Merck Frosst Canada, Inc.

Merck Canada Inc.

Aeromics, Inc.

Kaneq Pharma Inc.

Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Debiopharm International, S.a.

Merck Frosst Canada & Co.

John Colucci

Yongxin Han

Robert J Zamboni

Marie-Claire Wilson

Christopher I Bayly

Helmi Zaghdane

Michel L Belley

Michael Boyd

Robert N Young

Cheuk K Lau

Claude Dufresne

Paul Robert Mcguirk

George William Farr

Marc F Pelletier

Xavier Billot

Anthony Marfat

John Joseph Partridge

Michel Therien

Joey Lee Methot

Erich L Grimm

Carl Berthelette

Andre Giroux

Yves Gareau

Daniel J McKay

Karine M Villeneuve

Barry Hafkin

Zhaoyin Wang

Michel Gallant

Michael John Boyd

Jason Burch

Mario Girard

Julie Farand

Mohamed Helmi Zaghdane

Provided are novel prodrug salts of selective aquaporin inhibitors, their use as pharmaceuticals, and pharmaceutical compositions comprising them, and novel processes for their synthesis and novel intermediates for use in their synthesis. Also provided is use of a compound for the prophylaxis, treatment, and control of aquaporin-mediated conditions. Aquaporin inhibitors, e.g., inhibitors of AQP4 and/or AQP2, may be of utility in the treatment or control of diseases of water imbalance, for example edema (particularly edema of the brain and spinal cord), hyponatremia, and excess fluid retention, as well as diseases such as epilepsy, retinal ischemia and other diseases of the eye, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines.

Prodrug salts

In part, the present disclosure is directed to prodrug derivatives of (E)-N-methyl-N-((3-methylbenzofuran-2-yl)methyl)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide compounds with significant solubility and bioavailability profiles.

Prodrug derivatives of (E)-N-methyl-N-((3-methylbenzofuran-2-yl)methyl)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide

The invention encompasses the novel class of compounds represented by the formula below, which are inhibitors of the PTP-1B enzyme. The invention also encompasses pharmaceutical compositions which include the compounds shown (Formula I) above and methods of treating or preventing PTP-1B mediated diseases, including diabetes. 

Fused aromatic PTP-1B inhibitors

Compound of formula I are antagonists of the PGD2 receptor, CRTH2, and as such are useful in the treatment and/or prevention of CRTH2-mediated diseases such as asthma.

Indole derivatives as CRTH2 receptor antagonists

Prodrug derivatives of (E)-N-methyl-N-((3-M ethylbenzofuran-2-yl)methyl)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide

Compound of formula I are antagonists of the PGD2 receptor, CRTH2, and as such are useful in the treatment and/or prevention of CRTH2-mediated diseases such as asthma. 

The invention is directed to indole and indoline cyclopropyl amide derivatives as EP4 receptor antagonists useful for the treatment of EP4 mediated diseases or conditions, such as acute and chronic pain, osteoarthritis, rheumatoid arthritis and cancer. Pharmaceutical compositions and methods of use are also included.

Indole and indoline cyclopropyl amide derivatives as EP4 receptor antagonists

The invention is directed to quinoline derivatives as prostaglandin E type receptor antagonists useful for the treatment of EP4 mediated diseases or conditions, such as acute and chronic pain, osteoarthritis, rheumatoid arthritis and cancer. The derivatives have the following structure of formula (I): wherein A and B represents either a nitrogen atom or a CH group with the proviso that they cannot both simultaneously be CH, Q can represent a nitrogen or a carbon atom, and Y and Z are either a nitrogen atom, a N(O) group or a C(R) group. Pharmaceutical compositions comprising the derivatives of formula (I) are also included. 

Quinoline derivatives as EP4 antagonists

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Kirkland, Canada

John Colucci