Invention Grant
- Patent Title: Phospholidines that are Bcl family antagonists for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer
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Application No.: US16425276Application Date: 2019-05-29
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Publication No.: US10745429B2Publication Date: 2020-08-18
- Inventor: Anne-Marie Beausoleil , Ryan Hudson
- Applicant: Unity Biotechnology, Inc.
- Applicant Address: US CA Brisbane
- Assignee: Unity Biotechnology, Inc.
- Current Assignee: Unity Biotechnology, Inc.
- Current Assignee Address: US CA Brisbane
- Agency: Bozicevic, Field & Francis LLP
- Agent Rudy J. Ng
- Main IPC: C07F9/653
- IPC: C07F9/653 ; C07F9/6533 ; C07F9/6584 ; A61P35/00 ; A61P3/10 ; A61P19/02

Abstract:
This disclosure provides compounds with Bcl inhibitory activity based on a new chemical scaffold, as shown in Formula (I). The phospholidine compounds can include a P-phenyl phospholidine moiety which is substituted with an N-aryl or N-heteroaryl group. The P-phenyl phospholidine moiety can be optionally substituted at phosphorus with thio (═S) instead of oxo (═O). A second heteroatom attached to phosphorus can be cyclically linked to the N-substituted nitrogen atom of the phospholidine that is attached to the phosphorus to provide, together with the phosphorus atom through which they are connected, a heterocyclic ring. By incorporating such a cyclic constraint between two phosphorus substituents of the core linking moiety a favorable binding conformation can be promoted in the compounds. Selected compounds promote apoptosis in senescent cells, and can be developed for treating senescent-related conditions, such as osteoarthritis, ophthalmic disease, pulmonary disease, and atherosclerosis. Selected compounds promote apoptosis in cancer cells, and can be developed as chemotherapeutic agents.
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