Symphar S.a.

Ilex Products, Inc.

Other

Smithkline Beecham Corporation

Ilex Oncology Research S.a.

Craig Leigh Bentzen

Eric Joseph Niesor

Hieu Trung Phan

Lan Mong Nguyen

Raymond Azoulay

Vinh Van Diep

Robert John Ife

Yves Guyon-Gellin

Simon Floret

Lan Nguyen Mong

Lan N Mong

Pierre Maechler

Alexandre Bulla

Jean-Luc Thulliard

Jean Flach

Kyriacos Kalathakis

Harald Eschenhof

Jean-Robert Rossier

Yves Gyon Gellin

Lân Mong Nguyen

Anne Perez

Jean-Luc Thuillard

The present invention relates to methods of use of aminodiphosphonate to modulate apolipoprotein E levels and the use of such compounds in therapy, including cardiovascular and neurological disease states.

Aminodiphosphonate apolipoprotein E modulators

The present invention relates to novel &#x3b2;-substituted-&#x3b2;-aminoethylphosphonate derivatives and their uses for lowering plasma levels of apo (a), Lp(a), apo B, apo B associated lipoproteins (low density lipoproteins and very low density lipoproteins) and for lowering plasma levels of total cholesterol.

&#x3b2;-substituted &#x3b2;-aminoethyl phosphonate derivatives

The present invention relates to novel &agr;-substituted-&bgr;-aminoethylphosphonate and &agr;-substituted-&bgr;-aminovinylphosphonate derivatives and their uses for lowering plasma levels of apo (a), Lp(a), apo B, apo B associated lipoproteins (low density lipoproteins and very low density lipoproteins) and for lowering plasma levels of total cholesterol.

&agr;-Substituted &bgr;-aminoethyl phosphonate derivatives

Aminophosphonates alpha substituted by phenol groups of formula (I) have lipoprotein(a) lowering activity.

Compounds and pharmaceutical compositions containing them

Aminophosphonates alpha substituted by phenol groups, of formula (I) have lipoprotein(a) lowering activity.

Pharmaceutical aminophosphonic acid derivatives

Use of phenol substituted diphosphonates as antineoplastic agents

The present invention relates to novel aminophosphonate derivatives substituted in .alpha. position by phenol groups, of formula (I): ##STR1## in which: X.sup.1, X.sup.2, X.sup.3, R.sup.1, R.sup.2, A, B, Z and n are defined in claim 1, as well as their preparations and the pharmaceutical compositions comprising them.

Substituted aminophosphonate derivatives, process for their preparation

The invention relates to new gem-diphosphonates derivatives substituted by phenol groups of formula (I): ##STR1## as well as the process for their preparation and the pharmaceutical compositions containing them.

Method for lowering plasma lipid levels or blood pressure

Phenol substituted gem-diphosphonate derivatives, process for their

2-Substituted-1,3-propylidenediphosphonates of formula (I), where A, R.sup.1 and R.sup.2 are defined in claim 1, are therapeutically active compounds, namely for the treatment of cardiovascular diseases. They can be prepared by reacting phosphonating agents with 1,3- dibromopropanes or ditosylates of 1,3-propanediols substituted in position 2. ##STR1## .

Certain 2-substituted 1,3-propylidenediphosphonate derivatives,

The present invention relates to a pharmaceutical composition for increasing the relative quantity of circulating high density lipoproteins favorable augmentating the alpha/beta lipoprotein cholesterol ratios and clearing cholesterol and lipids from certain tissues and inducing hypotensive activity comprising administering to a human an effective amount of a compound of the formula: ##STR1## where X is H, OH, or ##STR2## R and R' identical or different are H, CH.sub.3 or C.sub.2 H.sub.5 ; m is zero or 1; and A is selected from the group comprising (CH.sub.3).sub.3 C--, Y--C.sub.6 H.sub.4 --, Y--C.sub.6 H.sub.4 --O--C(CH.sub.3).sub.2 --, Y--C.sub.6 H.sub.4 --C(CH.sub.3).sub.2 --, Y--C.sub.6 H.sub.4 --C(O)--C.sub.6 H.sub.4 --, Y--C.sub.6 H.sub.4 --(CH.sub.2).sub.n -- and Y--C.sub.6 H.sub.4 --O--(CH.sub.2).sub.n --, where n is an integer from 1 to 6 and Y is H, CH.sub.3, OCH.sub.3, a halogen, and a pharmaceutically acceptable excipient.

Anti-atherosclerotic pharmaceutical compositions containing

A method of increasing the quantity of circulating high density lipoproteins and clearing cholesterol from certain tissues, comprising administering to a human an effective amount of a compound of the formula ##STR1## where X is H, OH, ##STR2## or NH.sub.2 ; R and R' identical or different are H, CH.sub.3 or C.sub.2 H.sub.5 ; m is zero or 1; and A is selected from the group comprising (CH.sub.3).sub.3 C--, Y--C.sub.6 H.sub.4 --, Y--C.sub.6 H.sub.4 --O--C(CH.sub.3).sub.2 --, Y--C.sub.6 H.sub.4 --C(CH.sub.3).sub.2 --, Y--C.sub.6 H.sub.4 --C(O)--C.sub.6 H.sub.4 --, Y--C.sub.6 H.sub.4 --(CH.sub.2).sub.n -- and Y--C.sub.6 H.sub.4 --O--(CH.sub.2).sub.n --, where n is an integer from 1 to 6 and Y is H, CH.sub.3, OCH.sub.3 or Cl.

Therapeutic process with diphosphonate compounds

This invention relates to new diphosphonate compounds of formula (I) ##STR1## where X is H, OH, ##STR2## or NH.sub.2 ; R and R' identical or different are H, CH.sub.3 or C.sub.2 H.sub.5 ; m is zero or 1; and A is selected from the group comprising (CH.sub.3).sub.3 C--, Y--C.sub.6 H.sub.4 --, Y--C.sub.6 H.sub.4 --O--C(CH.sub.3).sub.2 --, Y--C.sub.6 H.sub.4 --C(CH.sub.3).sub.2 --, Y--C.sub.6 H.sub.4 --CO--C.sub.6 H.sub.4 --, Y--C.sub.6 H.sub.4 --(CH.sub.2).sub.n -- and Y--C.sub.6 H.sub.4 --O--(CH.sub.2).sub.n --, where n is an integer from 1 to 6 and Y is H, CH.sub.3, OCH.sub.3 or Cl. These compounds possess remarkable activity as hypoglycemic and/or antiatherogenic agents, and are usable in pharmaceutical compositions to alter lipoprotein profiles in favor of high density lipoproteins and to clear cholesterol from various tissues.

Diphosphonates

This invention relates to a separation method comprising the introduction of a sample of serum or plasma into a microcolumn containing a support which has a sulfated polysaccharide, preferably heparin, covalently bound to it so as to remove from said sample the .beta.-lipoproteins by binding thereof to this ligand, followed by washing the microcolumn with a first pH buffered solution and collecting the eluant representing a first fraction containing the .alpha.-lipoprotein portion of the sample. Then the microcolumn is washed wth a second pH buffered solution so as to release the ligand-bound .beta.-lipoproteins and to recover a second fraction containing the .beta.-lipoprotein portion of the sample. Afterwards, it is possible to separately determine the .alpha.- and .beta.-lipoprotein-cholesterol, as well as the respective .alpha./.beta. ratios of phospholipids, triglycerides and various apoproteines, and to calculate the respective ratios .alpha./.beta., all useful as clinical diagnostic indexes and allowing to obtain a complete lipoprotein profiling. The invention also concerns a kit comprising in a transportable box all the implements and reagents duly prepared so as to easily and quickly carry out the above method.

Growing community of inventors

Bogis-Bossey, Switzerland

Craig Leigh Bentzen