Aktiebolaget Hassle

Aktiebolaget Astra

Ab Hassle

Arne E Brandstrom

Per L Lindberg

Gunnel E Sunden

Bjorn M Wallmark

Bo R Lamm

Carl I Starke

Stig Ake Carlsson

Enar I Carlsson

Peder Bernhard Berntsson

Gert C Strandlund

Lars Ek

Sven E Sjostrand

Benny Roger Samuelsson

Mats P Nordberg

Bengt A Ablad

Kjell F Ankner

The novel compounds of the formulas I and I' ##STR1## wherein F is in 5 or 6 position and ##STR2## wherein in both formulas R is the group --CH.sub.2 OCOOR.sup.1, wherein R.sup.1 is a straight or branched alkyl containing 1-6 carbon atoms or benzyl, or R.sup.1 is the group ##STR3## wherein n is 1-6 and physiologically acceptable salts thereof as well as intermediates, pharmaceutical compositions containing such compounds as active ingredient, and the use of the compounds in medicine.

Therapeutically active fluoro substituted benzimidazoles

The present invention relates to an improved method for the synthesis of omeprazole, comprising the steps of reacting 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methylthio]-1H-benzimida zole with m-chloroperoxybenzoic acid in a methylene chloride solution at a substantially constant pH of about 8.0 to 8.6; extracting the reaction mixture with aqueous NaOH; separating the aqueous phase from the organic phase; and adding an alkyl formate to the aqueous phase, resulting in crystallization of omeprazole.

Method of synthesis of

The novel compounds of the formulas I and I' ##STR1## wherein F is in 5 or 6 position and ##STR2## wherein in both formulas R is the group --CH.sub.2 OCOOR.sup.1, wherein R.sup.1 is a straight or branched alkyl containing 1-6 carbon atoms or benzyl, or R.sup.1 is the group ##STR3## --(CH.sub.2).sub.n COOH or --(CH.sub.2).sub.n SO.sub.3 H wherein n is 1-6 and physiologically acceptable salts thereof as well as intermediates, pharmaceutical compositions containing such compounds as active ingredient, and the use of the compounds in medicine.

The novel compound 5-fluoro-2[[(4-cyclopropylmethoxy-2-pyridinyl)methyl]sulfinyl]-1H-benzimid azole and physiologically acceptable salts thereof as well as intermediates, pharmaceutical compositions containing the compound as active ingredient, and the use of the compound in medicine.

Therapeutically active cyclopropyl substituted compound

The novel compound 4-fluoro-2-[[(4-methoxy-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole and physiologically acceptable salts thereof as well as intermediates, pharmaceutical compositions containing such compounds as active ingredient, and the use of the compound in medicine.

Therapeutically active fluoro-substituted compound

5-Chloro-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole and physiologically acceptable salts thereof as well as an intermediate, pharmaceutical compositions containing such compound as active ingredient, and the use of the compound in medicine.

Therapeutically active chloro substituted benzimidazole

The novel compound 5-fluoro-2[[(4-cyclopropylmethoxy-2-pyridinyl) methyl]sulfinyl]-1H-benzimidazole and physiologically acceptable salts thereof as well as intermediates, pharmaceutical compositions containing the compound as active ingredient, and the use of the compound in medicine.

Therapeutically active compound and a process for its preparation

The novel compounds of the formula I ##STR1## wherein Cl is in 5 or 6 position and whereby R is the group --CH.sub.2 OCOOR.sup.1, wherein R.sup.1 is a straight or branched alkyl containing 1-6 carbon atoms or benzyl,

Therapeutically active chloro substituted benzimidazoles

Novel salts of omeprazole with Li.sup.+, Na.sup.+, K.sup.+, Mg.sup.2+, Ca.sup.2+, Ti.sup.4+, N.sup.+ (R.sup.1).sub.4 or ##STR1## as cation; processes for their preparation thereof, pharmaceutical compositions containing such salts and their use in medicine.

Base addition salts of omeprazole

Novel compounds of the formula IIIa ##STR1## wherein R.sup.1a, R.sup.2a, R.sup.3a and R.sup.4a are the same or different and are hydrogen, an alkyl, alkoxy optionally completely or predominantly substituted by fluorine or chlorine, halogen, --CN, --CF.sub.3, --NO.sub.2, --COR, --COOR, aryl, aryloxy or arylalkoxy group, or adjacent groups R.sup.1a, R.sup.2a, R.sup.3a and R.sup.4a together with the adjacent carbon atoms in the benzimidazole ring form a 5-, 6- or 7-membered monocyclic ring or a 9-, 10- or 11-membered bicyclic ring, which rings may be saturated or unsaturated and may contain 0-3 heteroatoms selected from N and O and which rings may be optionally substituted with 1-4 substitutents selected from alkyl groups with 1-3 carbon atoms, halogen preferably F or Cl, alkylene radicals containing 4-5 carbon atoms giving spiro compounds, or two or four of these substituents together form one or two oxy groups ##STR2## whereby if R.sup.1a, R.sup.2a, R.sup.3a and R.sup.4a together with the adjacent carbon atoms in the benzimidazole ring form two rings they may be condensed with each other, R.sup.5a is hydrogen or an alkyl group, R.sup.6a is hydrogen or an alkyl group or R.sup.5a and R.sup.6a are joined together to form an alkylene chain, R.sup.7a is hydrogen, an alkyl, alkoxy, alkenyloxy or alkynyloxy group, R.sup.8a is hydrogen or an alkyl group, or R.sup.6a and R.sup.7a, or R.sup.7a and R.sup.8a together with the adjacent carbon atoms in the pyridinium ring form a ring wherein the part constituted by R.sup.6a and R.sup.7a or R.sup.7a and R.sup.8a, is --CH.dbd.CH--CH.dbd.CH--, --O--(CH.sub.2).sub.p --, --CH.sub.2 (CH.sub.2).sub.p --, --O--CH.dbd.CH--, --NH--CH.dbd.CH--, ##STR3## or --S--(CH.sub.2).sub.p --, wherein p is 2, 3 or 4 and the O, S and N atoms always are attached to position 3 in the compound IIIa, R is a alkyl, cycloalkyl, aryl or arylalkyl group, and X.sup.- is a pharmaceutically acceptable anion, process for preparation thereof, pharmaceutical compositions containing such compounds and their use in medicine.

2-[8-quinolinyl]-sulphinyl-1H-benzimidazole

Novel compounds of the formula I ##STR1## and its salts; process for the preparation thereof, pharmaceutical compositions containing such compounds and their use in medicine to affect gastric acid secretion and provide gastrointestinal cytoprotection.

Substituted 2-pyridinyl benzimidazoles, and their use for inhibiting

Novel compounds of the formula IIIa ##STR1## wherein R.sup.1a, R.sup.2a, R.sup.3a and R.sup.4a are the same or different and are hydrogen, an alkyl, alkoxy optionally completely or predominantly substituted by fluorine or chlorine, halogen, --CN, --CF.sub.3, --NO.sub.2, --COR, --COOR, aryl, aryloxy or arylalkoxy group, or adjacent groups R.sup.1a, R.sup.2a, R.sup.3a and R.sup.4a together with the adjacent carbon atoms in the benzimidazole ring form a 5-, 6- or 7-membered monocyclic ring or a 9-, 10- or 11-membered bicyclic ring, which rings may be saturated or unsaturated and may contain 0-3 heteroatoms selected from N and O and which rings may be optionally substituted with 1-4 substitutents selected from alkyl groups with 1-3 carbon atoms, halogen perferably F or Cl, alkylene radicals containing 4-5 carbon atoms giving spiro compounds, or two or four of these substituents together form one or two oxy groups ##STR2## whereby if R.sup.1a, R.sup.2a, R.sup.3a and R.sup.4a together with the adjacent carbon atoms in the benzimidazole ring form two rings they may be condensed with each other, R.sup.5a is hydrogen or an alkyl group, R.sup.6a is hydrogen or an alkyl group or R.sup.5a and R.sup.6a are joined together to form an alkylene chain, R.sup.7a is hydrogen, an alkyl, alkoxy, alkenyloxy, or alkynyloxy group, R.sup.8a is hydrogen or an alkyl group, or R.sup.6a and R.sup.7a, or R.sup.7a and R.sup.8a together with the adjacent carbon atoms in the pyridinium ring form a ring wherein the part constituted by R.sup.6a and R.sup.7a or R.sup.7a and R.sup.8a, is --CH.dbd.CH--CH.dbd.CH--, --O--(CH.sub.2).sub.p --, --CH.sub.2 (CH.sub.2).sub.p --, --O--CH.dbd.CH--, --NH--CH.dbd.CH--, ##STR3## or --S--(CH.sub.2).sub.p --, wherein p is 2, 3 or 4 and the O, S and N atoms always are attached to position 3 in the compound IIIa, R is an alkyl, cycloalkyl, aryl or arylalkyl group, and X.sup.- is a pharmaceutically acceptable anion, process for preparation thereof, pharmaceutical compositions containing such compounds and their use in medicine.

Sulphenamides

Novel compounds of the formula ##STR1## wherein R is H or CH.sub.3, a process for their preparation, and their use as intermediates in the preparation of pharmaceutically useful compounds, e.g. substituted benzimidazoles containing a pyridine radical, i.a. omeprazole.

Processes for the preparation of omeprazole and intermediates therefore

Certain pyridyl-N-oxide intermediates for the preparation of omeprazole

Ortho-para-substituted phenoxy-hydroxypropylamines having the general formula ##STR1## and pharmaceutically acceptable, non-toxic acid addition salts thereof, wherein R.sup.1 is alkyl or hydroxyalkyl, R.sup.2 is alkoxyalkyl or alkylthioalkyl, and R.sup.3 is halogen, alkyl, alkenyl, alkinyl, alkoxymethyl, or alkoxy are disclosed, as are methods for their preparation. Pharmaceutical preparations are prepared whose active ingredients include at least one of the newly discovered phenoxy-hydroxypropylamine compounds. Therapeutically effective doses of these preparations selectively block the .beta.-receptors of the heart making them useful in treating heart diseases in animals including humans.

Growing community of inventors

Goteborg, Sweden

Arne E Brandstrom