Claims
- 1. A compound of formula I ##STR5## wherein R.sub.1 is acyloxy or hydroxy or tert-butyldimethylsilyloxy;
- R.sub.2 is hydroxy or tert-butyldimethylsilyloxy or is absent, whereby when R.sub.3 is cyclopropylmethyl or methylcyclopropylmethyl, R.sub.2 additionally can be hydrogen;
- R.sub.3 is methyl, ethyl, n-propyl, allyl, cyclopropylmethyl or methylcyclopropylmethyl;
- either
- R.sub.4 is hydrogen, hydroxy or tert-butyldimethylsilyloxy, acyloxy or is absent; and
- R.sub.5 is unprotected hydroxy, halogen of atomic number of from 9 to 53 or is absent; or
- R.sub.4 and R.sub.5 together form a group --OC(.dbd.O)O-- or --OC(.dbd.S)O--; and
- R.sub.6 is hydrogen or, when R.sub.4 and R.sub.5 together form a group --OC(.dbd.O)O--, is hydrogen or methoxy;
- or
- R.sub.4 and R.sub.6 together from a group oxo; and
- R.sub.5 is unprotected hydroxy or halogen of atomic number of from 9 to 53 or is absent;
- R.sub.7 is unprotected hydroxy or methoxy; and
- n is 1 or 2,
- where acyloxy is alkylcarbonyloxy of 2 to 8 carbon or benzoyloxy substituted by halogen of atomic number of from 9 to 53 and protected hydroxy is tert-butyldimethylsilyloxy; with the proviso that
- a) at least one of R.sub.1, R.sub.2, R.sub.4 and R.sub.5 is other than unprotected hydroxy;
- b) when R.sub.4 and R.sub.6 together form a group oxo, then either R.sub.3 is cyclopropylmethyl or methylcyclopropylmethy; or R.sub.5 is halogen of atomic number of from 9 to 53 or is absent; and
- c) when R.sub.1 is acyloxy, then either R.sub.4 and R.sub.6 are other than together a group oxo; or R.sub.4 and R.sub.6 together form a group oxo and R.sub.5 is halogen of atomic number of from 9 to 53 or is absent.
- 2. A compound according to claim 1 of formula I wherein
- R.sub.1 is acetoxy or hydroxy or tert-butyldimethylsilyloxy;
- R.sub.2 is hydroxy or tert-butyldimethylsilyloxy or is absent;
- R.sub.3 is methyl, ethyl, n-propyl or allyl; either
- R.sub.4 is hydrogen, hydroxy or tert-butyldimethylsilyloxy, acetoxy or is absent; and
- R.sub.5 is unprotected hydroxy or halogen of atomic number of from 9 to 53 or is absent; or
- R.sub.4 and R.sub.5 together form a group --OC(.dbd.O)O-- or --OC(.dbd.S)O--; and
- R.sub.6 is hydrogen or, when R.sub.4 and R.sub.5 together form a group --OC(.dbd.O)O--, is hydrogen or methoxy; or
- R.sub.4 and R.sub.6 together form a group oxo; and
- R.sub.5 is unprotected hydroxy or halogen of atomic number of from 9 to 53 or is absent;
- R.sub.7 is methoxy; and
- n is 1 or 2,
- with the provisos that
- a) at least one of R.sub.1, R.sub.2, R.sub.4 and R.sub.5 is other than unprotected hydroxy;
- b) when R.sub.4 and R.sub.5 together form a group oxo, then R.sub.5 is halogen of atomic number of from 9 to 53 or is absent; and
- c) when R.sub.1 is acetoxy, then either R.sub.4 and R.sub.6 are other than together a group oxo; or R.sub.4 and R.sub.6 together form a group oxo and R.sub.5 is halogen of atomic number of from 9 to 53 or is absent.
- 3. A compound according to claim 1 of formula I wherein
- R.sub.1 is acetoxy or hydroxy or tert-butyldimethylsilyloxy;
- R.sub.2 is hydrogen or hydroxy or tert-butyldimethylsilyloxy;
- R.sub.3 is cyclopropylmethyl or methylcyclopropylmethyl; either
- R.sub.4 and R.sub.5 are unprotected hydroxy; and
- R.sub.6 is hydrogen; or
- R.sub.4 and R.sub.6 together form a group oxo; and
- R.sub.5 is unprotected hydroxy;
- R.sub.7 is methoxy; and
- n is 2,
- with the provisos that
- a) at least one of R.sub.1, R.sub.2, R.sub.4 and R.sub.5 is other than unprotected hydroxy;
- b) when R.sub.1 is acetoxy, then R.sub.4 and R.sub.5 are other than together a group oxo.
- 4. A compound according to claim 1 of formula I wherein
- R.sub.1 is alkylcarbonyloxy of altogether 2 to 6 carbon atoms, benzoyloxy monosubstituted by halogen of atomic number of from 9 to 53 or hydroxy optionally protected by tert-butyldimethylsilyl;
- R.sub.2 is hydroxy optionally protected by tert-butyldimethylsilyl or is absent;
- R.sub.3 is ethyl, allyl, cyclopropylmethyl or methylcyclopropylmethyl; either
- R.sub.4 is hydrogen, unprotected hydroxy, acetoxy or is absent;
- R.sub.5 is unprotected hydroxy, halogen of atomic number of from 9 to 53 or is absent; or
- R.sub.4 and R.sub.5 together form a group --OC(.dbd.O)O-- or --OC(.dbd.S)O--; and
- R.sub.6 is hydrogen or, when R.sub.4 and R.sub.5 together form a group --OC(.dbd.O)O--, is hydrogen or methoxy; or
- R.sub.4 and R.sub.6 together form a group oxo; and
- R.sub.5 is unprotected hydroxy, halogen of atomic number of from 9 to 53 or is absent;
- R.sub.7 is methoxy; and
- n is 2,
- with the provisos that
- a) at least one of R.sub.1, R.sub.2, R.sub.4 and R.sub.5 is other than unprotected hydroxy;
- b) when R.sub.4 and R.sub.6 together form a group oxo, then either R.sub.3 is cyclopropylmethyl or methylcyclopropylmethyl; or R.sub.5 is halogen of atomic number of from 9 to 53 or is absent; and
- c) when R.sub.1 is alkylcarbonyloxy or benzoyloxy as defined in this claim, then either R.sub.4 and R.sub.6 are other than together a group oxo; or R.sub.4 and R.sub.6 together form a group oxo and R.sub.5 is halogen of atomic number of from 9 to 53 or is absent.
- 5. A compound of formula I according to claim 1 selected from
- 9(R)-dihydro-10-desoxy-.DELTA..sup.10, 11 -FK506 (compound of Example 11);
- 33-acetoxy-9(S)-dihydro-FK506-9,10-carbonate (compound of Example 20);
- 33-pivaloyloxy-9(S)-dihydro-FR520 (compound of Example 25);
- 9(R)-dihydro-10-desoxy-.DELTA..sup.10, 11 -FR520 (compound of Example 30);
- 21-desallyl-21-cyclopropylmethyl-FK506 (compound of Example 61); and
- 21-desallyl-21-methylcyclopropylmethyl-FK506 (compound of Example 65).
- 6. A pharmaceutical composition useful in inducing immunosuppression or treating inflammation comprising a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier therefor.
- 7. A method of inducing immunosupression or treating inflammation in a subject in need of said treatment, which comprises administering to the subject a therapeutically effective amount of a compound according to claim 1.
Priority Claims (2)
Number |
Date |
Country |
Kind |
3919466 |
Jun 1989 |
DEX |
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3934991 |
Oct 1989 |
DEX |
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Parent Case Info
This application is a continuation in part of U.S. patent application, Ser. No. 07/656,046, filed Feb. 14, 1991 now abandoned.
Foreign Referenced Citations (8)
Number |
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Country |
0323865 |
Jul 1989 |
EPX |
0349049 |
Jan 1990 |
EPX |
0349061 |
Jan 1990 |
EPX |
0353678 |
Feb 1990 |
EPX |
0358508 |
Mar 1990 |
EPX |
0364031 |
Apr 1990 |
EPX |
0364032 |
Apr 1990 |
EPX |
WO8905304 |
Jun 1989 |
WOX |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
656046 |
Feb 1991 |
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