Wyeth

Merck Sharp + Dohme Corp.

Ambrx, Inc.

Jeffrey Curtis Kern

Puwen Zhang

Eugene Anthony Terefenko

Robert M Garbaccio

Philip E Brandish

James J Mulhearn

Jay Edward Wrobel

Andrew Fensome

Ying Sun

Nick Knudsen

Eugene John Trybulski

Mark E Layton

Linda Liang

Diane Deborah Harrison

Jianing Wang

Dennis P Gately

Richard Winneker

Anthony Manibusan

Andrew Beck

Sanjiv Shah

Christopher D Cox

Izzat Tiedje Raheem

Gary Sondermann Grubb

Vadim Y Dudkin

Michael J Kelly, Iii

Michael A Rossi

Joseph E Pero

Alexander J Reif

Hannah D Fiji

Dennis Zaller

Vadim Dudkin

Michael J Iii Kelly

Phosphonate linkers and their use for delivering compounds with passive cell permeability into a cell wherein the phosphonate group facilitates cellular retention of the compound are described.

Phosphonate linkers and their use to facilitate cellular retention of compounds

Antibody drug conjugates (ADCs) comprising an antibody conjugated to an anti-inflammatory therapeutic agent via a phosphate-based linker with tunable extracellular and intracellular stability are described.

Antibody drug conjugate for anti-inflammatory applications

Phosphate-based linkers with tunable stability for intracellular delivery of drug conjugates are described. The phosphate-based linkers comprise a monophosphate, diphosphate, triphosphate, or tetraphosphate group (phosphate group) and a linker arm comprising a tuning element and optionally a spacer. A payload is covalently linked to the phosphate group at the distal end of the linker arm and the functional group at the proximal end of the linker arm is covalently linked to a cell-specific targeting ligand such as an antibody. These phosphate-based linkers have a differentiated and tunable stability in blood vs. an intracellular environment (e.g. lysosomal compartment).

Phosphate based linkers for intracellular delivery of drug conjugates

The present invention is directed to imidazopyridin-2-one derivatives which are potentiators of metabotropic glutamate receptors, particularly the mGluRreceptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. 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 metabotropic glutamate receptors are involved.

Imidazopyridin-2-one derivatives

The present invention is directed to pyrimidine compounds which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 10 (PDE10). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

Pyrimidine PDE10 inhibitors

This invention provides progesterone receptor modulators having the structure: wherein Rto R, X, and Q are as defined in the specification; or a pharmaceutically acceptable salt thereof.

7-aryl 1,5-dihydro-4,1-benzoxazepin-2(3H)-one derivatives and their use as progesterone receptor modulators

Compounds of formula I, wherein R-Rand n are defined herein, and pharmaceutical compositions and kits containing these compounds are provided.  Also provided are methods of inducing contraception, providing hormone replacement therapy, treating cycle-related symptoms, or treating or preventing benign or malignant neoplastic disease using the compounds of formula I or formula II, wherein R-R, R, and Rare defined herein. 

5-aryl-indan-1-one oximes and analogs useful as progesterone receptor modulators

Compounds having the structure of formula I are provided. In formula I, Ris H, OH, substituted or unsubstituted Cto Calkyl, Cto Cperfluoroalkyl, or COR; Ris H, substituted or unsubstituted Cto Calkyl, aryl, substituted or unsubstituted Cto Calkoxy, substituted or unsubstituted Cto Caminoalkyl; Rand Rare H, substituted or unsubstituted Cto Calkyl, Cto Cperfluoroalkyl, substituted or unsubstituted Cto Calkenyl, substituted or unsubstituted Cto Calkynyl, substituted or unsubstituted Cto Ccycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocyclic; or Rand Rare fused to form spirocyclic rings; Ris NHR, OR, NHSOR, or OSOR; Q is O, S, NR, or CRR; or a pharmaceutically acceptable salt, ester, or prodrug thereof. Such compounds are useful as progesterone receptor modulators and for treating progesterone receptor related conditions 

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Compounds of formula I or II are provided, wherein R-Rare defined herein, and pharmaceutical compositions and kits containing these compounds. Also provided are methods of inducing contraception, providing hormone replacement therapy, treating cycle-related symptoms, or treating or preventing benign or malignant neoplastic disease using the compounds of formula I, formula II, or formula III, wherein R-Rare defined herein: 

5-Aryl-indan-1-one and analogs useful as progesterone receptor modulators

The present invention provides methods of treating skin disorders includes delivering to a mammal a composition containing a compound of formula I, or tautomers thereof, in a regimen, wherein formula I is: and wherein R-Rand Qare defined as described herein. Specifically, methods for treating acne, hirsutism, and conditioning the skin are described. Also provided are novel PR modulators of formula II.

Cyclothiocarbamate derivatives as progesterone receptor modulators and methods of treating skin disorders

Compounds having the structure of formula I are provided. In formula I, Ris H, OH, substituted or unsubstituted Cto Calkyl, Cto Cperfluoroalkyl, or COR; Ris H, substituted or unsubstituted Cto Calkyl, aryl, substituted or unsubstituted Cto Calkoxy, substituted or unsubstituted Cto Caminoalkyl; Rand Rare H, substituted or unsubstituted Cto Calkyl, Cto Cperfluoroalkyl, substituted or unsubstituted Cto Calkenyl, substituted or unsubstituted Cto Calkynyl, substituted or unsubstituted Cto Ccycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocyclic; or Rand Rare fused to form spirocyclic rings; Ris NHR, OR, NHSOR, or OSOR; Q is O, S, NR, or CRR; or a pharmaceutically acceptable salt, ester, or prodrug thereof. Such compounds are useful as progesterone receptor modulators and for treating progesterone receptor related conditions. 

6-amino-1,4-dihydro-benzo[d][1,3] oxazin-2-ones and analogs useful as progesterone receptor modulators

The present invention provides methods of inducing contraception which includes delivering to a female a composition containing a compound of formula I or formula II, or tautomers thereof, in a regimen which involves delivering one or more of a selective estrogen receptor modulator, wherein formula I is: and wherein R&#x2013;Rand Qare defined as described herein. Methods of providing hormone replacement therapy and for treating carcinomas, dysfunctional bleeding, uterine leiomyomata, endometriosis, and polycystic ovary syndrome is provided which includes delivering a compound of formula I and a selective estrogen receptor modulator are also described.

Growing community of inventors

Gilbertsville, PA, United States of America

Jeffrey Curtis Kern