Merck Sharp + Dohme Corp.

Merck + Co., Inc.

Sirna Therapeutics, Inc.

Zhengwu James Deng

Christopher S Burgey

Daniel Vincent Paone

Diem N Nguyen

Theresa M Williams

Anthony W Shaw

Craig M Potteiger

John A Bawiec, Iii

Joseph P Vacca

Harold G Selnick

Matthew G Stanton

Craig A Stump

Steven L Colletti

Shaun R Stauffer

Weimin Wang

Anthony T Ginnetti

Brendan M Crowley

Ivory Hills

John Jin Lim

Ashley Nomland

Carolyn Segerdell

The instant invention provides for novel cationic lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that demonstrates enhanced efficacy along with lower liver toxicity as a result of lower lipid levels in the liver. The present invention employs low molecular weight cationic lipids with one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.

Low molecular weight cationic lipids for oligonucleotide delivery

The instant invention provides for novel cationic lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that is susceptible to hydrolytic instability that may translate into reduced liver residence times and reduced hepatocellular toxicity. The present invention employs acetals and ketals to provide a low pH sensitive chemical handle for degradation.

Cationic lipids for oligonucleotide delivery

The subject invention relates to novel P2X3 receptor antagonists that play a critical role in treating disease states associated with pain, in particular peripheral pain, inflammatory pain, or tissue injury pain that can be treated using a P2X3 receptor subunit modulator.

P2X3 receptor antagonists for treatment of pain

The subject invention relates to novel P2Xreceptor antagonists that play a critical role in treating disease states associated with pain, in particular peripheral pain, inflammatory pain, or tissue injury pain that can be treated using a P2Xreceptor subunit modulator.

P2X3, receptor antagonists for treatment of pain

[object Object]

Compounds of Formula (I): and Formula (II): (where variables R, R, A, B, D, W, X, Y and Z are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved. 

CGRP receptor antagonists

Compounds of Formula I: (where variables R1, R2, R3, R7, G, J, Q, T, W, X and Y are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache, and pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved. 

The present invention is directed to compounds of Formula I: (where variables R, R, R, R, A, B, G, J, Q, T, U, V, W, X and Y are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

The present invention is directed to compounds of Formula I: and Formula II: (where variables R, R, R, R, A, B, G, J, Q, T, U, V, W, X and Y are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

The present invention is directed to compounds of Formula I:and Formula II:(where variables R, R, R, R, A, B, G, J, Q, T, U, V, W, X and Y are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

Growing community of inventors

Eagleville, PA, United States of America

Zhengwu James Deng