Potent, simplified derivatives of immunosuppressive agents
AssigneeThe Texas A&M University System
InventorsDaniel Romo, Jun Liu, Nam Song Choi, Zonggao Shi
Life of this patent
Estimating the term…
Abstract
The present invention provides a compound of Formula I, all of its related stereoisomers, and their pharmaceutically acceptable salts, wherein A-B, K, Q, X, Y, Z, R and R1 are as defined in claim 1. The present invention also provides processes for the preparation thereof, the use thereof in treating immune mediated disease and conditions, and pharmaceutical compositions for use in such therapy. 1
Claims19
A compound of the formula:
- 40
- and its pharmaceutically accepted salts, wherein
- A-B is ethane, (E) and (Z)-ethene, (E) and (Z)-substituted ethene, ethyne,
- K is hydrogen or C1-C3 alkyl,
- Q=NH or O,
- X is hydrogen, hydroxy, alkoxy, alkyl, aminocarbonyl, amino, alkylamino, dialkylamino, alkoxycarbonylamino,
- Y is S, NH, or O,
- Z is hydrogen, hydroxy, aminocarbonyl, alkylamino, dialkylamino, alkoxycarbonylamino, but not t-butoxycarbonylamino when R4 is dimethylamino,
- R1 is hydrogen or C1-C3 alkyl, and
- R is selected from the following:
- (a) Alkene of the formula:
- 41
- wherein R2 is optionally substituted with one or more substituents selected from alkyl, alkylhydroxy, alkylalkoxy, alkylamino, alkylaminoalkyl, or alkylaminodialkyl;
- (b) Alkenylaryl of the formula:
- 42
- wherein R3 is optionally substituted with one or more substituents selected from hydrogen, alkyl, alkyenyl, ankynyl, hydroxy, alkoxy, amino, alkylamino, dialkylamino, trifluromethane, or fluoro;
- and
- (c) Methyldienylpentyl of the formula:
- 43
- wherein R4 is optionally substituted with one or more substituents selected from hydrogen, alkyl, alkyenyl, alkynyl, hydroxy, alkoxy, amino, alkylamino, or dialkylamino;
- and
- (d) Methylalkenylpentyl of the formula:
- 44
- wherein R4 is optionally substituted with one or more substituents selected from hydrogen, alkyl, alkyenyl, alkynyl, hydroxy, alkoxy, amino, alkylamino, or dialkylamino.
A compound of the formula:
- 45
- and its pharmaceutically accepted salts.
A compound of the formula:
- 46
- and its pharmaceutically accepted salts, wherein R1 is selected from hydroxyalkene, methoxyalkene, dimethyl amino alkene;
- and dimethyl amino methyldiene.
A compound of the formula:
- 47
- and its pharmaceutically accepted salts, wherein R1 is selected from hydroxyalkene, methoxyalkene, dimethyl amino alkene and dimethyl amino methyldiene;
- R2 is selected from amino, t-butoxycarbonylamino, hydrogen, phenoxycarbonylamino, and trifluromethylacetamide;
- and
- R3 is selected from methyl and hydrogen.
A compound of the formula:
- 48
- and its pharmaceutically accepted salts.
A compound of the formula:
- 49
- and its pharmaceutically accepted salts.
A compound of the formula:
- 50
- and its pharmaceutically accepted salts.
A compound of the formula:
- 51
- and its pharmaceutically accepted salts.
A compound of the formula:
- 52
- and its pharmaceutically accepted salts.
A compound of the formula:
- 53
- and its pharmaceutically accepted salts.
A compound of the formula:
- 54
- and its pharmaceutically accepted salts.
A compound of the formula:
- 55
- and its pharmaceutically accepted salts, wherein
- X=O, NH or NR;
- and
- Y=O, NH or NR.
A method of making a biotinylated derivative of PatA, comprising the steps of:
- 56
A method of synthesis of PatA derivatives comprising the steps of:
- 57 58
A method of synthesis of DMDA Pat A comprising the steps of:
- 59
A pharmaceutical composition for the inhibition of IL-2 transcription comprising a therapeutically effective amount of a compound of the formula:
- 60
- and its pharmaceutically accepted salts, wherein
- A-B is ethane, (E) and (Z)-ethene, (E) and (Z)-substituted ethene, ethyne,
- K is hydrogen or C1-C3 alkyl,
- Q=NH or O,
- X is hydrogen, hydroxy, alkoxy, alkyl, aminocarbonyl, amino, alkylamino, dialkylamino, alkoxycarbonylamino,
- Y is S, NH, or O,
- Z is hydrogen, hydroxy, aminocarbonyl, alkylamino, dialkylamino, alkoxycarbonylamino, but not t-butoxycarbonylamino when R4 is dimethylamino,
- R1 is hydrogen or C1-C3 alkyl, and
- R is selected from the following:
- (a) Alkene of the formula:
- 61
- wherein R2 is optionally substituted with one or more substituents selected from alkyl, alkylhydroxy, alkylalkoxy, alkylamino, alkylaminoalkyl, or alkylaminodialkyl;
- (b) Alkenylaryl of the formula:
- 62
- wherein R3 is optionally substituted with one or more substituents selected from hydrogen, alkyl, alkyenyl, ankynyl, hydroxy, alkoxy, amino, alkylamino, dialkylamino, trifluromethane, or fluoro;
- and
- (c) Methyldienylpentyl of the formula:
- 63
- wherein R4 is optionally substituted with one or more substituents selected from hydrogen, alkyl, alkyenyl, alkynyl, hydroxy, alkoxy, amino, alkylamino, or dialkylamino;
- and
- (d) Methylalkenylpentyl of the formula:
- 64
- wherein R4 is optionally substituted with one or more substituents selected from hydrogen, alkyl, alkyenyl, alkynyl, hydroxy, alkoxy, amino, alkylamino, or dialkylamino.
Dependencies are inferred from the claim text.