Cajanine structure analogous compound, preparation method and use

A method to prepare the compounds having the structure shown by the general formula I:

• wherein R1 is a substituted or unsubstituted heteroaryl, wherein said heteroaryl is pyrid-2-yl;
• R2 is H;
• R3 is carboxyl group;
• R4 is hydroxyl;
• R5 is iso-pentenyl;
• R6 is an alkoxy group;
• R7 is H,
• the method according to Scheme 1:
• the method comprising:
• reacting acetoacetic ester and diethyl ketone under basic conditions to produce Compound 2;
• alkylating Compound 2 under basic conditions in a polar solvent to produce Compound 3;
• forming Compound 4 via free radical halogenation of Compound 3 in a nonpolar solvent;
• reacting Compound 4 with a phosphite triester to produce Compound 5;
• reacting Compound 5 with a ketone or aldehyde to produce Compound 6;
• dealkylating Compound 6 in the presence of a dealkylating reagent to produce Compound 7;
• reacting Compound 7 with a halogenated hydrocarbon to produce Compound 8 and an oxyalkylated Compound 8′;
• hydrolyzing Compound 8 to thereby produce the compounds having the general formula I, wherein in Scheme 1, R8, R9, R10 are a substituted or unsubstituted hydrocarbon alkyl with 1-18 carbons.

A method to prepare the compounds having the structure shown by the general formula I:

• wherein R1 is a substituted or unsubstituted heteroaryl, wherein said heteroaryl is pyrid-2-yl;
• R2 is H;
• R3 is selected from the group consisting of alkoxyformyl, alkylthioformyl, and a substituted carbamoyl group;
• R4 is selected from the group consisting of H, hydroxy, a substituted or unsubstituted alkoxyl, a substituted or unsubstituted formyloxy, a substituted or unsubstituted amino, a halogen, and isoureido group;
• R5 is iso-pentenyl;
• R6 is selected from the group consisting of H, hydroxy, a substituted or unsubstituted alkoxy, a substituted or unsubstituted amino, a halogen, a mercapto, and an alkylthio group;
• R7 is selected from the group consisting of H, isopentenyl, isopentyl, 3′,7′-dimethyl octadien-2′,6′-yl, a substituted or unsubstituted aryl, an allyl, a halogen, and a substituted or an unsubstituted amino group;
• the method according to Scheme 2:
• the method comprising:
• reacting a general formula I compound (i) in the presence of a condensation reagent, with R9XH compounds to produce Compound 9;
• or (ii) with an acrylating agent to produce an acyl chloride, which in the presence of an acid binding agent condensates with R9XH compounds to produce Compound 9, wherein X is selected from O, S, and N, wherein in Scheme 2, R9 is a unsubstituted alkyl containing 1-18 carbons, a substituted or unsubstituted aryl or heteroaryl.

A method to prepare the compounds having the structure shown by the general formula I:

• wherein R1 is a substituted or unsubstituted heteroaryl, wherein said heteroaryl is pyrid-2-yl;
• R2 is H;
• R3 is carboxyl;
• R4 is hydroxyl;
• R5 is iso-pentenyl;
• wherein R1 is a substituted or unsubstituted heteroaryl, wherein said heteroaryl is pyrid-2-yl;
• R2 is H;
• R3 is selected from the group consisting of H, a carboxyl, a substituted or unsubstituted alkoxyformyl, a substituted or unsubstituted carbamoyl, and a substituted or unsubstituted formyl group;
• R4 is selected from the group consisting of H, hydroxy, a substituted or unsubstituted alkoxyl, a substituted or unsubstituted formyloxy, a substituted or unsubstituted amino, a halogen, and isoureido group;
• R5 is iso-pentenyl;
• R6 is an alkoxy group;
• R7 is a halogen;
• the method according to Scheme 4:
• the method comprising:
• reacting Compound 7 in an organic solvent with a halogenating reagent to produce Compound 11;
• coupling Compound 11 under basic conditions with an alkylating agent to produce Compound 12;
• hydrolyzing Compound 12 under alkaline or acidic conditions to produce Compound 13, wherein in Scheme 4 X is F or Cl or Br, and R8 and R9 may be identical or different, and R8 and R9 are each selected from the group consisting of H, and an alkyl containing 1-18 carbons.

A method to prepare the compounds having the structure shown by the general formula I:

• wherein R1 is a substituted or unsubstituted heteroaryl, wherein said heteroaryl is pyrid-2-yl;
• R2 is H;
• R3 is carboxyl group;
• R4 is alkoxy group;
• R5 is iso-pentenyl;
• R6 is alkoxy group;
• R7 is H;
• the method according to Scheme 5:
• the method comprising:
• reacting Compound 8 under basic conditions with an alkylating agent to produce Compound 14;
• hydrolyzing Compound 14 under basic or acidic conditions to produce Compound 15, wherein in Scheme 5 R8 and R8′ may be identical or difference, and R8 and R8′ are each an alkyl group with 1-18 carbons, and R9 is H or an alkyl group with 1-18 carbons.

A method to prepare the compounds having the structure shown by the general formula I:

• wherein R1 is a substituted or unsubstituted heteroaryl, wherein said heteroaryl is pyrid-2-yl;
• R2 is H;
• R3 is (1H-imidazol-1-yl)formyl group;
• R4 is selected from the group consisting of H, hydroxy, a substituted or unsubstituted alkoxyl, a substituted or unsubstituted formyloxy, a substituted or unsubstituted amino, a halogen, and isoureido group;
• R5 is iso-pentenyl;
• R6 is selected from the group consisting of H, hydroxy, a substituted or unsubstituted alkoxy, a substituted or unsubstituted amino, a halogen, a mercapto, and an alkylthio group;
• R7 is selected from the group consisting of H, isopentenyl, isopentyl, 3′,7′-dimethyl octadien-2′,6′-yl, a substituted or unsubstituted aryl, an allyl, a halogen, and a substituted or an unsubstituted amino group;
• the method according to Scheme 9;
• the method comprising:
• reacting 1-carboxy substituted derivatives with carbonyl diimidazole to produce Compound 22.

A method to prepare the compounds having the structure shown by the general formula I:

• wherein R1 is a substituted or unsubstituted heteroaryl, wherein said heteroaryl is pyrid-2-yl;
• R2 is H;
• R3 is N-(carbamoyl)carbamoyl or N-(methylamidino)carbamoyl;
• R4 is selected from the group consisting of H, hydroxy, a substituted or unsubstituted alkoxyl, a substituted or unsubstituted formyloxy, a substituted or unsubstituted amino, a halogen, and isoureido group;
• R5 is iso-pentenyl;
• R6 is selected from the group consisting of H, hydroxy, a substituted or unsubstituted alkoxy, a substituted or unsubstituted amino, a halogen, a mercapto, and an alkylthio group;
• R7 is selected from the group consisting of H, isopentenyl, isopentyl, 3′,7′-dimethyl octadien-2′,6′-yl, a substituted or unsubstituted aryl, an allyl, a halogen, and a substituted or an unsubstituted amino group;
• the method according to Scheme 10:
• the method comprising:
• reacting 1-carboalkoxy substituted derivatives with urea or guanidine to produce Compound 23, wherein X is O or NH.

A method to prepare the compounds having the structure shown by the general formula I:

• wherein R1 is a substituted or unsubstituted heteroaryl, wherein said heteroaryl is pyrid-2-yl;
• R2 is H;
• R3 is selected from the group consisting of H, a carboxyl, a substituted or unsubstituted alkoxyformyl, a substituted or unsubstituted carbamoyl, and a substituted or unsubstituted formyl group;
• R4 is substituted formyloxy;
• R5 is iso-pentenyl;
• R6 is selected from the group consisting of H, hydroxy, a substituted or unsubstituted alkoxy, a substituted or unsubstituted amino, a halogen, a mercapto, and an alkylthio group;
• R7 is selected from the group consisting of H, isopentenyl, isopentyl, 3′,7′-dimethyl octadien-2′,6′-yl, a substituted or unsubstituted aryl, an allyl, a halogen, and a substituted or an unsubstituted amino group;
• the method according to Scheme 11:
• the method comprising:
• reacting under basic conditions 2-hydroxyl substituted derivatives with acyl chloride to produce Compound 24, wherein R10 is selected from the group consisting of a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroaryl ring, and a substituted or unsubstituted amino group.

A method to prepare the compounds having the structure shown by the general formula I:

• wherein R1 is a substituted or unsubstituted heteroaryl, wherein said heteroaryl is pyrid-2-yl;
• R2 is H;
• R3 is selected from the group consisting H, a carboxyl group, a substituted or unsubstituted alkoxyformyl, a substituted or unsubstituted carbamoyl, and a substituted or unsubstituted formyl group;
• R4 is aminomethoxy group or (piperazin-2-yl)methoxy group;
• R5 is iso-pentenyl;
• R6 is selected from the group consisting of H, hydroxy, a substituted or unsubstituted alkoxy, a substituted or unsubstituted amino, a halogen, a mercapto, and an alkylthio group;
• R7 is selected from the group consisting of H, isopentenyl, isopentyl, 3′,7′-dimethyl octadien-2′,6′-yl, a substituted or unsubstituted aryl, an allyl, a halogen, and a substituted or an unsubstituted amino group;
• the method according to Scheme 12;
• the method comprising:
• reacting 2-hydroxyl substituted derivatives with N-benzyl aminomethanol to produce Compound 25;
• debenzylating Compound 25 to produce Compound 26.

A method to prepare the compounds having the structure shown by the general formula I:

• wherein R1 is a substituted or unsubstituted heteroaryl, wherein said heteroaryl is pyrid-2-yl;
• R2 is H;
• R3 is selected from the group consisting of H, a carboxyl, a substituted or unsubstituted alkoxyformyl, a substituted or unsubstituted carbamoyl, and a substituted or unsubstituted formyl group;
• R4 is isoureido group;
• R5 is iso-pentenyl;
• R6 is selected from the group consisting of H, hydroxy, a substituted or unsubstituted alkoxy, a substituted or unsubstituted amino, a halogen, a mercapto, and an alkylthio group;
• R7 is selected from the group consisting of H, isopentenyl, isopentyl, 3′,7′-dimethyl octadien-2′,6′-yl, a substituted or unsubstituted aryl, an allyl, a halogen, and a substituted or an unsubstituted amino group;
• the method according to Scheme 13:
• the method comprising:
• reacting 2-hydroxyl substituted derivatives with aminocyanide to produce Compound 27.

A method to prepare the compounds having the structure shown by the general formula I:

• wherein R1 is a substituted or unsubstituted heteroaryl, wherein said heteroaryl is pyrid-2-yl;
• R2 is H;
• R3 is selected from the group consisting of H, a carboxyl, a substituted or unsubstituted alkoxyformyl, a substituted or unsubstituted carbamoyl, and a substituted or unsubstituted formyl group;
• R4 is hydrazinoformyloxyl;
• R5 is iso-pentenyl;
• R6 is selected from the group consisting of H, hydroxy, a substituted or unsubstituted alkoxy, a substituted or unsubstituted amino, a halogen, a mercapto, and an alkylthio group;
• R7 is selected from the group consisting of H, isopentenyl, isopentyl, 3′,7′-dimethyl octadien-2′,6′-yl, a substituted or unsubstituted aryl, an allyl, a halogen, and a substituted or an unsubstituted amino group;
• the method according to Scheme 14:
• the method comprising:
• reacting 2-hydroxyl substituted derivatives with carbonyl chloride to produce Compound 28;
• reacting Compound 28 with hydrazine to produce Compound 29.

A method to prepare the compounds having the structure shown by the general formula I:

• wherein R1 is a substituted or unsubstituted heteroaryl, wherein said heteroaryl is pyrid-2-yl;
• R2 is H;
• R3 is selected from the group consisting of H, a carboxyl, a substituted or unsubstituted alkoxyformyl, a substituted or unsubstituted carbamoyl, and a substituted or unsubstituted formyl group;
• R4 is carboxyl formyloxyl;
• R5 is iso-pentenyl;
• R6 is selected from the group consisting of H, hydroxy, a substituted or unsubstituted alkoxy, a substituted or unsubstituted amino, a halogen, a mercapto, and an alkylthio group;
• R7 is selected from the group consisting of H, isopentenyl, isopentyl, 3′,7′-dimethyl octadien-2′,6′-yl, a substituted or unsubstituted aryl, an allyl, a halogen, and a substituted or an unsubstituted amino group;
• the method according to Scheme 15:
• the method comprising:
• reacting 2-hydroxyl substituted derivatives under basic conditions with 2-chloro-2-carbonylacetate methyl ester to produce Compound 30;
• hydrolyzing Compound 30 to produce Compound 31.

A method to prepare the compounds having the structure shown by the general formula I:

• wherein R1 is a substituted or unsubstituted heteroaryl, wherein said heteroaryl is pyrid-2-yl;
• R2 is H;
• R3 is carbamoyl;
• R4 is selected from the group consisting of H, hydroxy, a substituted or unsubstituted alkoxyl, a substituted or unsubstituted formyloxy, a substituted or unsubstituted amino, a halogen, and isoureido group;
• R5 is iso-pentenyl;
• R6 is selected from the group consisting of H, hydroxy, a substituted or unsubstituted alkoxy, a substituted or unsubstituted amino, a halogen, a mercapto, and an alkylthio group;
• R7 is selected from the group consisting of H, isopentenyl, isopentyl, 3′,7′-dimethyl octadien-2′,6′-yl, a substituted or unsubstituted aryl, an allyl, a halogen, and a substituted or an unsubstituted amino group;
• the method according to Scheme 16:
• the method comprising:
• reacting alkyloxyformyl substituted benzene derivatives via aminolysis to produce Compound 32, wherein in Scheme 16 R8′ is an alkyl group with 1-18 carbons.

A method of treating a subject suffering from at least one of a bacterial or viral infection, and a metabolic disease, the method comprising:

• administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, the compound having the structure shown in the general formula I:
• wherein R1 is a substituted or unsubstituted heteroaryl, wherein said heteroaryl is pyrid-2-yl;
• R2 is H;
• R3 is selected from the group consisting of H, a carboxyl, a substituted or unsubstituted alkoxyformyl, a substituted or unsubstituted carbamoyl, and a substituted or unsubstituted formyl group;
• R4 is selected from the group consisting of H, hydroxy, a substituted or unsubstituted alkoxyl, a substituted or unsubstituted formyloxy, a substituted or unsubstituted amino, a halogen, and isoureido group;
• R5 is iso-pentenyl;
• R6 is selected from the group consisting of H, hydroxy, a substituted or unsubstituted alkoxy, a substituted or unsubstituted amino, a halogen, a mercapto, and an alkylthio group;
• R7 is selected from the group consisting of H, isopentenyl, isopentyl, 3′,7′-dimethyl octadien-2′,6′-yl, a substituted or unsubstituted aryl, an allyl, a halogen, and a substituted or an unsubstituted amino group.

A pharmaceutical composition for a bacterial or viral infection, neuroprotection, or a metabolic disease, the composition comprising:

• a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, the compound having the structure shown in the general formula I:
• R6 is selected from the group consisting of H, hydroxy, a substituted or unsubstituted alkoxy, a substituted or unsubstituted amino, a halogen, a mercapto, and an alkylthio group;
• R7 is selected from the group consisting of H, isopentenyl, isopentyl, 3′,7′-dimethyl octadien-2′,6′-yl, a substituted or unsubstituted aryl, an allyl, a halogen, and a substituted or an unsubstituted amino group;
• one or more pharmaceutically acceptable pharmaceutical adjuvants.