Merck Patent Gesellschaft MIT Beschrankter Haftung

Hans-Eckart Radunz

Dieter Orth

Manfred Baumgarth

Reinhard Lissner

Hans-Jochen Schliep

Hans-Joachim Enenkel

Jurgen Maisenbacher

Joachim Gante

Filippus J Zeelen

Josef Kramer

Bernhard Riefling

Ernst Schulze

Klaus-Otto Minck

Michael Wolf

Alfred Jonczyk

Hans-Adolf Kurmeier

Erich Schacht

Peter Raddatz

Claus J Schmitges

Albrecht Wild

Klaus Otto Minck

Gunter Holzemann

Michael Klockow

Johannes Sombroek

Klaus Irmscher

Peter Muller

Harry Schwartz

Wolf-Dietrich Weber

Willy Kinzy

Martin Heinrich

Ernst Schorscher

Hans U Reissig

Hans-Jurgen Legeler

Hanns-Gerd Dammann

Bernd Simon

Gerd-Albrecht Luckenbach

Thomas Doll

Diterpenes of the formula I ##STR1## in which R.sup.1 is --CH.sub.2 --C(CH.sub.3).dbd.CH--R.sup.3 or --CH.sub.2 --CH(CH.sub.3)--CH.sub.2 --R.sup.3,

Diterpenes having immunomodulatory action

The invention relates to a process for the enantiomer-selective preparation of .gamma.-keto-.delta.-amino acid derivatives of the formula I ##STR1## characterized in that a compound of the formula II ##STR2## is converted, using a trialkylchlorosilane, into a compound of the formula III ##STR3## this compound is then reacted with a diazoacetate of the formula N.sub.2 CH.sub.2 COOR.sup.4 (R.sup.4 .noteq.H) to give a cyclopropane compound of the formula IV ##STR4## and then the compound IV is converted, by ring-opening and removal of the silyl groups, and where appropriate saponification, into the compound of the formula I, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 having the meanings indicated in claim 1.

Process for the enantiomer-selective preparation of

In a process for the reduction of ketones, the keto compounds are enantioselectively reduced to give secondary alcohols by means of microorganisms. Keto compounds of the formula

Process for the enzymatic production of ketones

New salicylic acid derivatives of the general formula I ##STR1## in which R.sup.1 is H or CH.sub.3,

Salicylic acid derivatives

Statine-containing peptides useful in medicaments

Compounds of the formula ##STR1## wherein A is C--C single bond, --CH.sub.2 --, --CH(CH.sub.3)--, --C(CH.sub.3).sub.2 --, --CH.sub.2 --CH.sub.2 --, CH(CH.sub.3)CH.sub.2 --, --C(CH.sub.3).sub.2 CH.sub.2 --, --CH.sub.2 --CH.sub.2 --CH.sub.2 -- or --CH.sub.2 O--; R.sup.1a and R.sup.1 each independently is hydrogen or a protective group which can be cleaved by solvolysis or by hydrogenolysis; R.sup.2 is H or alkyl of 1 to 3 C atoms; R.sup.3 is alkyl of 3 to 5 C atoms, phenyl or phenyl which is monosubstituted to trisubstituted by F, Cl, OH, OCH.sub.3, OC.sub.2 H.sub.5, CF.sub.3 or alkyl of 1 to 3 C atoms, or, when A is not --CH.sub.2 O--, can also be pyridyl, thienyl, naphthyl or alkoxy of 1 to 4 C atoms;  indicates a bond in the .beta.-position and wavy line ( ) means that the bond can be in the .alpha.- or .beta.-position, are valuable intermediates for the stereospecific preparation of 13-thiaprostaglandin derivatives. The latter are prepared by U.V. irradiation of the former to first prepare the corresponding 2-oxa-3-OH-6-alkylthio-7-OH-1,5-bicyclo(3.3.0)octane derivative, which is then exposed to a Wittig reaction and, optionally, hydrogenation or oxidation inter alia to prepare members of the F.sub.1 -, F.sub.2 -, E.sub.1 - and E.sub.2 series.

New intermediates for the preparation of 13-thiaprostaglandin derivatives

Sulfur-containing 6-ketoprostaglandins of the formula I ##STR1## in which D is a bond, alkylene having 1-3 C atoms, cis-alkenylene having 2-5 C atoms or alkinylene having 2-5 C atoms,

Sulfur-containing 6-ketoprostaglandins

13-thiaprostaglandins of Formula I ##STR1## wherein B is --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH--,

13-thiaprostaglandins having cytoprotective activity

13-Thiaprostanoic acid derivatives of the general formula I ##STR1## wherein A is --CO-- or --CHOH--; B is --CH.sub.2 CH.sub.2 -- or --CH.dbd.CH--; Q is 1,4-phenylene or 1,4-naphthylene; R.sup.1 is H or OH; R.sup.2 is H or CH.sub.3 ; R.sup.3 is alkyl with 1-8 carbon atoms or alkyl with 1-8 carbon atoms substituted by (a) phenyl, (b) phenyl substituted by at least one of CH.sub.3, F, Cl, Br, OH, OCH.sub.3 or CF.sub.3 ; (c) phenoxy or (d) phenoxy substituted by at least one of CH.sub.3, F, Cl, Br, OH, OCH.sub.3 or CF.sub.3 ; and R.sup.4 is NH.sub.2, CH.sub.3, phenyl, p-acetylaminophenyl, p-benzoylaminophenyl or phenylamino. These compounds are useful for lowering blood pressure as well as for other pharmaceutical purposes. They also are useful intermediates for the preparation of other known pharmaceuticals such s the 13-thiaprostaglandins.

13-Thiaprostaglandin derivatives

Benzothiazole derivatives of the formula I ##STR1## wherein R.sup.1 is H or CH.sub.3 ; R.sup.2 is phenyl, tolyl, xylyl or pyridyl; R.sup.3 is OH, alkoxy of 1-4 C atoms or -NHCH.sub.2 CH.sub.2 OH; and R.sup.4 is H, Cl, Br, OH or alkoxy of 1-4 C atoms,

Benzothiazole derivatives and pharmaceutical formulations containing them

Phenothiazine derivatives of the formula ##STR1## wherein R is H, F, Cl, Br, I, CH.sub.3, CF.sub.3, CN, CH.sub.3 O or CH.sub.3 CO; Y is S, SO, or SO.sub.2 ; Z is imidazol-1-yl, 2-methyl-imidazol-1-yl, pyrazol-1-yl or benzimidazol-1-yl; and n is 1, 2 or 3; or the physiologically acceptable acid addition salts thereof; are useful as antihypertensive agents, for example.

Phenothiazine derivatives and a process for their preparation

Pyrazole derivatives of the formula ##STR1## wherein R.sup.1 is H or Cl; R.sup.2 is 1-methyl-4-piperidyloxy-carbonyl, 2-(4-phenylpiperazino)-ethoxycarbonyl, benzoxazol-2-yl, benzthiazol-2-yl, tetrazol-5-yl or 3-R.sup.3 -4-R.sup.4 -thiazolidin-2-yl; R.sup.3 is H, alkanoyl of 1-7 carbon atoms or benzoyl; and R.sup.4 is H or COOH,

Pyrazole derivatives, pharmaceutical formulations thereof

13-Thiaprostanoic acid derivatives of the formula ##STR1## wherein A is --CO-- or --CHOH--, B is --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH-- R.sup.1 is H or alkyl of 1 to 4 carbon atoms, m is a whole number from 0 to 5, n is a whole number from 0 to 3 or, when B is --CH.dbd.CH--, additionally 4, 5, 6, 7, 8 or 9, R.sup.2 is alkoxy of 1 to 4 carbon atoms, phenoxy, pyridyl, thienyl, naphthyl, phenyl substituted by F, Cl, Br, OH, OCH.sub.3 or OF.sub.3 or phenoxy substituted by F, Cl, Br, OH, OCH.sub.3, CH.sub.3 or CF.sub.3 or, when B is --CH.dbd.CH--, additionally hydrogen, phenyl or tolyl, R.sup.3 is H, methyl or ethyl, possess pharmacological activity, including blood pressure lowering activity.

Thiaprostaglandins

Compounds of formula ##STR1## their mirror images and racemic mixtures, and the physiologically acceptable salts thereof,

New prostaglandin-like diketals

Compounds of the Formula ##STR1## and the physiologically acceptable salts thereof, wherein R.sup.1 and R.sub.2 each is hydrogen or benzyl; R.sup.3 is alkyl of 5-10 C-atoms or 2-hydroxyalkyl of 5-10 C-atoms; R.sup.4 is hydrogen, methyl or ethyl; R.sup.5 is alkyl of 5-10 C-atoms or --C.sub.n H.sub.2n COOR.sup.6 ; R.sup.6 is hydrogen or alkyl of 1-4 C-atoms; and n is 0, 4, 5 or 6 are effective for inhibiting adhesion and/or agglomeration of thrombocytes.

Growing community of inventors

Muhltal, Germany

Hans-Eckart Radunz