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AssigneeBASF SE
InventorsHans-Joachim Bohm, Stefan Koser, Helmut Mack, Thomas Pfeiffer, Werner Seitz, Hans Wolfgang Hoffken, Wilfried Hornberger, Thomas Zierke
Estimating the term…
Compounds of the formula I ##STR1## in which R.sup.1, A and B have the meanings stated in the description, and the preparation thereof are described. The novel compounds are suitable for controlling diseases.
A compound of the formula I ##STR16## and its stereoisomers and its salts with physiologically tolerated acids, in which the substituents have the following meanings:
Dependencies are inferred from the claim text.
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No references of this kind are recorded.
With the first amino acid being neutral: and aromatic or cycloaliphatic
Drugs for disorders of the blood or the extracellular fluid: antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
And aliphatic: the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
The side chain containing 2 to 4 carbon atoms: leu-amino acid
Term ended 5 Jun 2017 (estimated)
USPTO file history isn’t available for this patent, so only indexed dates are shown.
This application is a 371 of PCT/E95/04646 filed Nov. 25, 1995.
The present invention relates to dipeptide p-amidinobenzylamides with N-terminal sulfonyl or aminosulfonyl radicals, to the preparation thereof and to the use thereof as thrombin inhibitors.
EP 601 459 describes heterocyclic thrombin inhibitors which have a sulfonamide group.
a) Boc-D-Phenylalanylproline (p-cyanobenzyl)amide
2.0 g (14.6 mmol) of isobutyl chloroformate were added in 2 min to a solution of 5.1 g (14.2 mmol) of Boc-D-Phe-Pro-OH and 1.53 g (15.2 mmol) of N-methylmorpholine in 15 ml of DMF at -15.degree. C., the mixture was stirred for 10 min and then a solution of 1.9 g (14.2 mmol) of p-cyanobenzylamine (W. Walter et al., Ann. 660, 1962, 60) and 1.53 g of N-methylmorpholine in 3 ml of DMF was added. After stirring at -15.degree. C. for 3 h, a TLC check (CH.sub.2 Cl.sub.2 /MeOH, 9/1) showed no detectable starting compounds.
For isolation, the reaction mixture was poured into 200 ml of water, when an oil separated out and, after a short time, solidifed and was broken up and filtered off with suction. The still moist residue was dissolved in a mixture of 250 ml of ethyl acetate and 50 ml of ether and washed successively with a 5% strength aqueous citric acid, bicarbonate and saturated sodium chloride solutions. After drying over Na.sub.2 SO.sub.4, the solvent was removed by distillation under reduced pressure, and the residue was mixed with n-hexane and then filtered off with suction. Recrystallization from 50 ml of ethyl acetate afforded 5.6 g of TLC-pure product, m.p. 156.degree.-157.degree. C.