Claims
- 1. A compound of Formula I or a salt or prodrug thereof wherein X is O or S; A and B are OR2 or Y—NR3R4, wherein when A is OR2, B is Y—NR3R4 and vice versa, or when one of A or B is OR2, then the other can be CO2R7; Y is CH2 or C═O; Q is (CH2)m—CH(R1)—(CH2)n; R is OR6 or NHR7; R1 is hydrogen, C1-C6 branched or straight chain alkyl optionally substituted with hydroxyl, C1-C3 alkylphenyl or phenyl; R2 is hydrogen, C1-C10 branched or straight chain alkyl, C3-C10 cycloalkyl, C2-C10 branched or straight chain alkenyl, C2-C10 branched or straight chain alkynyl, (CH2)m—(CF2)nCF3, (CH2)nCH(R10)—(CH2)q-aryl or (CH2)p-aryl, where aryl is phenyl, pyridyl, thienyl or furyl; wherein phenyl is optionally substituted by one or more substituents sciected from F, Cl, Br, CF3, OCF3, OR6, C1-C6 branched or straight chain alkyl, COR, CN, SO2R9, or SONR7R8, and pyridyl, thienyl or furyl are optionally substituted by F, Cl, Br, CF3, OR6 or C1-C6 branched or straight chain alkyl; R3 and R4 are independently hydrogen, C1-C6 branchcd or straight chain alkyl, C(═O)R6, —CH(CH2OCOR8)-aryl or CH(R8)—(CH2)p-aryl where aryl is phenyl, pyridyl, thienyl or fury; wherein phenyl is optionally substituted by one or more substitucnts selectcd from F, Cl, Br, CF3, OCF3, OR6, C1-C6 branched or straight chain alkyl, COR, CN, SO2R7 or phenyl; or R3 and R4 when taken together may form a 4-7 membered ring optionally incorporating an additional heteroatom, selected from O, N or S, wherein the ring may be optionally substituted at any position with (CH2)p-aryl where aryl is phenyl optionally substituted by one or more substituents selected from F, Cl, Br, CF3, OCF3, C1-C6 branched or straight chain alkyl, COR, CN, SO2R8 or phenyl; R5 is hydrogen; R6 and R7 are independently hydrogen, C1-C10 branched or straight chain alkyl or (CH2)p-phenyl; R8 is hydrogen or C1-C3 alkyl; R9 is C1-C6 branched or straight chain alkyl or phenyl; R10 is hydrogen, C1-C10 branched or straight chain alkyl, (CH2)p-aryl where aryl is phenyl optionally substituted by one or more substituents selected from F, Cl, Br, CF3, OCF3, C1-C6 branched or straight chain alkyl, COR, CN, SO2R8; and m, n and p are integers wherein m is 0-3; n is 0-2; and p is 0-3.
- 2. A compound as claimed in claim 1 in which:X is O or S; A and B are OR2 or Y—NR3R4 wherein when A is OR2, B is Y—NR3R4, and vice versa, or when one of A or B is OR2, then the other can be CO2R7; Y is CH2or C═O; Q is CH(R1); R is OH; R1 is hydrogen, C1-C6 alkyl or C1-C3 alkylphenyl; R2 is hydrogen, C1-C10 branched or straight chain alkyl, (CH2)p-phenyl, wherein phenyl is optionally substituted by one or more substituents selected from F and CF3; R3 and R4 are independently hydrogen, C1-C6 branched or straight chain alkyl, (CH2)p-phenyl, C(═O)C1-C10 branched or straight chain alkyl, —CH(R8)-phenyl, CH(CH2OCOR8)-phenyl, or R3 and R4 together foini a morpholino, piperidinyl or piperazinyl group optionally substituted with (CH2)p-phenyl; R5 is hydrogen; and p is an integer from 0-3.
- 3. A compound as claimed in claim 1 which is:5-[[[3-(N-Methyl-N-phenylamino)carbonyl-4-(phenylmethoxy)]-phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid; 5-[[[3-(N,N-Dibenzylamino)carbonyl-4-(phenylmethoxyl)]-phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidincacetic acid; 5-[[[3-(N,N-Dipentylamino)carbonyl-4-(phenylmethoxyl)]-phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid; 5-[[[3-((S)-N-Benzyl-N-alpha-methylbenzylamino)carbonyl-4-(phenylmethoxyl)]-phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid; 5-[[[3-(N,N-Dibutylamino)carbonyl-4-(phenylmethoxyl)]-phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid; 5-[[[3-(N-Benzyl-N-butylamino)carbonyl-4-(phenylmethoxy)]-phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacctic acid; 5-[[[3-((R)-N-alpha-methylbenzylamino)carbonyl-4-(phenylmethoxy)]-phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid; 5-[[[3-((S )-N-methyl-N-alpha-methylbenzylamino)carbonyl-4-(phenylmethoxy)]-phenyl]methylene]-4-oxo-2-thioxo-3-thiaolidineacetic acid; 5-[[[3-(Dipentylamino)carbonyl-4-methoxy]phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid; 5-[[[3-((S)-N-Benzyl-N-alpha-methylbenzylamino)carbonyl-4-methoxy]-phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid; 5-[[[3-(N,N-Dipentylamino)carbonyl-4-[(2,4-difluorophenyl)-methoxyl]phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid; 5-[[[3-(N,N-Dipentylamino)carhonyl-4-(trifluorophenyl)-methoxy]phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid; 5-[[3-[(Dibenzylamino)methyl]-4-phenylmethoxy)phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid; 5-[[3-[(Dipentylamino)methyl]-4-(phenylmethoxy)phenyl]methylene]-4-oxo-2-thioxo--3-thiazolidineacetic acid; (R)-5-[[[3-(N-α-(Acetoxymethyl)benzyl-N-benzylamino)carbonyl-4-(phenylmethoxy)]-phenyl]methylene]-4-oxo-2-thioxo-34-thiazolidineacetic acid; 5-[[[3-(N,N-Dipentylamino)carhonyl-4-(2-phenylethoxy)]-phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidincacetic acid; or 5-[[4-(2-Phenylethoxy)-3-[(N-phenyl-N-2-n-propyl-n-petylcarbonyl)aminomethyl]-phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidincaetic acid.
- 4. A pharmaceutical composition comprising at least one compound as claimed in claim 1 and one or more pharmaceutically acceptable carriers, excipients and/or diluents.
- 5. A method for the preparation of a compound as claimed in claim 1 comprising condensing a rhodanine-3-acetic acid of Formula (A) or an analogue or derivative thereof wherein X is O or S, with a substituted benzaldehyde derivative, ArCHO, wherein Ar corresponds to a group having the structure under general acid-base catalysis conditions with the application of heat.
- 6. A method for the prophylaxis or treatment of an individual suffering from a fungal infection comprising administering to the individual a compound of Formula I or a salt or prodrug thereof wherein X is O or S; A and B are OR2 or Y—NR3R4, wherein when A is OR2, B is Y—NR3R4 and vice versa, or when one of A or B is OR2, then the other can be CO2R7; Y is CH2 or C═O; Q is (CH2)m—CH(R1)—(CH2)n; R is OR6 or NHR7; R1 is hydrogen, C1-C6 branched or straight chain alkyl optionally substituted with hydroxyl, C1-C3 alkylphenyl or phenyl; R2 is hydrogen, C1-C10 branched or straight chain alkyl, C3-C10 cycloalkyl, C2-C10 branched or straight chain alkenyl, C2-C10 branched or straight chain alkynyl, (CH2)m—(CF2)nCF3, (CH2)n—CH(R10)—(CH2)q-aryl or (CH2)p-aryl, where aryl is phenyl, pyridyl, thienyl or furyl; wherein phenyl is optionally substituted by one or more substituents selected from F, Cl, Br, CF3, OCF3, OR6, C1-C6 branched or straight chain alkyl, COR, CN, SO2R9, or SONR7R8, and pyridyl, thienyl or furyl are optionally substituted by F, Cl, Br, CF3, OR6 or C1-C6 branched or straight chain alkyl; R3 and R4 are independently hydrogen, C1-C6 branched or straight chain alkyl, C(═O)R6, —CH(CH2OCOR8)-aryl or CH(R8)—(CH2)p-aryl where aryl is phenyl, pyridyl, thienyl or furyl; wherein phenyl is optionally substituted by one or more substituents selected from F, Cl, Br, CF3, OCF3, OR6, C1-C6 branched or straight chain alkyl, COR, CN, SO2R7 or phenyl; or R3 and R4 when taken together may form a 4-7 membered ring optionally incorporating an additional heteroatom, selected from O, N or S, wherein the ring may be optionally substituted at any position with (CH2)p-aryl where aryl is phenyl optionally substituted by one or more substituents selected from F, Cl, Br, CF3, OCF3, C1-C6 branched or straight chain alkyl, COR, CN, SO2R8 or phenyl; R5 is hydrogen, C1-C6 branched or straight chain alkyl or phenyl optionally substituted by one or more substituents selected from F, Cl, Br3, OCF3, OR6, C1-C6 branched or straight chain alkyl, COR, CN or SO2R9; R6 and R7 are independently hydrogen or C1-C10 branched or straight chain alkyl or (CH2)p-phenyl; R8 is hydrogen or C1-C3 alkyl; R9 is C1-C6 branched or straight chain alkyl or phenyl; R10 is hydrogen, C1-C10 branched or straight chain alkyl, (CH2)p-aryl where aryl is phenyl optionally substituted by one or more substituents selected from F, Cl, Br, CF3, OCF3, C1-C6 branched or straight chain alkyl, COR, CN, SO2R8; and m, n and p are integers wherein m is 0-3; n is 0-2; and p is 0-3.
- 7. A method as claimed in claim 6 wherein the fungal infection is a Candida, Trichophyton, Microsporum, Cryptococcus neoformans, Aspergillus flavus, Aspergillus fumigatus, Coccidioidcs, Paracoccidioides, Histoplasma, Blastomyces or Epidermophyton infection.
- 8. The method according to claim 5 wherein the acid-base catalysis conditions comprise using sodium acetate in acetic acid or ammonium acetate in toluene, at the reflux temperature of the solvent.
- 9. A compound as claimcd in claim 1 which is:5-[[[3-(Phenylmethoxy)carbonyl-4-(phenylmethoxy)]phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid; 5-[[[3-(N-Morpholinyl)carbonyl-4-(phenylmethoxy)]phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid; 5-[[[3-(4-Phenyl-1-piperazinyl)carbonyl-4-(phenylmethoxy)]phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid; 5-[[[3-(4-Benzyl-1-piperidinyl)carbonyl-4-(phenylmethoxy)]phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidincacetic acid; 5-[[[3-(N-Benzyl-N-phenylamino)carbonyl-4-(phenylmethoxy)]phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid; alpha-Propyl 5-[[[3-(dibenzylamino)carbonyl-4-(phenylmethoxy)]phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid; alpha-Phenylmethyl 5-[[[3-(dibenzylamino)carbonyl-4 (phenylmethoxy)]phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid; 5-[[[3-(Dipenlylamino)carbonyl-4-hydroxy]phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacctic acid; 5-[[[4-(Dibenzylamino)carbonyl-3-(phenylmethoxy)]phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidincacetic acid; 5-[[4-Phenylmethoxy-3-[[N-phenylmethyl-N-(2-phenylethyl)amino]methyl]phenyl]-methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid; 5-[[4-Phenylmethoxy-3-[[(4-phenyl)-1-piperazinyl]methyl]phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacctic acid; 5-[[3-[N-Ethyl-N-(2-phenylethyl)amino]methyl-4-(phenylmethoxy)phenyl]-4-oxo-2-thioxo-3-thiazolidineacetic acid; or 5-[[4-Phenylmethoxy-3-[[(4-phenlylmethyl)-1-piperidinyl]methyl]phenyl]methylene]-4-oxo-2-thioxo-3-thiazol,dineacctic acid.
Priority Claims (1)
Number |
Date |
Country |
Kind |
0021419 |
Aug 2000 |
GB |
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CROSS REFERENCE TO RELATED APPLICATIONS
This is a Continuation of International Application No. PCT/GB01/03860 filed Aug. 30, 2001, which claims priority of United Kingdom Application No. 0021419.7, filed Aug. 31, 2000. The International Application was published in English on Mar. 21, 2002 as WO 02/22612 A1 under PCT Article 21(2).
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
3704296 |
Mousseron |
Nov 1972 |
A |
Foreign Referenced Citations (2)
Number |
Date |
Country |
0047109 |
Oct 1982 |
EP |
WO 0018747 |
Apr 2000 |
WO |
Non-Patent Literature Citations (2)
Entry |
AN 1997-010295, Derwent Publications Ltd., SU 1417436A (Chem Pharmacy Inst.) Abstract, Apr. 27, 1996. |
Search Report mailed Dec. 3, 2001in International Application No. PCT/6B01/03860. |
Continuations (1)
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Number |
Date |
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Parent |
PCT/GB01/03860 |
Aug 2001 |
US |
Child |
10/371979 |
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US |