US2002183348A1PendingUtilityA1
Novel polyketide derivatives
Priority: Oct 1, 1999Filed: Apr 12, 2002Published: Dec 5, 2002
Est. expiryOct 1, 2019(expired)· nominal 20-yr term from priority
C07D 498/18
49
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Claims
Abstract
The present invention relates to novel polyketides, host cells that produce the novel compounds, and methods fort their use. The compounds of the present invention are cyclic polyketides (also referred to as a “macrolides” or “macrolactones”) that include as part of their structure and bind to a FK binding protein wherein R 4 and R 5 are each selected from the group consisting of hydrogen, methyl, ethyl, and methoxy, provided that at least one of R 4 and R 5 is hydrogen, methyl, or ethyl. As will be explained in greater detail below, the compounds of the present invention have properties such as favorable P450 enzyme activity profiles that are desirable for use of these compounds as drugs.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A lactone having a K d in a FKBP bunding assay of approximately equal to or less than 1 μM and including a fragment
as part of its structure wherein R 4 and R 5 are each independently selected from the group consisting of hydrogen, hydroxyl, methyl, ethyl, and methoxy, provided that at least one of R 4 and R 5 is hydrogen, methyl or ethyl.
2 . The lactone as in claim 1 of the formula
wherein:
R is hydroxyl;
R 1 is selected from the group consisting of hydrogen, methyl, propyl, ethyl and allyl;
R 2 and R 3 are each independently hydrogen or hydroxyl;
R 4 and R 5 are each independently selected from the group consisting of hydrogen, hydroxyl, methyl,; ethyl, and methoxy, provided that at least one of R 4 and R 5 is hydrogen, methyl, or ethyl;
R 6 is selected from a group consisting
wherein R 7 is selected from the group consisting of hydrogen, hydroxyl, methyl, ethyl, and methoxy and R 8 is selected from a group consisting of hydrogen, hydroxyl, C 1 -C 10 alkyl, C 1 -C 10 alkoxy, aryl, aryloxy, arylalkyl, and arylalkoxy; and, a double bond exists between carbon-19 and carbon-20, or a double bond exists between carbon-18 and carbon-19 and R and R 2 together are oxygen forming a lactone ring.
3 . The lactone as in claim 1 of the formula
wherein:
R is hydroxyl;
R 1 is selected from the group consisting of hydrogen, methyl, ethyl, and allyl;
R 2 and R 3 are each independently hydrogen or hydroxyl;
R 4 and R 5 are each independently selected from the group consisting of hydrogen, hydroxyl, methyl, ethyl, and methoxy, provided that at least one of R 4 and R 5 is hydrogen, methyl, or ethyl;
R 7 and R 8 are each independently selected from a group consisting of hydrogen, hydroxyl, C 1 -C 10 alkyl, C 1 -C 10 alkoxy, aryl, aryloxy, arylalkyl, and arylalkoxy; and,
a double bond exists between carbon-19 and carbon-20, or
a double bond exists between carbon-18 and carbon-19 and R and R 2 together are oxygen forming a lactone ring.
4 . The lactone as in claim 3 wherein
R is hydroxyl;
R 1 is selected from the group consisting of hydrogen, methyl, ethyl, and allyl;
R 2 and R 3 are each independently hydrogen or hydroxyl;
R 4 and R 5 are each independently selected from the group consisting of hydrogen, hydroxyl, methyl, ethyl, and methoxy, provided that at least one of R 4 and R 5 is hydrogen, methyl, or ethyl;
R 7 is selected from the group consisting of hydrogen, hydroxyl, methyl, ethyl, C 1 -C 5 alkoxy and aryloxy;
R 8 is selected from a group consisting of hydrogen, hydroxyl,
wherein R 9 is selected from the group consisting of hydrogen, hydroxyl, halide, C 1 -C 5 alkyl, C 1 -C 5 hydroxyalkyl, and C 1 -C 5 alkoxy; and optionally, a double bond exists between carbon-19 and carbon-20, or a double bond exists between carbon-18 and carbon-19 and R and R 2 together are oxygen forming a lactone ring.
5 . A compound of the formula
wherein
R 1 is ethyl or allyl;
R 3 is hydrogen or hydroxyl;
R 4 , R 5 and R 7 are each independently selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, and methoxy; and
R 8 is selected from a group consisting of hydrogen, hydroxyl, C 1 -C 5 alkoxy, and heteroaryloxy, provided that at least one of R 4 and R 5 is hydrogen, methyl or ethyl.
6 . The compound as in claim 5 wherein
R 1 is ethyl or allyl;
R 3 is hydrogen or hydroxyl;
R 4 and R 5 are each independently selected from the group consisting of hydrogen, hydroxyl, methyl, ethyl, and methoxy,
R 7 is methoxy; and,
R 8 is hydroxyl or
where R 9 is selected from the group consisting of hydrogen, hydroxyl, hydroxymethyl and hydroxyethyl.
7 . The compound as in claim 6 of the formula
wherein
R 1 is ethyl or allyl; and
R 4 and R 5 are each independently selected from the group consisting of hydrogen, hydroxyl, methyl, ethyl, and methoxy.
8 . The compound as in claim 7 wherein
R 1 is ethyl;
R 4 is methoxy; and,
R 5 is selected from the group consisting of hydrogen, hydroxyl, methyl, and ethyl.
9 . The compound as in claim 7 wherein
R 1 is ethyl;
R 4 is ethyl; and,
R 5 is selected from the group consisting of hydrogen, hydroxyl, methyl, and ethyl.
10 . The compound as in claim 6 of the formula
wherein
R 1 is ethyl or allyl; and
R 4 and R 5 are each independently selected from the group consisting of hydrogen, hydroxyl, methyl, ethyl, and methoxy.
11 . The compound as in claim 6 of the formula
wherein
R 1 is ethyl or allyl; and
R 4 and R 5 are each independently selected from the group consisting of hydrogen, hydroxyl, methyl, ethyl, and methoxy.
12 . The compound as in claim 11 wherein
R 1 is ethyl;
R 4 is methoxy; and,
R 5 is selected from the group consisting of hydrogen, hydroxyl, methyl, and ethyl.
13 . The compound as in claim 11 wherein
R 1 is ethyl;
R 4 is ethyl; and,
R 5 is selected from the group consisting of hydrogen, hydroxyl, methyl, and ethyl.
14 . The compound as in claim 6 of the formula
15 . The compound as in claim 6 of the formula
16 . The compound as in claim 6 of the formula
17 . The compound as in claim 6 of the formula
18 . The compound as in claim 6 of the formula
19 . The compound as in claim 6 of the formula
20 . The compound as in claim 6 of the formula
21 . The compound as in claim 6 of the formula
22 . The compound as in claim 6 of the formula
23 . The compound as in claim 6 of the formula
24 . The compound as in claim 6 of the formula
25 . The compound as in claim 6 of the formula
26 . The compound as in claim 6 of the formula
27 . The compound as in claim 6 of the formula
28 . A recombinant host cell selected from the group consisting of KOS-45-170 (PTA-1811); KOS-60-135 (PTA-1810); KOS132-188; KOS132-191; KOS156-25; KOS156-9A; KOS156-9B; KOS156-26; KOS156-33A; KOS156-33B; and KOS156-33C.
29 . A compound produced by a recombinant host cell selected from the group consistingofKOS-45-170 (PTA-1811); KOS-60-135 (PTA-1810); KOS132-188; KOS132-191; KOS156-25; KOS156-9A; KOS156-9B; KOS156-26; KOS156-33A; KOS156-33B; and KOS156-33C.
30 . The compound of claim 29 of the formula
produced by KOS45-170.
31 . The compound of claim 29 of the formula
produced by KOS60-135.Join the waitlist — get patent alerts
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