IP Library › Granted Patent US 12,264,133
Granted Patent B2
US 12,264,133 · App. 17/452,025 · Granted Apr 1, 2025

Compounds, compositions and methods

Inventors: Bradley Paul Morgan (South San Francisco, CA); Alex Muci (South San Francisco, CA); Pu-Ping Lu (South San Francisco, CA); Todd Tochimoto (South San Francisco, CA); David J. Morgans, Jr. (South San Francisco, CA); Erica Anne Kraynack (South San Francisco, CA)
Assignee: CYTOKINETICS, INCORPORATED
C07D213/75C07D211/56C07D239/42C07D261/14C07D263/48C07D271/113C07D295/26C07D401/10C07D401/12C07D417/00C07D417/10C07D417/12C07D487/04C07D491/04C07D513/04
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Quick Facts
Patent No.
US 12,264,133
App. No.
17/452,025
Granted
Apr 1, 2025
Kind
B2
Abstract

Certain substituted urea derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure.

Claims (23)

1. A compound of Formula 1D:

or a pharmaceutically acceptable salt thereof.

2. A compound of Formula 1E:

or a pharmaceutically acceptable salt thereof.

3. A method of preparing the compound of claim 1 , or a pharmaceutically acceptable salt thereof, comprising contacting boc-piperazine and sodium triacetoxylborohydride with a mixture of a compound of Formula 1B:

and a compound of Formula 1C:

4. The method of claim 3 , wherein the mixture of the compound of Formula 1B and the compound of Formula 1C is prepared by step a) contacting 1B with diisobutyllithiumaluminum hydride to yield a reaction solution; and step b) admixing the reaction solution with ice and glacial acetic acid.

5. The method of claim 3 , wherein the mixture of the compound of Formula 1B and the compound of Formula 1C is a 20:80 mixture.

6. The method of claim 3 , wherein the contacting is performed in a mixture of HOAc and DCM.

7. The method of claim 4 , wherein step a) is performed in dry Et 2 O at a temperature of about 0° C.

8. A method of preparing the compound of claim 2 , or a pharmaceutically acceptable salt thereof, comprising reducing a compound of Formula 1D:

in the presence of 10% Pd/C in MeOH over an atmosphere of H 2 .

9. A compound of Formula 4B:

or a pharmaceutically acceptable salt thereof.

10. A compound of Formula 4C:

or a pharmaceutically acceptable salt thereof.

11. A method of preparing the compound of claim 10 , or a pharmaceutically acceptable salt thereof, comprising reducing a compound of Formula 4B:

in the presence of Pt/C, K 2 CO 3 , and H 2 .

12. The method of claim 11 , wherein the reducing is performed in THF.

13. The method of claim 11 , wherein an internal reaction temperature is ≤30° C.

14. The method of claim 11 , wherein the compound of Formula 4B is prepared by admixing a compound of Formula 4A:

with methyl piperazine-1-carboxylate.

15. The method of claim 14 , wherein the admixing is performed in the presence of DIPEA in DCM.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 30, 2022
From: MORGAN, BRADLEY PAUL; MUCI, ALEX; LU, PU-PING; TOCHIMOTO, TODD; MORGANS, DAVID J., JR.; KRAYNACK, ERICA ANNE
To: CYTOKINETICS, INCORPORATED
Reel/Frame 060370/0942 →
Continuity (11)
Continuation 17200174 · Mar 12, 2021
Continuation 16459754 · Jul 2, 2019
Continuation 16021418 · Jun 28, 2018
Continuation 15480618 · Apr 6, 2017
Continuation 14837201 · Aug 27, 2015
Continuation 14489705 · Sep 18, 2014
Continuation 13946353 · Jul 19, 2013
Continuation 13341413 · Dec 30, 2011
Continuation 11630062
Provisional Application 60581197 · Jun 17, 2004
Related Publication 20220185779A1 · Jun 16, 2022
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