Phenyl-oxazolyl derivatives, preparation method thereof, and related application of the phenyl-oxazolyl derivatives as an impdh inhibitor

A group of phenyl-oxazolyl derivatives or pharmaceutically acceptable salts thereof, having a general structure shown in (I):

• wherein:
• R1 is selected from the group consisting of H, a halogen, hydroxyl, C1-C3 alkyl, and C1-C3 alkoxyl;
• R2 is optional and selected from the group consisting of H, a substituted or unsubstituted, saturated or unsaturated C1-C12 alkyl, a carbonyl, and a sulfonyl;
• R is selected from the group consisting of H, cyano group, substituted or unsubstituted, saturated or unsaturated C1-C12 alkyl, C1-C12 alkoxyl or aryloxyl, alkylmercapto or arylmercapto group, amino group, substituted amino group, sulfonic acid group, sulfonyl, substituted or unsubstituted monocyclic to tricyclic aryl group, and substituted or unsubstituted heterocyclic group;
• said heterocyclic group is selected from the group consisting of a five to six membered monocyclic heterocyclic group, five to six membered bicyclic or tricyclic heterocyclic group;
• wherein the heterocyclic group contains 1 to 3 hetero atoms;
• wherein the heteroatoms are N, O, S;
• wherein j=0-1, m=0-3, n=0-6, and j, m and n may be the same or different.

A method to prepare compounds having a general structure shown in (I), the method comprising:

• providing compound A;
• providing compound B;
• reacting compound A and compound B as follows:
• wherein:
• R1 is selected from the group consisting of H, a halogen, hydroxyl, C1-C3 alkyl, C1-C3 alkoxyl;
• R2 is optional and selected from the group consisting of H, a substituted or unsubstituted, saturated or unsaturated C1-C12 alkyl, a carbonyl, and a sulfonyl;
• R is selected from the group consisting of H, cyano group, substituted or unsubstituted, saturated or unsaturated C1-C12 alkyl, C1-C12 alkoxyl or aryloxyl, alkylmercapto or arylmercapto group, amino group, substituted amino group, sulfonic acid group, sulfonyl, substituted or unsubstituted monocyclic to tricyclic aryl group, and substituted or unsubstituted heterocyclic group;
• said heterocyclic group is selected from the group consisting of a five to six membered monocyclic heterocyclic group, five to six membered bicyclic or tricyclic heterocyclic group;
• wherein the heterocyclic group contains 1 to 3 hetero atoms;
• wherein the heteroatoms are N, O, S;
• wherein j=0-1, m=0-3, n=0-6, and j, m and n may be the same or different;
• wherein each of M, X is selected from the group consisting of formyl, halogen, and acyl.

A pharmaceutical composition comprising a therapeutically effective amount of phenyl-oxazolyl derivatives or pharmaceutically acceptable salts thereof, having a general structure shown in (I):

• wherein:
• R1 is selected from the group consisting of H, a halogen, hydroxyl, C1-C3 alkyl, and C1-C3 alkoxyl;
• R2 is optional and selected from the group consisting of H, a substituted or unsubstituted, saturated or unsaturated C1-C12 alkyl, a carbonyl, and a sulfonyl;
• R is selected from the group consisting of H, cyano group, substituted or unsubstituted, saturated or unsaturated C1-C12 alkyl, C1-C12 alkoxyl or aryloxyl, C1-C12 alkylmercapto or arylmercapto group, amino group, substituted amino group, sulfonic acid group, sulfonyl, substituted or unsubstituted monocyclic to tricyclic aryl group, and substituted or unsubstituted heterocyclic group;
• said heterocyclic group is selected from the group consisting of a five to six membered monocyclic heterocyclic group, five to six membered bicyclic or tricyclic heterocyclic group;
• wherein the heterocyclic group contains 1 to 3 hetero atoms;
• wherein the heteroatoms are N, O, S;
• wherein j=0-1, m=0-3, n=0-6, and j, m and n may be the same or different;
• wherein the phenyl-oxazolyl derivatives or salts thereof are an active ingredient, and the composition also comprises at least one pharmaceutically acceptable carrier material.

A method of inhibiting IMPDH, the method comprising:

• providing phenyl-oxazolyl derivatives or pharmaceutically acceptable salts thereof, having a general structure shown in (I):
• wherein:
• R1 is selected from the group consisting of H, a halogen, hydroxyl, C1-C3 alkyl, C1-C3 alkoxyl;
• R2 is optional and selected from the group consisting of H, a substituted or unsubstituted, saturated or unsaturated C1-C12 alkyl, a carbonyl, and a sulfonyl;
• R is selected from the group consisting of H, cyano group, substituted or unsubstituted, saturated or unsaturated C1-C12 alkyl, C1-C12 alkoxyl or aryloxyl, C1-C12 alkylmercapto or arylmercapto group, amino group, substituted amino group, sulfonic acid group, sulfonyl, substituted or unsubstituted monocyclic to tricyclic aryl group, and substituted or unsubstituted heterocyclic group;
• said heterocyclic group is selected from the group consisting of a five to six membered monocyclic heterocyclic group, five to six membered bicyclic or tricyclic heterocyclic group;
• wherein the heterocyclic group contains 1 to 3 hetero atoms;
• wherein the heteroatoms are N, O, S;
• wherein j=0-1, m=0-3, n=0-6, and j, m and n may be the same or different, the method comprising:
• administering the phenyl-oxazolyl derivatives or salts thereof of structure (I) to an organism.