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US 2002/0165250 A1Published application
Materials and method for treating or preventing pathogenic fungal infection
AssigneeARIAD Gene Therapeutics, Inc.
InventorsDennis A. Holt, Terence P. Keenan, Timothy P. Clackson, Leonard Rozamus, Wu Yang, Michael Z. Gilman
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Abstract
This invention concerns derivatives of rapamycin and their antifungal uses. Also disclosed are materials and methods relevant to the identification of non-immunosuppressive anti-fungal rapamycin derivatives. Use of compounds, among others, of the formula 1 is disclosed, where the various substitutents are as defined.
Claims18
A rapalog of the formula:
- 123
- and, one of RC7a and RC7b is H and the other is —H, halo, —OR1, —SR1, —OC(O)R1, —OC(O)NHR1, —NHR1, —NHR1R2, —NHC(O)R1, —NH—SO2—R1 or —R2, where R2=aliphatic, heteroaliphatic, aryl, heteroaryl or alkylaryl,
- RC30 is halo, —OR3 or (═O),
- RC24 is ═O, ═NR4═NOR4 or ═NNHR4, —NHOR4 or —NHNHR4, —OR4, —OC(O)R4 or —OC(O)NR4, halo or —H,
- RC14 is ═O, —OR6, —NR6, —H, —NC(O)R6, —OC(O)R6 or —OC(O)NR6
- R3 is H, —R7, —C(O)R7 or —C(O)NHR7 or a cyclic moiety bridging C28 and C30
- RC28 is halo or —OR3
- RC29 is H, OH or OMe
- where each ring substituent is present in either stereochemical orientation unless otherwise indicated, and where R1, R4, R5, R6, R7, R9, R10 and R11 are independently selected from H, aliphatic, heteroaliphatic, aryl or heteroaryl;
- and R8 is H, halo, —CN, ═O, —OH, —NR9R10, OSO2CF3, OSO2F, OSO2R4′, OCOR4′, OCONR4′R5′, or OCON(OR4′)R5′;
- or a pharmaceutically acceptable derivative thereof.
8 more elements
A compound of the formula:
- 124
- one of RC7a and RC7b is H and the other is —H, halo, —OR1, —SR1, —OC(O)R1, —OC(O)NHR1, —NHR1, —NHR1R2, —NHC(O)R1, —NH—SO2—R1 or —R2, where R2=aliphatic, heteroaliphatic, aryl, heteroaryl or alkylaryl,
- RC13 is H, halo, —OR5, —OC(O)R5, —OC(O)NHR5, —SR5, —SC(O)R5, —SC(O)NHR5, —NR5R5′, —N(R5)(CO)R5′
- RC14 is ═O, —OR6, —NR6, —H, —NC(O)R6, —OC(O)R6 or —OC(O)NR6
- R3 is H, —R7, —C(O)R7 or —C(O)NHR7 or a cyclic moiety bridging C28 and C30
- RC28 is halo or —OR3
- RC29 is H, OH or OMe p1 where each ring substituent is present in either stereochemical orientation unless otherwise indicated, and where R1, R4, R5, R6, R7, R9, R10 and R11 are independently selected from H, aliphatic, heteroaliphatic, aryl or heteroaryl;
- and R8 is H, halo, —CN, ═O, —OH, —NR9R10, OSO2CF3, OSO2F, OSO2R4′, OCOR4′, OCONR4′R5′, or OCON(OR4′)R5′;
- or a pharmaceutically acceptable derivative thereof, with the proviso that in embodiments in which all substituents other than RC24, RC30 and RC7 are identical with those in rapamycin, RC7a is a moiety other than OMe.
6 more elements
A compound, other than a compound depicted in Table II, of the formula:
- 125
- and, one of RC7a and RC7b is H and the other is —H, halo, —OR1, —SR1, —OC(O)R1, —OC(O)NHR1, —NHR1, —NHR1R2, —NHC(O)R1, —NH—SO2—R1 or —R2, where R2=aliphatic, heteroaliphatic, aryl, heteroaryl or alkylaryl,
- RC30 is halo, —OR3 or (═O),
- RC24 is ═O, ═NR4═NOR4 or ═NNHR4, —NHOR4 or —NHNHR4, —OR4, —OC(O)R4 or —OC(O)NR4, halo or —H,
- RC13 is H, halo, —OR5, —OC(O)R5, —OC(O)NHR5, —SR5, —SC(O)R5, —SC(O)NHR5, —NR5R5′, —N(R5)(CO)R5′
- RC14 is ═O, —OR6, —NR6, —H, —NC(O)R6, —OC(O)R6 or —OC(O)NR6
- R3 is H, —R7, —C(O)R7 or —C(O)NHR7 or a cyclic moiety bridging C28 and C30
- RC28 is halo or —OR3
- RC29 is H, OH or OMe
- where each ring substituent is present in either stereochemical orientation unless otherwise indicated, and where R1, R4, R5, R6, R7, R9, R10 and R11 are independently selected from H, aliphatic, heteroaliphatic, aryl or heteroaryl;
- and R8 is H, halo, —CN, ═O, —OH, —NR9R10, OSO2CF3, OSO2F, OSO2R4′, OCOR4′, OCONR4′R5′, or OCON(OR4′)R5′;
- in which RC7a is other than —OMe;
- or a pharmaceutically acceptable derivative thereof.
10 more elements
Dependencies are inferred from the claim text.