US5549974A
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Methods for the solid phase synthesis of thiazolidinones, metathiazanones, and derivatives thereof
Assignee: SmithKline Beecham Corp
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Filing: 1994-06-23
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Granted: 1996-08-27
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Expires: 2014-06-23
Abstract
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.
Inventors
- 👤 Christopher P. Holmes
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 15:03
CPC Classifications
C; C07; C07D; C07D403/00; C07D403/02; C07D403/04; B; B82; B82Y; B82Y30/00; C07C; C07C233/00; C07C233/01; C07C233/16; C07C233/17; C07C233/18; C07D277/00; C07D277/02; C07D277/08; C07D277/12; C07D277/14; C07D277/20; C07D277/32; C07D277/34; C07D279/00; C07D279/04; C07D279/06; C07D317/00; C07D317/08; C07D317/10; C07D317/14; C07D317/28; C07D417/00; C07D417/02; C07D417/04; C07K; C07K1/00; C07K1/006; C07K1/04; C07K1/06; C07K1/08; C07K1/084; G; G06; G06K; G06K19/00; G06K19/06; B01; B01J; B01J2219/00; B01J2219/00274; B01J2219/00583; B01J2219/0059; B01J2219/00596; B01J2219/00709; B01J2219/00711; B01J2219/00718; B01J2219/0072; B01J2219/00725; C07B; C07B2200/00; C07B2200/11; C40; C40B; C40B40/00; C40B40/04; C40B40/10; G06K2019/06215; G06K2019/06234; Y; Y10; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2991; Y10T428/2993; Y10T428/2996; Y10T428/2998; Y10T428/31504; Y10T428/31678
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
254 words
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 3 is hydrogen and R 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 5 , R 6 , R 7 , and R 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.
Claim 2
Dependent Claim
254 words
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 3 is hydrogen and R 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 5 , R 6 , R 7 , and R 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.
Claim 3
Dependent Claim
22 words
The library of claim 1, wherein each compound of said plurality of different compounds is covalently linked to the same solid support.
Claim 4
Dependent Claim
11 words
The library of claim 2, wherein the solid support is glass.
Claim 5
Dependent Claim
22 words
The library of claim 1, wherein each compound of said plurality of different compounds is covalently linked to a different solid support.
Claim 6
Dependent Claim
12 words
The library of claim 4, wherein the solid support is a bead.
Claim 7
Dependent Claim
25 words
The library of claim 5, wherein the beads further comprise a linker and wherein one end of the linker is attached to the amino component.
Claim 8
Dependent Claim
10 words
The library of claim 6, wherein the linker is cleavable.
Claim 9
Dependent Claim
24 words
The library of claim 5, wherein each of the beads further comprises a support-bound identifier tag, wherein the tag identifies a molecule attached thereto.
Claim 10
Dependent Claim
11 words
The library of claim 8, wherein the tag is an oligonucleotide.
Claim 11
Dependent Claim
9 words
The library of claim 1, wherein n is 0.
Claim 12
Dependent Claim
253 words
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 5 , R 6 , R 7 , and R 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 3 is hydrogen and R 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.
Claim 13
Dependent Claim
253 words
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 5 , R 6 , R 7 , and R 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 3 is hydrogen and R 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.
References Cited (Backward Citations)
US4225609A
Cited
US5061720A
Cited
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