Cell Therapeutics, Inc.

Alistair J Leigh

Gail E Underiner

J Peter Klein

Anil M Kumar

John Michnick

David J Porubek

Glenn C Rice

Elisa Eiseman

Disclosed are enantiomers diastereomers, salts, solvates, hydrates and mixtures thereof, of formula I: ##STR1## The core moiety is non-cyclic or at least one five- to seven-membered ring, n is an integer from about 4 to about 16, R.sub.1 and R.sub.2 are hydrogen, halogen or C.sub.1-12 alkyl or alkenyl, and (CH.sub.2).sub.n may be substituted by a hydroxyl, halogen, oxygen, a (C.sub.1-4) alkyl group or a dimethylamino group. The compounds and pharmaceutical composition thereof are useful in methods for treating an individual having a disease or treatment-induced toxicity, mediated by second messenger activity.

Epoxide-containing compounds

Therapeutic compounds with at least one carboxylic acid, ester or amide-substituted side chain have the formula:

Therapeutic compounds containing xanthinyl

Methods for using therapeutic compounds containing xanthinyl

Therapeutic compounds, including resolved enantiomers and/or diastereomers, hydrates, salts, solvates and mixtures thereof, having a formula: ##STR1## wherein R.sub.0 is selected from the group consisting of hydrogen, halo, hydroxyl, amino, substituted or unsubstituted C.sub.(1-10) alkyl, C.sub.(2-10) alkenyl, cyclic or heterocyclic groups, wherein the substituents of substituted C.sub.(1-10) alkyl, C.sub.(2-10) alkenyl are other than halo; n is an integer from one to sixteen; R.sub.1, R.sub.2, and R.sub.3 are independently selected from the group consisting of a halo; haloacetoxy; hydrogen; hydroxy; oxo; --N.dbd.C.dbd.S; --N.dbd.C.dbd.O; --0--C.tbd.N; --C.tbd.N; --N.dbd.N.dbd.N; and --C--(R.sub.5).sub.3, R.sub.5 being independently a halo or hydrogen, at least one R.sub.5 being halo, at least one of R.sub.1, R.sub.2, and R.sub.3 being halo, cyano, isocyano, isothiocyano, azide or haloacetoxy group; R.sub.4 is hydrogen, C.sub.(1-6) alkyl, C.sub.(1-6) alkenyl, cyclo C.sub.(4-6) alkyl, or phenyl; one or more hydrogen atoms of (CH.sub.2).sub.n --CH.sub.a --CH.sub.b --CH.sub.c may be replaced with: i) at least one of halogen atom, hydroxyl, oxo, substituted or unsubstituted C.sub.(1-10) alkyl, C.sub.(1-10) alkoxyalkyl, or C.sub.(2-10) alkenyl; or ii) one or more unsaturated bonds; and any two adjacent carbon atoms of (CH.sub.2).sub.n --CH.sub.a --CH.sub.b --CH.sub.c may be instead separated by at least one oxygen atom. These compounds are useful in treating or preventing diseases by inhibiting selective second messenger pathways.

Electronegative-substituted long chain xanthine compounds

Compounds and pharmaceutical compositions thereof comprise the formula:

Substituted amino alkyl compounds

Disclosed are enantiomers, diastereomers, salts, solvates, hydrates and mixtures thereof, of formula I: ##STR1## The core moiety is a monocyclic ring structure having five to six ring atoms and two nitrogen atoms at the 1 and 3 positions, n is an integer from 4 to 16, R.sub.1 and R.sub.2 are hydrogen, halogen or C.sub.1-12 alkyl or alkenyl, and (CH.sub.2).sub.n may be optionally substituted by a hydroxyl, halogen, oxygen, a C.sub.1-4 alkyl group or a dimethylamino group. The compounds and pharmaceutical composition thereof are useful in methods for treating an individual having a disease or treatment-induced toxicity mediated through a second messenger.

Therapeutic compounds containing pyrimidinyl moieties

Acetal-and ketal-substituted compounds and pharmaceutical compositions thereof have the following formula:

Acetal-and ketal-substituted pyrimidine compounds

Oxime-substituted compounds are preferably cyclic or heterocyclic compounds. The oxime-substituted compounds and pharmaceutical compositions thereof have the formula:

Oxime substituted therapeutic compounds

There is disclosed a compound having the formula: ##STR1## wherein n is an integer from 5 to 9, wherein the core moiety is a heterocylic moiety wherein C.sub.a, C.sub.b, and C.sub.c are an R or S enantiomer or racemic mixture and the C.sub.a, C.sub.b, and C.sub.c carbon atoms are bonded together by a single bond, double bond, ether or ester linkages, wherein R.sub.1, R.sub.2 and R.sub.3 are independently halo, hydroxy, hydrogen, keto, isothiocyano, azide or haloacetoxy with the proviso that at least one of R.sub.1, R.sub.2 or R.sub.3 must be a halo, isothiocyano, azide or haloacetoxy group, wherein R.sub.4 is hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkenyl, cyclo C.sub.4-6 alkyl, or phenyl, and wherein halo refers to fluoro, chloro, bromo and iodo and salts thereof and pharmaceutical compositions thereof.

Halogen, isothiocyanate or azide substituted xanthines

A process for synthesizing enantiomerically pure chiral secondary alcohol compounds linked to a heterocyclic core moiety, using a natural chiral molecule starting material. The inventive process is particularly useful for bulk manufacturing of chiral secondary alcohol compounds.

Asymmetric synthesis of chiral secondary alcohols

There is disclosed an olefin-substituted compound having the formula:

Olefin substituted long chain compounds

There is disclosed compounds and pharmaceutical compositions having a xanthine core of the formula: ##STR1## wherein each of one or two R is independently ##STR2## wherein n is an integer from about 3 to about 18 forming a hydrocarbon chain, wherein the hydrocarbon chain may have one or more double bonds (preferably in a cis configuration), and may be substituted by a hydroxyl, halo or dimethylamino group and/or interrupted by an oxygen atom. The compounds lower elevated levels of unsaturated, non-arachidonate phosphatidic acid (PA) and diacylglycerol (DAG) derived from said PA within seconds of the primary stimulus and their contact with cells. The modulatory effect depends on the nature of the target cell and the stimulus applied.

Acetal or ketal substituted xanthine compounds

Compounds of the formula ##STR1## wherein each of one or two R is independently ##STR2## wherein n is an integer from 4 to 18, each R.sub.1 ' and R.sub.2 ' is independently H, alkyl (1-4C) or alkenyl (1-4C); and R.sub.3 ' and R.sub.4 ' are independently H or CH.sub.3 ; and wherein the alkyl or alkenyl may be substituted by a hydroxyl, halo or dimethylamino group and/or interrupted by an oxygen atom, H or alkyl (1-4C), including resolved enantiomers and/or diastereomers and mixtures thereof. Preferably, n is from 6 to 10, R.sub.1 ' and R.sub.2 ' are independently H or methyl and R.sub.3 ' and R.sub.4 ' are H. In particular, the compounds lower elevated levels of unsaturated, non-arachidonate phosphatidic acid (PA) and diacylglycerol (DAG) derived from said PA within seconds of the primary stimulus and their contact with said cells. The modulatory effect depends on the nature of the target cell and the stimulus applied.

Growing community of inventors

Brier, WA, United States of America

Alistair J Leigh