Merck + Co., Inc.

Martin S Springer

Sander G Mills

Malcolm MacCoss

Salvatore J Siciliano

William K Hagmann

Zenon D Konteatis

Bruce L Daugherty

Thomas E Rollins

Julie A Demartino

The eosinophil eotaxin receptor has been isolated, cloned and sequenced. This receptor is a human &bgr;-chemokine receptor and has been designated &ldquo;CC CKR3&rdquo;. The eosinophil eotaxin receptor may be used to screen and identify compounds that bind to the eosinophil eotaxin receptor. Such compounds would be useful in the treatment and prevention of atopic conditions including allergic rhinitis, dermatitis, conjunctivitis, and particularly bronchial asthma.

Eosinophil eotaxin receptor

The present invention is directed spiro-substituted azacycles of formula I: (wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, k, l and m are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-1, CCR-2, CCR-2A, CCR-2B, CCR-3, CCR-4, CCR-5, CXCR-3, and/or CXCR-4.

Spiro-substituted azacycles as modulators of chemokine receptor activity

The present invention is directed to spiro-substituted azacycles of the Formula 1: ##STR1## (wherein R.sub.1, l, m, Q, W, X, Y, and Z are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-1, CCR-2, CCR-2A, CCR-2B, CCR-3, CCR-4, CCR-5, CXCR-3, and/or CXCR-4.

The present invention is directed to aminoquinolines of Formula I: ##STR1## (wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-1, CCR-2, CCR-2A, CCR-2B, CCR-3, CCR-4, CCR-5, CXCR-3, and/or CXCR-4.

Substituted aminoquinolines as modulators of chemokine receptor activity

The invention is an assay, including a series of peptides, which allow screening for inhibitors of C5a binding targeted to the subsite on the C5a receptor occupied by the C-terminus of C5a. These peptides allow compound testing efforts to be targeted to this same subsite so that C5a agonists and antagonists can be identified. These peptides have much greater affinity (Ki&lt;10 nM) than does the natural C-terminus of C5a (Ki=300 .mu.M) and have been labeled to allow for detection of molecules which inhibit binding of these peptides at this receptor subsite. The invention is useful to develop agonists, partial agonists, and antagonists of C5a, and the invention includes compounds identified according to the method of this invention and methods of their use.

Assay to identify human C5a antagonists and agonists

A method is disclosed for isolating and purifying C5a receptor from human polymorphonuclear leukocytes. C5a is a complement-derived protein which is important as a mediator of inflammatory responses. C5a receptor may be used to screen create and quantify C5a antagonists useful as anti-inflammatory agents and immunoregulants and to generate monoclonal and polyclonal anti-C5a receptor antibodies useful as anti-inflammatory agents and immunoregulants.

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Westfield, NJ, United States of America

Martin S Springer