Indene derivatives as pharmaceutical agents

1. A compound of formula (I):

wherein:

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

C1, C4, C11, C12, C15 and C16 are each independently optionally substituted with one or two of the following, which are independently selected: hydrogen, alkyl, —R 8 —OR 7 , or —R 8 —N(R 7 ) 2 , provided that C4 is not substituted by two methyl groups;

C9 and C14 are each independently optionally substituted with hydrogen, alkyl, —R 8 —OR 7 , or —R 8 —N(R 7 ) 2 ;

R 1 is —OR 7 or —N(R 7 ) 2 ;

R 2 and R 3 are each independently selected from the group consisting of —R 8 —OR 7 , —R 8 —OC(O)R 9 , —R 10 —N(R 7 ) 2 , —R 10 —N(R 9 )C(O)R 9 , —R 10 —N(R 9 )S(O) t R 9 (where t is 1 or 2), —R 10 —N(R 9 )C(NR 9 )N(R 9 ) 2 , alkyl, alkenyl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclylalkyl, optionally substituted heteroarylalkyl and optionally substituted heteroarylalkenyl;

R 4a is hydrogen and R 4b is alkenyl or alkynyl;

or R 4a and R 4b are each alkyl;

R 5 is alkyl or a direct bond to the carbon at C14, provided that when R 4a is hydrogen and R 4b is alkenyl or alkynyl, R 5 is alkyl and when R 4a and R 4b are both alkyl, R 5′ is a direct bond to the carbon at C14;

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, solvate or prodrug thereof, in isolation or in a mixture.

2. The compound of claim 1 having the following formula (Ia):

wherein:

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

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

C9 and C14 are each independently substituted with hydrogen;

R 1 is —OR 7 or —N(R 7 ) 2 ;

R 2 and R 3 are each independently selected from the group consisting of —R 8 —OR 7 , —R 8 —OC(O)R 9 , —R 10 —N(R 7 ) 2 , —R 10 —N(R 9 )C(O)R 9 , —R 10 —N(R 9 )S(O) t R 9 (where t is 1 or 2), —R 10 —N(R 9 )C(NR 9 )N(R 9 ) 2 , alkyl, alkenyl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclylalkyl, optionally substituted heteroarylalkyl and optionally substituted heteroarylalkenyl;

R 4a is hydrogen and R 4b is alkenyl or alkynyl;

or R 4a and R 4b are each alkyl;

R 5 is alkyl or a direct bond to the carbon at C14, provided that when R 4a is hydrogen and R 4b is alkenyl or alkynyl, R 5 is alkyl and when R 4a and R 4b are both alkyl, R 5′ is a direct bond to the carbon at C14;

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, solvate or prodrug thereof.

3. The compound of claim 2 wherein:

R 1 is —OR 7 ;

R 2 is —R 8 —OR 7 ;

R 3 is selected from the group consisting of —R 8 —OR 7 , —R 8 —OC(O)R 9 , —R 10 —N(R 7 ) 2 , —R 10 —N(R 9 )C(O)R 9 , —R 10 —N(R 9 )S(O) t R 9 (where t is 1 or 2), —R 10 —N(R 9 )C(NR 9 )N(R 9 ) 2 , alkyl, alkenyl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclylalkyl, optionally substituted heteroarylalkyl and optionally substituted heteroarylalkenyl;

R 4a is hydrogen and R 4b is alkenyl or alkynyl;

or R 4a and R 4b are each alkyl;

R 5 is alkyl or a direct bond to the carbon at C14, provided that when R 4a is hydrogen and R 4b is alkenyl or alkynyl, R 5 is alkyl and when R 4a and R 4b are both alkyl, R 5′ is a direct bond to the carbon at C14;

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.

4. The compound of claim 3 which is 5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-aminomethyl-7aβ-methyl-1β-(propen-2-yl)octahydroindene.

5. The compound of claim 3 which is 5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-aminomethyl-1,1-dimethyl-2,3,4,5,6,7-hexahydro-1H-indene, or a pharmaceutically acceptable salt thereof.

6. The compound of claim 5 wherein the pharmaceutically acceptable salt is a pharmaceutically acceptable acid addition salt formed from an inorganic or organic acid.

7. The compound of claim 6 wherein the inorganic or organic acid is selected from:

hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, acetic acid, 2,2-dichloroacetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, camphoric acid, camphor-10-sulfonic acid, capric acid, caproic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glutaric acid, 2-oxo-glutaric acid, glycerophosphoric acid, glycolic acid, hippuric acid, isobutyric acid, lactic acid, lactobionic acid, lauric acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, mucic acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, propionic acid, pyroglutamic acid, pyruvic acid, salicylic acid, 4-aminosalicylic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, p-toluenesulfonic acid, trifluoroacetic acid or undecylenic acid.

8. The compound of claim 5 which is 5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-aminomethyl-1,1-dimethyl-2,3,4,5,6,7-hexahydro-1H-indene.

9. The compound of claim 5 which is 5-(1β-methyl-4β-hydroxy-2β-hydroxymethylcyclohexyl)-4α-aminomethyl-1,1-dimethyl-2,3,4,5,6,7-hexahydro-1H-indene, ammonium chloride salt.

10. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1 , as a single stereoisomer, a mixture of stereoisomers, or as a racemic mixture of stereoisomers; or a pharmaceutically acceptable salt, solvate or prodrug thereof, in isolation or in a mixture.