.g. statine or derivatives thereof
    • 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
    • C07K5/0207—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)4-C(=0), e.g. 'isosters', replacing two 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
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/021—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)n-C(=0)-, n being 5 or 6; for n > 6, classification in C07K5/06 - C07K5/10, according to the moiety having normal peptide bonds
    • 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
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • 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
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • 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
    • C07K5/06—Dipeptides
    • C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Diabetes (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Endocrinology (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Nutrition Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)

Abstract

Forbindelser med formel 1 hvor er veksthormon-frigjørende peptid-mimetika som er anvendelige ved behandling og forebyggelse av osteoporose. Z er -COCR1R2CLCOANR4R5; L er NR8, O eller CH2; W er hydrogen, eller, i kombinasjon med X, en benzokondensasjon hvor W og X er koblet sammen til en fenylring som eventuelt er substituert med en til tre substituenter uavhengig av hverandre, valgt fra R3*, T-R3b og R12; Y er hydrogen, C,-C8-alkyl, C4-Ci0-cykloalkyl, aryl-K-, fenyl-{Ci-C<ralkyl)-K- eller tienyl-fCi-Cs-alkyO-K-, hvor hver ring eventuelt er substituert med en til tre substituenter uavhengig av hverandre valgt fra R3", R3b og R12, hvor K er en binding, O, S(0)m eller NR21. X er OR2. R2. ^2¿M¿N¿Aryl 9 N¿C----- 9 .o-c¿ eller eller X i kombinasjon med W, er en benzokondensasjon, hvor W og X er bundet sammen til en fenylring som eventuelt er substituert med en til tre substituenter uavhengig av hverandre, valgt fra R3", -T-R* og R12; R1 er Ci-Cio-alkyl, aryl, aryHd-Cs-alkyl) og eller Ci-Cs-alkyl-K'-Ci-C5-alkyl, aryHCo-Cj-alkyO-K^d-Cs-alkyl), (C3-C7)-cykloalkyl- (CrCs-alkylJ-K^d-Cs-alkyl), hvor K1 er O, S(0)m. N(R2)C(0), C(0)N(R2), OC(0), C(0)0, -CR2=CR2- eller -CsC-, hvor arylgruppene er definert nedenfor og RJ samt alkylgruppene kan være ytterligere substituert med 1-5 halogenatomer, SfOJmR2*. 1 til 3 av OR2* eller C(O)OR2* og arylgruppene kan være ytterligere substituert med fenyl, fenoksy, arylalkyloksy, halogenfenyl, 1 til 3 av Ci-Cs-alkyl, 1 til 3 halogenatomer, 1 til 2 av OR2, metylendioksy, S(0)mR2,1 til 2 av CF3, OCF3, nitro, N(R2)(R2), N(R2)C(0)(R2), C(0)OR2, C{0)N{R2)(R2), S02N(R2)R2), N{R2)S02-aryl eller N(R2)SO2R2; R2e er hydrogen, Ct-C6-alkyl, C3-C7-cykloalkyl og kan være forbundet med R1 for å danne en C3-C8-ring som eventuelt innbefatter oksygen, svovel eller NR2"; R2 er hydrogen, Ct-Ce-alkyl, C3-Crcykloalkyl, Ci-Ce-halogenert alkyl; R21 er hydrogen eller Ci-Cs-alkyl; R2b er hydrogen-Ci-Ca-alkyl, C,-C8-halogenert alkyl, C3-C«-cykloalkyl, alkylaryl eller aryl; R31 er H, F, Cl, Br, l, OCF3, OCF2H, CH3, OCH3 eller CF3; R12 er H, F, Cl, Br, l. OCF3| OCF2H, CH3, OCH3 eller CF3; T er en binding eller utgjør fenyl eller en 5- eller 6-leddet heterocyklus som inneholder 1 til 3 heteroatomer valgt fra nitrogen, svovel eller oksygen, og som hver : eventuelt er substituert med en til tre substituenter valgt fra F, Cl, Br, l, CH3, OCH3, OCF3 og CF3; R* er hydrogen, CONR8R9, S02NRV, COOH, COO(C,-C«)-alkyl, NR2S02R9. NR2CONRV, NR2S02NR'R9, NR2C(0)R9, imidazolyl, tiazolyl eller tetrazolyl; R4 og R5 er uavhengig av hverandre, hydrogen, Ci-C6-alkyl, substituert Ci-Cs- alkyl, hvor subslituentene kan være 1 til 5 halogenatomer, 1 til 3 hydroksy, 1 til 3 C,-Cia-alkanoyloksy, 1 til 3 Ci-Ce-alkoksy, fenyl, fenoksy, 2-furyl, Ci-Ce- , alkoksykarbonyl, S(0)m(C,-C6-alkyl); eller R4 og R5 sammen utgjør -(CH2)rL.(CH2),-, hvor L. er C(R2)j, S(O)m eller N(R2), r og s er uavhengig av hverandre, 1 til 3 og R2 er som definert ovenfor; R9 er hydrogen eller d-Ca-alkyl og kan være forbundet med R2c for å danne en C3-C8-ring;
NO962162A 1995-05-29 1996-05-28 Dipeptider som bevirker frigjöring av veksthormon NO962162L (no)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IB1995/000410 WO1996038471A1 (en) 1995-05-29 1995-05-29 Dipeptides which promote release of growth hormone

Publications (2)

Publication Number Publication Date
NO962162D0 NO962162D0 (no) 1996-05-28
NO962162L true NO962162L (no) 1996-12-02

Family

ID=11004334

Family Applications (1)

Application Number Title Priority Date Filing Date
NO962162A NO962162L (no) 1995-05-29 1996-05-28 Dipeptider som bevirker frigjöring av veksthormon

Country Status (15)

Country Link
US (1) US5936089A (no)
EP (1) EP0828754B1 (no)
JP (1) JP3133073B2 (no)
KR (1) KR960041192A (no)
CN (1) CN1143647A (no)
AT (1) ATE288444T1 (no)
AU (1) AU5455496A (no)
CA (1) CA2220055C (no)
DE (1) DE69533991T2 (no)
ES (1) ES2235171T3 (no)
FI (1) FI974368A0 (no)
IL (1) IL118330A0 (no)
MX (1) MX9709278A (no)
NO (1) NO962162L (no)
WO (1) WO1996038471A1 (no)

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WO1996038471A1 (en) 1996-12-05
DE69533991D1 (de) 2005-03-10
FI974368A (fi) 1997-11-28
JPH10510511A (ja) 1998-10-13
JP3133073B2 (ja) 2001-02-05
CA2220055A1 (en) 1996-12-05
AU5455496A (en) 1996-12-12
CN1143647A (zh) 1997-02-26
EP0828754A1 (en) 1998-03-18
ATE288444T1 (de) 2005-02-15
IL118330A0 (en) 1996-09-12
NO962162D0 (no) 1996-05-28
ES2235171T3 (es) 2005-07-01
FI974368A0 (fi) 1997-11-28
CA2220055C (en) 2001-04-24
DE69533991T2 (de) 2006-04-13
US5936089A (en) 1999-08-10
EP0828754B1 (en) 2005-02-02

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