Inhibitors of ubiquitin e1
AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsAllan M. Weissman, Yili Yang, Jane P. Jensen
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Abstract
The present invention features pyrazolidinyl compounds, pharmaceutical compositions of substituted pyrazolidinyl compounds and methods of treating a patient suffering from cancer or viral infection, the method comprising administering to a patient one or more pyrazolidinyl compounds of the invention.
Claims20
A method of treating a mammal in need of treatment or prevention of a disorder or disease that is responsive to inhibition of ubiquitin E1 comprising:
- administering to the subject an effective amount of one or more pyrazolidinyl compounds of Formula (I), or a pharmaceutically acceptable salt, solvate or hydrate thereof:
- wherein,
- each X is independently O, S, or NR1;
- each R1 is independently H, alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, heteroaralkyl, C(O)R, C(O)OR, or C(O)NRR2, each optionally substituted with a substituent;
- each R2 is independently H, alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, or heteroaralkyl, each optionally substituted with a substituent;
- each R is independently H, alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, or heteroaralkyl, each optionally substituted with a substituent;
- Y is H, alkyl, alkenyl, alkynyl, cycloalkyl, nitro, or halogen;
- wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, heteroaralkyl, aryl, or heteroaryl groups may be substituted with H, halogen, nitro, cyano, alkoxy, thioalkoxy, NR3R4, S(O)R5, or S(O)2R5;
- wherein each of R3 and R4 are independently selected from H, alkyl, aralkyl, or aryl;
- wherein R5 is OH, OR3, NH2, or NHR3;
- Z is H, alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, heteroaralkyl, aryl, heteroaryl, halogen, C(O)R3, C(O)OR3, C(O)SR3, C(O)NR3R4, C(S)OR3, C(NR1)OR3, or C(NR1)NR3R4;
- and
- n is 0-5.
A method of treating a mammal suffering from or susceptible to a viral infection comprising administering a compound of Formula (I), or a pharmaceutically acceptable salt, solvate or hydrate thereof:
- wherein,
- each X is independently O, S, or NR1;
- each R1 is independently H, alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, heteroaralkyl, C(O)R, C(O)OR, or C(O)NRR2, each optionally substituted with a substituent;
- each R2 is independently H, alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, or heteroaralkyl, each optionally substituted with a substituent;
- each R is independently H, alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, or heteroaralkyl, each optionally substituted with a substituent;
- Y is H, alkyl, alkenyl, alkynyl, cycloalkyl, nitro, or halogen;
- wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, heteroaralkyl, aryl, or heteroaryl groups may be substituted with H, halogen, nitro, cyano, alkoxy, thioalkoxy, NR3R4, S(O)R5, or S(O)2R5;
- wherein each of R3 and R4 are independently selected from H, alkyl, aralkyl, or aryl;
- wherein R5 is OH, OR3, NH2, or NHR3;
- Z is H, alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, heteroaralkyl, aryl, heteroaryl, halogen, C(O)R3, C(O)OR3, C(O)SR3, C(O)NR3R4, C(S)OR3, C(NR1)OR3, or C(NR1)NR3R4;
- and
- n is 0-5.
A method of treating a subject suffering from or susceptible to a disease or disorder of inflammation or where an immune response is exhibited, comprising administering a compound of Formula (I), or a pharmaceutically acceptable salt, solvate or hydrate thereof:
- wherein,
- each X is independently O, S, or NR1;
- each R1 is independently H, alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, heteroaralkyl, C(O)R, C(O)OR, or C(O)NRR2, each optionally substituted with a substituent;
- each R2 is independently H, alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, or heteroaralkyl, each optionally substituted with a substituent;
- each R is independently H, alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, or heteroaralkyl, each optionally substituted with a substituent;
- Y is H, alkyl, alkenyl, alkynyl, cycloalkyl, nitro, or halogen;
- wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, heteroaralkyl, aryl, or heteroaryl groups may be substituted with H, halogen, nitro, cyano, alkoxy, thioalkoxy, NR3R4, S(O)R5, or S(O)2R5;
- wherein each of R3 and R4 are independently selected from H, alkyl, aralkyl, or aryl;
- wherein R5 is OH, OR3, NH2, or NHR3;
- Z is H, alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, heteroaralkyl, aryl, heteroaryl, halogen, C(O)R3, C(O)OR3, C(O)SR3, C(O)NR3R4, C(S)OR3, C(NR1)OR3, or C(NR1)NR3R4;
- and
- n is 0-5.
Dependencies are inferred from the claim text.