Treatment of relapsed and/or refractory solid tumors and non-hodgkin's lymphomas

Patent metadata

Field	Value
Publication number	US-10328077-B2
Application number	US-201715673084-A
Country	US
Kind code	B2
Filing date	Aug 9, 2017
Priority date	Aug 10, 2016
Publication date	Jun 25, 2019
Grant date	Jun 25, 2019

Abstract

Methods are provided for the treatment of relapsed and/or refractory solid tumors (including neuroendocrine carcinomas (NEC)) and non-Hodgkin's lymphomas (NHLs) and the like, using substituted heterocyclic derivative compounds and pharmaceutical compositions comprising compounds useful for the inhibition of lysine specific demethylase-1 (LSD-1).

First claim

We claim:

1. A method for the treatment of human merkel cell carcinoma, gastric neuroendocrine carcinoma, or small cell lung cancer comprising the administration to a patient in need thereof an effective amount of a compound having the structure of Formula (I), or a pharmaceutically acceptable salt thereof,

wherein,
W is N, C—H, or C—F;
X is hydrogen, halogen, —CN, optionally substituted alkyl, optionally substituted alkynyl, optionally substituted carbocyclylalkynyl, optionally substituted aryl, or optionally substituted heteroaryl;
Y is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted cycloalkylalkyl;
Z is an optionally substituted group chosen from alkyl, carbocyclyl, C-attached heterocyclyl, N-attached heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, —O-heterocyclyl, —N(R)-heterocyclyl, —O-heterocyclylalkyl, —N(R)-heterocyclylalkyl, —N(R)(C 1 -C 4 alkylene)-NR 2 , —O(C 1 -C 4 alkylene)-NR 2 ; and
R is hydrogen or C 1 -C 4 alkyl.

2. The method of claim 1 , or a pharmaceutically acceptable salt thereof, wherein W is C—H.

3. The method of claim 1 , or a pharmaceutically acceptable salt thereof, wherein W is C—F.

4. The method of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is selected from the group consisting of hydrogen, halogen, optionally substituted alkyne, optionally substituted carbocyclylalkynyl, optionally substituted aryl, and optionally substituted heteroaryl.

5. The method of claim 4 , or a pharmaceutically acceptable salt thereof, wherein X is optionally substituted aryl.

6. The method of claim 5 , or a pharmaceutically acceptable salt thereof, wherein the optionally substituted aryl is an optionally substituted phenyl.

7. The method of claim 4 , or a pharmaceutically acceptable salt thereof, wherein X is an optionally substituted heteroaryl.

8. The method of claim 7 , or a pharmaceutically acceptable salt thereof, wherein X is selected from the group consisting of optionally substituted pyridinyl, optionally substituted pyrazolyl, and optionally substituted indazolyl.

9. The method of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is heterocyclylalkyl selected from the group consisting of optionally substituted —O-heterocyclylalkyl, optionally substituted —N(H)-heterocyclylalkyl, and optionally substituted —N(Me)-heterocyclylalkyl.

10. The method of claim 9 , or a pharmaceutically acceptable salt thereof, wherein said heterocyclylalkyl group has the formula R c -heterocyclyl in which R c is an optionally substituted C 1 -C 3 alkylene chain or an optionally substituted C 1 alkylene chain.

11. The method of claim 9 , or a pharmaceutically acceptable salt thereof, wherein said heterocyclylalkyl group has the formula R c -heterocyclyl in which heterocyclyl is an optionally substituted nitrogen-containing 4-, 5-, 6-, or 7-membered heterocyclyl.

12. The method of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is an optionally substituted N-attached heterocyclyl.

13. The method of claim 12 , or a pharmaceutically acceptable salt thereof, wherein said optionally substituted N-attached heterocyclyl is 4-, 5-, 6-, or 7-membered N-attached heterocyclyl.

14. The method of claim 13 , or a pharmaceutically acceptable salt thereof, wherein said optionally substituted N-attached heterocyclyl is 6-membered N-attached heterocyclyl.

15. The method of claim 12 , or a pharmaceutically acceptable salt thereof, wherein said optionally substituted N-attached heterocyclyl is an optionally substituted piperidine.

16. The method of claim 15 , or a pharmaceutically acceptable salt thereof, wherein the optionally substituted piperidine is 4-aminopiperidine.

17. The method of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y is an optionally substituted alkyl selected from the group consisting of optionally substituted C 1 -C 3 alkyl, optionally substituted C 1 alkyl, and methyl group.

Assignees

• Celgene Corp

Inventors

• Xu Jiangchun
• Cho Robert
• Nguyen Aaron

Classifications

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title

• A61K31/513 Primary

  having oxo groups directly attached to the heterocyclic ring, e.g. cytosine · CPC title

• A61K31/7048

  having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} · CPC title