Osteoblast-specific mitogens and drugs containing such compounds

Abstract

Osteoblast-specific mitogens and drugs containing such compounds can be used for treating metabolic bone diseases. Novel compounds for this treatment include lysophosphatidylic acid derivatives selected from the group consisting of compounds of formula: wherein R 1 =alkenyl or alkynyl having from 6 to 24 carbon atoms; n=0-12; X=oxygen; the compounds (all-cis-5,8,11,14)-eicosatetraenoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-9, cis-12-octadecadienoic acid 2-hydroxy-3-phosphonooxypropyl ester; (all-cis-9,12,15)-octadecatrienoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-9-octadecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; and erucic acid 2-hydroxy-3-phosphonooxypropylester being excluded, and the physiologically tolerable salts, esters, optically active forms, and racemates of said compounds.

1 - 6 . Cancel  
     
     
         7 . A lysophosphatidylic acid derivative selected from the group consisting of compounds of formula (I)  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1 =alkenyl or alkynyl having from 6 to 24 carbon atoms;  
 n=0-12;  
 X=O,  
 the compounds (all-cis-5,8,11,14)-eicosatetraenoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-9, cis-12-octadecadienoic acid 2-hydroxy-3-phosphonooxypropyl ester; (all-cis-9,12,15)-octadecatrienoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-9-octadecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; and erucic acid 2-hydroxy-3-phosphonooxypropylester being excluded: and the physiologically tolerable salts, esters, optically active forms, and racemates of said compounds.  
 
     
     
         8 . A compound selected from the group consisting of octanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 7-methyloctanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 7,7-dimethyloctanoic acid 2-hydroxy-3-phosphonooxypropyl ester; nonanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 4-methylnonanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 8-methylnonanoic acid 2-hydroxy-3-phosphonooxypropyl ester; undecanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 10-methylundecanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 11-methyldodecanoic acid 2-hydroxy-3-phosphonooxypropyl ester; tridecanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 12-methyltridecanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 13-methyltetradecanoic acid 2-hydroxy-3-phosphonooxypropyl ester; pentadecanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 14-methylpentadecanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 15-methylhexadecanoic acid 2-hydroxy-3-phosphonooxypropyl ester; heptadecanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 16-methylheptadecanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 17-methyloctadecanoic acid 2-hydroxy-3-phosphonooxypropyl ester; nonadecanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 18-methylnonadecanoic acid 2-hydroxy-3-phosphonooxypropyl ester; eicosanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 19-methyleicosanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 19-methyleicosanoic acid 2-hydroxy-3-phosphonooxy-propyl ester; heneicosanoic acid 2-hydroxy-3-phosphonooxypropyl ester; docosanoic acid 2-hydroxy-3-phosphonooxypropyl ester; tricosanoic acid 2-hydroxy-3-phosphonooxypropyl ester; tetracosanoic acid 2-hydroxy-3-phosphonooxypropyl ester; heptacosanoic acid 2-hydroxy-3-phosphonooxypropyl ester; octacosanoic acid 2-hydroxy-3-phosphonooxypropyl ester; triacontanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 6-heptenoic acid 2-hydroxy-3-phosphonooxypropyl ester; and trans-9-hexadecenoic acid 2-hydroxy-3-phosphonooxypropyl ester.  
     
     
         9 . A compound selected from the group consisting of (all-cis-11,14,17)-eicosatrienoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-10-heptadecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-10-nonadecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-3,cis-6-nonadienoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-10-pentadecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-12-octadecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-13-octadecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-7-octadecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-8-eicosenoic acid 2-hydroxy-3-phosphonooxypropyl ester; trans-9-tetradecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; trans-9-octadecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; (all-trans-9,11,13,15)-octadecatetraenoic acid 2-hydroxy-3-phosphonooxypropylester; (all-cis-9,11,13,15) octadecatetraenoic acid 2-hydroxy-3-phosphonooxypropylester; cis-11-octadecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; (all-cis-13,16,19)-docosatrienoic acid 2-hydroxy-3-phosphonooxypropyl ester; (all-cis-13,16,19)-docosatrienoic acid 2-hydroxy-3-phosphonooxypropyl ester; (all-cis-8,11,14)-eicosatrienoic acid 2-hydroxy-3-phosphonooxypropyl ester; trans-11-octadecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; trans-13-docosenoic acid 2-hydroxy-3-phosphonooxypropyl ester; trans-9,trans-12-octadecadienoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-9-tetradecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-9-hexadecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; 10-undecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-11,cis-14-eicosadienoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-11-eicosenoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-15-tetracosenoic acid 2-hydroxy-3-phosphonooxypropyl ester; 11-dodecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; 9-decenoic acid 2-hydroxy-3-phosphonooxypropyl ester; 16-heptadecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; and (all-cis-11,14,17)-eicosatrienoic acid 2-hydroxy-3-phosphonooxypropyl ester.  
     
     
         10 . A compound selected from the group consisting of cis-13-eicosenoic acid 2-hydroxy-3-phosphonooxypropyl ester (64) (all-cis-7,10,13,16)-docosatetraenoic acid 2-hydroxy-3-phosphonooxypropylester; 22-tricosenoic acid 2-hydroxy-3-phosphonooxypropyl ester; 9-tetradecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; 13-eicosenoic acid 2-hydroxy-3-phosphonooxypropyl ester; 10,12-nonacosadiynoic acid 2-hydroxy-3-phosphonooxypropyl ester; 10,12-octadecadiynoic acid 2-hydroxy-3-phosphonooxypropyl ester; 9-octadecanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 10-undecanoic acid 2-hydroxy-3-phosphonooxypropyl ester; 10,12-tricosadiynoic acid 2-hydroxy-3-phosphonooxypropyl ester; 10,12-pentacosadiynoic acid-2-hydroxy-3-phosphonooxypropyl ester; and 10,12-heptacosadiynoic acid 2-hydroxy-3-phosphonooxypropyl ester.