Hoechst Aktiengesellschaft

Christoph Naumann

Hans-Jochen Lang

Dieter Regnat

Anne-Marie Moura

Jurgen K Sandow

Ahmed M Tafesh

Kazuyuki Kitamura

Mizuho Inazu

Katsuhiro Yoshikawa

Hans-Jerg Kleiner

Matthias Krull

Denis Carniato

Hans Jochen Lang

Matthias Beller

Christian Kohlpaintner

Ruth Raiss

Osamu Komiyama

Masakazu Katoh

Herrmann Hoffmann

Ryoichi Satoh

Yoshiko Terui

There are described compounds of the formula I ##STR1## in which R.sup.1 is (C.sub.1 -C.sub.10)-alkyl, (C.sub.1 -C.sub.8)-alkanoyl, (C.sub.6 -C.sub.10)-aryl or Het, each of which can be substituted by halogen, --OH, --NH.sub.2, --NH--CO--R.sup.7, --O--CO--R.sup.7 and --N--(R.sup.8).sub.2 where R.sup.7 =(C.sub.1 -C.sub.6)-alkyl and R.sup.8, independently of one another, is hydrogen or (C.sub.1 -C.sub.2)-alkyl or in which R.sup.1 is the radical of the formula II ##STR2## in which n is an integer from 3 to 10, m is zero to 3, R.sup.6, independently of one another, is (C.sub.1 -C.sub.6)-alkyl which is optionally substituted by halogen or --NH--CO--R.sup.7, where R.sup.7 =(C.sub.1 -C.sub.6)-alkyl, and X is absent or is (C.sub.1 -C.sub.10)-alkyl, and R.sup.2, R.sup.3, R.sup.4 or R.sup.5, independently of one another, are hydrogen, (C.sub.1 -C.sub.5) -alkyl, lithium, sodium, potassium or Si(R), where R=(C.sub.1 -C.sub.5)-alkyl, and their physiologically tolerable salts, a process for preparation of these compounds of the formula I and their use as pharmaceuticals in the prophylaxis and treatment of osteoporosis and hypercalcemia.

Imidobisphosphoric acids, and use thereof

The present invention relates to a process for preparing aromatic amines by reacting an aromatic nitro compound with carbon monoxide in a solvent mixture comprising water and a water-insoluble organic solvent by means of a catalyst comprising palladium and a water-soluble phosphine under a pressure of from 5 to 300 bar and at a temperature of from 50 to 200.degree. C., and separating the aqueous phase and the organic phase.

Process for preparing aromatic amines

Phosphepinium Salts Thereof The present invention relates to phosphonium salts of the formula (I) ##STR1## in which Ar--Ar is a biphenyl radical, a 1-phenylnaphthyl radical or a 1,1'-binaphthyl radical, each CH.sub.2 group is arranged in the ortho position to the Ar--Ar bond, R is F, an alkyl radical or an alkoxy radical respectively having 1 to 8 carbon atoms, n is an integer from 0 to 4, R.sup.1 and R.sup.2 are identical or different and, independently of each other, are an alkyl radical having 1 to 10 carbon atoms, a cycloaliphatic radical having 5 to 10 carbon atoms, or are a radical Ar.sup.1 --(R.sup.3).sub.m, where Ar.sup.1 is a phenyl or naphthyl radical, R.sup.3 is F, Cl, CF.sub.3, SO.sub.3 H, SO.sub.3 Me (Me.dbd.Li, Na or K), a dialkylamino radical having 2 to 8 carbon atoms, an alkyl radical or an alkoxy radical respectively having 1 to 8 carbon atoms and m is an integer from 0 to 5, or R.sup.1 and R.sup.2 together with the P atom form a ring having 4 to 8 members to which may be fused one or two aromatic rings or ring systems including 6 to 10 carbon atoms and X.sup.- is a monovalent anion or the equivalent of a polyvalent anion of a mineral acid, carboxylic acid, sulfonic acid or an alcohol. The invention further relates to a process for the preparation of the phosphonium salts and use thereof.

Phosphepinium salts

Imidobisphosphoric acids, process for their preparation, and use thereof. There are described compounds of the formula I ##STR1## in which R.sup.1 is (C.sub.1 -C.sub.10)-alkyl, (C.sub.1 -C.sub.8)-alkanoyl, (C.sub.6 -C.sub.10)-aryl or Het, each of which can be substituted by halogen, --OH, --NH.sub.2, --NH--CO--R.sup.7, --O--CO--R.sup.7 and --N--(R.sup.8).sub.2 where R.sup.7 =(C.sub.1 -C.sub.6)-alkyl and R.sup.8, independently of one another, is hydrogen or (C.sub.1 -C.sub.4)-alkyl or in which R.sup.1 is the radical of the formula II ##STR2## in which n is an integer from 3 to 10, m is zero to 3, R.sup.6, independently of one another, is (C.sub.1 -C.sub.6)-alkyl which is optionally substituted by halogen or --NH--CO--R.sup.7, where R.sup.7 =(C.sub.1 -C.sub.6)-alkyl, and X is absent or is (C.sub.1 -C.sub.10)-alkyl, and R.sup.2, R.sup.3, R.sup.4 or R.sup.5, independently of one another, are hydrogen, (C.sub.1 -C.sub.5)-alkyl, lithium, sodium, potassium or Si(R), where R=(C.sub.1 -C.sub.5) -alkyl, and their physiologically tolerable salts, a process for preparation of these compounds of the formula I and their use as pharmaceuticals in the prophylaxis and treatment of osteoporosis and hypercalcemia.

Imidobisphosphoric acids, and use therefor

Phosphines of the formula (I) and the preparation of these phosphines ##STR1## where Ar--Ar is a biphenyl radical, a 1-phenylnaphthyl radical or a 1,1'-binaphthyl radical, the CH.sub.2 group and the CH.sub.3 radical are each in the ortho position to the Ar--Ar bond, R is F, an alkyl radical or alkoxy radical each having from 1 to 8 carbon atoms, n is an integer from 0 to 4, R.sup.1 and R.sup.2 independently of one another, are an alkyl radical having from 1 to 10 carbon atoms, a cycloaliphatic radical having from 5 to 10 carbon atoms, or a radical Ar.sup.1 -(R.sup.3).sub.m, where Ar.sup.1 is a phenyl or naphthyl radical, R.sup.3 is F, Cl, CF.sub.3, SO.sub.3 H, SO.sub.3 Me (Me=Li, Na or K), a dialkylamino radical having from 2 to 8 carbon atoms, an alkyl radical or alkoxy radical each having from 1 to 8 carbon atoms and m is an integer from 0 to 5, or R.sup.1 and R.sup.2 together with the phosphorus atom form a 4-membered to 8-membered ring to which can be fused.

Compounds of the phosphine group, their preparation and their use

A diphosphine of the formula (I) ##STR1## in which Ar--Ar is a biphenyl radical, a 1-phenyl-naphthyl radical or a 1,1'-binaphthyl radical, the CH.sub.2 groups am each located in the ortho-position relative to the Ar--Ar bond, R is F or an alkyl radical or alkoxy radical having in each case 1 to 8 carbon atoms, n is an integer from 0 to 4, the radicals PR.sup.1 R.sup.2 and PR.sup.3 R.sup.4 differ from one another, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 independently of one another are each an alkyl radical having 1 to 10 carbon atoms, a cycloaliphatic radical having 5 to 10 carbon atoms, or a radical Ar.sup.1 --(R.sup.5).sub.m, in which AR.sup.1 is a phenyl radical, R.sup.5 is F, CF.sub.3, or an alkyl radical having 1 to 4 carbon atoms and m is 0 to 1, or R.sup.1, R.sup.2, R.sup.3 and R.sup.4 independently of one another and including the particular P atom to which they are bonded, form a ring having 4 to 8 members, onto which one or two aromatic rings or ring systems containing 6 to 10 carbon atoms are optionally fused. The invention furthermore relates to a process for the preparation of these diphosphines.

Diphosphines and process for their preparation

The present invention relates to sulfonated diphosphines of the formula (I) ##STR1## where M is hydrogen, ammonium, a monovalent metal or the equivalent of a polyvalent metal, a, b, c and d are each 0 or 1, with the proviso that a+b+c+d is an integer from 1 to 4, Ar is an m-(MSO.sub.3)--C.sub.6 H.sub.4 radical and M is as defined above, n is 0, 1 or 2, Ph is a phenyl radical, R.sup.1 and R.sup.2 are identical or different and are each an alkyl radical having from 1 to 10 carbon atoms or a cycloaliphatic radical having from 5 to 10 carbon atoms in the ring, and a process for their preparation.

Sulfonated diphosphines and a process for their preparation

Compounds of the tautomeric formula Ia, Ib or Ic, ##STR1## where R is a radical of the formula ##STR2## are effective compounds for the treatment and prophylaxis of degenerative bone disorders. They are used as pharmaceuticals.

Guanidinealkyl-1,1-bisphosphonic acid derivatives, process for their

Guanidinealkyl-1,1-bisphosphonic acid derivatives, process for their preparation and their use Compounds of the tautomeric formula Ia, Ib or Ic, ##STR1## where R is a radical of the formula ##STR2## are effective compounds for the treatment and prophylaxis of degenerative bone disorders. They are used as pharmaceuticals.

Guanidinealkyl-1,1-bisphosphonic acid derivatives process for their

Substituted aminoethane-1,1-bisphosphonic acids and aminoethane-1,1-alkylphosphinophosphonic acids, processes for their preparation and use thereof The invention relates to compounds of the formula I ##STR1## in which R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are a hydrogen atom or (C.sub.5 -C.sub.5)-alkyl, m is the integer 0 or 1, x is (C.sub.1 -C.sub.10)-alkyl, mono- or polysubstituted, a 5- or 6-membered ring having one nitrogen atom and optionally a further nitrogen or oxygen atom; aryl having 6 or 10 carbon atoms, which can be substituted; or cycloalkyl, to processes for the preparation of the compound of the formula I; to pharmaceuticals, and to their use for the treatment of osteoporosis and degenerative joint diseases.

N-cycloalkylaminoethane-1,1-bis (phosphonic acid) useful for the

The invention relates to alkenylaminoalkane-1,1-diphosphonic acid derivatives of the formula I ##STR1## in which R.sup.1 to R.sup.5, a, b, and Z have the meaning given in the description and to processes for their preparation. The invention furthermore relates to copolymers comprising 0.1-50 mol %, preferably 1-15 mol %, of at least one alkenylaminoalkane-1,1-diphosphonate unit of the formula I and 99.9-50 mol %, preferably 99-85 mol %, of at least one carboxylic acid unit of the formula II

Alkenylaminoalkane-1,1-diphosphonic acid derivatives and copolymers

The invention describes tautomeric compounds of the formula Ia, Ib or Ic ##STR1## and/or their physiologically tolerable salts, in which R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are a hydrogen atom, substituted (C.sub.1 -C.sub.7)-alkyl, (C.sub.3 -C.sub.10)-cycloalkyl, substituted phenyl or (C.sub.1 -C.sub.4)-alkylphenyl, R.sup.2 is substituted phosphoric acid, R.sup.2 and R.sup.3, R.sup.2 and R.sup.5 or R.sup.4 and R.sup.5 form a monocyclic 5- to 7-membered saturated or unsaturated heterocyclic ring which is mono- or polysubstituted, R.sup.8, R.sup.9, R.sup.10 and R.sup.11 are a hydrogen atom or (C.sub.1 -C.sub.5)-alkyl, X is a hydrogen atom, hydroxyl or halogen, l and n are an integer from 0 to 7, m is an integer from 0 to 2, and the sum of the numbers l, m and n is less than or equal to 10, a process for the preparation of the compounds of the formula Ia, Ib or Ic, pharmaceuticals and their use for the prophylaxis or treatment of osteoporosis.

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Niedernhausen, Germany

Christoph Naumann