Cyclerion Therapeutics, Inc.

Ironwood Pharmaceuticals, Inc.

Tisento Therapeutics Inc.

Takashi Nakai

Rajesh R Iyengar

Ara Mermerian

Paul A Renhowe

Thomas Wai-Ho Lee

Glen Robert Rennie

Nicholas Robert Perl

Joel D Moore

Timothy Claude Barden

G-Yoon Jamie Im

Joon Jung

Karthik Iyer

James Edward Sheppeck

Colleen Hudson

Mark G Currie

Xiang Y Yu

Lei Jia

Kimberly Kafadar Long

George Todd Milne

Charles Kim

James Jia

Song Xue

Ahmad Hashash

Vishnu Vardhan Reddy Karnati

Jason Matthew Rohde

Wayne C Schairer

William Kissel

Yuguang Wang

Fenger Zhou

Debra Jane Wallace

Angelika Fretzen

Kim Tang

Peter Germano

Kevin Sprott

Daniel P Zimmer

Bo Peng

Wilmin Bartolini

Regina Graul

Helen Cumberbatch

Paul Allen Renhowe

Paul Allan Renhowe

Mark Currie

The present disclosure relates to stimulators of soluble guanylate cyclase (sGC), pharmaceutical formulations comprising them and their uses thereof, alone or in combination with one or more additional agents, for treating various diseases, wherein an increase in the concentration of nitric oxide (NO) and/or an increase in the concentration of cyclic Guanosine Monophosphate (cGMP) might be desirable. Various compounds are disclosed, including those of Formula I:

sGC stimulators

The present disclosure relates to novel processes for the preparation of compounds of Formula I. Some of these compounds are useful as stimulators of soluble guanylate cyclase (sGC). Others are useful intermediates towards the preparation of said stimulators. These processes are amenable to large scale preparation and produce stable 3-(2-pyrimidinyl) pyrazoles of Formula I in high purity and yields. The present invention has the additional advantage of facile reaction conditions, amenable to scale up for large scale manufacturing. The disclosure also provides novel intermediates useful in the preparation of said compounds.

Processes and intermediates for the preparation of soluble guanylate cyclase stimulators

The present disclosure relates to novel processes for the preparation of compounds of Formula I. Some of these compounds are useful as stimulators of soluble guanylate cyclase (sGC). Others are useful intermediates towards the preparation of said stimulators. These processes are amenable to large scale preparation and produce stable 3-(2-pyrimidinyl)pyrazoles of Formula I in high purity and yields. The present invention has the additional advantage of facile reaction conditions, amenable to scale up for large scale manufacturing. The disclosure also provides novel intermediates useful in the preparation of said compounds.

The present disclosure relates to stimulators of soluble guanylate cyclase (sGC), pharmaceutically acceptable salts, pharmaceutical formulations comprising them as well as their phosphate ester prodrugs, and their uses alone or in combination with one or more additional agents, for treating various diseases, wherein an increase in the concentration of nitric oxide (NO) and/or an increase in the concentration of cyclic Guanosine Monophosphate (cGMP), or both, or the upregulation of the NO pathway is desirable. The compounds are of Formula I.

The present disclosure relates to novel processes for the preparation of compounds of Formula I. Some of these compounds are useful as simulators of soluble guanylate cyclase (sGC). Others are useful intermediates towards the preparation of said simulators. These processes are amenable to large scale preparation and produce stable 3-(2-pyrimidinyl)pyrazoles of Formula I in high purity and yields. The present invention has the additional advantage of facile reaction conditions, amenable to scale up for large scale manufacturing. The disclosure also provides novel intermediates useful in the preparation of said compounds. 

Compounds of Formulae I' and I are described, which are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds are also useful for treating, preventing or managing various disorders that are herein disclosed. 

The present disclosure relates to stimulators of soluble guanylate cyclase (sGC), pharmaceutical formulations comprising them and their uses thereof, alone or in combination with one or more additional agents, for treating various diseases, wherein an increase in the concentration of nitric oxide (NO) and/or an increase in the concentration of cyclic Guanosine Monophosphate (cGMP) might be desirable. Various compounds are disclosed, including those of Formula (I). 

SGC stimulators

The present patent application discloses the compounds according to Formula (I) shown below, or pharmaceutically acceptable salts thereof wherein J, n, R, R, R, R, R, m and X as defined herein. 

Phosphorus prodrugs of pyrazolo-substituted pyrimidine sGC stimulators

The present disclosure relates to stimulators of soluble guanylate cyclase (sGC), pharmaceutical formulations comprising them and their uses thereof, alone or in combination with one or more additional agents, for treating various diseases, wherein an increase in the concentration of nitric oxide (NO) or an increase in the concentration of cyclic Guanosine Monophosphate (cGMP), or both, or an upregulation of the NO pathway is desirable. The compounds are of Formula I: 

The present patent application discloses at least the compounds according to Formula I' shown below, or pharmaceutically acceptable salts thereof, wherein ring D, ring A, ring E, J, n, J, J, X, Z, Z, R, R, Y, R, o and W are as defined herein.

Compounds of Formula I are described. They are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds may be useful for treating, preventing or managing various disorders that are herein disclosed. 

Growing community of inventors

Newton, MA, United States of America

Takashi Nakai