US2004034020A1PendingUtilityA1

Methods of treating periodontal disease

48
Priority: Aug 13, 1998Filed: Feb 3, 2003Published: Feb 19, 2004
Est. expiryAug 13, 2018(expired)· nominal 20-yr term from priority
Inventors:Susan Mary DalugeCynthia JurgensenMichael Tolar MartinMartin Osterhout
A61P 37/02A61P 37/00A61P 9/00A61P 43/00A61P 29/00A61P 31/04A61P 31/00A61P 35/00A61P 1/00A61P 1/04A61P 1/02A61P 11/06A61P 17/06C07D 473/06
48
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Claims

Abstract

The present invention relates to methods of treating periodontal disease.

Claims

exact text as granted — not AI-modified
1 . A compound formula (1):  
       
         
           
           
               
               
           
         
       
       wherein 
 Z represents a 5 or 6 membered cycloalkyl, aryl, substituted cycloalkyl, or substituted aryl, said cycloalkyl, aryl, substituted cycloalkyl or substituted aryl optionally containing one or more heteroatoms selected from O, N or S;  
 R 1  represents hydrogen or methyl;  
 R 2  represents hydrogen, C 1-12 , alkyl, aryl, or aralkyl;  
 k represents 0 or 1;  
 n represents an integer of 1 to 50;  
 X represents —O—, —N(H)—, —N(C 1-6 alkyl)-, —N(C 3-8 cycloalkyl)-, —N(C 1-8 alkyl)(C 3-8  cycloalkyl), —N[(CH 2 CH 2 O) m (C 1-12  alkyl, aryl, or aralkyl)]-, —CH 2 O—, —CH 2 NH—, —CH 2 N(C 1-6 alkyl), —CH 2 N(C 3-8 cycloalkyl)-, or —C 1-12 alkyl-;  
 m represents 0-12;  
 Q represents (—CH 2 ) p , (—CH═CH—) p , (—C≡C—) p , (—(O) p1 CH2-) p  or (—CH 2 (O) p1 ) p  where 
 p and p 1  independently represent an inteiger of from 0 to 4;  
 y and y′ independently represent integers from 0 to 10;  
 
 R 3  represents H, straight or branched C 1-12 alkyl (optionally substituted by phenyl, —CO— phenyl, CN, —CO(C 1-3 ) alkyl, —CO 2 (C 1-3 )alkyl, or containing one or more O atoms in the alkyl chain); C 1-6  straight or branched alkenyl, C 1-6  straight or branched alkynyl or a group —C 1-3 alkyl-NR 8 R 9  
 wherein R 8  and R 9  are independently H, C 1-3 alkyl or together form a 5 or 6 membered heterocyclic group, optionally containing other heteroatoms selected from O, N or S;  
 
 R 4  and R 5  independently represent 
 C 3-8  cycloalkyl  
 straight chain or branched C 1-6 alkyl  
 hydrogen  
 straight chain or branched C 2-6 alkenyl  
 aryl or substituted aryl;  
 heterocyclic group or substituted heterocyclic group, including heteroaryl and substituted heteroaryl groups;  
 
 R 6  and R 7  independently represent 0 or S;  
  with the proviso that when 
 y and y′ both represent 1,  
 k represents 1,  
 p 1  represents zero,  
 R 2  represents H or Me.  
 R 3  represents H.  
 X represents O or NH, and  
 Z represents phenyl  
 
 R 4  and R 5  do not both represent cydohexyl; or a solvate thereof.  
 
     
     
         2 . A compound formula (Ia):  
       
         
           
           
               
               
           
         
       
       wherein 
 Z represents a 5 or 6 membered cycloalkyl, aryl, substituted cycloalkyl, or substituted aryl, said cycloalkyl, aryl, substituted cycloalkyl or substituted aryl optionally containing one or more heteroatoms selected from O, N or S;  
 R 1  represents hydrogen or methyl;  
 R 2  represents hydrogen, C 1-12 , alkyl, aryl, or aralkyl;  
 k represents 0 or 1;  
 n represents an integer of 1 to 50;  
 X represents —O—, —N(H)—, —N(C 1-6 alkyl)-, —N(C 3-8 cycloalkyl)-, —N[(CH 2 CH 2 O) m (C 1-12  alkyl, aryl, or aralkyl)]-, —CH 2 O—, —CH 2 NH—, —CH 2 N(C 1-6 alkyl)-, —CH 2 N(C 3-8 cycloalkyl)-, or —C 1-12 alkyl-;  
 m represents 0-12;  
 Q represents (—CH 2 ) p , (—CH═CH—) p , (—C≡C—) p , (—(O) p1 CH2-) p  or (—CH 2 (O) p1 ) p  where 
 p and p 1  independently represent an integer of from 0 to 4;  
 y and y′ independently represent integers from 0 to 10;  
 
 R 3  represents H, straight chain or branched C 1-12 alkyl (optionally substituted by phenyl, —CO— phenyl, CN, —CO(C 1-3 ) alkyl, —CO 2 (C 1-3 )alkyl, or containing one or more O atoms in the alkyl chain); C 1-6  straight or branched alkenyl, C 1-6  straight or branched alkynyl or a group —C 1-3 alkyl-NR 8 R 9  
 wherein R 8  and R 9  are independently H, C 1-3 alkyl or together form a 5 or 6 membered heterocyclic group, optionally containing other heteroatoms selected from O, N or S;  
 
 R 4  and R 5  independently represent 
 C 3-8  cycloalkyl  
 straight chain or branched C 1-6 alkyl  
 hydrogen  
 straight chain or branched C 2-6 alkenyl  
 aryl or substituted aryl, or  
 heterocyclic group or substituted heterocyclic group, including heteroaryl and substituted heteroaryl groups;  
 
 R 6  and R 7  independently represent O or S;  
  with the proviso that when 
 y and y′ both represent 1,  
 k represents 1,  
 p represents zero,  
 R 3  represents H,  
 X represents O or NH, and  
 Z represents phenyl  
 
 R 4  and R 5  do not both represent cyclohexyl; or a solvate thereof.  
 
     
     
         3 . A compound as in claims  1  or  2  wherein R 3  represents C 1-3 alkyl-NR 8 R 9 .  
     
     
         4 . A compound according to claims  1  or  2 , where Z represents a phenyl ring, thiophene ring or pyridine ring.  
     
     
         5 . A compound according to  claim 4  where Z represents a phenyl ring.  
     
     
         6 . A compound according to  claim 5  where the  
       
         
           
           
               
               
           
         
       
       grouping is attached to the phenyl ring in the para position.  
     
     
         7 . A compound according to any of claims  1 - 6  where R 1  is H.  
     
     
         8 . A compound according to any of claims  1 - 7  where R 2  is methyl or ethyl.  
     
     
         9 . A compound according to any of claims  1 - 8  where k is 1.  
     
     
         10 . A compound according to any of claims  1 - 9  where n is from 8-20.  
     
     
         11 . A compound according to  claim 10  where n is from 8-15.  
     
     
         12 . A compound according to any of claims  1 - 11  where X is −—O—, —N(H)—, or —N(CH 3 )—.  
     
     
         13 . A compound according to any preceding claim where Q is (—CH═CH—) p .  
     
     
         14 . A compound according to  claim 13  where p represents 1.  
     
     
         15 . A compound according to any preceding claim where R 3  is methyl.  
     
     
         16 . A compound according to any preceding claim where y and y′ are the same.  
     
     
         17 . A compound according to  claim 16  where y and y′ are 1.  
     
     
         18 . A compound according to any preceding claim where R 4  and R 5  are independently selected from C 1-6  alkyl, C 3-8  cycloalkyl and aryl.  
     
     
         19 . A compound according to  claim 18 , where R 4  anc R 5  are independently selected from cyclobutyl, cyclopentyl, cyclohexyl, propyl, butyl, isopropyl, isobutyl and phenyl.  
     
     
         20 . A compound according to  claim 18  or  19  where R 4  and R 5  are the same.  
     
     
         21 . A compound according to any preceding claim where R 6  and R 7  are are the same.  
     
     
         22 . A compound according to  claim 21  where R 6  and R 7  are O.  
     
     
         23 . A compound according to claims  1  or  2  where X is −—O— and R 1  is H.  
     
     
         24 . A compound according to claims  1  or  2  which is 
 (E)-4-(1,3-bis(benzyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-[1.3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(cyclopentylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(propyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(cyclopropylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-3-((1-propyl-3-benzyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(cycloheptylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(cyclohexylethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(phenyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(2-methyl-propyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-((1-propyl-3-cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(bicyclo(2.2.1)hept-2-ylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1-cyclohexylmethyl-3-butyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-((1-cyclohexylmethyl-3-propyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(benzyl)-1,2,3,6-tetrahydro-2-thiox-6-oxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1-methyl-3-(3-cyanobenzyl))-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-((1,3-bis(3-fluorobenzyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-((1,3-bis(2-fluorobenzyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-((1,3-bisphenethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-((1-cyclohexylmethyl-3-methyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-((1-H-3-(2-methyl-propyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(4-fluorobenzyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Hexaethylene Glycol dodecyl Ether Ester;  
 (E)-4-(1,3-bis(cyclobutylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1-methyl-3-cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethyiene Glycol Methyl Ether Ester;  
 (E)-4-(1-methyl-3-isobutyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 4-(1,3-bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)benzoic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(cyclohexyl)-l, 2 , 3 , 6 -tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Amide;  
 (E)-4-(1,3-bis(cyclopentylmethyl)-1,2,3,6-tetrahydro-6-oxo-2-thioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Amide;  
 (E)-4-(1,3-bis(2-methyl-propyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Amide;  
 (E)-4-((1-clohexylmethyl-3-propyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethyiene Glycol Methyl Ether Amide;  
 4-(1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)benzoic Acid Nonaethylene Glycol Methyl Ether Amide;  
 4-(1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)benzoic Acid-N-methyl-Nonaethylene Glycol Methyl Ether Amide;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-benzyl-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-(2-oxo-2-phenylethyl)-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-methyl-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-(2-propynyl)-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo7-(2-oxo-2-methylethyl)-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyil)-2,3,6,7-tetrahydro-2,6-dioxo-7-(3-morpholinopropyl)-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-ethyl-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-(2-ethoxy-2-oxoethyl)-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-(2-methyl-2-propenyl)-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-(cyanomethyl)-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-benzyl-1H-purin-8-yl)benzoic Acid Nonaethylene Glycol Methyl Ether Ester;  
 4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-methyl-1H-purin-8-yl)benzoic Acid Nonaethylene Glycol Methyl Ether Ester;  
 4-[(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-methyl-1H-purin-8-yl)phenyl] propionic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-methyl-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Amide;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-benzyl-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Amide;  
 4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-benzyl-1H-purin-8-yl)benzoic Acid Nonaethylene Glycol Methyl Ether Amide;  
 4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-methyl-1H-purin-8-yl)benzoic Acid Nonaethylene Glycol Methyl Ether Amide;  
 1,3-Bis(cyclohexylmethyl)-8-[4-(2,5,8,11,14,17,20,23,26,29-decaoxatriacont-1-yl)phenyl]-3,7-dihydro-1H-purine-2,6-dione;  
 (E)-3-[5-[1,3-bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-1H-purin-8-yl]-2-thienyl]-2-propenoic Acid Nonaethylene Glycol Methyl Ether Ester;  
 6-(1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)nicotinic Acid Nonaethylene Glycol Methyl Ether Amide;  
 (E)-3-(1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid N-cyclopropylmethyl Nonaethylene Glycol Methyl Ether Amide;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Hexaethylene Glycol Benzyl Ether Amide;  
 (E)-4-[(3-Cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-methyl-1H-purin-8-yl]cinnamic Acid Heptaethylene Glycol Methyl Ether Ester;  
 (E)-4-[(3-Cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-methyl-1H-purin-8-yl]cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-[(3-Cyclohexytmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-1,7-dimethyl-1H-purin-8-yl]cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 4-[1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]benzylamine Heptaethylene Glycol Methyl Ether;  
 4-[1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]benzylamine N-Heptaethylene Glycol Methyl Ether Hydrochloride;  
 4-[1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]benzylamine N-Nonaethylene Glycol Methyl Ether;  
 1,3-Bis(cyclohexylmethyl)-8-[3-(2,5,8,11,14,17,20,23,26,29-decaoxatriacont-1-yl)phenyl]-3,7-dihydro-1H-purine-2,6-dione;  
 (E)-4-(1,3-Bis(cyclohexyimethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-methyl-1H-purin-8-yl)cinnamic Acid Heptaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-methyl-1H-purin-8-yl)cinnamic Acid Pentaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-propyl-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester.  
 
     
     
         25 . A compound according to  claim 24  which is 
 (E)-4-(1,3-bis(benzyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-[1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(cyclopentylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(propyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(cycloheptylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(cyclohexylethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(phenyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(2-methyl-propyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-((1-propyl-3-cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(bicyclo(2.2.1)hept-2-ylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1-cyclohexylmethyl-3-butyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-((1-cyohexyimethyl-3-propyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(3-fluorobenzyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-((1,3-bis(2-fluorobenzyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bisphenethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-((1-H-3-(2-methyl-propyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(4-fluorobenzyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Hexaethylene Glycol dodecyl Ether Ester;  
 (E)-4-(1,3-bis(cyclobutylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1-methyl-3-isobutyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 4-(1,3-bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)benzoic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-3-(1,3-bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Amide;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid-N-methyl Nonaethyiene Glycol Methyl Ether Amide;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Amide;  
 4-(1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)benzoic Acid Nonaethylene Glycol Methyl Ether Amide;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-benzyl-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-(2-oxo-2-phenylethyl)-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-methyl-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethy)-2,3,6,7-tetrahydro-2,6-dioxo-7-(2-propynyl)-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-(2-oxo-2-methylethyl)-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-(3-morpholinopropyl)-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-ethyl-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-(2-ethoxy-2-oxoethyl)-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-(2-methyl-2-propenyl)1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-(cyanomethyl)-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-benzyl-1H-purin-8-yl)benzoic Acid Nonaethylene Glycol Methyl Ether Ester;  
 4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-methyl-1H-purin-8-yl)benzoic Acid Nonaethylene Glycol Methyl Ether Ester;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-methyl-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Amide;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-benzyl-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Amide;  
 4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-benzyl-1H-purin-8-yl)benzoic Acid Nonaethylene Glycol Methyl Ether Amide;  
 1,3-Bis(cyclohexylmethyl)-8-[4-(2,5,8,11,14,17,20,23,26,29-decaoxatriacont-1-yl)phenyl]-3,7-dihydro-1H-purine-2,6-dione;  
 (E)-3-4[5-[1,3-bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-1H-purin-8-yl]-2-thienyl]-2-propenoic Acid Nonaethylene Glycol Methyl Ether Ester;  
 6-(1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)nicotinic Acid Nonaethylene Glycol Methyl Ether Amide;  
 (E)-3-(1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid N-cyclopropylmethyl Nonaethylene Glycol Methyl Ether Amide;  
 (E)-4-[(3-Cyclohexymethyl)-2,3,6,7-tetrahydro 2,6-dioxo-7-methyl-1H-purin-8-yl]cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;  
 4-[1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]benzylamine N-Heptaethylene Glycol Methyl Ether Hydrochloride;  
 1,3-Bis(cyclohexylmethyl)-8-[3-(2,5,8,11,14,17,20,23,26,29-decaoxatriacont-1-yl)phenyl]-3,7-dihydro-1H-purine-2,6-dione;  
 (E)-4-(1,3-bis(cyclopentylmethyl)-1,2,3,6-tetrahydro-6-oxo-2-thioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Amide;  
 (E)-4-(1,3-Bis(cyclohexylmethyl)-2,3,6,7-tetrahydro-2,6-dioxo-7-propyl-1H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester.  
 
     
     
         26 . A compound according to any preceding claim for use in therapy.  
     
     
         27 . A pharmaceutical composition comprising a compound according to any of claims  1 - 25  together with a pharmaceutically acceptable diluent or carrier.  
     
     
         28 . Use of a compound according to any of claims  1 - 25  for the manufacture of a medicament for the treatment of inflammatory conditions, immune disorders, tissue injury, infectious diseases, cancer and any disorder in which altered leucocyte adhesion contributes to the pathogenesis of the disease.  
     
     
         29 . Use of a cell adhesion molecule inhibitor in the manufacture of medicament for the treatment of periodontal disease.  
     
     
         30 . Use of a compound according to any of claims  1 - 25  for the manufacture of a medicament for the treatment of periodontal disease.  
     
     
         31 . Use of a compound of formula (Ib)  
       
         
           
           
               
               
           
         
       
       or a solvate thereof wherein: 
 X is 4 or —NH—;  
 Q is (—CH 2 —) p , (—CH═CH—) p ,(—C≡C—) p  where p is an integer of from 0 to 4;  
 R 1  is hydrogen or methyl;  
 R 2  and R 3  independently represent O or S.  
 n is an integer of 1 to 50; and  
 R is hydrogen or methyl  
 for the manufacture of a medicament for the treatment of periodontal disease.  
 
     
     
         32 . Use of a compound which is: 
 (E)-4-(1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Decaethylene Glycol Methyl Ether Ester; and    (E)-4-(1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester,    (E)-3-[1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin8-yl]cinnamic Acid Nonaethylene Glycol Methyl Ether Ester; (E)-4-[1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin8-yl)cinnamic acid Nonaethylene Glycol Methyl Ether Amide;    (E)-4-[1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]benzoic acid Nonaethylene Glycol Methyl Ether Ester    for the manufacture of a medicament for the treatment of periodontal disease.    
     
     
         33 . Use of (E)-4-(1,3-Bis(cyclohexylmethyl)1,2,3,6-tetrahydro-2,6-dioxo-9H-purin8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester in the manufacture of a medicament for the treatment of periodontal disease.  
     
     
         34 . A method of treating inflammatory conditions, immune disorders, tissue injury, infectious diseases, cancer and any disorder in which altered leucocyte adhesion contributes to the pathogenesis of the disease, which comprises administering to a subject a therapeutically effective amount of a compound according to any of claims  1 - 25 .  
     
     
         35 . A method of treating periodontal disease, which comprises administering to a subject a therapeuticaly effective amount of a cell adhesion molecule inhibitor.  
     
     
         36 . A method of treating periodontal disease, which comprises administering to a subject a therapeutically effective amount of a compound according to any of claims  1 - 25 .  
     
     
         37 . A method of treating periodontal disease, which comiprises administering to a subject a therapeutically effective amount of a compound of formula (Ib)  
       
         
           
           
               
               
           
         
       
       or a solvate thereof wherein: 
 X is —O— or —NH—;  
 Q is —CH 2 —) p , (—CH═CH—) p , (—C≡C—) p  where p is an integer of from 0 to 4;  
 R 1  is hydrogen or methyl;  
 R 2  and R 3  independently represent O or S.  
 n is an integer of 1 to 50; and  
 R is hydrogen or methyl.  
 
     
     
         38 . A method of treating periodontal disease, which comprises administering to a subject a therapeutically effective amount of a compound which is: 
 (E)-4-(1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Decaethylene Glycol Methyl Ether Ester; and    (E)-4-(1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester;    (E)-3-[1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin8-yl]cinnamic Acid Nonaethylene Glycol Methyl Ether Ester,    (E)-4-[1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin8-yl)cinnamic acid Nonaethylene Glycol Methyl Ether Amide;    (E)-4-[1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]benzoic acid Nonaethylene Glycol Methyl Ether Ester.    
     
     
         39 . A method of treating periodontal disease which comprises administration of a therapeutically effective amount of (E)-4-(1,3-Bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)cinnamic Acid Nonaethylene Glycol Methyl Ether Ester.  
     
     
         40 . A process for preparing the compounds of formula (I) or (Ia), or solvates thereof which comprises reacting the compound of formula (II)  
       
         
           
           
               
               
           
         
       
       or an activated derivative thereof with a compound of formula (III)  
       
         
           
           
               
               
           
         
       
       wherein Q, X, R 1 , R 2 , R 4   1 , R 5 , R 6 , y, y′ and n are as defined in  claim 1;  
 and optionally converting the compound of formula (I) so formed to a different compound of formula (t) or to a corresponding solvate.

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