Yeda Research and Develpment & Co. Ltd

Other

New York University

Yehuda Mazur

Gad Lavie

Daniel Meruelo

David Lavie

Aureliu J Acher

Avner Rotman

Harald Bock

Dalia Freeman

Lea Shragina

Moshe Avramoff

Hypericin, helianthrone and derivatives thereof of general formula (I)wherein the dotted line between positions 11 and 12 represent an optional C11-C12 bond; R is independently selected from the group consisting of hydroxy, C-Calkoxy, NH&#x2014;C-Calkyl, and NH-hydroxy(C-C)alkyl; R' is independently selected from the group consisting of hydroxy and C-Calkoxy; R&#x2033; is independently selected from the group consisting of hydrogen, hydroxy, C-Calkoxy, NH&#x2014;C-Calkyl, and NH-hydroxy(C-C)alkyl; and R, R, R, R, Rand Rare independently selected from the group consisting of hydrogen, hydroxy, chloro, bromo, C-Calkyl, C-Calkoxy, and C-Calkoxycarbonyl, provided that R&#x2033; is not hydrogen when there is a C11-C12 bond, are useful as inhibitors of angiogenesis and can be used to prevent formation of metastases and restenosis and for the treatment of angiogenesis-associated ophthalmologic disorders. In addition, the helianthrones of formula (I) can be used for the treatment of tumors in the absence of light irradiation. New compounds include those of formula I which are other than hypericin and known hypericin derivatives and there is either a C11-C12 bond or at least one R&#x2033; is other than hydrogen.

Helianthrone derivatives as anti-cancer agents

Novel antiviral (including antiretroviral) compounds are mono- or dicarboxylic acid esters of hypericin in which one or both of the methyl groups of hypericin are substituted by carboxylic acid ester groups of the formula COOR in which R is alkyl, the chain of which is optionally interrupted by one or more oxygen or sulphur atoms. R is preferably methyl, ethyl, propyl, butyl, 2-methoxyethyl or 2-(2-methoxyethoxy)ethyl. The compounds may be formulated into pharmaceutical compositions and may be used in any manner which has previously been known for hypericin.

Antiviral agents

A method for treating cancer comprising administering a 1,3,4,6-tetrahydroxy-helianthrone derivative. The compounds can be used in the absence of light irradiation or for photodynamic therapy of solid tumors wherein the tumor site is subjected to light irradiation after administration of the active ingredient. A preferred compound is 10,13-dimethyl-1,3,4,6-tetrahydroxy-helianthrone.

Disclosed herein are antiviral agents, pharmaceutical formulations comprising effective amounts of these agents and methods for treating mammals suffering from infections caused by viruses. The agents are analogs, isomers, homologs, derivatives and salts of aromatic polycyclic diones.

Compositions and methods for treating viral infections

Novel 3,7-disubstituted phenothiazinium salts are active in the photochemical disinfection of aqueous effluents. The novel salts are of the general formula ##STR1## wherein: either R.sub.1 is a saccharide residue;

Phenothiazinium salts and their use for disinfecting aqueous effluents

A process for preparing hypericin comprises oxidative dimerization of emodin anthrone and conversion of the intermediate protohypericin to hypericin by irradiation with visible light.

Preparation of hypericin

A process for the production of 1.alpha.-hydroxy provitamin D.sub.3 which comprises treating 1.alpha., 2.alpha.-epoxy-cholesta-4,6-diene-3-one at a low temperature with liquid ammonia; with ammonium chloride and with lithium metal to produce 1.alpha.,3.beta.-dihydroxycholest-6-ene, converting this to the corresponding 1.alpha.,3.beta.-di(lower alkanoyl) derivative, reacting the latter with bromine to give 1.alpha.,3.beta.-di(lower alkanoyloxy) 6.beta.,7.alpha.-dibromocholestane, which is dehydrobrominated to give 1.alpha.,3.beta.-di(lower alkanoyloxy)-cholesta-5,7-diene, which is converted to the desired provitamin. The 1.alpha.,3.beta.-di(lower alkanoyloxy)cholest-6-ene can be oxidized to the corresponding 5-ene-7-one, which is converted to the 7-p-toluenesulfonyl hydrazone derivative, which is converted to the 1.alpha.-hydroxy provitamin D.sub.3 di(lower alkanoyloxy) derivative or to the 1.alpha.-hydroxy provitamin D.sub.3. Novel compounds are 1.alpha.,3.beta.-dihydroxy-cholest-6-ene, its di(lower alkanoyloxy) derivative; 1.alpha.,3.beta.-di(lower alkanoyloxy)-6.beta.,7.alpha.-dibromocholestane; 1.alpha.,3.beta.-diacetoxycholest-5-ene-7-one and the corresponding 7-p-toluenesulfonylhydrazone derivative.

Process for the production of 1.alpha.-hydroxy provitamin D.sub.3 and

Process for the production of hydroxylated derivatives of cholesterol and 7-dehydrocholesterol which comprises subjecting a saturated unsubstituted or substituted derivative of cholestane, dissolved in a suitable solvent, in the presence of peracetic acid, to irradiation with ultra-violet radiation of a wavelength below 350m.mu. , or heating in a suitable solvent, separating the reaction products, which if desired, are converted to other derivatives, and recovering the residue of the starting material. Novel derivatives are obtained and these are: 3.beta.-acetoxy,25-hydroxy,5.alpha.-cholestane; 3.beta.-acetoxy, 5.alpha.,25-dihydroxy cholestane; 3.beta.,5.alpha.,25-trihydroxy cholestane; 3-keto, 5.alpha.,25-dihydroxy cholestane; 3-keto,25-hydroxy-.DELTA..sup.4 -cholestane; 3.beta.,25-diacetoxy-5.alpha.-hydroxy-cholestane; 3.beta.-acetoxy, 25-trichloroacetoxy-5.alpha.-hydroxy-cholestane, 25-trichloroacetoxy-cholesterol and 25-acetoxy-cholesterol.

Growing community of inventors

Rehovot, Israel

Yehuda Mazur