Prodrug and protected forms of 5-hydroxymethylfurfuranal (5-HMF) and its derivatives
Prodrugs and derivatives of 5-hydoxymethyl-2-furfural (5-HMF) with protected or modified aldehyde and/or alcohol moieties are provided. The prodrugs or derivatives exhibit increased bioavailability, e.g. due to having extended half-lives in circulation. The drugs are therefore administered i) at lower doses and/or ii) less frequently than 5-HMF, while still maintaining the beneficial therapeutic effects of 5-HMF.
1. A prodrug or protected form of 5-hydoxymethyl-2-furfural (5-HMF) with a generic formula:
where:
X is R 12 —O—· where R 12 is alkyl or aryl, and the bond marked with * bonds directly to CH 2 of Formula I;
Y is
where R is alkyl, and where the bond marked with * bonds directly to carbon at position 2 of the furan ring of Formula I;
and
Z is H, OH, alkyl, aryl, O-alkyl, O-aryl or O-heteroaryl.
2. A method of treating or prophylactically treating sickle cell disease in a subject in need thereof, comprising
administering to the subject a therapeutically effective amount of a prodrug or protected form of 5-hydoxymethyl-2-furfural (5-HMF) with a generic formula:
where:
X is R 12 —O—· where R 12 is alkyl or aryl, and the bond marked with * bonds directly to CH 2 of Formula I;
Y is
where R is alkyl, and where the bond marked with * bonds directly to carbon at position 2 of the furan ring of Formula I;
and
Z is H, OH, alkyl, aryl, O-alkyl, O-aryl or O-heteroaryl.
3. A method of treating or prophylactically treating hypoxia in a subject in need thereof, comprising
administering to the subject a therapeutically effective amount of a prodrug or protected form of 5-hydoxymethyl-2-furfural (5-HMF) with a generic formula:
where:
X is R 12 —O—· where R 12 is alkyl or aryl, and the bond marked with * bonds directly to CH 2 of Formula I
Y is
where R is alkyl, and where the bond marked with * bonds directly to carbon at position 2 of the furan ring of Formula I;
and
Z is H, OH, alkyl, aryl, O-alkyl, O-aryl or O-heteroaryl.
4. The prodrug or protected form of 5-hydroxymethyl-2-furfural (5-HMF) having the structure