Merck Sharp + Dohme Corp.

Merck Canada Inc.

Codexis, Inc.

Carmela Molinaro

John A McCauley

Peter D Williams

Oscar Miguel Moradei

Thomas J Greshock

Christopher James Bungard

David Jonathan Bennett

Christian Beaulieu

Vouy Linh Truong

Sheldon N Crane

Satyanarayana Tummanapalli

Nobuyoshi Yasuda

Joseph E Lynch

Frank Xing Chen

Yong-Li Zhong

Jianguo Yin

W Peter Wuelfing

Teresa Andreani

Daniel Mckay

Oscar Alvizo

Melissa Ann Mayo

Stephan Jenne

Margie Tabuga Borra-Garske

Auric Anthony Sowell-Kantz

Katharine M Holloway

Christian Nadeau

Philippe G Nantermet

Michael John Boyd

M Katharine Holloway

William D Shipe

Ronald K Chang

Catherine M Wiscount

Vouy-Linh Truong

Jesse J Manikowski

Karine M Villeneuve

Stephanie Lessard

Daniel Simard

Vijayasaradhi Sivalenka

Daniel McKay

Li Hao

Kate Holloway

Sanjay Kumar Singh

Sivalenka Vijayasaradhi

Amelie Roy

Helen Juteau

John A Mccauley

Tummanapalli Satyanarayana

The present application provides engineered polypeptides having imine or oxime reductase activity, polynucleotides encoding the engineered polypeptides, host cells capable of expressing the engineered polypeptides, and methods of using these engineered polypeptides with a range of ketone and amine substrate compounds to prepare secondary and tertiary amine product compounds.

Engineered imine reductases and methods for the reductive amination of ketone and amine compounds

The present application provides engineered polypeptides having imine or oxime reductase activity, polynucleotides encoding the engineered polypeptides, host cells capable of expressing the engineered polypeptides, and methods of using these engineered polypeptides with a range of ketone amine substrate compounds to prepare secondary and tertiary amine product compounds.

The invention encompasses a novel process for making piperidinone carboxamide indane and azainane derivatives, which are CGRP receptor antagonists useful for the treatment of migraine.

Intermediates for preparing CGRP receptor antagonists

The present invention is directed to 2,6-morpholine derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein Z, Z, V, V, V, R, R, and X are defined herein. The invention also relates to methods of using the 2,6-morpholine derivatives of the invention for the inhibition of HV protease, the inhibition of HV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. 

HIV protease inhibitors

Process for making CGRP receptor antagonists

The present invention is directed to 2,5,6-substituted morpholine derivatives and their use in the inhibition of HIV protease, the inhibition of HIV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

The present invention is directed to 5-heteroarylmorpholine derivatives and their use in the inhibition of HIV protease, the inhibition of HIV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

The compounds encompassed by Formula I include compounds which are HIV protease inhibitors and other compounds which can be metabolized in vivo to HIV protease inhibitors. The compounds and their pharmaceutically acceptable salts are useful for the prophylaxis or treatment of infection by HIV and the prophylaxis, treatment, or delay in the onset of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

The disclosure encompasses a novel process for making piperidinone carboxamide indane and azainane derivatives, having less steps and improved yields as compared to previous synthetic methods for making these compounds, which are CGRP receptor antagonists, useful for the treatment of migraine. Conditions for an amide bond formation between an acid and amine include for example reacting the compounds of Formulae B (after salt break) and C with an amide coupling reagent and optionally an additive and an acid and/or a base in a non-reactive solvent.

Compounds of Formula I are disclosed wherein R, R, R, R, R, R, R, R, R, R, R, Rand Rare defined herein. The compounds encompassed by Formula I include compounds which are HIV protease inhibitors and other compounds which can be metabolized in vivo to HIV protease inhibitors. The compounds and their pharmaceutically acceptable salts are useful for the prophylaxis or treatment of infection by HIV and the prophylaxis, treatment, or delay in the onset of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. 

Growing community of inventors

Colonia, NJ, United States of America

Carmela Molinaro