Indene derivatives as pharmaceutical agents

1. A compound of formula (Ia):

wherein:

the A, C or D ring is independently fully saturated;

C1, C4, C11, C12, C15 and C16 are each independently substituted with two hydrogens;

C9 and C14 are each independently substituted with hydrogen;

R 1 is —OR 7 ;

R 2 is —R 8 —OR 7 ;

R 3 is —R 10 —N(R 7 ) 2 ;

R 4a and R 4b together form alkylidene or haloalkylidene;

R 5 is alkyl;

R 6 is hydrogen, —R 8 —OR 7 or —R 8 —N(R 7 ) 2 ;

each R 7 is independently selected from the group consisting of hydrogen, —R 10 —OR 9 , —R 10 —N(R 9 ) 2 , alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl;

each R 8 is independently selected from the group consisting of a direct bond, a straight or branched alkylene chain, and a straight or branched alkenylene chain;

each R 9 is independently selected from the group consisting of hydrogen, alkyl, aryl and aralkyl; and

each R 10 is independently selected from the group consisting of a straight or branched alkylene and a straight or branched alkenylene chain,

as a single stereoisomer, a mixture of stereoisomers, or as a racemic mixture of stereoisomers;

or a pharmaceutically acceptable salt.

2. The compound of claim 1 selected from the group consisting of the following:

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-aminomethyl-7aβ-methyl-1-ethylideneoctahydroindene, ammonium chloride salt;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium chloride salt;

5-(1β-methyl-2β,4β-dihydroxycyclohexyl)-4α-(2-aminoethyl)-7aβ-methyl-1-methyleneoctahydroindene;

5-(1β-methyl-2β,4β-dihydroxycyclohexyl)-4α-(2-aminoethyl)-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-2β,4β-dihydroxycyclohexyl)-4α-aminomethyl-7aβ-methyl-1-methyleneoctahydroindene;

5-(1β-methyl-2β,4β-dihydroxycyclohexyl)-4α-aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-aminomethyl-7aβ-methyl-1-difluoromethyleneoctahydroindene;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-aminomethyl-7aβ-methyl-1-difluoromethyleneoctahydroindene, ammonium chloride salt;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-aminomethyl-7aβ-methyl-1-dichloromethyleneoctahydroindene, ammonium chloride salt;

5-(1β-methyl-4α,5α-dihydroxy-2β-hydroxymethylcyclohexyl)-4α-aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-2β,4β-dihydroxycyclohexyl)-4α-(4-dimethylaminobut-2Z-en-1-yl)-7aβ-methyl-1-methyleneoctahydroindene;

5-(1β-methyl-2β,4β-dihydroxycyclohexyl)-4α-(4-dimethylaminobut-2Z-en-1-yl)-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-(ethyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-(benzyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-(cyclopropylmethyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-(dimethyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-(dimethyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-(methyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-(methyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-(2-methylpropyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-(2-methylpropyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-(1-methylpiperidin-4-yl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium diacetate salt;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-(3-nitrobenzyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-(piperonyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-(pyrrol-2-yimethyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-(furfuryl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-(pyridin-3-ylmethyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-2β,4β-dihydroxycyclohexyl)-4α-(2-methylpropyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-2β,4β-dihydroxycyclohexyl)-4α-(pyridin-3-ylmethyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene;

5-(1β-methyl-2β,4β-dihydroxycyclohexyl)-4α-(2-hydroxyethyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-2β,4β-dihydroxycyclohexyl)-4α-(furfuryl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-2β,4β-dihydroxycyclohexyl)-4α-(2-dimethylaminoethyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-2β,4β-dihydroxycyclohexyl)-4α-(2-cyclohex-1-en-1-ylethyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-2β,4β-dihydroxycyclohexyl)-4α-(2-morpholin-4-ylethyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene, ammonium acetate salt;

5-(1β-methyl-2β,4β-dihydroxycyclohexyl)-4α-(3-methylphenyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene;

5-(1β-methyl-2β,4β-dihydroxycyclohexyl)-4α-(benzyl)aminomethyl-7aβ-methyl-1-methyleneoctahydroindene; and

5-(1β-methyl-2β,4β-dihydroxycyclohexyl)-4α-(2-(3-methylphenyl)aminoethyl)-7aβ-methyl-1-methyleneoctahydroindene.

3. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (Ia):

wherein:

the A, C or D ring is independently fully saturated;

C1, C4, C11, C12, C15 and C16 are each independently substituted with two hydrogens;

C9 and C14 are each independently substituted with hydrogen;

R 1 is —OR 7 ;

R 2 is —R 8 —OR 7 ;

R 3 is —R 10 —N(R 7 ) 2 ;

R 4a and R 4b together form alkylidene or haloalkylidene;

R 5 is alkyl;

R 6 is hydrogen, —R 8 —OR 7 or —R 8 —N(R 7 ) 2 ;

each R 7 is independently selected from the group consisting of hydrogen, —R 10 —OR 9 , —R 10 —N(R 9 ) 2 , alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl;

each R 8 is independently selected from the group consisting of a direct bond, a straight or branched alkylene chain, and a straight or branched alkenylene chain;

each R 9 is independently selected from the group consisting of hydrogen, alkyl, aryl and aralkyl; and

each R 10 is independently selected from the group consisting of a straight or branched alkylene and a straight or branched alkenylene chain,

as a single stereoisomer, a mixture of stereoisomers, or as a racemic mixture of stereoisomers;

or a pharmaceutically acceptable salt.