CYCLOPAMINE ANALOGS
First Claim
Patent Images
1. A compound represented by the following structure:
- or a pharmaceutically acceptable salt thereof;
wherein;
R1 is H, alkyl, —
OR, amino, sulfonamido, sulfamido, —
OC(O)R5, —
N(R5)C(O)R5, or a sugar;
R2 is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, nitrile, or heterocycloalkyl;
or R1 and R2 taken together form ═
O, ═
S, ═
N(OR), ═
N(R)—
, ═
N(NR2), ═
C(R)2;
R3 is H, alkyl, alkenyl, or alkynyl;
R4 is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl, haloalkyl, —
OR, —
C(O)R5, —
CO2R5, —
SO2R5, —
C(O)N(R5)(R5), —
[C(R)2]q-R5, —
[(W)—
N(R)C(O)]qR5, —
[(W)—
C(O)]qR5, —
[(W)—
C(O)O]qR5, —
[(W)—
OC(O)]qR5, —
[(W)—
SO2]qR5, —
[(W)—
N(R5)SO2]qR5, —
[(W)—
C(O)N(R5)]qR5, —
[(W)—
O]qR5, —
[(W)—
N(R)]qR5, —
W—
NR3+X—
, or —
[(W)—
S]qR5;
each W is, independently, a diradical;
each q is, independently, 1, 2, 3, 4, 5, or 6;
X- is a halide;
each R5 is, independently, H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl or -[C(R)2]p-R6;
wherein p is 0-6;
or any two occurrences of R5 on the same substituent can be taken together to form a 4-8 membered optionally substituted ring which contains 0-3 heteroatoms selected from N, O, S, and P;
each R6 is, independently, hydroxyl, —
N(R)COR, —
N(R)C(O)OR, —
N(R)SO2(R), —
C(O)N(R)2, —
OC(O)N(R)(R), —
SO2N(R)(R), —
N(R)(R), —
COOR, —
C(O)N(OH)(R), —
OS(O)2OR, —
S(O)2OR, —
OP(O)(OR)(OR), —
NP(O)(OR)(OR), or —
P(O)(OR)(OR);
each R is independently H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl or aralkyl;
each of R7 and R7′
is H, or R7 and R7′
taken together form ═
O; and
each of R8 and R9 are H, or R8 and R9 taken together form a bond;
provided that when R2, R3, R4, are H, R1 is not hydroxyl or a sugar;
provided that when R4 is hydroxyl, R1 is not a sugar or hydroxyl;
provided that when R4 is hydroxyl, R1 and R2 together are not C═
O;
provided that when R3, R4, R8, R9 are H and R7 and R7′
are taken together form ═
O, then R1 cannot be hydroxyl and R2 cannot be H;
provided that when R3, R4, R8, R9 are H and R7 and R7′
are taken together form ═
O, then R1 cannot be acetate and R2 cannot be H;
provided that when R3, R4, R7, R7′
, R8, and R9 are H, then R1 and R2 taken together cannot be ═
O; and
provided that when R3, R4, R7, R7′
, R8, R9 are H, then R1 and R2 cannot be H.
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Accused Products
Abstract
The invention provides novel derivatives of cyclopamine having the following formula:
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Citations
17 Claims
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1. A compound represented by the following structure:
-
or a pharmaceutically acceptable salt thereof; wherein; R1 is H, alkyl, —
OR, amino, sulfonamido, sulfamido, —
OC(O)R5, —
N(R5)C(O)R5, or a sugar;R2 is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, nitrile, or heterocycloalkyl;
orR1 and R2 taken together form ═
O, ═
S, ═
N(OR), ═
N(R)—
, ═
N(NR2), ═
C(R)2;R3 is H, alkyl, alkenyl, or alkynyl; R4 is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl, haloalkyl, —
OR, —
C(O)R5, —
CO2R5, —
SO2R5, —
C(O)N(R5)(R5), —
[C(R)2]q-R5, —
[(W)—
N(R)C(O)]qR5, —
[(W)—
C(O)]qR5, —
[(W)—
C(O)O]qR5, —
[(W)—
OC(O)]qR5, —
[(W)—
SO2]qR5, —
[(W)—
N(R5)SO2]qR5, —
[(W)—
C(O)N(R5)]qR5, —
[(W)—
O]qR5, —
[(W)—
N(R)]qR5, —
W—
NR3+X—
, or —
[(W)—
S]qR5;each W is, independently, a diradical; each q is, independently, 1, 2, 3, 4, 5, or 6; X- is a halide; each R5 is, independently, H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl or -[C(R)2]p-R6;
wherein p is 0-6;
or any two occurrences of R5 on the same substituent can be taken together to form a 4-8 membered optionally substituted ring which contains 0-3 heteroatoms selected from N, O, S, and P;each R6 is, independently, hydroxyl, —
N(R)COR, —
N(R)C(O)OR, —
N(R)SO2(R), —
C(O)N(R)2, —
OC(O)N(R)(R), —
SO2N(R)(R), —
N(R)(R), —
COOR, —
C(O)N(OH)(R), —
OS(O)2OR, —
S(O)2OR, —
OP(O)(OR)(OR), —
NP(O)(OR)(OR), or —
P(O)(OR)(OR);each R is independently H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl or aralkyl; each of R7 and R7′
is H, or R7 and R7′
taken together form ═
O; andeach of R8 and R9 are H, or R8 and R9 taken together form a bond; provided that when R2, R3, R4, are H, R1 is not hydroxyl or a sugar; provided that when R4 is hydroxyl, R1 is not a sugar or hydroxyl; provided that when R4 is hydroxyl, R1 and R2 together are not C═
O;provided that when R3, R4, R8, R9 are H and R7 and R7′
are taken together form ═
O, then R1 cannot be hydroxyl and R2 cannot be H;provided that when R3, R4, R8, R9 are H and R7 and R7′
are taken together form ═
O, then R1 cannot be acetate and R2 cannot be H;provided that when R3, R4, R7, R7′
, R8, and R9 are H, then R1 and R2 taken together cannot be ═
O; andprovided that when R3, R4, R7, R7′
, R8, R9 are H, then R1 and R2 cannot be H.- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17)
or a pharmaceutically acceptable salt thereof.
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17. A pharmaceutical composition comprising a compound of claim 1, and at least one pharmaceutically acceptable excipient.
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16. An isolated compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof .
Specification