Claims for Patent: 9,714,226

Summary for Patent: 9,714,226

Title:	Hydrazide containing nuclear transport modulators and uses thereof
Abstract:	The invention generally relates to nuclear transport modulators, e.g., CRM1 inhibitors, and more particularly to a compound represented by structural formula I: ##STR00001## or a pharmaceutically acceptable salt thereof, wherein the values and alternative values for the variables are as defined and described herein. The invention also includes the synthesis and use of a compound of structural formula I, or a pharmaceutically acceptable salt or composition thereof, e.g., in the treatment, modulation and/or prevention of physiological conditions associated with CRM1 activity.
Inventor(s):	Sandanayaka; Vincent P. (Northboro, MA), Shacham; Sharon (Newton, MA), McCauley; Dilara (Arlington, MA), Shechter; Sharon (Andover, MA)
Assignee:	Karyopharm Therapeutics Inc. (Newton, MA)
Application Number:	14/940,310
Patent Claims:	1. A compound of structural formula I: ##STR00173## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is selected from hydrogen and methyl; R.sup.2 is selected from pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrazin-2-yl, and quinoxalin-2-yl, pyrimidin-4-yl, 1,1-dioxotetrahydrothiophen-3-yl and cyclopropyl, wherein R.sup.2 is optionally substituted with one or more substituents independently selected from methyl and halogen; or R.sup.1 and R.sup.2 are taken together with their intervening atoms to form 4-hydroxypiperidin-1-yl, pyrrolidin-1-yl, azepan-1-yl, 4-benzylpiperazin-1-yl, 4-ethylpiperazin-1-yl, 3-hydroxyazetidin-1-yl, or morpholin-4-yl; R.sup.3 is selected from hydrogen and halo; and represents a single bond wherein a carbon-carbon double bond bound thereto is in an (E)- or (Z)-configuration. 2. The compound according to claim 1, wherein the compound is represented by structural formula II: ##STR00174## or a pharmaceutically acceptable salt thereof. 3. The compound of claim 2, wherein: R.sup.1 is selected from hydrogen and methyl; and R.sup.2 is selected from pyridin-2-yl, pyridin-4-yl, pyrazin-2-yl and pyrimidin-4-yl, wherein R.sup.2 is optionally substituted with a single substituent selected from methyl and chloro; or R.sup.1 and R.sup.2 are taken together to form 4-hydroxypiperidin-1-yl. 4. The compound of any one of claims 1-3, wherein R.sup.3 is hydrogen. 5. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is represented by any one of the following structural formulas: ##STR00175## ##STR00176## ##STR00177## ##STR00178## 6. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is represented by any one of the following structural formulas: ##STR00179## ##STR00180## 7. A composition comprising a compound of any one of claims 1-6, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 8. The composition of claim 7, further including a second therapeutic compound.