Methods for the solid phase synthesis of thiazolidinones, metathiazanones, and derivatives thereof
AssigneeAffymax Technologies N.V.
InventorChristopher P. Holmes
Life of this patent
Estimating the term…
Abstract
The invention provides an efficient and versatile method for the combinatorial synthesis and screening of libraries of 4-thiazolidinones, metathiazanones, and derivatives thereof. In order to expediently synthesize a combinatorial library of derivatives based upon these core structures, a general methodology for the solid phase synthesis of these derivatives is also provided. Arrays of thiazolidinones, metathiazanones, and derivatives thereof useful as peptidomimetics and for the identification of agents having antifungal, antihistaminic, or antimicrobial activity or use in the treatment of inflammation, hypertension, renal failure, congestive heart failure, uremia and other conditions can be prepared using this method.
Claims11
A library of 4-thiazolidinones, metathiazinones, or derivatives thereof comprising a plurality of different compounds, each compound covalently linked to a solid support, wherein each of said compounds comprises at least one 4-thiazolidinone group, metathiazinone group, or a group derived from a 4-thiazolidinone group or metathiazinone group which group is prepared by the method which comprises:
- (a) on a surface of a solid support, providing an amine component having the formula:
- R--NH.sub.2,
- wherein R is selected from the group consisting of alkyl, alkoxy, amino, aryl, aryloxy, heteroaryl, and arylalkyl or salts thereof;
- (b) treating the amine component with a carbonyl component having a formula:
- ##STR15## wherein R.sup.3 is hydrogen and R.sup.4 is selected from the groups consisting of consisting of alkyl, aryl, heteroaryl, and arylalkyl;
- and a thiol component having a formula:
- ##STR16## wherein R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are independently selected from the groups consisting of hydrogen, alkyl, alkoxy, aryl, aryloxy, heteroaryl, carboxyl, carboxyalkyl, carboxyaryl, and arylalkyl and n is either 0 or 1 wherein n being 0 represents a valence bond;
- under conditions effective to cyclize the components and form a solid support-bound 4-thiazolidinone, metathiazinone, or a derivative thereof and
- provided that at least one of the following conditions is satisfied:
- i) at least two different amine components are used
- ii) at least two different carbonyl components are used;
- iii) at least two different thiol components are used;
- or
- iv) at least two different sets of conditions effective to cyclize the components are used.
A library of 4-thiazolidinones, metathiazinones, or derivatives thereof comprising a plurality of different compounds, each compound covalently linked to a solid support, wherein each of said compounds comprises at least one 4-thiazolidinone group, metathiazinone group, or a group derived from a 4-thiazolidinone group or metathiazinone group which group is prepared by the method which comprises:
- (a) on a surface of a solid support, providing a thiol component having a formula:
- ##STR17## wherein R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are independently selected from the groups consisting of hydrogen, alkyl, alkoxy, aryl, aryloxy, heteroaryl, carboxyl, carboxyalkyl, carboxyaryl, and arylalkyl and n is either 0 or 1 wherein n being 0 represents a valence bond;
- (b) treating the thiol component with an amine component having the formula:
- R--NH.sub.2,
- wherein R is selected from the group consisting of hydrogen, alkyl, alkoxy, amino, aryl, aryloxy, heteroaryl, and arylalkyl or salts thereof, and a carbonyl component having a formula:
- ##STR18## wherein R.sup.3 is hydrogen and R.sup.4 is selected from the groups consisting of alkyl, aryl, heteroaryl, and arylalkyl;
- under conditions effective to cyclize the components and form a solid support-bound 4-thiazolidinone, metathiazinone, or a derivative thereof and
- provided that at least one of the following conditions is satisfied:
- i) at least two different amine components are used
- ii) at least two different carbonyl components are used;
- iii) at least two different thiol components are used;
- or
- iv) at least two different sets of conditions effective to cyclize the components are used.
Dependencies are inferred from the claim text.