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US 2015/0087658 A1Published application
Substituted aminopyrimidine compounds and methods of use
AssigneesCalitor Sciences, LLC, Sunshine Lake Pharma Co., Ltd.
InventorsNing Xi, Liang Wang, Tingjin Wang
Life of this patent
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Abstract
The invention relates to the preparation and use of new aminopyrimidine derivatives as drug candidates in free form or in pharmaceutically acceptable salt form and formulations thereof for the modulation of a disorder or disease which is mediated by the activity of the PI3K enzymes. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of disorders or diseases, such as disorders of immunity and inflammation in which PI3K enzymes play a role in leukocyte function, and hyperproliferative disorders associated with PI3K activity, including but not restricted to leukemias and solid tumors, in mammals, especially humans.
Claims22
A compound having Formula (I):
- or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, wherein:
- X is (C3-C7)heterocyclyl, —(C1-C4)alkylene-(C3-C7)heterocyclyl, (C6-C10)aryl, —(C1-C4)alkylene-(C6-C10)aryl, 5-10 membered heteroaryl, or —(C1-C4)alkylene-(5-10 membered heteroaryl), wherein X is optionally substituted by 1, 2, 3, 4 or 5 R1 groups;
- Y is
- wherein Y is optionally substituted by 1, 2, 3, 4 or 5 R2 groups;
- each R1 and R2 is independently H, F, Cl, Br, CN, NO2, oxo (═O), —C(═O)Ra, —C(═O)ORa, —C(═O)NRaRb, —OC(═O)NRaRb, —OC(═O)ORa, —N(Rc)(═O)NRaRb, —N(Rc)C(═O)ORa, —N(Rc)C(═O)Ra, —S(═O)2NRaRb, —S(═O)2Ra, —N(Rc)S(═O)2Ra, —N(Rc)—(C1-C4)alkylene-S(═O)2Ra, —(C1-C4)alkylene-C(═O)NRaRb, —(C1-C4)alkylene-N(Rc)C(═O)NRaRb, —(C1-C4)alkylene-N(Rc)C(═O)ORa, —(C1-C4)alkylene-OC(═O)NRaRb, —(C1-C4)alkylene-S(═O)2NRaRb, —(C1-C4)alkylene-N(Rc)S(═O)2Ra, ORa, NRaRb, —(C1-C4)alkylene-ORa, —(C1-C4)alkylene-NRaRb, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C8)cycloalkyl, —(C1-C4)alkylene-(C3-C8)cycloalkyl, (C3-C7)heterocyclyl, —(C1-C4)alkylene-(C3-C7)heterocyclyl, (C6-C10)aryl, —(C1-C4)alkylene-(C6-C10)aryl, 5-10 membered heteroaryl, or —(C1-C4)alkylene-(5-10 membered heteroaryl), wherein each of the (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C8)cycloalkyl, —(C1-C4)alkylene-(C3-C8)cycloalkyl, (C3-C7)heterocyclyl, —(C1-C4)alkylene-(C3-C7)heterocyclyl, (C6-C10)aryl, —(C1-C4)alkylene-(C6-C10)aryl, 5-10 membered heteroaryl and —(C1-C4)alkylene-(5-10 membered heteroaryl) is optionally substituted with 1, 2, 3 or 4 substitutents independently selected from F, Cl, Br, CN, ORa, NRaRb, (C1-C6)alkyl, —(C1-C4)alkylene-ORB and —(C1-C4)alkylene-NRaRb;
- each of R3 and R4 is independently H, F, CN, —C(═O)Ra, —C(═O)ORB, —C(═O)NRaRb, —(C1-C4)alkylene-C(═O)NRaRb, —(C1-C4)alkylene-N(Rc)C(═O)NRaRb, —(C1-C4)alkylene-N(Rc)C(═O)ORB, —(C1-C4)alkylene-OC(═O)NRaRb, —(C1-C4)alkylene-S(═O)2NRaRb, —(C1-C4)alkylene-N(Rc)S(═O)2Rb, —(C1-C4)alkylene-ORB, —(C1-C4)alkylene-NRaRb, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C8)cycloalkyl, —(C1-C4)alkylene-(C3-C8)cycloalkyl, (C3-C7)heterocyclyl, —(C1-C4)alkylene-(C3-C7)heterocyclyl, (C6-C10)aryl, —(C1-C4)alkylene-(C6-C10)aryl, 5-10 membered heteroaryl, or —(C1-C4)alkylene-(5-10 membered heteroaryl), wherein each of the (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C8)cycloalkyl, —(C1-C4)alkylene-(C3-C8)cycloalkyl, (C3-C7)heterocyclyl, —(C1-C4)alkylene-(C3-C7)heterocyclyl, (C6-C10)aryl, —(C1-C4)alkylene-(C6-C10)aryl, 5-10 membered heteroaryl and —(C1-C4)alkylene-(5-10 membered heteroaryl) is optionally substituted with 1, 2, 3 or 4 substitutents independently selected from F, Cl, Br, CN, ORa, NRaRb, (C1-C6)alkyl, —(C1-C4)alkylene-ORB and —(C1-C4)alkylene-NRaRb;
- or R3 and R4, together with the carbon atom they are attached to, form an optionally substituted 3-8 membered carbocyclic or heterocyclic ring;
- and
- each Ra, Rb and Rc is independently H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, —(C1-C4)alkylene-(C3-C6)cycloalkyl, (C3-C6)heterocyclyl, —(C1-C4)alkylene-(C3-C6)heterocyclyl, (C6-C10)aryl, —(C1-C4)alkylene-(C6-C10)aryl, 5-10 membered heteroaryl, or —(C1-C4)alkylene-(5-10 membered heteroaryl), wherein each of the (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, —(C1-C4)alkylene-(C3-C6)cycloalkyl, (C3-C6)heterocyclyl, —(C1-C4)alkylene-(C3-C6)heterocyclyl, (C6-C10)aryl, —(C1-C4)alkylene-(C6-C10)aryl, 5-10 membered heteroaryl and —(C1-C4)alkylene-(5-10 membered heteroaryl) is optionally substituted with 1, 2, 3 or 4 substitutents independently selected from F, Cl, CN, N3, OH, NH2, (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)alkoxy and (C1-C6)alkylamino;
- or Ra and Rb, together with the nitrogen atom they are attached to, form an optionally substituted 3-8 membered heterocyclic ring.
7 more elements
Dependencies are inferred from the claim text.