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1. (WO2018048806) CXCR4 ANTAGONISTS AND METHODS OF USE

Pub. No.:    WO/2018/048806    International Application No.:    PCT/US2017/050106
Publication Date: Fri Mar 16 00:59:59 CET 2018 International Filing Date: Wed Sep 06 01:59:59 CEST 2017
IPC: A61K 38/00
C07K 4/00
Applicants: MAINLINE BIOSCIENCES
Inventors: ZHANG, Junge
YAN, Liang Zeng
Title: CXCR4 ANTAGONISTS AND METHODS OF USE
Abstract:
The present invention provides compounds that are antagonists of CXCR4 and methods for using the same for treatment of a clinical condition associated with CXCR4 activation. In particular, compounds of the invention include cyclic peptides. Compounds of the invention can be used to treat a variety of clinical conditions, including but not limited to, cancers, pulmonary fibrosis, HIV infection, rheumatoid arthritis, and other immune disorders. In addition, compounds of the invention can also be used in stem cell therapy. In one particular embodiment, compounds of the invention are cyclic peptides of the formula (I): (SEQ ID NO:1) or a pharmaceutically acceptable salt thereof, wherein a is 0 or 1; AA1 along with the sulfur atom that is attached thereto is 3-mercaptopropionic acid, optionally substituted cysteine, or optionally substituted homocysteine; AA2 along with the sulfur atom that is attached thereto is cysteine or homocysteine; Ar1 is an optionally substituted aryl; X1 is Arg, Dap, Dab, Orn, Lys, Dap(iPr), Dab(iPr), Orn(iPr), or Lys(iPr); X2 is Arg, Dap, Dab, Orn, Lys, Dap(iPr), Dab(iPr), Orn(iPr), Lys(iPr), a D-isomer thereof, or absent; X3 is Gly or absent; X4 is Phe, 2Nal, 1Nal, or absent; X5 is Gly or absent; R2 is -OR4 or -NHR5; R4 is H or alkyl; and R5 is H, alkyl, optionally substituted aryl, optionally substituted aralkyl.