RU2003105463A - PEPTIDE STRUCTURES SUITABLE FOR COMPETITIVE MODULATION OF CATALYSIS BY DIPEPTIDYLPEPTIDASE IV - Google Patents

PEPTIDE STRUCTURES SUITABLE FOR COMPETITIVE MODULATION OF CATALYSIS BY DIPEPTIDYLPEPTIDASE IV

Info

Publication number
RU2003105463A
RU2003105463A RU2003105463/04A RU2003105463A RU2003105463A RU 2003105463 A RU2003105463 A RU 2003105463A RU 2003105463/04 A RU2003105463/04 A RU 2003105463/04A RU 2003105463 A RU2003105463 A RU 2003105463A RU 2003105463 A RU2003105463 A RU 2003105463A
Authority
RU
Russia
Prior art keywords
acid
amino acid
pro
gly
compound according
Prior art date
Application number
RU2003105463/04A
Other languages
Russian (ru)
Inventor
Ханс Ульрих ДЕМУТ (DE)
Ханс Ульрих ДЕМУТ
Торстен ХОФФМАНН (DE)
Торстен Хоффманн
Зузанне МАНХАРТ (DE)
Зузанне МАНХАРТ
Маттиас ХОФФМАНН (DE)
Маттиас Хоффманн
Йохен ХАЙНС (DE)
Йохен ХАЙНС
Original Assignee
Пробиодруг Аг (De)
Пробиодруг Аг
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 Пробиодруг Аг (De), Пробиодруг Аг filed Critical Пробиодруг Аг (De)
Publication of RU2003105463A publication Critical patent/RU2003105463A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/07—Tetrapeptides
    • 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
    • A61P3/08—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
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • 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
    • C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
    • 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
    • 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
    • C07K5/081—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing O or S as heteroatoms, e.g. Cys, Ser
    • 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)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Diabetes (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Oncology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Claims (19)

1. Соединение, представленное общей формулой (I)1. The compound represented by General formula (I)
Figure 00000001
Figure 00000001
 и его фармацевтически приемлемые соли, гдеand its pharmaceutically acceptable salts, where А представляет собой любую аминокислоту, кроме D-аминокислоты,A is any amino acid except D-amino acid, В представляет собой аминокислоту, выбранную из Pro, Ala, Ser, Gly, Hyp, ацетидин-(2)-карбоновой кислоты и пипеколиновой кислоты,B is an amino acid selected from Pro, Ala, Ser, Gly, Hyp, acetidine- (2) -carboxylic acid and pipecolinic acid, С представляет собой любую аминокислоту, кроме Pro, Hyp, ацетидин-(2)-карбоновой кислоты, пипеколиновой кислоты, и кроме N-алкилированных аминокислот, например, N-метилвалина и саркозина,C is any amino acid except Pro, Hyp, acetidine- (2) -carboxylic acid, pipecolinic acid, and in addition to N-alkylated amino acids, for example, N-methylvaline and sarcosine, D представляет собой любую аминокислоту или отсутствует, иD represents any amino acid or is absent, and Е представляет собой любую аминокислоту или отсутствует, или гдеE is any amino acid or is absent, or where С представляет собой любую аминокислоту, кроме Pro, Hyp, ацетидин-(2)-карбоновой кислоты, пипеколиновой кислоты, и кроме N-алкилированных аминокислот, например, N-метилвалина и саркозина, и кроме D-аминокислоты,C is any amino acid except Pro, Hyp, acetidine- (2) -carboxylic acid, pipecolinic acid, and in addition to N-alkylated amino acids, for example, N-methylvaline and sarcosine, and in addition to D-amino acid, D представляет собой аминокислоту, выбранную из Pro, Ala, Ser, Gly, Hyp, ацетидин-(2)-карбоновой кислоты и пипеколиновой кислоты, иD is an amino acid selected from Pro, Ala, Ser, Gly, Hyp, acetidine- (2) -carboxylic acid and pipecolic acid, and Е представляет собой любую аминокислоту, кроме Pro, Hyp, ацетидин-(2)-карбоновой кислоты, пипеколиновой кислоты, и кроме N-алкилированных аминокислот, например, N-метилвалина и саркозина.E is any amino acid, except Pro, Hyp, acetidine- (2) -carboxylic acid, pipecolinic acid, and in addition to N-alkylated amino acids, for example, N-methylvaline and sarcosine. 2. Соединение по п.1, отличающееся тем, что2. The compound according to claim 1, characterized in that А представляет собой любую аминокислоту, кроме D-аминокислоты,A is any amino acid except D-amino acid, В представляет собой аминокислоту, выбранную из Pro, Ala, Ser, Gly, Hyp, ацетидин-(2)-карбоновой кислоты и пипеколиноаой кислоты,B is an amino acid selected from Pro, Ala, Ser, Gly, Hyp, acetidine- (2) -carboxylic acid and pipecolinoic acid, С представляет собой любую аминокислоту, кроме Pro, Hyp, ацетидин-(2)-карбоновой кислоты, пипеколиновой кислоты, и кроме N-алкилированных аминокислот, например, N-метилвалина и саркозина,C is any amino acid except Pro, Hyp, acetidine- (2) -carboxylic acid, pipecolinic acid, and in addition to N-alkylated amino acids, for example, N-methylvaline and sarcosine, D представляет собой любую аминокислоту или отсутствует, иD represents any amino acid or is absent, and Е представляет собой любую аминокислоту или отсутствует.E is any amino acid or is absent. 3. Соединение по п.1, отличающееся тем, что3. The compound according to claim 1, characterized in that А представляет собой любую аминокислоту, кроме D-аминокислоты,A is any amino acid except D-amino acid, В представляет собой аминокислоту, выбранную из Pro, Ala, Ser, Gly, Hyp, ацетидин-(2)-карбоновой кислоты и пипеколиновой кислоты,B is an amino acid selected from Pro, Ala, Ser, Gly, Hyp, acetidine- (2) -carboxylic acid and pipecolinic acid, С представляет собой любую аминокислоту, кроме Pro, Hyp, ацетидин-(2)-карбоновой кислоты, пипеколиновой кислоты, и кроме N-алкилированных аминокислот, например, N-метилвалина и саркозина, и кроме D-аминокислоты,C is any amino acid except Pro, Hyp, acetidine- (2) -carboxylic acid, pipecolinic acid, and in addition to N-alkylated amino acids, for example, N-methylvaline and sarcosine, and in addition to D-amino acid, D представляет собой аминокислоту, выбранную из Pro, Ala, Ser, Gly, Hyp, ацетидин-(2)-карбоновой кислоты и пипеколиновой кислоты, иD is an amino acid selected from Pro, Ala, Ser, Gly, Hyp, acetidine- (2) -carboxylic acid and pipecolic acid, and Е представляет собой любую аминокислоту, кроме Pro, Hyp, ацетидин-(2)-карбоновой кислоты, пипеколиновой кислоты, и кроме N-алкилированных аминокислот, например, N-метилвалина и саркозина.E is any amino acid, except Pro, Hyp, acetidine- (2) -carboxylic acid, pipecolinic acid, and in addition to N-alkylated amino acids, for example, N-methylvaline and sarcosine. 4. Соединение по любому из предшествующих пунктов, отличающееся тем, что4. The compound according to any one of the preceding paragraphs, characterized in that А представляет собой L-аминокислоту.A is an L-amino acid. 5. Соединение по любому из предшествующих пунктов, отличающееся тем, что5. The compound according to any one of the preceding paragraphs, characterized in that С представляет собой L-аминокислоту.C is an L-amino acid. 6. Соединение по любому из предшествующих пунктов, отличающееся тем, что6. The compound according to any one of the preceding paragraphs, characterized in that Е отсутствует.E is absent. 7. Соединение по любому из предшествующих пунктов, отличающееся тем, что7. The compound according to any one of the preceding paragraphs, characterized in that D и Е отсутствуют.D and E are absent. 8. Соединение по любому из предшествующих пунктов, отличающееся тем, что8. The compound according to any one of the preceding paragraphs, characterized in that А представляет собой т-бутил-Gly, Ile или Val.A is t-butyl-Gly, Ile or Val. 9. Соединение по любому из предшествующих пунктов, отличающееся тем, что9. The compound according to any one of the preceding paragraphs, characterized in that В представляет собой Pro.B is a Pro. 10. Соединение по любому из предшествующих пунктов, отличающееся тем, что10. The compound according to any one of the preceding paragraphs, characterized in that С представляет собой т-бутил-Gly, Ile или Val.C is t-butyl-Gly, Ile or Val. 11. Соединение по любому из предшествующих пунктов, отличающееся тем, что11. The compound according to any one of the preceding paragraphs, characterized in that А представляет собой Pro, Ala, Ser, Gly, Hyp, ацетидин-(2)-карбоновую кислоту или пипеколиновую кислоту.A is Pro, Ala, Ser, Gly, Hyp, acetidine- (2) -carboxylic acid or pipecolinic acid. 12. Соединение по п.1, а именно, т-бутил-Gly-Pro-Ile; т-бутил-Gly-Pro-Val; Val-Pro-т-бутил-Gly; Ile-Pro-т-бутил-Gly или т-бутил-Gly-Pro-т-бутил-Gly и их фармацевтически приемлемые соли.12. The compound according to claim 1, namely, t-butyl-Gly-Pro-Ile; t-butyl-Gly-Pro-Val; Val-Pro-t-butyl-Gly; Ile-Pro-t-butyl-Gly or t-butyl-Gly-Pro-t-butyl-Gly and their pharmaceutically acceptable salts. 13. Соединение по любому из предшествующих пп., отличающееся тем, что соединение представляет собой свободную ислую пептидную форму или пептидную форму с С-концевым амидом.13. A compound according to any one of the preceding claims, characterized in that the compound is a free isl peptide form or a peptide form with a C-terminal amide. 14. Соединение по п.13, отличающееся тем, что свободная кислая пептидная форма или пептидная форма с С-концевым амидом отличается модификацией боковой цепи, выбранной из следующей группы: добавление гомосерина, добавление пироглутаминовой кислоты, образование дисульфидной связи, дезамидирование остатков аспарагина или глутамина, метилирование, т-бутилирование, т-бутоксикарбонилирование, 4-метилбензилирование, тиоанизилирование, тиокрезилирование, бензилоксиметилирование, 4-нитрофенилирование, бензилоксикарбонилирование, 2-нитробензоилирование, 2-нитросульфенилирование, 4-толуолсульфонилирование, пентафторфенилирование, дифенилметилирование, 2-хлорбензилоксикарбонилирование, 2,4,5-трихлорфенилирование, 2-бромбензилоксикарбонилирование, 9-флуоренилметилоксикарбонилирование, трифенилметилирование, 2,2,5,7,8-пентаметилхроман-6-сульфонилирование, гидроксилирование, окисление метионина, формилирование, ацетилирование, анизилирование, бензилирование, бензоилирование, трифторацетилирование, карбоксилирование аспарагиновой кислоты или глутаминовой кислоты, фосфорилирование, сульфатирование, цистеинилирование, гликозилирование пентозами, дезоксигексозами, гексозаминами, гексозами или N-ацетилгексозаминами, фарнезилирование, миристолизирование, биотинилирование, пальмитоилирование, стеароилирование, геранилгеранилирование, глутатионилирование, 5’-аденозилирование, АДФ-рибозилирование, модификация с N-гликолилнейраминовой кислотой, N-ацетилнейраминовой кислотой, пиридоксальфосфатом, липоевой кислотой, 4’-фосфопантетеином или N-гидроксисукцинимидом.14. The compound according to item 13, wherein the free acid peptide form or the peptide form with a C-terminal amide is characterized by a modification of the side chain selected from the following group: addition of homoserine, addition of pyroglutamic acid, formation of a disulfide bond, deamidation of asparagine or glutamine residues , methylation, t-butylation, t-butoxycarbonylation, 4-methylbenzylation, thioanisylation, thiocresylation, benzyloxymethylation, 4-nitrophenylation, benzyloxycarbonylation, 2-nitrobenzoic irradiation, 2-nitrosulfenylation, 4-toluenesulfonylation, pentafluorophenylation, diphenylmethylation, 2-chlorobenzyloxycarbonylation, 2,4,5-trichlorophenylation, 2-bromobenzyloxycarbonylation, 9-fluorenylmethyloxycarbonylation, triphenylmethylmethane-6,5,5,5 sulfonylation, hydroxylation, methionine oxidation, formylation, acetylation, anisylation, benzylation, benzoylation, trifluoroacetylation, carboxylation of aspartic acid or glutamic acid, phosphorylated sulfation, cysteinylation, glycosylation of pentoses, deoxyhexoses, hexosamines, hexoses or N-acetylhexosamines, farnesylation, myristolization, biotinylation, palmitoylation, stearoylation, geranyl geranylation, glutathionylation, acidification, glutathionylation, 5'-acidification, -acetylneuraminic acid, pyridoxalphosphate, lipoic acid, 4'-phosphopanthetein or N-hydroxysuccinimide. 15. Пролекарства соединения по любому из предшествующих пунктов.15. Prodrugs of a compound according to any one of the preceding paragraphs. 16. Фармацевтическая композиция, включающая по меньшей мере одно соединение или пролекарство по любому из пп.1-15 и фармацевтически приемлемый носитель и/или разбавитель.16. A pharmaceutical composition comprising at least one compound or prodrug according to any one of claims 1 to 15 and a pharmaceutically acceptable carrier and / or diluent. 17. Способ получения фармацевтической композиции, включающий смешивание по меньшей мере одного соединения или пролекарства по любому из пп.1-15 и фармацевтически приемлемого носителя и/или разбавителя.17. A method of obtaining a pharmaceutical composition, comprising mixing at least one compound or prodrug according to any one of claims 1 to 15 and a pharmaceutically acceptable carrier and / or diluent. 18. Применение соединения, пролекарства или композиции по любому из пп.1-15 для получения лекарственного средства для профилактики или лечения состояния, опосредованного модулированием активности дипептидилпептидазы IV.18. The use of a compound, prodrug or composition according to any one of claims 1 to 15 for the manufacture of a medicament for the prophylaxis or treatment of a condition mediated by modulation of the activity of dipeptidyl peptidase IV. 19. Применение по п.17, отличающееся тем, что состояния выбирают из нарушенной толерантности к глюкозе, сахарного диабета, глюкозурии и метаболического ацидоза.19. The application of claim 17, wherein the conditions are selected from impaired glucose tolerance, diabetes mellitus, glucosuria and metabolic acidosis.
RU2003105463/04A 2001-06-27 2002-06-27 PEPTIDE STRUCTURES SUITABLE FOR COMPETITIVE MODULATION OF CATALYSIS BY DIPEPTIDYLPEPTIDASE IV RU2003105463A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP01114796.4 2001-06-27
EP01114796 2001-06-27

Publications (1)

Publication Number Publication Date
RU2003105463A true RU2003105463A (en) 2004-11-27

Family

ID=8177756

Family Applications (2)

Application Number Title Priority Date Filing Date
RU2003105463/04A RU2003105463A (en) 2001-06-27 2002-06-27 PEPTIDE STRUCTURES SUITABLE FOR COMPETITIVE MODULATION OF CATALYSIS BY DIPEPTIDYLPEPTIDASE IV
RU2003105464/15A RU2299066C2 (en) 2001-06-27 2002-06-27 Novel inhibitors of dipeptidyl peptidase iv and their using as anticancer agents

Family Applications After (1)

Application Number Title Priority Date Filing Date
RU2003105464/15A RU2299066C2 (en) 2001-06-27 2002-06-27 Novel inhibitors of dipeptidyl peptidase iv and their using as anticancer agents

Country Status (8)

Country Link
EP (1) EP1399469A2 (en)
JP (1) JP2004530729A (en)
CN (2) CN1471538A (en)
CA (1) CA2419888A1 (en)
NO (1) NO20030900L (en)
RU (2) RU2003105463A (en)
WO (1) WO2003002593A2 (en)
ZA (3) ZA200301312B (en)

Families Citing this family (111)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MY140561A (en) 2002-02-20 2009-12-31 Nycomed Gmbh Dosage form containing pde 4 inhibitor as active ingredient
DE10211555A1 (en) * 2002-03-15 2003-10-02 Imtm Inst Fuer Medizintechnolo Use of the inhibitors of enzymes with activities of the aminopeptidase N and / or the dipeptidyl peptidase IV and pharmaceutical preparations thereof for the therapy and prevention of dermatological diseases with sebocytic hyperproliferation and changed differentiation states
US7105526B2 (en) 2002-06-28 2006-09-12 Banyu Pharmaceuticals Co., Ltd. Benzimidazole derivatives
US7772188B2 (en) 2003-01-28 2010-08-10 Ironwood Pharmaceuticals, Inc. Methods and compositions for the treatment of gastrointestinal disorders
US7550590B2 (en) 2003-03-25 2009-06-23 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
JP4806628B2 (en) 2003-05-05 2011-11-02 プロビオドルグ エージー Glutaminyl cyclase inhibitor
WO2004098625A2 (en) 2003-05-05 2004-11-18 Probiodrug Ag Medical use of inhibitors of glutaminyl and glutamate cyclases
KR20100106630A (en) 2003-05-05 2010-10-01 프로비오드룩 아게 Use of effectors of glutaminyl and glutamate cyclases
US7169926B1 (en) 2003-08-13 2007-01-30 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
ZA200602051B (en) 2003-08-13 2007-10-31 Takeda Pharmaceutical 4-pyrimidone derivatives and their use as peptidyl peptidase inhibitors
US7678909B1 (en) 2003-08-13 2010-03-16 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
WO2005026148A1 (en) 2003-09-08 2005-03-24 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
BRPI0415409A (en) 2003-10-15 2006-12-05 Probiodrug Ag use of glutaminyl and glutamate cyclase effectors
EP2338490A3 (en) 2003-11-03 2012-06-06 Probiodrug AG Combinations useful for the treatment of neuronal disorders
KR20170005163A (en) 2003-11-17 2017-01-11 노파르티스 아게 Use of dipeptidyl peptidase iv inhibitors
EP2165703A3 (en) 2004-01-20 2012-03-28 Novartis Pharma AG Direct compression formulation and process
BRPI0507485A (en) 2004-02-05 2007-07-10 Probiodrug Ag new glutaminyl cyclase inhibitors
US7732446B1 (en) 2004-03-11 2010-06-08 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
CN102127053A (en) 2004-03-15 2011-07-20 武田药品工业株式会社 Dipeptidyl peptidase inhibitors
CN1938286A (en) 2004-03-29 2007-03-28 默克公司 Diaryltriazoles as inhibitors of 11-beta-hydroxysteroid dehydrogenase-1
EP1734963A4 (en) 2004-04-02 2008-06-18 Merck & Co Inc Method of treating men with metabolic and anthropometric disorders
US7687638B2 (en) 2004-06-04 2010-03-30 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
WO2006019965A2 (en) 2004-07-16 2006-02-23 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
ATE553077T1 (en) 2004-07-23 2012-04-15 Nuada Llc PEPTIDATE INHIBITORS
US7915252B2 (en) 2004-08-06 2011-03-29 Merck Sharp & Dohme Sulfonyl compounds as inhibitors of 11-beta-hydroxysteroid dehydrogenase-1
US7872124B2 (en) 2004-12-21 2011-01-18 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
JP5068174B2 (en) 2004-12-23 2012-11-07 カンピナ ネーデルランド ホールディング ビー．ブイ． Protein hydrolyzate concentrated in peptides inhibiting DPP-IV and uses thereof
DOP2006000008A (en) 2005-01-10 2006-08-31 Arena Pharm Inc COMBINED THERAPY FOR THE TREATMENT OF DIABETES AND RELATED AFFECTIONS AND FOR THE TREATMENT OF AFFECTIONS THAT IMPROVE THROUGH AN INCREASE IN THE BLOOD CONCENTRATION OF GLP-1
RU2417985C2 (en) 2005-05-30 2011-05-10 Баниу Фармасьютикал Ко., Лтд. Novel piperidine derivatives
JP2011201923A (en) * 2005-07-01 2011-10-13 Snow Brand Milk Products Co Ltd Dipeptidyl peptidase iv inhibitor
AU2006282260A1 (en) 2005-08-24 2007-03-01 Msd K.K. Phenylpyridone derivative
EP1939194A4 (en) 2005-09-07 2010-12-08 Banyu Pharma Co Ltd Bicyclic aromatic substituted pyridone derivative
BRPI0616463A2 (en) 2005-09-29 2011-06-21 Merck & Co Inc compound, pharmaceutical composition, and use of a compound
AU2006307046A1 (en) 2005-10-27 2007-05-03 Msd K.K. Novel benzoxathiin derivative
NZ568292A (en) 2005-11-10 2011-08-26 Msd Kk Spiro[cyclohexane-1,1'-(3'H)-4'-azaisobenzofuran]-4-carboxamide derivatives
WO2007054577A1 (en) 2005-11-14 2007-05-18 Probiodrug Ag Cyclopropyl-fused pyrrolidine derivatives as dipeptidyl peptidase iv inhibitors
EP1954299B1 (en) 2005-11-30 2016-01-13 Campina Nederland Holding B.V. Use of a protein hydrolysate for enhancing activity of glucagon-like peptide-1
EP1801098A1 (en) 2005-12-16 2007-06-27 Merck Sante 2-Adamantylurea derivatives as selective 11B-HSD1 inhibitors
PE20071221A1 (en) 2006-04-11 2007-12-14 Arena Pharm Inc GPR119 RECEPTOR AGONISTS IN METHODS TO INCREASE BONE MASS AND TO TREAT OSTEOPOROSIS AND OTHER CONDITIONS CHARACTERIZED BY LOW BONE MASS, AND COMBINED THERAPY RELATED TO THESE AGONISTS
EP2007734A1 (en) 2006-04-12 2008-12-31 Probiodrug AG Enzyme inhibitors
CA2664113C (en) 2006-09-22 2013-05-28 Merck & Co., Inc. Use of platencin and platensimycin as fatty acid synthesis inhibitors to treat obesity, diabetes and cancer
JPWO2008038692A1 (en) 2006-09-28 2010-01-28 萬有製薬株式会社 Diaryl ketimine derivatives
WO2008055945A1 (en) 2006-11-09 2008-05-15 Probiodrug Ag 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases
ATE554085T1 (en) 2006-11-30 2012-05-15 Probiodrug Ag NEW INHIBITORS OF GLUTAMINYL CYCLASE
EP1935420A1 (en) 2006-12-21 2008-06-25 Merck Sante 2-Adamantyl-butyramide derivatives as selective 11beta-HSD1 inhibitors
CA2682727C (en) 2007-04-02 2016-03-22 Banyu Pharmaceutical Co., Ltd. Indoledione derivative
JP5667440B2 (en) 2007-04-18 2015-02-12 プロビオドルグ エージー Thiourea derivatives as glutaminyl cyclase inhibitors
AU2008248186B2 (en) 2007-05-07 2014-02-06 Merck Sharp & Dohme Corp. Method of treatment using fused aromatic compounds having anti-diabetic activity
MX354786B (en) 2007-06-04 2018-03-21 Synergy Pharmaceuticals Inc AGONISTS OF GUANYLATE CYCLASE USEFUL FOR THE TREATMENT OF GASTROINTESTINAL DISORDERS, INFLAMMATION, CANCER and OTHER DISORDERS.
US8969514B2 (en) 2007-06-04 2015-03-03 Synergy Pharmaceuticals, Inc. Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
CA2714617A1 (en) 2008-03-06 2009-09-11 Banyu Pharmaceutical Co., Ltd. Alkylaminopyridine derivative
US20110015198A1 (en) 2008-03-28 2011-01-20 Banyu Pharmaceutical Co., Inc. Diarylmethylamide derivative having melanin-concentrating hormone receptor antagonism
EP2146210A1 (en) 2008-04-07 2010-01-20 Arena Pharmaceuticals, Inc. Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditions modulated by PYY
EP2110374A1 (en) 2008-04-18 2009-10-21 Merck Sante Benzofurane, benzothiophene, benzothiazol derivatives as FXR modulators
CA2726917C (en) 2008-06-04 2018-06-26 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
EP2301936A1 (en) 2008-06-19 2011-03-30 Banyu Pharmaceutical Co., Ltd. Spirodiamine-diarylketoxime derivative
WO2010009319A2 (en) 2008-07-16 2010-01-21 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders
EP2319841A1 (en) 2008-07-30 2011-05-11 Msd K.K. (5-membered)-(5-membered) or (5-membered)-(6-membered) fused ring cycloalkylamine derivative
CA2741125A1 (en) 2008-10-22 2010-04-29 Merck Sharp & Dohme Corp. Novel cyclic benzimidazole derivatives useful anti-diabetic agents
EP2350010B1 (en) 2008-10-30 2014-03-26 Merck Sharp & Dohme Corp. Isonicotinamide orexin receptor antagonists
CN102271509A (en) 2008-10-31 2011-12-07 默沙东公司 Novel cyclic benzimidazole derivatives useful anti-diabetic agents
JP5514831B2 (en) 2008-11-17 2014-06-04 メルク・シャープ・アンド・ドーム・コーポレーション Substituted bicyclic amines for the treatment of diabetes
AR077642A1 (en) 2009-07-09 2011-09-14 Arena Pharm Inc METABOLISM MODULATORS AND THE TREATMENT OF DISORDERS RELATED TO THE SAME
CA2768577A1 (en) 2009-07-23 2011-01-27 Schering Corporation Benzo-fused oxazepine compounds as stearoyl-coenzyme a delta-9 desaturase inhibitors
WO2011011506A1 (en) 2009-07-23 2011-01-27 Schering Corporation Spirocyclic oxazepine compounds as stearoyl-coenzyme a delta-9 desaturase inhibitors
SG178953A1 (en) 2009-09-11 2012-04-27 Probiodrug Ag Heterocylcic derivatives as inhibitors of glutaminyl cyclase
WO2011058193A1 (en) 2009-11-16 2011-05-19 Mellitech [1,5]-diazocin derivatives
WO2011079778A1 (en) 2009-12-30 2011-07-07 China Shanghai Fochon Pharmaceutical Co Ltd 3-(3-aminopiperidin-1-yl)-5-oxo-1,2,4-triazine derivates as dipeptidyl peptidase iv(dpp-iv) inhibitors
US8895596B2 (en) 2010-02-25 2014-11-25 Merck Sharp & Dohme Corp Cyclic benzimidazole derivatives useful as anti-diabetic agents
US9181233B2 (en) 2010-03-03 2015-11-10 Probiodrug Ag Inhibitors of glutaminyl cyclase
AU2011226074B2 (en) 2010-03-10 2015-01-22 Vivoryon Therapeutics N.V. Heterocyclic inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5)
CN102918027A (en) 2010-04-06 2013-02-06 艾尼纳制药公司 Modulators of the gpr119 receptor and the treatment of disorders related thereto
US8541596B2 (en) 2010-04-21 2013-09-24 Probiodrug Ag Inhibitors
US20130156720A1 (en) 2010-08-27 2013-06-20 Ironwood Pharmaceuticals, Inc. Compositions and methods for treating or preventing metabolic syndrome and related diseases and disorders
US9616097B2 (en) 2010-09-15 2017-04-11 Synergy Pharmaceuticals, Inc. Formulations of guanylate cyclase C agonists and methods of use
BR112013008100A2 (en) 2010-09-22 2016-08-09 Arena Pharm Inc "gpr19 receptor modulators and the treatment of disorders related thereto."
EP2677869B1 (en) 2011-02-25 2017-11-08 Merck Sharp & Dohme Corp. Novel cyclic azabenzimidazole derivatives useful as anti-diabetic agents
US9580471B2 (en) 2011-03-01 2017-02-28 Synergy Pharmaceuticals, Inc. Process of preparing guanylate cyclase C agonists
ES2570167T3 (en) 2011-03-16 2016-05-17 Probiodrug Ag Benzimidazole derivatives as glutaminyl cyclase inhibitors
WO2012135570A1 (en) 2011-04-01 2012-10-04 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
US20140066369A1 (en) 2011-04-19 2014-03-06 Arena Pharmaceuticals, Inc. Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto
US20140051714A1 (en) 2011-04-22 2014-02-20 Arena Pharmaceuticals, Inc. Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto
US20140038889A1 (en) 2011-04-22 2014-02-06 Arena Pharmaceuticals, Inc. Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto
WO2012170702A1 (en) 2011-06-08 2012-12-13 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
WO2013055910A1 (en) 2011-10-12 2013-04-18 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
AR088352A1 (en) 2011-10-19 2014-05-28 Merck Sharp & Dohme ANTAGONISTS OF THE RECEIVER OF 2-PIRIDILOXI-4-NITRILE OREXINE
CN106831980B (en) * 2011-11-04 2020-09-15 株式会社日皮 DPP-4 inhibitor
EP2824110A4 (en) * 2012-03-09 2015-12-30 Morinaga Milk Industry Co Ltd Dipeptidyl peptidase-iv inhibitor
CA2880901A1 (en) 2012-08-02 2014-02-06 Merck Sharp & Dohme Corp. Antidiabetic tricyclic compounds
WO2014074668A1 (en) 2012-11-08 2014-05-15 Arena Pharmaceuticals, Inc. Modulators of gpr119 and the treatment of disorders related thereto
WO2014130608A1 (en) 2013-02-22 2014-08-28 Merck Sharp & Dohme Corp. Antidiabetic bicyclic compounds
EP2970119B1 (en) 2013-03-14 2021-11-03 Merck Sharp & Dohme Corp. Novel indole derivatives useful as anti-diabetic agents
WO2014151200A2 (en) 2013-03-15 2014-09-25 Synergy Pharmaceuticals Inc. Compositions useful for the treatment of gastrointestinal disorders
EP2970384A1 (en) 2013-03-15 2016-01-20 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase and their uses
JP6606491B2 (en) 2013-06-05 2019-11-13 シナジー ファーマシューティカルズ インコーポレイテッド Ultra high purity agonist of guanylate cyclase C, method for producing and using the same
AU2014323008B2 (en) 2013-09-23 2018-02-08 Dr. August Wolff Gmbh & Co. Kg Arzneimittel Anti-inflammatory tripeptides
WO2015051496A1 (en) 2013-10-08 2015-04-16 Merck Sharp & Dohme Corp. Antidiabetic tricyclic compounds
DK3186242T3 (en) 2014-08-29 2021-12-20 Tes Pharma S R L ALFA-AMINO-BETA-CARBOXYMUCONSIDE-SEMIALDEHYDE-DECARBOXYLASE INHIBITORS
GB201415598D0 (en) 2014-09-03 2014-10-15 Univ Birmingham Elavated Itercranial Pressure Treatment
AU2016229982B2 (en) 2015-03-09 2020-06-18 Intekrin Therapeutics, Inc. Methods for the treatment of nonalcoholic fatty liver disease and/or lipodystrophy
CN105362272A (en) * 2015-12-14 2016-03-02 上海壹志医药科技有限公司 Pharmaceutical application of rotundine
AR109950A1 (en) 2016-10-14 2019-02-06 Tes Pharma S R L A-AMINO-b-CARBOXIMUCONIC SEMIAL DEHYDE DECARBOXYLASE ACID INHIBITORS
EP3551176A4 (en) 2016-12-06 2020-06-24 Merck Sharp & Dohme Corp. Antidiabetic heterocyclic compounds
WO2018118670A1 (en) 2016-12-20 2018-06-28 Merck Sharp & Dohme Corp. Antidiabetic spirochroman compounds
EP3606527A1 (en) 2017-04-03 2020-02-12 Coherus Biosciences, Inc. Ppar-gamma agonist for treatment of progressive supranuclear palsy
ES2812698T3 (en) 2017-09-29 2021-03-18 Probiodrug Ag Glutaminyl cyclase inhibitors
KR20210111248A (en) 2018-11-20 2021-09-10 테스 파마 에스.알.엘. Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
US11098029B2 (en) 2019-02-13 2021-08-24 Merck Sharp & Dohme Corp. 5-alkyl pyrrolidine orexin receptor agonists
EP4010314B1 (en) 2019-08-08 2024-02-28 Merck Sharp & Dohme LLC Heteroaryl pyrrolidine and piperidine orexin receptor agonists
CN110551203B (en) * 2019-09-25 2023-02-10 成都奥达生物科技有限公司 Exenatide analogue
TW202227417A (en) 2020-08-18 2022-07-16 美商默沙東藥廠 Bicycloheptane pyrrolidine orexin receptor agonists

Also Published As

Publication number Publication date
CN1471538A (en) 2004-01-28
NO20030900D0 (en) 2003-02-26
RU2299066C2 (en) 2007-05-20
JP2004530729A (en) 2004-10-07
WO2003002593A3 (en) 2003-09-04
CA2419888A1 (en) 2003-01-09
EP1399469A2 (en) 2004-03-24
ZA200300833B (en) 2004-02-10
ZA200301312B (en) 2004-03-30
ZA200300595B (en) 2004-02-13
WO2003002593A2 (en) 2003-01-09
CN1688599A (en) 2005-10-26
NO20030900L (en) 2003-04-24

Similar Documents

Publication Publication Date Title
RU2003105463A (en) PEPTIDE STRUCTURES SUITABLE FOR COMPETITIVE MODULATION OF CATALYSIS BY DIPEPTIDYLPEPTIDASE IV
ES2572952T3 (en) Glucagon analogs showing physiological solubility and stability
AU2017216533B2 (en) Improved peptide pharmaceuticals
ES2302390T3 (en) GLP-1 ANALOGS
RU2288232C9 (en) Glp-1 analogs
ES2319936T3 (en) METHODS TO REGULATE GASTROINTESTINAL MOTILITY.
JP2011001381A (en) Glp-1 pharmaceutical composition
JP2005529862A5 (en)
JP2006213716A (en) New amylin agonist peptide and use therefor
JP2005530732A5 (en)
RU2003109746A (en) SYNTHETIC PROTEINS STIMULATING ERYTHROPOESIS
JP2013537879A (en) Site-specific PEG-modified exendin-4 analogs and uses thereof
EP3840774A1 (en) Acylated calcitonin mimetics
CA2069943A1 (en) Synthetic calcitonin peptides
ES2393335T3 (en) GLP-1 analogues
EP4021929A1 (en) Ham15-52 analogues with improved amylin receptor (hamy3r) potency
WO2015180634A1 (en) Long-acting enterocrinin polypeptide analogue for treating type 2 diabetes and uses thereof
ES2356595T3 (en) NEW MIXED ACTIVITY COMPOUNDS OF THE AMILINA.
US20240116998A1 (en) Glucagon-like peptide-1 receptor antagonists
US20210371463A1 (en) Modified Netrin-1 Peptides and Compositions for Cardioprotection
JP2009502976A (en) Peptide conjugates for oral delivery of hydrophilic peptide analgesics
DK2773365T3 (en) Peptide FOR THE TREATMENT OF DISEASES AND DISORDERS
CN1935839B (en) Analogues of GLP-1
MX2022008748A (en) Oral peptide administration.
TW202415676A (en) Glucagon-like peptide-1 receptor antagonists

Legal Events

Date Code Title Description
FA93 Acknowledgement of application withdrawn (no request for examination)

Effective date: 20050722