Use of agonists of formyl peptide receptor 2 for treating dermatological diseases

Abstract

The present invention relates to a method for treating dermal inflammation and dermal diseases by local or systemic delivery, in a subject in need of such treatment, which comprises administering a pharmaceutical composition comprising a therapeutically effective amount of at least one agonist of Formyl peptide receptor 2 (FPR2).

What is claimed is: 
     
         1 . A method of treating dermal inflammation and dermal diseases by local or systemic delivery, in a subject in need of such treatment, which comprises administering a pharmaceutical composition comprising a therapeutically effective amount of at least one agonist of Formyl peptide receptor 2. 
     
     
         2 . The method of  claim 1 , wherein the dermal inflammation and dermal diseases are selected from: dermal wound healing, hypertrophic scars, keloids, burns, rosacea, atopic dermatitis, acne, psoriasis, seborrheic dermatitis, actinic keratoses, basal cell carcinoma, squamous cell carcinoma, melanoma, viral warts, photoaging, photodamage, melasma, post-inflammatory hyperpigmentation, disorders of pigmentation, alopecia, scarring and non-scarring forms. 
     
     
         3 . The method of  claim 1 , wherein the agonist of FPR2 is represented by Formula I: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is sec-butyl, C 6-10  aryl, —CH 2 —(C 6-10 )aryl, —CH 2 -heterocycle, C 4-8  cycloalkyl or C 3-8  cycloalkenyl or heterocycle; 
         R 2  is halogen or methyl; 
         R 3  is halogen; 
         R 4  is H, methyl or halogen; 
         R 5  is OR 6  or NH 2 ; and 
         R 6  is H or C 2-4  alkyl. 
       
     
     
         4 . The method of  claim 3 , wherein the agonist of FPR2 is selected from:
 (2S,3S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-3-methylpentanoic acid;   (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanoic acid;   (2S)-2-{[(4-bromophenyl)carbamoyl]amino}pentanoic acid;   (2S)-2-{[(4-iodophenyl)carbamoyl]amino}-4-methylpentanoic acid; and   (2S)-4-methyl-2-({[4-(methylsulfanyl)phenyl]carbamoyl}amino)pentanoic acid.   
     
     
         5 . The method of  claim 1 , wherein the agonist of FPR2 is represented by Formula II: 
       
         
           
           
               
               
           
         
         wherein: 
         a is 1 and b is 0; 
         a is 0 and b is 1; 
         a is 1 and b is 1; 
         R 1  is optionally substituted C 1-8  alkyl, optionally substituted C 3-8  cycloalkyl, optionally substituted heterocycle, optionally substituted C 3-8  cycloalkyl, optionally substituted C 6-10  aryl, optionally substituted C 3-8  cycloalkenyl, —NR 11 R 12  or —OR 13 ; 
         R 2  is optionally substituted C 1-8  alkyl or optionally substituted C 6-10  aryl; 
         R 3  is hydrogen, optionally substituted C 1-8  alkyl, halogen, —COOR 15 , —OR 13 , —NR 11 R 12 , NO 2 , optionally substituted heterocycle, optionally substituted C 3-8  cycloalkyl, optionally substituted C 6-10  aryl or optionally substituted C 3-8  cycloalkenyl; 
         R 4  is hydrogen, optionally substituted C 1-8  alkyl, halogen, —COOR 15 , —OR 13 , —NR 11 R 12 , NO 2 , optionally substituted heterocycle, optionally substituted C 3-8  cycloalkyl, optionally substituted C 6-10  aryl or optionally substituted C 3-8  cycloalkenyl; 
         R 5  is halogen, —CF 3  or —S(O) n R 14 ; 
         n is 0, 1 or 2; 
         R 6  is hydrogen, optionally substituted C 1-8  alkyl, halogen, —COOR 15 , —OR 13 , —NR 11 R 12 , NO 2 , optionally substituted heterocycle, optionally substituted C 3-8  cycloalkyl, optionally substituted C 6-10  aryl or optionally substituted C 3-8  cycloalkenyl; 
         R 7  is hydrogen, optionally substituted C 1-8  alkyl, halogen, —COOR 15 , —OR 13 , —NR 11 R 12 , NO 2 , optionally substituted heterocycle, optionally substituted C 3-8  cycloalkyl, optionally substituted C 6-10  aryl or optionally substituted C 3-8  cycloalkenyl; 
         R 8  is hydrogen, optionally substituted C 1-8  alkyl or optionally substituted C 6-10  aryl; 
         R 9  is hydrogen, optionally substituted C 1-8  alkyl or optionally substituted C 6-10  aryl; 
         R 10  is hydrogen, optionally substituted C 1-8  alkyl or optionally substituted C 6-10  aryl; 
         R 9a  is hydrogen, optionally substituted C 1-8  alkyl or optionally substituted C 6-10  aryl; 
         R 10a  is hydrogen, optionally substituted C 1-8  alkyl or optionally substituted C 6-10  aryl; 
         R 11  is hydrogen or optionally substituted C 1-8  alkyl; 
         R 12  is hydrogen or optionally substituted C 1-8  alkyl; 
         R 13  is hydrogen or optionally substituted C 1-8  alkyl; 
         R 14  is hydrogen, CF 3  or optionally substituted C 1-8  alkyl; and 
         R 15  is hydrogen or optionally substituted C 1-8  alkyl. 
       
     
     
         6 . The method of  claim 5 , wherein the agonist of FPR2 is selected from:
 {[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}pentanoyl]amino}acetic acid;   {[(2S,3S)-2-{[(4-bromophenyl)carbamoyl]amino}-3-methylpentanoyl]amino}acetic acid;   (2S,3S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-3-methylpentanoic acid;   2-{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanoyl]amino}-2-methylpropanoic acid;   {[(2S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-4-methylpentanoyl]amino}acetic acid;   {[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanoyl]amino}acetic acid;   2-{[(4-bromophenyl)carbamoyl]amino}-N-(2-oxoazepan-3-yl)-3-phenylpropanamide;   {[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-3-phenylpropanoyl]amino}acetic acid;   3-{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-3-phenylpropanoyl]amino}propanoic acid;   (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-(2-hydroxyethyl)-3-phenylpropanamide;   {[(2S,3S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-3-methylpentanoyl]amino}acetic acid;   (2S,3S)—N-(2-amino-2-oxoethyl)-2-{[(4-bromophenyl)carbamoyl]amino}-3-methylpentanamide;   (2S,3S)—N-(2-amino-2-oxoethyl)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-3-methylpentanamide;   (2S,3S)-2-{[(4-bromophenyl)carbamoyl]amino}-3-methyl-N-(2-oxopropyl)pentanamide;   (2S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-N-(2-oxopropyl)-3-phenylpropanamide;   (2S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-N-(2-hydroxyethyl)-3-phenylpropanamide;   methyl {[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}pentanoyl]amino}acetate;   propan-2-yl{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}pentanoyl]amino}acetate;   {[(2S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}pentanoyl]amino}acetic acid;   (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-(2-hydroxyethyl)-4-methylpentanamide;   (2S)—N-(2-amino-2-oxoethyl)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanamide;   (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methyl-N-(2-oxopropyl)pentanamide;   (2S)—N-(2-amino-2-oxoethyl)-2-{[(4-bromophenyl)carbamoyl]amino}pentanamide;   (2S)—N-(2-amino-2-oxoethyl)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}pentanamide;   (2S)—N-(2-amino-2-oxoethyl)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-4-methylpentanamide;   (2S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-4-methyl-N-(2-oxopropyl)pentanamide;   (2S)-2-{[(2S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-4-methylpentanoyl]amino}propanoic acid;   (2S)-2-{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanoyl]amino}propanoic acid;   (2S)-2-{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanoyl]amino}-3-methylbutanoic acid;   (2S)—N-[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanamide;   (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-(2-hydroxy-2-methylpropyl)-4-methylpentanamide;   (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-(1,3-dihydroxypropan-2-yl)-4-methylpentanamide;   (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-(2,3-dihydroxypropyl)-4-methylpentanamide;   (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-[(2R)-1-hydroxypropan-2-yl]-4-methylpentanamide;   tert-butyl (2S)-2-{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanoyl]amino}pentanoate;   (2S)-2-{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanoyl]amino}pentanoic acid   (2S)—N-[(2S)-1-amino-1-oxopentan-2-yl]-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanamide;   (2S)-{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanoyl]amino}(phenyl)ethanoic acid;   (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methyl-N-(1H-tetrazol-5-ylmethyl)pentanamide;   [(2-{[(4-bromophenyl)carbamoyl]amino}-2,4-dimethylpentanoyl)amino]acetic acid;   (2-{[(4-bromophenyl)carbamoyl]amino}-2-ethylbutanoyl)amino]acetic acid;   (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-[(3-hydroxy-1,2-oxazol-5-yl)methyl]-4-methylpentanamide;   (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-[2-(dimethylamino)-2-oxoethyl]-4-methylpentanamide;   {[(2S)-4-methyl-2-({[4-(trifluoromethyl)phenyl]carbamoyl}amino)pentanoyl]amino}acetic acid;   {[(2S)-4-methyl-2-({[4-(methylsulfanyl)phenyl]carbamoyl}amino)pentanoyl]amino}acetic acid;   (2S)-4-methyl-N-(1H-tetrazol-5-ylmethyl)-2-({[4-(trifluoromethyl)phenyl]carbamoyl}amino)pentanamide;   2-methyl-2-{[(2S)-4-methyl-2-({[4-(trifluoromethyl)phenyl]carbamoyl}amino)pentanoyl]amino}propanoic acid;   {[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-(methylsulfanyl)butanoyl]amino}acetic acid;   {[2-{[(4-bromophenyl)carbamoyl]amino}-3-(1H-indol-3-yl)propanoyl]amino}acetic acid;   tert-butyl {[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanoyl](methyl)amino}acetate; and   {[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanoyl](methyl)amino}acetic acid.   
     
     
         7 . The method of  claim 1 , wherein the agonist of FPR2 is represented by Formula III: 
       
         
           
           
               
               
           
         
         R 1  is halogen, hydrogen, optionally substituted C 1-8  alkyl, OR 9 , C(O)R 10 , NO 2 , NR 13 R 14 , CN, SR 15  or SO 2 R 16 ; 
         R 2  is halogen, optionally substituted C 1-8  alkyl, CF 3 , OR 9 , C(O)R 10 , NO 2 , NR 13 R 14 , CN, SR 15  or SO 2 R 16 ; 
         R 3  is hydrogen, optionally substituted C 1-8  alkyl, optionally substituted C 3-8  cycloalkyl, optionally substituted C 3-8  cycloalkenyl, optionally substituted C 6-10  aryl, optionally substituted heterocycle, or together with R 5  forms a 10- or 11-membered polycyclic ring which is optionally substituted; 
         R 4  is hydrogen, optionally substituted C 1-8  alkyl, 
       
       
         
           
           
               
               
           
         
       
       optionally substituted C 3-8  cycloalkyl, optionally substituted C 3-8  cycloalkenyl, optionally substituted C 6-10  aryl, optionally substituted heterocycle, or together with R 5  forms a spiro monocyclic or polycyclic, carbocyclic or heterocyclic, saturated or unsaturated 5 to 10 member ring which is optionally substituted;
 R 5  is hydrogen, optionally substituted C 1-8  alkyl, optionally substituted C 3-8  cycloalkyl, optionally substituted C 3-8  cycloalkenyl, optionally substituted C 6-10  aryl, optionally substituted heterocycle, or together with R 4  forms a spiro monocyclic or polycyclic carbocyclic or heterocyclic, saturated or unsaturated 5 to 10 member ring which is optionally substituted or together with R 3  forms a 5 or 6 member ring which is optionally substituted; 
 R 6  is halogen, hydrogen, optionally substituted C 1-8  alkyl, OR 9 , C(O)R 10 , NO 2 , NR 13 R 14 , CN, SR 15  or SO 2 R 16 ; 
 R 7  is halogen, hydrogen, optionally substituted C 1-8  alkyl, OR 9 , C(O)R 10 , NO 2 , NR 13 R 14 , CN, SR 15  or SO 2 R 16 ; 
 R 8  is halogen, hydrogen, optionally substituted C 1-8  alkyl, OR 9 , C(O)R 10 , NO 2 , NR 13 R 14 , CN, SR 15  or SO 2 R 16 ; 
 R 9  is hydrogen, C(O)(C 1-8  alkyl) or optionally substituted C 1-8  alkyl; 
 R 10  is hydrogen, optionally substituted C 1-8  alkyl, O(C 1-8  alkyl), NR 11 R 12  or OH; 
 R 11  is hydrogen, optionally substituted C 6-10  aryl or optionally substituted C 1-8  alkyl; 
 R 12  is hydrogen, optionally substituted C 6-10  aryl or optionally substituted C 1-8  alkyl; 
 R 13  is hydrogen, optionally substituted C 6-10  aryl or optionally substituted C 1-8  alkyl; 
 R 14  is hydrogen, optionally substituted C 6-10  aryl, optionally substituted C 1-8  alkyl, C(O)(C 1-8  alkyl) or SO 2 (C 1-8  alkyl); 
 R 15  is hydrogen, optionally substituted C 1-8  alkyl or O(C 1-8  alkyl); 
 R 16  is OH, O(C 1-8  alkyl), (C 1-8  alkyl) or NR 11 R 12 ; 
 R 17  is hydrogen, optionally substituted C 6-10  aryl or optionally substituted C 1-8  alkyl; 
 R 18  is hydrogen, C(O)(C 1-8  alkyl), optionally substituted C 6-10  aryl, or optionally substituted C 1-8  alkyl; 
 R 19  is hydrogen, C(O)(C 1-8  alkyl), optionally substituted C 6-10  aryl or optionally substituted C 1-8  alkyl; 
 R 20  is hydrogen, optionally substituted C 6-10  aryl or optionally substituted C 1-8  alkyl; 
 R 21  is hydrogen, optionally substituted C 6-10  aryl or optionally substituted C 1-8  alkyl; 
 n is 1, 2, 3, 4, or 5; 
 m is 1, 2, 3, 4, or 5. 
 
     
     
         8 . The method according to  claim 7 , wherein the FPR2 agonist is selected from:
 1-(4-bromophenyl)-3-[4-ethyl-2,5-dioxo-4-(2-phenylethyl)imidazolidin-1-yl]urea;   1-(4-bromophenyl)-3-[4-ethyl-2,5-dioxo-4-(propan-2-yl)imidazolidin-1-yl]urea;   1-(4-bromophenyl)-3-(4,4-diethyl-2,5-dioxoimidazolidin-1-yl)urea;   1-(4-bromo-2-fluorophenyl)-3-(4,4-diethyl-2,5-dioxoimidazolidin-1-yl)urea;   1-(4-bromophenyl)-3-(2,4-dioxo-1,3-diazaspiro[4.5]dec-3-yl)urea;   1-(4-bromophenyl)-3-[4-methyl-2,5-dioxo-4-(2-phenylethyl)imidazolidin-1-yl]urea;   1-(4-bromophenyl)-3-[4-methyl-2,5-dioxo-4-(2-phenylethyl)imidazolidin-1-yl]urea;   1-(4-bromo-2-fluorophenyl)-3-[4-ethyl-2,5-dioxo-4-(propan-2-yl)imidazolidin-1-yl]urea;   1-(4-bromophenyl)-3-[2,5-dioxo-4,4-di(propan-2-yl)imidazolidin-1-yl]urea;   1-(4-bromophenyl)-3-(4,4-dicyclopropyl-2,5-dioxoimidazolidin-1-yl)urea;   1-(4-bromophenyl)-3-[4-ethyl-2,5-dioxo-4-(propan-2-yl)imidazolidin-1-yl]urea;   1-(4-bromophenyl)-3-[4-ethyl-2,5-dioxo-4-(propan-2-yl)imidazolidin-1-yl]urea;   1-(4-bromo-2-fluorophenyl)-3-[4-ethyl-2,5-dioxo-4-(2-phenylethyl)imidazolidin-1-yl]urea;   1-(4-bromophenyl)-3-{4-[2-(furan-2-yl)ethyl]-4-methyl-2,5-dioxoimidazolidin-1-yl}urea;   1-(4-bromophenyl)-3-{4-[2-(4-fluorophenyl)ethyl]-4-methyl-2,5-dioxoimidazolidin-1-yl}urea;   1-(4-bromophenyl)-3-{4-[2-(3-fluorophenyl)ethyl]-4-methyl-2,5-dioxoimidazolidin-1-yl}urea;   1-(4-bromophenyl)-3-{4-[2-(4-hydroxyphenyl)ethyl]-4-methyl-2,5-dioxoimidazolidin-1-yl}urea;   1-(4-bromophenyl)-3-{4-methyl-2,5-dioxo-4-[2-(thiophen-2-yl)ethyl]imidazolidin-1-yl}urea;   1-(4-bromo-2-fluorophenyl)-3-{4-[2-(4-hydroxyphenyl)ethyl]-4-methyl-2,5-dioxoimidazolidin-1-yl}urea;   1-(4-bromophenyl)-3-{4-methyl-4-[2-(5-methylfuran-2-yl)ethyl]-2,5-dioxoimidazolidin-1-yl}urea;   1-(4-bromo-2-fluorophenyl)-3-{4-[2-(3-fluoro-4-hydroxyphenyl)ethyl]-4-methyl-2,5-dioxoimidazolidin-1-yl}urea;   1-(4-bromophenyl)-3-{4-[2-(3-fluoro-4-hydroxyphenyl)ethyl]-4-methyl-2,5-dioxoimidazolidin-1-yl}urea;   1-(4-bromo-2-fluorophenyl)-3-{4-[2-(2-hydroxyphenyl)ethyl]-4-methyl-2,5-dioxoimidazolidin-1-yl}urea;   1-(4-bromo-2-fluorophenyl)-3-{4-[2-(3-hydroxyphenyl)ethyl]-4-methyl-2,5-dioxoimidazolidin-1-yl}urea;   1-(4-bromophenyl)-3-{4-[2-(3-hydroxyphenyl)ethyl]-4-methyl-2,5-dioxoimidazolidin-1-yl}urea;   1-(4-bromophenyl)-3-{4-[2-(2-hydroxyphenyl)ethyl]-4-methyl-2,5-dioxoimidazolidin-1-yl}urea;   1-(4-bromophenyl)-3-[4-(hydroxymethyl)-2,5-dioxo-4-(propan-2-yl)imidazolidin-1-yl]urea;   2-[1-{[(4-bromophenyl)carbamoyl]amino}-2,5-dioxo-4-(propan-2-yl)imidazolidin-4-yl]-N-(2-hydroxyethyl)acetamide;   methyl 2-[2-(1-{[(4-bromophenyl)carbamoyl]amino}-4-ethyl-2,5-dioxoimidazolidin-4-yl)ethyl]benzoate;   2-[1-{[(4-bromophenyl)carbamoyl]amino}-2,5-dioxo-4-(propan-2-yl)imidazolidin-4-yl]-N-(1,3-dihydroxypropan-2-yl)acetamide;   2-[2-(1-{[(4-bromophenyl)carbamoyl]amino}-4-ethyl-2,5-dioxoimidazolidin-4-yl)ethyl]benzoic acid;   2-[2-(1-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-4-ethyl-2,5-dioxoimidazolidin-4-yl)ethyl]benzoic acid;   3-({[1-{[(4-bromophenyl)carbamoyl]amino}-2,5-dioxo-4-(propan-2-yl)imidazolidin-4-yl]acetyl}amino)propanoic acid;   2-[1-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-2,5-dioxo-4-(propan-2-yl)imidazolidin-4-yl]-N-(2-hydroxyethyl)acetamide;   2-{2-[1-{[(4-bromophenyl)carbamoyl]amino}-2,5-dioxo-4-(propan-2-yl)imidazolidin-4-yl]ethyl}benzoic acid;   diethyl[2-({[1-{[(4-bromophenyl)carbamoyl]amino}-2,5-dioxo-4-(propan-2-yl)imidazolidin-4-yl]acetyl}amino)ethyl]phosphonate;   ethyl 3-{[(4-bromophenyl)carbamoyl]amino}-2,4-dioxo-1,3-diazaspiro[4.5]decane-8-carboxylate;   1-(4-bromophenyl)-3-{4-[2-(2-fluorophenyl)ethyl]-4-methyl-2,5-dioxoimidazolidin-1-yl}urea; and   3-({[1-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-2,5-dioxo-4-(propan-2-yl)imidazolidin-4-yl]acetyl}amino)propanoic acid.   
     
     
         9 . The method according to  claim 1 , wherein the agonist of FPR2 is represented by Formula VII: 
       
         
           
           
               
               
           
         
         wherein: 
         n is 0or 1; 
         R 1  is hydrogen, substituted or unsubstituted C 1-8  alkyl, halogen, —NR 8 R 9 , —NC(O)R 20 , —OR 10 , —OC(O)R 21 —SR 11 , —C(O)R 12 , CN or NO 2 ; 
         R 2  is hydrogen, substituted or unsubstituted C 1-8  alkyl, halogen, —NR 8 R 9 , —NC(O)R 20 , —OR 10 , —OC(O)R 21 , —SR 11 , —C(O)R 12 , CN or NO 2 ; 
         R 3  is hydrogen, substituted or unsubstituted C 1-8  alkyl, halogen, —NR 8 R 9 , —NC(O)R 20 , —OR 10 , —OC(O)R 21 , —SR 11 , —C(O)R 12 , CN, NO 2 , CF 3 , S(O)R 15  or S(O) 2 R 16 ; 
         R 4  is hydrogen, substituted or unsubstituted C 1-8  alkyl, halogen, —NR 8 R 9 , —NC(O)R 20 , —OR 10 , —OC(O)R 21 , —SR 11 , —C(O)R 12 , CN or NO 2 ; 
         R 5  is hydrogen, substituted or unsubstituted C 1-8  alkyl, halogen, —NR 8 R 9 , —NC(O)R 20 , —OR 10 , —OC(O)R 21 , SR 11 , —C(O)R 12 , CN or NO 2 ; 
         R 6  is hydrogen, substituted or unsubstituted C 1-8  alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C 3-8  cycloalkyl, substituted or unsubstituted C 6-10  aryl, substituted or unsubstituted C 3-8  cycloalkenyl or —CH 2 R 19 ; 
         R 7  is substituted or unsubstituted heterocycle, —SR 11 , —NR 8 R 9 , —N(H)C(O)N(H)S(O) 2 R 19 , —BR 13 R 14 , —S(O)R 15 , —C(O)N(H)(CN), —C(O)N(H)S(O) 2 R 19 , —S(O)(N)(PO 3 H 2 )—, —S(O) 2 R 16  or —P(O)R 17 R 18 ; 
         R 8  is hydrogen, substituted or unsubstituted C 1-8  alkyl substituted or unsubstituted C 3-8  cycloalkyl, substituted or unsubstituted heterocycle, or substituted or unsubstituted C 6-10  aryl; 
         R 9  is hydrogen, substituted or unsubstituted C 1-8  alkyl substituted or unsubstituted C 3-8  cycloalkyl, substituted or unsubstituted heterocycle, or substituted or unsubstituted C 6-10  aryl; 
         R 10  is hydrogen or substituted or unsubstituted C 1-8  alkyl; 
         R 11  is hydrogen, substituted or unsubstituted C 1-8  alkyl or —CF 3 ; 
         R 12  is hydrogen, substituted or unsubstituted C 1-8  alkyl, hydroxyl, —OR 24  or —NR 8 R 9 ; 
         R 13  is —OR 22 ; 
         R 14  is —OR 23 ; 
         R 15  is substituted or unsubstituted C 1-8  alkyl; 
         R 16  is substituted or unsubstituted C 1-8  alkyl, —NR 8 R 9 , —NHS(O) 2 R 19  or hydroxyl; 
         R 17  is OR 10  or NR 8 R 9 ; 
         R 18  is OR 10  or NR 8 R 9 ; 
         R 19  is substituted or unsubstituted heterocycle, substituted or unsubstituted C 3-8  cycloalkyl, substituted or unsubstituted C 6-10  aryl or substituted or unsubstituted C 3-8  cycloalkenyl; 
         R 20  is hydrogen, substituted or unsubstituted C 1-8  alkyl substituted or unsubstituted C 3-8  cycloalkyl, substituted or unsubstituted heterocycle, or substituted or unsubstituted C 6-10  aryl; 
         R 21  is hydrogen, substituted or unsubstituted C 1-8  alkyl substituted or unsubstituted C 3-8  cycloalkyl, substituted or unsubstituted heterocycle, or substituted or unsubstituted C 6-10  aryl; 
         R 22  is hydrogen, substituted or unsubstituted C 1-8  alkyl, or together with R 23  can form a cycle; 
         R 23  is hydrogen, substituted or unsubstituted C 1-8  alkyl, or together with R 22  can form a cycle; 
         R 24  is hydrogen, substituted or unsubstituted C 1-8  alkyl substituted or unsubstituted C 3-8  cycloalkyl, substituted or unsubstituted heterocycle, or substituted or unsubstituted C 6-10  aryl. 
       
     
     
         10 . The method of  claim 9 , wherein the FPR2 agonist is selected from:
 {[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}pentanoyl]amino}acetic acid;   2-{[(4-bromophenyl)carbamoyl]amino}-N-(2-oxoazepan-3-yl)-3-phenylpropanamide;   ethyl hydrogen ({[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanoyl]amino}methyl)phosphonate;   diethyl({[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanoyl]amino}methyl)phosphonate;   diethyl({[(2S,3S)-2-{[(4-bromophenyl)carbamoyl]amino}-3-methylpentanoyl]amino}methyl)phosphonate;   ethyl hydrogen ({[(2S,3S)-2-{[(4-bromophenyl)carbamoyl]amino}-3-methylpentanoyl]amino}methyl)phosphonate;   diethyl({[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}pentanoyl]amino}methyl)phosphonate;   diethyl({[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-3-phenylpropanoyl]amino}methyl)phosphonate;   diethyl (2-{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanoyl]amino}ethyl)phosphonate;   ethyl hydrogen ({[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}pentanoyl]amino}methyl)phosphonate;   dipropan-2-yl({[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}pentanoyl]amino}methyl)phosphonate;   ethyl hydrogen ({[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-3-phenylpropanoyl]amino}methyl)phosphonate;   {[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanoyl]amino}methanesulfonic acid;   propan-2-yl hydrogen {[(2-{[(4-bromophenyl)carbamoyl]amino}pentanoyl)amino]methyl}phosphonate;   dipropan-2-yl({[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methylpentanoyl]amino}methyl)phosphonate;   diethyl({[(2S)-4-methyl-2-({[4-(trifluoromethyl)phenyl]carbamoyl}amino)pentanoyl]amino}methyl)phosphonate;   ethyl hydrogen ({[(2S)-4-methyl-2-({[4-(trifluoromethyl)phenyl]carbamoyl}amino)pentanoyl]amino}methyl)phosphonate;   {[(2S)-4-methyl-2-({[4-(trifluoromethyl)phenyl]carbamoyl}amino)pentanoyl]amino}methanesulfonic acid; and   diethyl({[(2S)-4-methyl-2-({[4-(methylsulfanyl)phenyl]carbamoyl}amino)pentanoyl]amino}methyl)phosphonate.   
     
     
         11 . The method of  claim 1 , wherein the FPR2 agonist is selected from:
 2-({[(4-chlorophenyl)amino]carbonyl}amino)-3-phenylpropanoic acid;   (2S)-2-({[(4-methoxyphenyl)amino]carbonyl}amino)-3-phenylpropanoic acid;   (2S)-3-phenyl-2-[({[4-(trifluoromethyl)phenyl]amino}carbonyl)amino]propanoic acid;   (2S)-2-({[(3,4-dichlorophenyl)amino]carbonyl}amino)-3-phenylpropanoic acid;   (2S)-2-({[(4-nitrophenyl)amino]carbonyl}amino)-3-phenylpropanoic acid;   3-phenyl-2-[({[4-(trifluoromethoxy)phenyl]amino}carbonyl)amino]propanoic acid;   2-({[(3,4-dimethoxyphenyl)amino]carbonyl}amino)-3-phenylpropanoic acid;   methyl 2-({[(4-iodophenyl)amino]carbonyl}amino)-3-phenylpropanoate;   (2S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-3-phenylpropanoic acid;   (2R)-2-({[(4-bromophenyl)amino]carbonyl}amino)-3-phenylpropanoic acid;   3-phenyl-2-{[(pyridin-3-ylamino)carbonyl]amino}propanoic acid;   (2S,3S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-3-methylpentanoic acid;   2-({[(4-bromophenyl)amino]carbonyl}amino)(phenyl)acetic acid;   2-({[(4-bromophenyl)amino]carbonyl}amino)-3-(1H-indol-3-yl)propanoic acid;   (2S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-3-methylbutanoic acid;   (2S)-2-({[(4-bromo-2-fluorophenyl)amino]carbonyl}amino)-3-methylbutanoic acid;   1-(4-chlorophenyl)-3-(2,4-dioxo-1,3-diazaspiro[4,5]decan-3-yl)urea;   1-(4-chlorophenyl)-3-(4-ethyl-4-methyl-2,5-dioxoimidazolidin-1-yl)urea;   1-[4-methyl-2,5-dioxo-4-(2-phenylethyl)imidazolidin-1-yl]-3-phenylurea;   1-(8-methyl-2,4-dioxo-1,3-diazaspiro[4,5]decan-3-yl)-3-(p-tolyl)urea;   1-(2-fluorophenyl)-3-[4-methyl-2,5-dioxo-4-(2-phenylethyl)imidazolidin-1-yl]urea;   N-(4-bromophenyl)-2-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)acetamide;   N-(4-bromophenyl)-2-(4,4-diethyl-2,5-dioxoimidazolidin-1-yl)acetamide;   N-(4-bromophenyl)-2-(2,4-dioxo-1,3-diazaspiro[4   N-(4-bromophenyl)-2-(2,5-dioxo-4,4-dipropylimidazolidin-1-yl)acetamide;   N-(4-bromophenyl)-2-(4-ethyl-2,5-dioxo-4-phenylimidazolidin-1-yl)acetamide;   N-(4-bromophenyl)-2-(4-cyclopropyl-4-methyl-2,5-dioxoimidazolidin-1-yl)acetamide;   N-(4-bromophenyl)-2-(2,4-dioxo-1,3-diazaspiro[4   N-(4-bromophenyl)-2-(4-ethyl-4-methyl-2,5-dioxoimidazolidin-1-yl)acetamide;   N-(4-chlorophenyl)-2-(4,4-diethyl-2,5-dioxoimidazolidin-1-yl)acetamide;   2-(4,4-diethyl-2,5-dioxoimidazolidin-1-yl)-N-(4-fluorophenyl)acetamide;   N-(4-bromophenyl)-2-[4-methyl-2,5-dioxo-4-(2-phenylethyl)imidazolidin-1-yl]acetamide;   N-(4-bromophenyl)-1,3,3a,4,7,7a-hexahydro-1,3-dioxo-4,7-methano-2H-isoindole-2-acetamide; and   N-(4-bromophenyl)-1,3,3a,4,7,7a-hexahydro-1,3-dioxo-2H-isoindole-2-acetamide.