Merck Sharp + Dohme Corp.

Merck + Co., Inc.

Arena Pharmaceuticals, Inc.

Subharekha Raghavan

Joie Garfunkle

Emma R Parmee

Jian Guo

Alan Whitehead

Linda Brockunier

John E Stelmach

Raphaelle Berger

Olga Ornoski

Yong Zhang

James R Tata

Darby Schmidt

Zhiqiang Yang

Jonathan A Groeper

Rui Liang

Jianmin Fu

Cameron James Smith

Shouwu Miao

Yi-Heng Chen

Guizhen Dong

Dann LeRoy Parker, Jr

Libo Xu

Keith Rosauer

Gang Ji

Teresa Beeson

Xiaoqing Han

Falong Jiang

Ashok Arasappan

Dong-Ming Shen

Hong Shen

Steven L Colletti

Jason M Cox

Zhijian Lu

Fa-Xiang Ding

John S Debenham

Guoqing Li

Derun Li

Dongfang Meng

Thomas A Rano

Rui Zhang

Zahid Hussain

George Scott Tria

Tracy Huening

Hong-Dong Li

Hong Li

Sherman Tim Waddell

Yuan Cheng

David Askin

Yusheng Xiong

Kevin Tyler Chapman

Zhuyan Guo

Richard John Varsolona

Graeme Semple

Tawfik Gharbaoui

Xibin Liao

Brian T Campbell

Joseph Leslie Duffy

Jiang Chang

Jae-Kyu Jung

Nancy J Kevin

Mark G Charest

R Scott Hoerrner

Fengqi Zhang

Sriram Tyagarajan

Thomas O Schrader

Zhong Lai

Alexander J Kim

Jason Eugene Imbriglio

Jiafang He

Joseph D Armstrong, Iii

Timothy A Cernak

Philip J Skinner

Spencer Dreher

Ashley Rouse Lins

Fred Fleitz

Daniel E Petrillo

Brian Anthony Kirk

Robert M Purick

Weichun Chen

Abigail Lee Smenton

Zhiquang Yang

Raphelle Berger

John Stelmach

Linda L Brockunier

Olga A Ornoski

Darby Rye Schmidt

The present invention is directed to pyrazolopyrimidine compounds of the general structural formula I: which may be useful as therapeutic agents for the treatment of disorders associated with phosphodiesterase 9 (PDE9). The present invention also relates to the use of such compounds for treating cardiovascular and cerebrovascular diseases, such as hypertension, chronic kidney disease and heart failure, and neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

Substituted pyrazolo[3,4-d]pyrimidines as PDE9 inhibitors

Provided are methods for treating or preventing a fibrotic disease selected from systemic sclerosis, cystic fibrosis, non-alcoholic steatohepatitis, Peyronie's disease, or interstitial lung disease; the method comprising administering a therapeutically effective amount of a compound of Formula (I) (wherein R, R, R, R, and Rare as herein described) or a pharmaceutically acceptable salt thereof, to a patient in need of such therapy. 

Methods for using triazolo-pyrazinyl soluble guanylate cyclase activators in fibrotic disorders

The invention provides certain fused pyrazine compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, R, R, R, R, R, R, and the subscript t are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate ('cGMP'), and are generally suitable for the therapy and prophylaxis of diseases or disorders which are associated with a disturbed cGMP balance. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of the abovementioned diseases and disorders and for preparing pharmaceuticals for this purpose. 

Fused pyrazine derivatives useful as soluble guanylate cyclase stimulators

The invention provides compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, Z, R, R, R, R, and the subscripts m, p, and q are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate ('cGMP'), and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose.

Soluble guanylate cyclase stimulators

A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate ('cGMP') and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or pharmaceutically acceptable salt thereofs, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical compositions which comprise compounds of Formula I or pharmaceutically acceptable salts thereof. 

Substituted imidazo[1,2-a]pyrazines as soluble guanylate cyclase activators

A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate ('cGMP') and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical compositions which comprise compounds of Formula I or a pharmaceutically acceptable salt thereof. 

Imidazo-pyrazinyl derivatives useful as soluble guanylate cyclase activators

A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate ('cGMP') and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical compositions which comprise compounds of Formula I or a pharmaceutically acceptable salt thereof.

Triazolo-pyrazinyl derivatives useful as soluble guanylate cyclase activators

A compound of Formula II or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate ('cGMP') and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula II, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of Formula II or a pharmaceutically acceptable salt thereof. 

Imidazo-pyrazine derivatives useful as soluble guanylate cyclase activators

A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate ('cGMP') and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of Formula I or a pharmaceutically acceptable salt thereof. 

Soluble guanylate cyclase activators

A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate ('cGMP') and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of Formula I or a pharmaceutically acceptable salt thereof.

A compound of Formula (I): or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate ('cGMP') and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of Formula (I) or a pharmaceutically acceptable salt thereof. 

The invention relates to compounds having the structure of Formula (I) and pharmaceutically acceptable salts thereof, which are soluble guanylate cyclase activators. The compounds are capable of modulating the body's production of cyclic guanosine monophosphate ('cGMP') and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The compounds are useful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, pulmonary hypertension, angina pectoris, thromboses, restenosis, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver. 

Compounds of Formula I are capable of modulating the body's production of cyclic guanosine monophosphate ('cGMP') and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of the Formula I, to their use for the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of the Formula I. 

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Teaneck, NJ, United States of America

Subharekha Raghavan