Glaxo Inc.

Glaxo Wellcome Inc.

Aktis Oncology, Inc.

Paul L Feldman

Marcus F Brackeen

Michael Ross Johnson

Dasa Lipovsek

Harry J Leighton

Michael K James

Hyun Joo Kil

Isaiah Nathaniel Gober

Matthew Roden

James M Way

Ved Srivastava

Jeffrey Alan Stafford

Brian Scott Goodman

Trevor Price

Jeff Kovacs

Michael Lawrence Doligalski

William C Blackwell, Iii

Provided herein are polypeptides and conjugates thereof, including radionuclide conjugates, useful in compositions and methods of treating, diagnosing, monitoring, and/or imaging a disease, disorder, or condition associated with expression of one or more targets, including Nectin-4.

Nectin-4 binding miniproteins, conjugates and uses thereof

Novel pyrrolidine compounds which are useful for inhibiting the function of Type IV phosphodiesterase (PDE-IV) as well as methods for making the same are disclosed. Applications in treating inflammatory diseases and other diseases involving elevated levels of cytokines, as well as central nervous system (CNS) disorders, are also disclosed.

Substituted pyrrolidines

Novel piperidinyl intermediates as set forth below wherein R, R.sup.1 and Ar are as set forth in the specification and W is either hydrogen or benzyloxycarbonyl. The intermediates are useful in the preparation of N-phenyl-N-(4-piperidinyl) amides having potent analgesic activity. ##STR1##

Intermediates for making analgesic N-phenyl-N-(3-OR.sup.1

N-Phenyl-N-(4-piperdinyl)amide derivatives are disclosed having the general formula (I): ##STR1## wherein X, Ar, R and R.sup.1 are defined, including isomeric forms thereof and acid addition salts thereof. The compounds exhibit analgesic activity. The invention embraces the compounds (I), pharmaceutical compositions of (I) and methods of providing analgesia with (I). Also included are certain novel intermediates for making (I).

Analgesic N-phenyl-N-(3-OR.sub.1 -3-ME-4-piperidinyl)amides

Analgesic n-phenyl-n-(3-or 1-3-me-4-piperidinyl)amides

A method of preparing certain substituted alkali metal 4-carboxy-piperidine salts (I) by alkaline hydrolysis of certain novel substituted 1,3,8-triazaspiro[4.5]decane-2, 4-diones (IV) which in turn are obtained from certain novel substituted chlorosulphonylamido piperidines (III).

Preparation of substituted alkali metal piperidine-4-carboxylates

N-Phenyl-N-(4-piperdinyl)amide derivatives are disclosed having the general formula (I): ##STR1## wherein X is a member selected from the group consisting of alkoxy-carbonyl-lower alkyl, lower alkyl-carbonyloxy-lower alkyl, alkenyloxy-carbonyl-lower alkyl, and (C.sub.1-2)alkoxy-(C.sub.1-2)-alkoxy-carbonyl-lower alkyl, and Ar, R, R.sup.1 and R.sup.2 are defined hereinafter, including isomeric forms thereof and acid addition salts thereof. The compounds exhibit analgesic activity having relatively short durations of analgesic action. The invention embraces the compounds (I), pharmaceutical compositions of (I) and methods of providing analgesia with (I). Also included are certain novel intermediates for making (I).

N-phenyl-N-(4-piperidinyl)amides useful as analgesics

Growing community of inventors

Durham, NC, United States of America

Paul L Feldman