Fatty acid analogues for equilibrating bone mineral density

Abstract

The invention comprises the use of compounds comprising non β-oxidizable fatty acid entities according to formula (I) or (II) for the preparation of a pharmaceutical composition for the prevention and/or treatment of conditions associated with low/decreased bone mineral density (BMD), and/or for increasing the BMD by decreasing the bone resorption.

1 - 10 . (canceled) 
   
   
       11 . A pharmaceutical composition for the prevention and/or treatment of conditions associated with low/decreased bone mineral density (BMD) comprising compound represented by the general formula (I), 
     
       
         
         
             
             
         
       
     
     wherein R1, R2, and R3 represent
 i) a hydrogen atom; or 
 ii) a group having the formula CO—R wherein R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or 
 iii) a group having the formula CO—(CH 2 ) 2n+1 —X—R′, wherein X is a sulphur atom, a selenium atom, an oxygen atom, a CH 2  group, a SO group or a SO 2  group; n is an integer from 0 to 11; and R′ is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R′ contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group consisting of an oxygen atom, a sulphur atom, a selenium atom, a CH 2  group, a SO group, and a SO 2  group; 
 iv) an entity selected from the group comprising —PO 3 CH 2 CHNH 3 COOH (serine), PO 3 CH 2 CH 2 NH 3  (ethanolamine), PO 3 CH 2 CH 2 N(CH 3 ) 3  (choline), PO 3 CH 2 CHOHCH 2 OH (glycerol) and PO 3 (CHOH) 6  (inositol); 
 
     wherein R1, R2, and R3 are chosen independently from i), ii), iii), or iv), but at least one of R1, R2, or R3 is defined by iii); or a compound represented by the general formula R″—COO—(CH 2 ) 2n+1 —X—R′, wherein X is a sulphur atom, a selenium atom, an oxygen atom, a CH 2  group, a SO group or a SO 2  group; n is an integer from 0 to 11; and R′ is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein 
     the main chain of said R′ contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a CH 2  group, a SO group and a SO 2  group; and R″ is a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms; or a salt, prodrug or complex of said compounds. 
   
   
       12 . A pharmaceutical composition for the prevention and/or treatment of conditions associated with low/decreased bone mineral density (BMD) comprising compound represented by the general formula (II), 
     
       
         
         
             
             
         
       
       wherein A1, A2 and A3 are chosen independently and represent an oxygen atom, a sulphur atom or an N-R4 group in which R4 is a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms; wherein R1, R2, and R3 represent 
       i) a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 23 carbon atoms; or 
       ii) a group having the formula CO—R in which R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or 
       iii) a group having the formula CO—(CH 2 ) 2n+1 —X—R′, wherein X is a sulphur atom, a selenium atom, an oxygen atom, a CH 2  group, a SO group or a SO 2  group; n is an integer from 0 to 11; and R′ is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R′ contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group consisting of an oxygen atom, a sulphur atom, a selenium atom, a CH 2  group, a SO group and a SO 2  group; 
       iv) an entity selected from the group comprising —PO 3 CH 2 CHNH 3 COOH (serine), PO 3 CH 2 CH 2 NH 3  (ethanolamine), PO 3 CH 2 CH 2 N(CH 3 ) 3  (choline), PO 3 CH 2 CHOHCH 2 OH (glycerol) and PO 3 (CHOH) 6  (inositol); 
     
     wherein R1, R2, and R3 are chosen independently from i), ii), iii), or iv), but at least one of R1, R2, or R3 is defined by iii); or a salt, prodrug or complex of said compound. 
   
   
       13 . The pharmaceutical composition of  claim 11  or  12 , for the treatment and/or prevention of osteopenia, osteoporosis, secondary osteoporosis, posttransplantation bone disease, Paget's disease, idiopathic juvenile bone loss, multiple myeloma, osteosarcoma, parathyroidectomy, thermal injuries, hyperparathyroidism, periodontal diseases, bone disease caused by hemodyalysis, and scurvy. 
   
   
       14 . The pharmaceutical composition of  claim 13 , where secondary osteoporosis is selected from the group consisting of glucocorticoid induced osteoporosis, hyperthyroidisem induced osteoporosis, immobilization induced osteoporosis, heparin induced osteoporosis, and immunosuppressant induced osteoporosis. 
   
   
       15 . The pharmaceutical composition of  claim 11  or  12 , for the prevention and/or treatment of an abnormally low bone mineral density (BMD). 
   
   
       16 . A pharmaceutical composition for increasing BMD by decreasing bone resorption comprising compound represented by the general formula (I), 
     
       
         
         
             
             
         
       
     
     wherein R1, R2, and R3 represent
 i) a hydrogen atom; or 
 ii) a group having the formula CO—R wherein R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or 
 iii) a group having the formula CO—(CH 2 ) 2n+1 —X—R′, wherein X is a sulphur atom, a selenium atom, an oxygen atom, a CH 2  group, a SO group or a SO 2  group; n is an integer from 0 to 11; and R′ is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R′ contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group consisting of an oxygen atom, a sulphur atom, a selenium atom, a CH 2  group, a SO group, and a SO 2  group; 
 iv) an entity selected from the group comprising —PO 3 CH 2 CHNH 3 COOH (serine), PO 3 CH 2 CH 2 NH 3  (ethanolamine), PO 3 CH 2 CH 2 N(CH 3 ) 3  (choline), PO 3 CH 2 CHOHCH 2 OH (glycerol) and PO 3 (CHOH) 6  (inositol); 
 
     wherein R1, R 2, and R3 are chosen independently from i), ii), iii), or iv), but at least one of R1, R2, or R3 is defined by iii); or a compound represented by the general formula R″—COO—(CH 2 ) 2n+1 —X—R′, wherein X is a sulphur atom, a selenium atom, an oxygen atom, a CH 2  group, a SO group or a SO 2  group; n is an integer from 0 to 11; and R′ is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R′ contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a CH 2  group, a SO group and a SO 2  group; and R″ is a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms; or a salt, prodrug or complex of said compounds. 
   
   
       17 . A pharmaceutical composition for increasing BMD by decreasing bone resorption comprising compound represented by the general formula (II), 
     
       
         
         
             
             
         
       
       wherein A1, A2 and A3 are chosen independently and represent an oxygen atom, a sulphur atom or an N-R4 group in which R4 is a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms; wherein R1, R2, and R3 represent 
       i) a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 23 carbon atoms; or 
       ii) a group having the formula CO—R in which R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or 
       iii) a group having the formula CO—(CH 2 ) 2n+1 —X—R′, wherein X is a sulphur atom, a selenium atom, an oxygen atom, a CH 2  group, a SO group or a SO 2  group; n is an integer from 0 to 11; and R′ is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R′ contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group consisting of an oxygen atom, a sulphur atom, a selenium atom, a CH 2  group, a SO group and a SO 2  group; 
       iv) an entity selected from the group comprising —PO 3 CH 2 CHNH 3 COOH (serine), PO 3 CH 2 CH 2 NH 3  (ethanolamine), PO 3 CH 2 CH 2 N(CH 3 ) 3  (choline), PO 3 CH 2 CHOHCH 2 OH (glycerol) and PO 3 (CHOH) 6  (inositol); 
     
     wherein RI, R2, and R3 are chosen independently from i), ii), iii), or iv), but at least one of R1, R2, or R3 is defined by iii); or a salt, prodrug or complex of said compound. 
   
   
       18 . The pharmaceutical composition of  claim 11 , wherein the compound is chosen from the group consisting of tetradecylthioacetic acid (TTA), tetradecylselenoacetic acid, and 3-thia-15-heptadecyne. 
   
   
       19 . The pharmaceutical composition of  claim 16 , wherein the compound is chosen from the group consisting of tetradecylthioacetic acid (TTA), tetradecylselenoacetic acid, and 3-thia-15-heptadecyne.