Merck Sharp + Dohme Corp.

Howard Hughes Medical Institute

Merck Canada Inc.

Jonathan B Grimm

Luke D Lavis

Michael D Altman

Kevin J Wilson

Thomas Allen Miller

Alan B Northrup

Michelle R Machacek

Solomon D Kattar

Andrew M Haidle

John Michael Ellis

Kaleen Konrad Childers

Timothee Lionnet

David James Witter

Phieng Siliphaivanh

Ryan D Otte

Matthew Christopher

Anthony Donofrio

Kerrie Spencer

Hua Zhou

Matthew G Stanton

Jongwon Lim

Maria Emilia Di Francesco

Daniel Guay

Alessia Petrocchi

Tony Siu

Michael Hale Reutershan

Paul A Tempest

Christian Beaulieu

Peng Zhang

Neville J Anthony

Fang Liu

Jacques Yves Gauthier

David L Sloman

B Wesley Trotter

Yves Ducharme

Jonathan R Young

Joshua Close

David Joseph Guerin

Brian M Andresen

Lingyun Wu

Paul E Harrington

Kenneth L Arrington

Christian Fischer

Catherine M White

Qiaolin Deng

Eric R Schreiter

Richard Wayne Heidebrecht, Jr

Zhengjian Zhang

Andrey Revyakin

Joel Slaughter

Jiji Chen

Eric Thomas Romeo

Karin M Otte

Rachel Nicola MacCoss

Richard W Heidebrecht, Jr

Sandra Lee Knowles

Liping Wang

Brandon Mitsuo Taoka

Jason Burch

Marc Blouin

Vouy Linh Truong

Yuan Liu

Sathesh P Bhat

Anna A Zabierek

Hyun Chong Woo

Brandon D Cash

Bernard Cote

Joel S Robichaud

Jed Hubbs

Chaomin Li

Brendan O'Boyle

Adam J Schell

Scott Peterson

Dilrukshi Vitharana

Byron Dubois

Kaleen M Konrad

Matthew L Maddess

Gabriela De Almeida

Marie-Eve Lebrun

Kristina Dupont-Gaudet

Ekundayo Osimboni

Laurel M Heckman

Paul J Tempest

Brandon M Taoka

Thomas Miller

Sathesh Bhat

Jean-Francois Fournier

Brendan M O'boyle

Kerrie B Spencer

Audrey Revyakin

Timothee Lionette

Brendan M O'BOYLE

A compound of the following structure is provided:

Red-shifted fluorophores

Provided are a photoactive fluorophore, a photoactive ligand, and a photoactive complex. The photoactive fluorophore includes a photoactivatable derivative of an azetidine-containing Janelia-Fluor dye. The photoactive ligand includes a photoactive fluorophore and a protein tag. The photoactive complex includes a photoactive ligand conjugated to a protein. Also provided are methods of in vivo labeling with and photoactivation of the photoactive fluorophore, ligand, and complex.

Photoactive fluorophores and methods of in vivo labeling

The present invention is generally directed to the synthesis and use of fluorophores. It is more specifically directed to the synthesis and use of deuterated fluorophores. In one case, the present invention provides a compound of the structure shown in FIG.

Deuterated fluorophores

The present invention is generally directed to the synthesis and use of fluorophores. It is more specifically directed to the synthesis and use of deuterated fluorophores. In one case, the present invention provides a compound of the structure shown in.

The presently-disclosed subject matter includes azetidine-substituted fluorescent compounds, where the compounds may be used as probes, dyes, tags, and the like. The presently-disclosed subject matter also includes kits comprising the same as well as methods for using the same to detect a target substance.

Azetidine-substituted fluorescent compounds

The presently-disclosed subject matter relates to analyte-activated photolabile compounds. The compounds include the formula: wherein Z includes a maskable molecule; L is selected from a bond, C, C(O), O, alkyl, (O)alkyl, and alkoxy; Ris selected from H, halogen, alkyl, and acyl; each Ris independently selected from H, alkyl, aryl, and acyl, and is optionally substituted with one or more heteroatoms independently selected from COOH and COO(alkyl); and Ris selected from H, alkyl, aryl, halogen, CN, OH, O(alkyl), O(aryl), SH, S(alkyl), S(aryl), amine, CHO, COOH, COO(alkyl), COO(aryl), POH, and SOH, and is optionally substituted with one or more heteroatoms independently selected from N, O, and S, halogen, OH, O(alkyl), O(aryl), SH, S(alkyl), S(aryl), amine, NO, CHO, COO, COOH, COO(alkyl), COO(aryl), C(O)NR, POH, and/or SOH. Also provided are methods of detecting calcium and treating a subject with the analyte-activated photolabile compounds.

Ion-activated photolabile compounds

The invention provides certain thiazole-substituted aminoheteroaryl compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein X, X, X, X, Y, Y, Y, Y, and Rare as defined herein. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using the compounds for treating diseases or conditions mediated by Spleen Tyrosine Kinase (Syk). 

Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors

Provided are triazole derivatives of Formula I which are potent inhibitors of spleen tyrosine kinase and pharmaceutical composition. The triazole derivatives are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD, rheumatoid arthritis, and cancer.

Triazolyl derivatives as Syk inhibitors

The present invention provides novel imidazole analogs of Formula I which are potent inhibitors of spleen tyrosine kinase, and are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD, rheumatoid arthritis, and cancer.

Imidazolyl analogs as syk inhibitors

The present invention provides novel pyrimidine amines of formula I which are potent inhibitors of spleen tyrosine kinase, and are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD, rheumatoid arthritis and cancer.

Aminopyrimidines as Syk inhibitors

The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3 TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.

Inhibitors of janus kinases

The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3, TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.

Inhibitors of Janus kinases

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Ashburn, VA, United States of America

Jonathan B Grimm