Bristol-myers Squibb Compnay

Ensemble Therapeutics Corporation

Percy H Carter

Jun Li

T G Murali Dhar

Robert Michael Borzilleri

John V Duncia

Robert J Cherney

Daniel S Gardner

Douglas G Batt

Joseph B Santella

Michael G Yang

John T Hynes

Soo Sung Ko

Cullen L Cavallaro

Anurag S Srivastava

Lyndon A M Cornelius

George V De Lucca

Rui-Qin Liu

Dharmpal S Dodd

Zili Xiao

Tg Murali Dhar

Gardner S Creech

Mahboubeh Kheirabadi

David S Nirschl

Jingwu Duan

Dean A Wacker

Matthew Ernst Voss

Yong Zhang

Martin D Eastgate

Satheesh Kesavan Nair

Rulin Zhao

Jayakumar Sankara Warrier

Michael Matthew Miller

Gregory D Brown

Hong Wu

Andrew J Tebben

Boguslaw Mudryk

Victor W Rosso

Feng Qiu

Michael E Randazzo

Peggy Ann Scherle

Ian Mangion

Kimberly A Solomon

Qihong Zhao

Joseph E Dinchuk

Paul Davies

Benjamin Adam Seigal

Lyndon AM Cornelius

TG Murali Dhar

Boguslaw M Mudryk

Nicholas Terrett

Anurag Srivastava

Ian K Mangion

The disclosure is directed to the synthesis and improved methods for purifying macrocyclic peptides produced by solid phase peptide synthesis. The synthesized peptide is capped with an alkyne-functionalized or azide-functionalized compound of formula (I): prior to cleavage of the peptide from the solid phase support.

Non-chromatographic purification of macrocyclic peptides by a resin catch and release

The disclosure is directed to compounds and methods for preparing purified macrocyclic peptide using 'catch-release' methods. These methods comprise reacting a free amino group of a resin-bound linear peptide with an azide- or alkyne-functionalized cap to form a resin-bound capped linear peptide having an azide- or alkyne-functionalized cap; cleaving the capped linear peptide from the resin to form a free capped linear peptide having an azide- or alkyne-functionalized cap; reacting the free capped linear peptide having an azide-functionalized cap with an alkyne-functionalized catch resin, or reacting the free capped linear peptide having an akynyl-functionalized cap with an azide functionalized catch resin, to form a catch-resin bound capped linear peptide; reacting the catch-resin bound capped linear peptide under conditions sufficient to effect macrocyclization of the linear peptide and release of the macrocyclic peptide from the catch resin.

The present application describes modulators of MCP-1 or CCR-2 of formula 

Benzylpyrrolidinone derivatives as modulators of chemokine receptor activity

The present invention provides a novel antagonist: N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide: or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having unexpected dual CCR-2 and CCR-5 receptor activity. Crystalline forms, metabolites, pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases are also disclosed. The present disclosure also provides processes for preparing compounds of Formula (I) as provided herein, including N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide. Compounds that are useful intermediates of the process are also provided herein.

N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-A][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide, a dual modulator of chemokine receptor activity, crystalline forms and processes

[object Object]

The present application describes modulators of MIP-1&#x3b1; of formula (I): or stereoisomers or pharmaceutically acceptable salts thereof, wherein m, T, W, R, R, R, Rand Rare as defined herein. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis using said modulators are disclosed.

Piperazinyl derivatives as modulators of chemokine receptor activity

The present application describes modulators of MCP-1 or CCR-2 of formula, (I) or stereoisomers or prodrugs or pharmaceutically acceptable salts thereof, wherein T, W, X, Y, Z, R, R, Rand R, are defined herein. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and transplant rejection using modulators of formula, (I) are disclosed. 

Cyclohexenyl modulators of chemokine receptor activity

The present application describes modulators of MIP-1&#x3b1; of formula (I) or stereoisomers or prodrugs or pharmaceutically acceptable salts thereof, wherein m, Q, T, W, Z, R, R, R, R, Rand R, are as defined herein. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis using the modulators of formula (I) are disclosed. 

Piperidinyl derivatives as modulators of chemokine receptor activity

The application describes modulators of MIP-1&#x3b1; or CCR-1 of the formula (I) or stereoisomers or prodrugs or pharmaceutically acceptable salts thereof, wherein ring A, T, V, R, Rand R, are defined herein. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and transplant rejection using modulators of formula (I) are disclosed. 

Hydroxyalkanyl amides as modulators of chemokine receptor activity

The present application describes prodrugs of the compound of formula (I): or stereoisomers or pharmaceutically acceptable salts thereof. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis using the prodrug compounds of the invention are disclosed.

Prodrugs of a piperidinyl derivative as modulators of chemokine receptor activity

The present application describes modulators of MIP-1&#x3b1; of formula (I), or stereoisomers or prodrugs or pharmaceutically acceptable salts thereof, wherein n, A, T, R, Rand R, are as defined herein. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis using the modulators of formula (I) are disclosed. 

Cyclic derivatives as modulators of chemokine receptor activity

The present application describes modulators of MIP-1&#x3b1; or CCR-1 of formula (I) or stereoisomers or prodrugs or pharmaceutically acceptable salts thereof, wherein n, ring A, T, V, X, R, Rand R, are defined herein. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and transplant rejection using modulators of formula (I) are disclosed. 

Cyclic modulators of chemokine receptor activity

The present application describes substituted piperidinyl modulators of MIP-1&#x3b1; or CCR-1 or stereoisomers or pharmaceutically acceptable salts thereof. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and transplant rejection using said modulators are disclosed.

The present application describes modulators of MCP-1 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma, multiple sclerosis, artherosclerosis, and rheumatoid arthritis.

Lactams of alkylated acyclic diamine derivatives as modulators of chemokine receptor activity

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Princeton, NJ, United States of America

Percy H Carter