Methods and compositions for dental tissue repair and/or regeneration

Abstract

The present invention provides methods and compositions for promoting dental tissue repair and/or regeneration, methods for promoting differentiation of dental pulp stem cells, methods for treating periodontal diseases, and methods for treating infection of a dental pulp in a subject in need thereof by contacting the tissue with a composition comprising a triacrylate capable of promoting dental pulp stem cells adhesion and/or proliferation.

1 - 21 . (canceled) 
     
     
         22 . A compound of Formula II, comprising the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof; wherein 
         R is selected from the group consisting of hydrogen, bromo, iodo, fluoro, C 1 -C 12  alkyl, C 2 -C 12  alkenyl, C 2 -C 12 alkynyl, C 3 -C 12  cycloalkyl, C 2 -C 11  heterocyclyl, C 6 -C 14  aryl, —N(R d ) 2 , —SR d , and —OR e ; wherein the C 1 -C 12  alkyl, C 2 -C 12  alkenyl, C 2 -C 12 alkynyl, C 3 -C 12  cycloalkyl, C 2 -C 11  heterocyclyl, and C 6 -C 14  aryl groups are optionally substituted by one or more groups selected from the group consisting of halogen, hydroxy, cyano, amino, C 1 -C 12 alkyl, C 1 -C 12  alkenyl, C 1 -C 12 alkynyl, C 1 -C 12 alkoxy, C 3 -C 12  cycloalkyl, C 2 -C 11  heterocyclyl, C 6 -C 14  aryl, C 1 -C 12 alkylamino, and di(C 1 -C 12 alkyl)amino; 
         R d  is independently selected from the group consisting of hydrogen, C 1 -C 12 alkyl, C 2 -C 12  alkenyl, C 2 -C 12 alkynyl, C 3 -C 12  cycloalkyl, C 6 -C 14  aryl, and C 2 -C 11  heterocyclyl, or wherein the two R d  groups may form a heterocyclyl with the nitrogen to which they are connected, wherein the C 1 -C 12 alkyl, C 2 -C 12  alkenyl, C 2 -C 12 alkynyl, C 3 -C 12  cycloalkyl, C 6 -C 14  aryl, and C 2 -C 11  heterocyclyl are optionally substituted by one of more groups selected from halogen, hydroxy, and C 1 -C 4  alkoxy; and 
         R e  is independently selected from the group consisting of C 2 -C 12 alkyl, C 2 -C 12  alkenyl, C 2 -C 12 alkynyl, benzyl, and phenyl, wherein the C 2 -C 12 alkyl, C 2 -C 12  alkenyl, C 2 -C 12 alkynyl, benzyl, and phenyl are optionally substituted from the group consisting of halogen, hydroxy, and C 1 -C 4  alkoxy. 
       
     
     
         23 . The compound of  claim 22 , wherein
 R is selected from the groups consisting of hydrogen, bromo, iodo, fluoro, C 1 -C 6 alkyl, C 2 -C 6  alkenyl, C 2 -C 6 alkynyl, C 3 -C 8  cycloalkyl, C 2 -C 6  heterocyclyl, C 6 -C 2  aryl, —N(R d ) 2 , —SR d , and —OR e ; wherein C 1 -C 6 alkyl, C 2 -C 6  alkenyl, C 2 -C 6 alkynyl, C 3 -C 6  cycloalkyl, C 2 -C 6  heterocyclyl, C 6 -C 12  aryl are optionally substituted by one to four groups selected from halogen, hydroxy, and C 1 -C 4  alkoxy;   R d  is independently selected from the groups consisting of hydrogen, C 1 -C 6 alkyl, C 3 -C 8  cycloalkyl, C 6 -C 14  aryl, and C 2 -C 11  heterocyclyl, wherein the C 1 -C 6 alkyl, C 3 -C 8  cycloalkyl, C 6 -C 14  aryl, and C 2 -C 11  heterocyclyl are optionally substituted by one of more groups selected from halogen, hydroxy, and C 1 -C 4  alkoxy; and   R e  is independently selected from the groups consisting of C 2 -C 6 alkyl, benzyl, and phenyl, the C 2 -C 6 alkyl, benzyl, and phenyl are optionally substituted from the groups consisting of halogen, hydroxy, and C 1 -C 4  alkoxy.   
     
     
         24 . The compound of  claim 22 , wherein
 R is selected from the group consisting of hydrogen, C 1 -C 12 alkyl, C 2 -C 12  alkenyl, C 2 -C 12 alkynyl, C 3 -C 12  cycloalkyl, C 2 -C 11  heterocyclyl, C 6 -C 14  aryl, —N(R d ) 2 , —SR d , and —OR e ; wherein the C 1 -C 12 alkyl, C 2 -C 12  alkenyl, C 2 -C 12 alkynyl, C 3 -C 12  cycloalkyl, C 2 -C 11  heterocyclyl, and C 6 -C 14  aryl groups are optionally substituted by one or more groups selected from the group consisting of halogen, hydroxy, cyano, amino, C 1 -C 12 alkyl, C 1 -C 12  alkenyl, C 1 -C 12 alkynyl, C 1 -C 12 alkoxy, C 3 -C 12  cycloalkyl, C 2 -C 11  heterocyclyl, C 6 -C 14  aryl, C 1 -C 12 alkylamino, and di(C 1 -C 12 alkyl)amino;   R d  is independently selected from the group consisting of hydrogen, C 1 -C 12 alkyl, C 2 -C 12  alkenyl, C 2 -C 12 alkynyl, C 3 -C 12  cycloalkyl, C 6 -C 14  aryl, and C 2 -C 11  heterocyclyl, or wherein the two R d  groups may form a heterocyclyl with the nitrogen to which they are connected, wherein the C 1 -C 12 alkyl, C 2 -C 12  alkenyl, C 2 -C 12 alkynyl, C 3 -C 12  cycloalkyl, C 6 -C 14  aryl, and C 2 -C 11  heterocyclyl are optionally substituted by one of more groups selected from halogen, hydroxy, and C 1 -C 4  alkoxy; and   R e  is independently selected from the group consisting of C 2 -C 12 alkyl, C 2 -C 12  alkenyl, C 2 -C 12 alkynyl, benzyl, and phenyl, wherein the C 2 -C 12 alkyl, C 2 -C 12  alkenyl, C 2 -C 12 alkynyl, benzyl, and phenyl are optionally substituted from the group consisting of halogen, hydroxy, and C 1 -C 4  alkoxy.   
     
     
         25 . The compound of  claim 22 , wherein
 R is selected from the group consisting of hydrogen, C 1 -C 12  alkyl, —N(R d ) 2 , —SR d , and —OR e ; wherein the C 1 -C 12  alkyl is optionally substituted by one or more groups selected from the group consisting of halogen, hydroxy, cyano, amino, C 1 -C 12  alkyl, C 1 -C 12 alkylamino, and di(C 1 -C 12 alkyl)amino;   R d  is independently selected from the group consisting of hydrogen and C 1 -C 12  alkyl, or wherein the two R d  groups may form a heterocyclyl with the nitrogen to which they are connected, wherein the C 1 -C 12  alkyl is optionally substituted by one of more groups selected from halogen, hydroxy, and C 1 -C 4  alkoxy; and   R e  is independently selected from the group consisting of C 2 -C 12 alkyl, benzyl, and phenyl, wherein the C 2 -C 12 alkyl, benzyl, and phenyl are optionally substituted from the group consisting of halogen, hydroxy, and C 1 -C 4  alkoxy.   
     
     
         26 . The compound of  claim 22 , wherein the aryl is anthracenyl, naphthyl, and phenyl. 
     
     
         27 . The compound of  claim 22 , wherein the heterocyclyl is aziridinyl, oxiranyl, thiiranyl, oxaziridinyl, dioxiranyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, thiolanyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, dioxolanyl, dithiolanyl, oxathiolanyl, piperidinyl, tetrahydropyranyl, thianyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxanyl, dithianyl, trioxanyl, trithianyl, azepanyl, oxepanyl, thiepanyl, dihydrofuranyl, imidazolinyl, dihydropyranyl, azirinyl, oxirenyl, thiirenyl, diazirinyl, azetyl, oxetyl, thietyl, pyrrolyl, furanyl, thiophenyl (or thienyl), imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, furazanyl, oxadiazolyl, thiadiazolyl, dithiazolyl, triazolyl, tetrazolyl, pyridinyl, pyranyl, thiopyranyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazinyl, thiazinyl, dioxinyl, dithiinyl, oxathianyl, triazinyl, tetrazinyl, azepinyl, oxepinyl, thiepinyl, diazepinyl, thiazepinyl 3-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[3.1.1]heptanyl, 2-azaspiro[3.3]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, or 5-azaspiro [2.3]hexanyl. 
     
     
         28 . A compound of Formula III, comprising the structure: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         29 . A compound of Formula IV, comprising the structure: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         30 . A composition for use in dental tissue repair and/or regeneration, comprising the compound of  claim 22 . 
     
     
         31 . The composition of  claim 30 , wherein the triacrylate is polymerized triacrylate. 
     
     
         32 . The composition of  claim 31 , wherein the triacrylate is polymerized by ultraviolet (UV) irradiation. 
     
     
         33 . The composition of  claim 30 , wherein the dental tissue is a dental pulp tissue; or a dentin tissue. 
     
     
         34 . (canceled) 
     
     
         35 . The composition of  claim 30 , wherein the composition further promotes migration and/or differentiation of DPSCs. 
     
     
         36 . The composition of  claim 30 , wherein the composition is suitable for treating a dental pulp infection. 
     
     
         37 . The composition of  claim 30 , wherein the composition is suitable for delivering to a natural or artificial cavity or chamber of a tooth in a subject. 
     
     
         38 . The composition of  claim 37 , wherein the composition is delivered by injection. 
     
     
         39 - 119 . (canceled) 
     
     
         120 . A composition comprising the compound of  claim 22 . 
     
     
         121 . A composition comprising the compound of  claim 28 . 
     
     
         122 . A composition comprising the compound of  claim 29 .