Claims
- 1. A macrolide of formula VIII
- S--L--M VIII
- wherein
- S represents a 1-oxo-7-aza-spiro-{5,5}-undecan-8-one-2-yl residue;
- L represents a linker comprising a linear sequence of from 6 to 11 carbon atoms; and
- M represents a macrocyclic ring wherein
- positions 2 to 6 of said macrocyclic ring are provided by a substituted or unsubstituted piperidazinyl carboxylic acid residue of formula I ##STR64## wherein the assigned numbers represent the position of the atoms of the residue in the macrocyclic ring,
- positions 7 to 9 of said macrocyclic ring are provided by an aromatic .alpha.-amino acid residue wherein the carboxy moiety of the aromatic .alpha.-amino acid residue occupies the 7-position of said macrocyclic ring, and the .alpha.-amino moiety of the aromatic .alpha.-amino acid residue occupies the 9-position of said macrocyclic ring,
- positions 10 to 12 of said macrocyclic ring are provided by an aliphatic .alpha.-amino acid residue wherein the carboxy moiety of the aliphatic .alpha.-amino acid residue occupies the 10-position of said macrocyclic ring and the .alpha.-amino moiety of the aliphatic a-amino acid residue occupies the 12-position of said macrocyclic ring,
- the remainder of the macrocyclic ring comprising a hydroxy carboxylic acid residue having a chain length of 6 to 20 carbon atoms, the oxy moiety of which completes a macrocyclic lactone linkage and the carbonyl moiety of which forms an amide linkage with the .alpha.-amino group at the 12-position of the macrocyclic ring, in free or protected form, or a salt thereof.
- 2. A macrolide according to claim 1 wherein the 1-oxo-7-aza-spiro-{5,5}-undecan-8-one-2-yl residue is of the formula ##STR65## wherein --a--b-- is --(Me)C.dbd.CH-- or --(Me)CH--CH(OH)-- and R.sub.5 is H or Me.
- 3. A macrolide according to claim 1, in which the hydroxy carboxylic acid residue is a residue of formula II ##STR66## wherein R.sub.1 is H, OH or represents an extra bond and R.sub.2 is H or represents an extra bond;
- R.sub.3 is H;
- R.sub.4 is --CO--CH.sub.3 or --CH(OH)--CH.sub.3 or
- R.sub.3 and R.sub.4 together represent a structure of formula III ##STR67## in free or protected form, or salt thereof.
- 4. A macrolide according to claim 1, in which the linker between the 1-oxo-7-aza-spiro-{5,5}-undecan-8-one-2-yl residue and the macrolide ring is a group of formula VII ##STR68## wherein c represents linkage to the 1-oxo-7-aza-spiro-{5,5}-undecan-8-one-2-yl residue;
- d represents linkage to the macrocyclic ring and
- R.sub.6 and R.sub.7 are each OH or together represent an additional bond, in free or protected form.
- 5. A compound according to claim 1 of formula IX ##STR69## wherein --a--b-- is --(Me)C.dbd.CH-- or --(Me)CH--CH(OH)--;
- --e--f-- is --CH(OH)--CH(OH)-- or --CH.dbd.CH--;
- --g--h-- is as defined above for --a--b--, and
- R.sub.3 is H;
- R.sub.4 is --CO--CH.sub.3 or --CH(OH)--CH.sub.3 or R.sub.3 and R.sub.4 together represent a structure of formula III ##STR70## and R.sub.5 is H or Me; in free or protected form or salt thereof.
- 6. A compound according to claim 5 having the following conformation ##STR71## wherein when --a--b-- is --(Me)CH--CH(OH)--, it has the configuration: ##STR72## when --e--f-- is --CH(OH)--CH(OH)--, it has the (S),(S) configuration or the (R),(R) configuration;
- when --g--h--is --(Me)CH--CH(OH)--, it has the configuration: ##STR73## when --g--h-- is --(Me)C.dbd.CH--, it has the configuration: ##STR74## and when R.sub.3 and R.sub.4 are fused together they are is of configuration ##STR75##
- 7. A Sanglifehrin selected from the group consisting of Sanglifehrin A, B, C and D.
- 8. A macrolide according to claim 1 in protected form wherein the 14 to 17 positions of the macrocyclic ring comprise a residue of formula X:
- 9. A macrolide according to claim 8 wherein the residue of formula X has the configuration
Priority Claims (2)
Number |
Date |
Country |
Kind |
9513596 |
Jul 1995 |
DEX |
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9515495 |
Jul 1995 |
DEX |
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Parent Case Info
This application is a continuation-in-part of U.S. patent application Ser. No. 08/701,604 filed on the Aug. 22, 1996 now abandoned, which in turn is a continuation-in-part of international patent application PCT/EP 96/02952 filed on Jul. 4, 1996, in respect of the designation of the United States of America contained in the said international patent application.
US Referenced Citations (3)
Number |
Name |
Date |
Kind |
5284877 |
Organ et al. |
Feb 1994 |
|
5344925 |
Goulet et al. |
Sep 1994 |
|
5346893 |
Failli et al. |
Sep 1994 |
|
Foreign Referenced Citations (2)
Number |
Date |
Country |
9506649 |
Mar 1995 |
WOX |
9515328 |
Jun 1995 |
WOX |
Non-Patent Literature Citations (2)
Entry |
Nakagawa et al., (CA 113:74347, abstract of Agric. Biol. Chem. (1990), 54(3), pp. 791-794, 1990. |
Takeuchi et al., (CA 116:104496, abstract of JP 03240791), 1991. |
Related Publications (1)
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Number |
Date |
Country |
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PCTEP9602952 |
Jul 1996 |
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Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
701604 |
Aug 1996 |
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