초록 ▼

The present invention relates to production of polyketides and other natural products and to libraries of compounds and individual novel compounds. Therefore in aspect the present invention provides 17-desmethylrapamycin and analogues thereof, methods for their production, including recombinant stra

The present invention relates to production of polyketides and other natural products and to libraries of compounds and individual novel compounds. Therefore in aspect the present invention provides 17-desmethylrapamycin and analogues thereof, methods for their production, including recombinant strains, and isolation and uses of the compounds of the invention. In a further aspect the present invention provides for the use of 17-desmethylrapamycin and analogues thereof in the induction or maintenance of immunosuppression, the stimulation of neuronal regeneration or the treatment of cancer, B-cell malignancies, fungal infections, transplantation rejection, graft vs. host disease, autoimmune disorders, diseases of inflammation vascular disease and fibrotic diseases, and in the regulation of wound healing.

대표청구항 ▼

The invention claimed is: 1. A compound having the following formula: wherein: x represents a direct bond, —CH2—, —S—CH2—, —CH2—S— or —S(═O)—CH2—; or —CHR5-x-CHR6— represents R1 represents %

The invention claimed is: 1. A compound having the following formula: wherein: x represents a direct bond, —CH2—, —S—CH2—, —CH2—S— or —S(═O)—CH2—; or —CHR5-x-CHR6— represents R1 represents ═O or (H,H); R2 represents OH or OMe; R3 represents H, OH or OMe; R4 represents a structural fragment selected from groups A, B, C, D, E and F, in which the wavy line indicates the position of attachment of the fragment, R7 represents H or OH and R8 represents H, OH, halo, thiol or C1-4 alkyl; or R4 alternatively represents a 5- to 7-membered heterocycle containing one or more heteroatoms selected from the group consisting of O, S and N, which heterocycle is optionally substituted with one or more substituents selected from C1-4 alkyl, OH, F and Cl; and R5 and R6 are each independently H or OH, or pharmaceutically acceptable salts thereof. 2. A compound according to claim 1, wherein R4 represents a structural fragment selected from the groups A, B, C, E and F, as defined in claim 2, in which R7 represents H or OH and R8 represents H, OH, Cl or F. 3. A compound according to claim 2, wherein R4 represents a structural fragment selected from the groups A(i), C(i), E(i) and F(i): wherein R7 represents H or OH and R8 represents H, or OH. 4. A compound according to claim 1, wherein when R5 represents OH, R6 represents H and when R6 represents OH R5 represents H. 5. A compound according to claim 1, wherein x represents a direct bond or CH2. 6. A compound according to claim 1, wherein x represents CH2. 7. A compound according to claim 1, wherein R2 represents OH. 8. A compound according to claim 1 wherein R1 represents (H, H), R2 represents OH, R3 represents H, R4 represents the structural fragment C(i), as defined in claim 4, except that R7 represents OH and R8 represents H, and x represents CH2. 9. A compound according to claim 1 wherein R1 represents (H, H) or ═O, R2 represents OH or OMe, R3 represents OH or OMe, R4 represents the structural fragment C(i), as defined in claim 4, except that R7 represents OH and R8 represents H, or OH, and x represents CH2. 10. A compound according to claim 1 wherein R1 represents ═O, R2 represents OH or OMe, R3 represents H, OH or OMe, R4 represents the structural fragment C(i), as defined in claim 4, except that R7 represents OH and R8 represents F or Cl, and x represents CH2. 11. A compound according to claim 1 wherein R1 represents ═O, R2 represents OH, R3 represents OMe, R4 represents the structural fragment C(i), as defined in claim 4, except that R7 represents OH and R8 represents H, and x represents CH2. 12. A compound according to claim 1 wherein R1 represents ═O, R2 represents OH, R3 represents OH, R4 represents the structural fragment C(i), as defined in claim 4, except that R7 represents OH and R8 represents H, and x represents CH2. 13. A compound having the following formula: wherein R1 represents ═O, R2 represents OH, R3 represents OMe, R4 represents the structural fragment C(i), as defined in claim 4, except that R7 represents OH and R8 represents OMe, and x represents CH2. 14. A pharmaceutical composition comprising a compound according to any one of claims 1-7 and 8-13 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.