Ciba-geigy Corporation

Novartis Corporation

Novartis Ag

Eric K Baylis

Ludwig Maier

Stuart J Mickel

Roger G Hall

Helmut Bittiger

Hans-Rudolf Olpe

Wolfgang Frostl

Roger J Taylor

Stephen P Collingwood

Anthony D Baxter

Chantal Schmit

John G Dingwall

Colin D Campbell

Wilfred Pickles

Alain De Mesmaeker

Robin Alec Fairhurst

Stephen Paul Collingwood

Roger John Taylor

Anthony David Baxter

Peter S Wardleworth

Alain Mesmaeker

Wolfgang Froostl

Dinucleotide and oligonucleotide analogues

A compound of formula ##STR1## where R.sup.1 and R.sup.2 are independently a C.sub.1 -C.sub.10 aliphatic radical, or R.sup.1 is a C.sub.1 -C.sub.10 aliphatic radical and R.sup.2 is a C.sub.6 -C.sub.10 aromatic radical, and R.sup.3 is a C.sub.1 -C.sub.8 aliphatic radical, a C.sub.3 -C.sub.8 cycloaliphatic radical, a C.sub.6 -C.sub.15 aromatic radical or a C.sub.7 -C.sub.13 araliphatic radical, provided that R.sup.3 is not methyl when R.sup.1 and R.sup.2 are each methyl, that R.sup.3 is not ethyl when R.sup.1 and R.sup.2 are each methyl and that R.sup.2 is not p-aminophenyl when R.sup.1 is methyl and R.sup.3 is ethyl with an organic compound having at least one group reactive with a P--H bond.

Method of synthesizing an organophosphorus compound

A dinucleotide analogue of formula ##STR1## where B.sup.1 and B.sup.2 are each independently a monovalent nucleoside base radical;

Oligonucleotide analogues

A compound of formula ##STR1## where R.sup.1 is hydrogen or a protecting group Q; R.sup.2 is hydrogen, a C.sub.1 -C.sub.8 aliphatic radical, a C.sub.6 -C.sub.15 aromatic radical, a C.sub.3 -C.sub.8 cycloaliphatic radical, a C.sub.7 -C.sub.13 araliphatic radical, an alkali metal ion or an ammonium ion; R.sup.3 and R.sup.4 are independently hydrogen, halogen or hydroxy; R.sup.5 is C.sub.6 -C.sub.10 aryloxythiocarbonyloxy, the C.sub.6 -C.sub.10 aryl group being unsubstituted or substituted, or R.sup.5.sub.a ; R.sup.5.sub.a is hydrogen, fluorine, chlorine, hydroxy, --OR.sup.8, --OCOR.sup.8 or silyloxy substituted by three C.sub.1 -C.sub.15 hydrocarbyl groups; R.sup.6 is hydrogen, a C.sub.1 -C.sub.10 aliphatic radical, a C.sub.6 -C.sub.15 aromatic radical, a C.sub.7 -C.sub.16 araliphatic radical, --COR.sup.9, --SO.sub.2 R.sup.9 or silyl substituted by three C.sub.1 -C.sub.15 hydrocarbyl groups; R.sup.7 is a monovalent nucleoside base radical, hydroxyl, --OR.sup.8 or --OCOR.sup.8, and R.sup.9 are independently a C.sub.1 -C.sub.10 aliphatic radical, a C.sub.3 -C.sub.8 cycloaliphatic radical, a C.sub.6 -C.sub.15 aromatic radical or a C.sub.7 -C.sub.16 araliphatic radical; or R.sup.5 and the indicated R.sup.6 O-together denote an isopropylidenedioxy group or R.sup.5 and R.sup.7 together denote an isopropylidenedioxy group, provided that when R.sup.5 and R.sup.7 together denote isopropylidenedioxy, R.sup.1 R.sup.2, R.sup.3 R.sup.4 and R.sup.6 are not all hydrogen. The disclosure further relates to a method of preparing the compounds of formula I by reacting a olefinic acetonide with a phosphinate compound and to the use of the compounds of formula I as pharmaceutical agents.

Nucleoside phosphinate compounds and compositions

A compound of formula ##STR1## where R.sup.1 and R.sup.2 are independently a C.sub.1 -C.sub.10 aliphatic radical, or R.sup.1 is a C.sub.1 -C.sub.10 aliphatic radical and R.sup.2 is a C.sub.6 -C.sub.10 aromatic radical, and R.sup.3 is a C.sub.1 -C.sub.8 aliphatic radical, a C.sub.3 -C.sub.8 cycloaliphatic radical, a C.sub.6 -C.sub.15 aromatic radical or a C.sub.7 -C.sub.13 araliphatic radical, provided that R.sup.3 is not methyl when R.sup.1 and R.sup.2 are each methyl, that R.sup.3 is not ethyl when R.sup.1 and R.sup.2 are each methyl and that R.sup.2 is not p-aminophenyl when R.sup.1 is methyl and R.sup.3 is ethyl.

Phosphinate esters

Dinucleoside phosphinates and their pharmaceutical compositions

Compounds of the formula I ##STR1## wherein R denotes an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic radical having 2 or more carbon atoms, and wherein one of the groups R.sup.1, R.sup.2 and R.sup.3 represents hydrogen or an aliphatic, cycloaliphatic, araliphatic or aromatic radical, another one of R.sup.1, R.sup.2 and R.sup.3 is hydrogen or, in the case of R.sup.1 and R.sup.2, is hydroxy, and the remaining one of R.sup.1, R.sup.2 and R.sup.3 is hydrogen, or wherein R denotes methyl, R.sub.1 denotes hydrogen or hydroxy, R.sub.2 denotes an aromatic radical and R.sub.3 represents hydrogen, and their salts have GABA.sub.B -antagonistic properties and can be used as GABA.sub.B -antagonists. They are obtained when in a compound of formula II ##STR2## in which R, R.sup.1, R.sup.2 and R.sup.3 have their previous significances, Z represents --NH.sub.2 and R.sup.4 denotes a hydroxy-protective group R.sup.5 or, when R.sup.1 and R.sup.3 denote hydrogen and R.sup.2 denotes hydrogen or alkyl, denotes an alkali metal or ammonium ion R.sup.6, or Z represents a protected or latent amino group Z.sup.o and R.sup.4 denotes hydrogen or a hydroxy-protective group R.sup.5, any group R.sup.5 or R.sup.6 is replaced by hydrogen, and/or any group Z.sup.o is converted into --NH.sub.2.

Substituted propane-phosphinic acid compounds

Compounds of the formula I ##STR1## wherein R denotes an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic radical having 2 or more carbon atoms, and wherein one of the groups R.sup.1, R.sup.2 and R.sup.3 represents hydrogen or an aliphatic, cycloaliphatic, araliphatic or aromatic radical, another one of R.sup.1, R.sup.2 and R.sup.3 is hydrogen or, in the case of R.sup.1 and R.sup.2, is hydroxy, and the remaining one of R.sup.1, R.sup.2 and R.sup.3 is hydrogen, or wherein R denotes methyl, R.sub.1 denotes hydrogen or hydroxy, R.sub.2 denotes an aromatic radical and R.sub.3 represents hydrogen, and their salts have GABA.sub.B -antagonistic properties and can be used as GABA.sub.B -antagonists. They are obtained when in a compound of formula II ##STR2## in which R, R.sup.1, R.sup.2 and R.sup.3 have their previous significances, Z represents --NH.sub.2 and R.sup.4 denotes a hydroxy-protective group R.sup.5 or, when R.sup.1 and R.sup.3 denote hydrogen and R.sup.2 denotes hydrogen or alkyl, denotes an alkali metal or ammonium ion R.sup.6, or Z represents a protected or latent amino group Z.sup.0 and R.sup.4 denotes hydrogen or a hydroxy-protective group R.sup.5, any group R.sup.5 or R.sup.6 is replaced by hydrogen, and/or any group Z.sup.0 is converted into --NH.sub.2.

Compounds of the formula I ##STR1## wherein R denotes an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic radical having 2 or more carbon atoms, and wherein one of the groups R.sup.1, R.sup.2 and R.sup.3 represents hydrogen or an aliphatic, cycloaliphatic, araliphatic or aromatic radical, another one of R.sup.1, R.sup.2 and R.sup.3 is hydrogen or, in the case of R.sup.1 and R.sup.2, is hydroxy, and the remaining one of R.sup.1, R.sup.2 and R.sup.3 is hydrogen, or wherein R denotes methyl, R.sub.1 denotes hydrogen or hydroxy, R.sub.2 denotes an aromatic radical and R.sub.3 represents hydrogen, and their salts have GABA.sub.B -antagonistic properties and can be used as GABA.sub.B -antagonists. They are obtained when in a compound of formula II ##STR2## in which R, R.sup.1, R.sup.2 and R.sup.3 have their previous significances, Z represents --NH.sub.2 and R.sup.4 denotes a hydroxy-protective group R.sup.5 or, when R.sup.1 and R.sup.3 denote hydrogen and R.sup.2 denotes hydrogen or alkyl, denotes an alkali metal or ammonium ion R.sup.6, or Z represents a protected or latent amino group Z.degree. and R.sup.4 denotes hydrogen or a hydroxy-protective group R.sup.5, any group R.sup.5 or R.sup.6 is replaced by hydrogen, and/or any group Z.degree. is converted into --NH.sub.2.

Compounds of the formula I ##STR1## wherein R denotes an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic radical having 2 or more carbon atoms, and wherein one of the groups R.sup.1, R.sup.2 and R.sup.3 represents hydrogen or an aliphatic, cycloaliphatic, araliphatic or aromatic radical, another one of R.sup.1, R.sup.2 and R.sup.3 is hydrogen or, in the case of R.sup.1 and R.sup.2, is hydroxy, and the remaining one of R.sup.1, R.sup.2 and R.sup.3 is hydrogen, and their salts have GABA.sub.B -antagonistic properties and can be used as GABA.sub.B -antagonists. They are obtained when in a compound of formula II ##STR2## in which R, R.sup.1, R.sup.2 and R.sup.3 have their previous significances, Z represents --NH.sub.2 and R.sup.4 denotes a hydroxy-protective group R.sup.5 or, when R.sup.1 and R.sup.3 denote hydrogen and R.sup.2 denotes hydrogen or alkyl, denotes an alkali metal or ammonium ion R.sup.6, or Z represents a protected or latent amino group Z.sup.0 and R.sup.4 deontes hydrogen or a hydroxy-protective group R.sup.5, any group R.sup.5 or R.sup.6 is replaced by hydrogen, and/or any group Z.sup.0 is converted into --NH.sub.2.

A process for the production of aliphatylphosphinic acid derivatives, especially of alkyl dialkoxyalkylphosphinates having the formula I ##STR1## in which R is C.sub.1 -C.sub.4 -alkyl and R' is hydrogen or C.sub.1 -C.sub.4 -alkyl, comprising reacting, in the presence of an acidic catalyst, aqueous phosphonic acid with the corresponding trialkyl orthoester having the formula II:

Process for the manufacture of aliphatylphosphinic acid derivatives

The present invention provides a process for the production of physiologically-useful .alpha.-aminophosphonic acids and peptide derivatives of the formula: ##STR1## wherein R and R.sub.1 may be the same or different and each can be hydrogen, deuterium or an optionally substituted lower alkyl group, lower alkenyl, lower alkynyl, cycloalkyl, aryl or heterocyclic radical containing one or more oxygen, nitrogen or sulphur atoms and which may be fused to an aromatic ring, a lower alkyl group substituted by a cycloalkyl radical, a lower alkyl group substituted by an aryl radical, a lower alkyl group substituted by a heterocyclic radical as defined above or R and R.sub.1 together form a polymethylene chain optionally interrupted by an oxygen, nitrogen or sulphur atom, or R.sub.1 represents, together with the C(R)--N&lt; residue to which it is attached, the atoms required to complete a heterocyclic radical; and

Chemical process for the production of .alpha.-aminophosphonic acids and

Phosphonous acid derivatives of the general formula I ##STR1## or the corresponding zwitterion form, in which R, R.sub.1, R.sub.2 and R.sub.3 have the meanings given hereinafter, are valuable microbicides. They are being manufactured according to known methods of peptide synthesis and may be used to protect plants from the attack of plant-pathogenic bacteria and fungi.

Phosphonous acid derivatives, processes for their preparation and their

Agent for influencing plant growth, in particular a herbicidal and plant growth-inhibiting agent containing in addition to carriers and/or other additives, at least one compound of the formula: ##STR1## in which R is hydrogen an alkyl group having from 1 to 5C atoms, which is unsubstituted or substituted by hydroxyl, salts thereof with either strong monobasic or polybasic acids or with inorganic or organic bases, or optical isomers thereof, as the active component.

Growing community of inventors

Stockport, United Kingdom

Eric K Baylis