WO1997015568A1 - Antagoniste du recepteur de fibrinogene - Google Patents

Antagoniste du recepteur de fibrinogene Download PDF

Info

Publication number
WO1997015568A1
WO1997015568A1 PCT/US1996/016882 US9616882W WO9715568A1 WO 1997015568 A1 WO1997015568 A1 WO 1997015568A1 US 9616882 W US9616882 W US 9616882W WO 9715568 A1 WO9715568 A1 WO 9715568A1
Authority
WO
WIPO (PCT)
Prior art keywords
mammal
inhibiting
fibrinogen
compound
aggregation
Prior art date
Application number
PCT/US1996/016882
Other languages
English (en)
Inventor
John H. Hutchinson
Wasyl Halczenko
Original Assignee
Merck & Co., Inc.
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 GBGB9603245.3A external-priority patent/GB9603245D0/en
Application filed by Merck & Co., Inc. filed Critical Merck & Co., Inc.
Priority to EP96936810A priority Critical patent/EP0863893A1/fr
Priority to AU74640/96A priority patent/AU702025B2/en
Priority to JP9516710A priority patent/JPH11513980A/ja
Publication of WO1997015568A1 publication Critical patent/WO1997015568A1/fr

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Definitions

  • a number of low molecular weight polypeptide factors have been isolated from snake venom. These factors apparently have high affinity for the gp Ilb/IlIa complex.
  • Huang et al., J. Biol Chem., 262, 16157-16163 (1987); Huang et al., Biochemistry, 28, 661-666 (1989) describe the primary structure of the venom trigramin which is a 72 amino acid polypeptide that contains the RGD subunit.
  • Echistatin is another compound which has high affinity for the gp Ilb/DIa complex. This polypeptide contains 49 amino acids and has the RGD subunit and various disulfide bridges.
  • WO 9014103 describes the use of antibody-poly-peptide conjugates wherein said polypeptides contain the Arg-Gly-Asp (RGD) sequence.
  • ADP-stimulated platelet aggregation assay used to determine inhibition associated with the compounds claimed in the instant invention, human platelets are isolated from fresh blood, collected into acid citrate/dextrose by differential centrifugation followed by gel filtration on Sepharose 2B in divalent ion-free Tyrode's buffer (pH 7.4) containing 2% bovine serum albumin. Platelet aggregation is measured at 37°C in a Chronolog aggregometer.
  • benzenesulfonate benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, calcium edetate, camsylate, carbonate, chloride, clavulanate, citrate, dihydrochloride, edetate, edisylate, estolate, esylate, fumarate, gluceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynapthoate, iodide, isothionate, lactate, lactobionate, laurate, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulfate, mucate, napsylate, nitrate, oleate, oxalate, pamaote, palmitate, panthothenate, phosphate/diphosphat
  • pharmaceutically effective amount shall mean that amount of a drug or pharmaceutical agent that will elicit the
  • the active drug can form the active ingredient, and is typically administered in admixture with suitable pharmaceutical diluents, excipients or carriers (collectively referred to herein as "carrier” materials) suitably selected with respect to the intended form of administration, that is, oral tablets, capsules, elixirs, syrups and the like, and consistent with convention pharmaceutical practices.
  • carrier suitable pharmaceutical diluents, excipients or carriers
  • Suitable binders include starch, gelatin, natural sugars such as glucose or beta-lactose, corn-sweeteners, natural and synthetic gums such as acacia, tragacanth or sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes and the like.
  • Lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and the like.
  • Disintegrators include, without limitation, starch methyl cellulose, agar, bentonite, xanthan gum and the like.
  • 1 -8b was prepared as described above for 1 -8a using ethanol rather than methanol in the conversion of 1-1 to 1-2.
  • All of the active compound, cellulose, and a portion of the com starch are mixed and granulated to 10% com starch paste.
  • the resulting granulation is sieved, dried and blended with the remainder of the com starch and the magnesium stearate.
  • the resulting granulation is then compressed into tablets containing 25.0, 50.0, and 100.0 mg, respectively, of active ingredient per tablet.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Cette invention concerne un antagoniste du récepteur de fibrinogène, la 5-[(4-Pipéridinyl)méthoxy]-2-indolecarbonyl-2(S)-phénylsulfonyl-amino- beta -alanine.
PCT/US1996/016882 1995-10-26 1996-10-22 Antagoniste du recepteur de fibrinogene WO1997015568A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP96936810A EP0863893A1 (fr) 1995-10-26 1996-10-22 Antagoniste du recepteur de fibrinogene
AU74640/96A AU702025B2 (en) 1995-10-26 1996-10-22 Fibrinogen receptor antagonist
JP9516710A JPH11513980A (ja) 1995-10-26 1996-10-22 線維素原受容体拮抗薬

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US589095P 1995-10-26 1995-10-26
US60/005,890 1995-10-26
GB9603245.3 1996-02-16
GBGB9603245.3A GB9603245D0 (en) 1996-02-16 1996-02-16 Fibrinogen receptor antagonist

Publications (1)

Publication Number Publication Date
WO1997015568A1 true WO1997015568A1 (fr) 1997-05-01

Family

ID=26308724

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1996/016882 WO1997015568A1 (fr) 1995-10-26 1996-10-22 Antagoniste du recepteur de fibrinogene

Country Status (5)

Country Link
EP (1) EP0863893A1 (fr)
JP (1) JPH11513980A (fr)
AU (1) AU702025B2 (fr)
CA (1) CA2233861A1 (fr)
WO (1) WO1997015568A1 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994008962A1 (fr) * 1992-10-14 1994-04-28 Merck & Co., Inc. Antagonistes des recepteurs du fibrinogene

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994008962A1 (fr) * 1992-10-14 1994-04-28 Merck & Co., Inc. Antagonistes des recepteurs du fibrinogene

Also Published As

Publication number Publication date
AU702025B2 (en) 1999-02-11
AU7464096A (en) 1997-05-15
CA2233861A1 (fr) 1997-05-01
EP0863893A1 (fr) 1998-09-16
JPH11513980A (ja) 1999-11-30

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