Back to results
US 2014/0005386 A1Published application
p53-Mdm2 ANTAGONISTS
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorAlexander Doemling
Life of this patent
Estimating the term…
Abstract
Novel p53-Mdm2 antogonists that conform to Formula I or to Formula II: where the prescribed substituent groups are defined, are useful in treating or preventing cancer. In particular, the compounds and their pharmaceutical compositions are useful for treating relapsed/refractory acute myeloid and lymphoid leukemia and refractory chronic lymphocytic leukemia/small cell lymphocytic lymphomas.
Claims20
A compound according to Formula I,
- wherein
- R1 and R2 are each independently selected from the group consisting of hydrogen, straight or branched chain (C1-C6)alkyl, (C3-C14)aryl, formyl, acetyl, benzyl, (C3-C4)aryl(C1-C6)alkylene-, —C(O)— (C1-C6)alkyl, (C3-C14)heteroaryl-(C1-C6)alkylene-, and (C3-C14)heterocycloalkyl-(C1-C6)alkylene-;
- R3 is a
- Ra is selected from the group consisting of hydrogen, —C(O)R′, and —C(O)OR′;
- Rb is hydrogen, Cl, Br, or F;
- Rc is H or —C(O)ORd, wherein Rd is hydrogen or straight or branched chain (C1-C6)alkyl;
- R4 is hydrogen;
- R5 is selected from the group consisting of straight or branched chain (C1-C6)alkyl, (C3-C14)aryl, benzyl, (C3-C14)aryl(C1-C6)alkylene-, (C3-C14)cycloalkyl, and (C3-C14)heteroaryl-(C1-C6)alkylene-;
- wherein any alkyl, benzyl, aryl, (C3-C14)aryl(C1-C6)alkylene-, heteroaryl, cycloalkyl, (C3-C14)heteroaryl-(C1-C6)alkylene-, or heterocycloalkyl is optionally substituted with one or more members selected from the group consisting of —OH, —Cl, —F, —Br, —I, -oxy(C3-C14)aryl, (C1-C6)alkyl, (C3-C14)aryl, (C3-C14)heteroaryl, (C3-C4)aryl(C1-C6)alkylene-, (C3-C14)heterocycloalkyl-(C1-C6)alkylene-, —C(O)R′, —C(O)OR′, and oxo;
- R′ is selected from the group consisting of hydrogen, straight or branched chain (C1-C6)alkyl, —NH—(OH), —NH—(C1-C6)alkylene-(C3-C14)heteroaryl, —(C3-C14)heterocycloalkylene-N(R″)(R′″), —NH—(C1-C6)alkylene-ORe, —NH—(C1-C6)alkylene-N(R″)(R′″) and —(C1-C6)alkylene-OH;
- R″ and R′″ are each independently selected from the group consisting of hydrogen, straight or branched chain (C1-C6)alkyl, and —(C1-C6)alkylene-OH, —(C1-C6)alkylene-N(Rf)(Rg), or R″ and R′″ together with the nitrogen atom to which they are bonded form a an aryl ring, a saturated or unsaturated (C3-C14) cyclic structure that optionally has 1-3 heteroatoms selected from —N, —S, or —O;
- and
- Re, Rf, and Rg, are each independently hydrogen or straight or branched chain (C1-C6)alkyl,
- or a pharmaceutically acceptable salt, ester, stereoisomer, or tautomer thereof.
11 more elements
A compound according to Formula II,
- wherein
- X is —(O)—, or —NH—;
- R6 is selected from the group consisting of hydrogen, straight or branched chain (C1-C6)alkyl, —NH—(OH), and —OH;
- R7 is hydrogen or straight or branched chain —(C1-C6)alkyl;
- R8 and R10 are hydrogen;
- R9 is a
- Ra is selected from the group consisting of hydrogen, —C(O)R′, and —C(O)OR′;
- Rb is hydrogen, Cl, Br, or F;
- Rc is H or —C(O)ORd;
- Rd is hydrogen or straight or branched chain (C1-C6)alkyl;
- R11 is selected from the group consisting of straight or branched chain (C1-C6)alkyl, (C3-C14)aryl, benzyl, (C3-C14)aryl(C1-C6)alkylene-, (C3-C14)cycloalkyl, and (C3-C14)heteroaryl-(C1-C6)alkylene-;
- wherein any alkyl, benzyl, aryl, (C3-C14)aryl(C1-C6)alkylene-, heteroaryl, cycloalkyl, or heterocycloalkyl is optionally substituted with one or more members selected from the group consisting of —OH, —Cl, —F, —Br, —I, -oxy(C3-C14)aryl, (C1-C6)alkyl, (C3-C14)aryl, (C3-C14)heteroaryl, (C3-C14)aryl(C1-C6)alkylene-, (C3-C4)heterocycloalkyl-(C1-C6)alkylene-, —C(O)R′, —C(O)OR′, and oxo;
- R′ is selected from the group consisting of hydrogen, straight or branched chain (C1-C6)alkyl, —NH—(OH), —NH—(C1-C6)alkylene-(C3-C14)heteroaryl, and —(C1-C6)alkylene-OH;
- or a pharmaceutically acceptable salt, ester, stereoisomer, or tautomer thereof.
11 more elements
Dependencies are inferred from the claim text.