Hoffmann-La Roche Inc.

Klaus Muller

Paul Hadvary

Jean Ackermann

Kurt Hilpert

Georges Hirth

Richard Barner

David Banner

Beat Wirz

Hans Peter Wessel

Jean-Marie Cassal

Gerard Schmid

Klaus Gubernator

Thomas B Tschopp

Ludvik Labler

Daniel Obrecht

Kaspar Burri

Arnold Trzeciak

Alfred Grieder

Wilhelm Bannwarth

Andreas Knierzinger

Christine Abrecht

Fernand Gerber

Kasper F Burri

This invention is directed to tetrahydronaphthalene compounds of the formula ##STR1## wherein R.sup.1 is hydrogen, bromine, cyano, formyl, hydroxy, lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy, aryloxy, lower aralkoxy or aryl; R.sup.2 is an amino acid residue or a chain of 2 to 20 amino acid residues wherein reactive moieties in the side chains of the amino acid residue(s) is/are protected or unprotected, and wherein the amino group of the N-terminal amino acid is a free or protected amino group; A.sup.1, A.sup.2, A.sup.3 and A.sup.4 each are .alpha.-amino acid residues wherein A.sup.1 and A.sup.2 are in the L configuration and A.sup.3 and A.sup.4 are in the D configuration when the .alpha.-C atom of said .alpha.-amino acid residue is asymmetric; X is oxygen or sulphur; Y is a residue of the formula ##STR2## n is 0 or 1; R.sup.3 is hydrogen or lower alkyl; R.sup.4 is hydrogen or lower alkyl; and Z and the two C atoms together are an aromatic ring selected from the group of benzene, furan, thiophene, pyridine or pyrimidine, wherein said aromatic ring is substituted or unsubstituted; and salts thereof and their intermediates. The compounds are useful as mimetics of exposed helical domains of proteins in order to clarify their role with respect to interactions with other proteins or with DNA or RNA through .alpha.-helical conformation. They are therefore valuable aids in the determination of biologically active peptide sequences and are accordingly so-called 'research tools'. They are also potentially useful as medicaments.

Tetrahydronaphthalene compounds

There are described compounds of the formula ##STR1## Wherein the variables have been defined herein. The compounds are useful as research tools in the determination of biologically active peptides sequences and also potentially suitable as medicaments, some of them being useful in the prevention or control of the formation of blood platelet thrombi, and some compounds are useful as intermediates.

Tri- and tetracyclic compounds

Tri-and tetracyclic compounds

Compounds of the formula ##STR1## wherein L, M, R, T and X are set forth in the description, as well as hydrates or solvates thereof, which inhibit thrombin-induced platelet aggregation and clotting of fibrinogen in plasma, are described. The compounds of formula I are prepared by amidination or, depending on whether L is NH or O, by amide formation or esterification.

Guanidine derivatives

The present invention is concerned with tetrahydronaphthalene derivatives which are mimics of domains of peptides or proteins which can interact with other proteins or with DNA or RNA through .alpha.-helical conformation, said tetrahydronaphthalene derivatives having the formulae: ##STR1## are valuable aids in the determination of biologically active peptide sequences and are accordingly so-called 'research tools'. They are, however, also potentially suitable as medicaments.

Tetrahydronaphthalene derivatives

Guanidine derivatives compositions and use

Glycerine derivatives of the formula ##STR1## wherein the residues R.sup.1, R.sup.2 and R.sup.3 have the significance given in the description, and their hydrates, which inhibit blood platelet activating factor (PAF), are described.

Glycerin derivatives

Glycerol derivatives of the formula ##STR1## wherein one of the residues R.sup.1, R.sup.2 and R.sup.3 is a group U of the formula OY.sup.1 or --X.sup.1 --CO--(A.sup.1).sub.n --Z.sup.1, another residue is a group V of the formula OY.sup.2 or --X.sup.2 --CO--(A.sup.2).sub.p --Z.sup.2, and the remaining residue is a group W of the formula --X.sup.3 T--(C.sub.2-6 -alkylene)-N.sup.+ R A.sup.- in which one of X.sup.1, X.sup.2 and X.sup.3 is oxygen or NQ.sup.1 and the other two are oxygen and the remaining symbols have the significance given below, and their hydrates are described and are prepared by introducing or generating the residues R.sup.1, R.sup.2 and R.sup.3 in corresponding glycerol derivatives. The compounds of formula I are active as inhibitors of blood platelet activating factor or as inhibitors of the growth of tumors.

Glycerol derivatives

Glycerine derivatives of the formula ##STR1## wherein the residues R.sup.1, R.sup.2 and R.sup.3 have the significance given in the description, and their hydrates, which inhibit blood platelet activating factor (PAF), are descried.

Glycerin derivatives and inhibition of blood PAF

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Munchenstein, Switzerland

Klaus Muller