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Details for Patent: 6,211,200

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Details for Patent: 6,211,200

Title: Metal complexes
Abstract:Invented are zinc chelated G-CSF receptor ligands, pharmaceutical compositions containing these compounds, and methods of using these compounds as agonist of the G-CSF receptor. Also invented are novel processes used in preparing these compounds. Also invented are novel G-CSF receptor binding moieties of the invented zinc chelated G-CSF receptor ligands.
Inventor(s): Luengo; Juan I. (Audubon, PA), Miller; Stephen G. (San Diego, CA)
Assignee: SmithKline Beecham Corporation (Philadelphia, PA) Ligand Pharmaceuticals (San Diego, CA)
Filing Date:Oct 30, 1998
Application Number:09/183,935
Claims:1. A method for agonizing the G-CSF receptor in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a G-CSF receptor binding moiety;

except compounds of the formula: ##STR5##

wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are independently aryl, where aryl is cyclic or polycyclic aromatic C.sub.3 -C.sub.12, optionally containing one or more heteroatoms, provided that when C is 3 the aromatic ring contains at least two heteroatoms, and when C is 4 the aromatic ring contains at least one heteroatom, and optionally substituted with one or more substituents selected from the group consisting of: C(O)NR.sup.6 R.sup.7 and NR.sup.6 R.sup.7, aryloxy, cycloalkyl, substituted cycloalkyl, akyl, C.sub.6 -C.sub.12 aryl, alkoxy, acyloxy, substituted C.sub.6 -C.sub.12 aryl, amino, N-acylamino, nitro, cyano, halogen, hydroxy, --C(O)OR.sup.6, --S(O).sub.n R.sup.5, protected --OH and alkyl substituted with one or more substituents selected from the group consisting of: alkoxy, acyloxy, C.sub.6 -C.sub.2 aryl, substituted C.sub.6 -C.sub.12 aryl, amino, N-acylano, oxo, hydroxy, cycloalkyl, substituted cycloalkyl, --C(O)OR.sup.6, --S(O).sub.n R.sup.7, aryloxy, nitro, cyano, halogen and protected --OH, where

R.sup.6 is hydrogen or alkyl,

n is 0-2,

R.sup.7 is hydrogen or alkyl and

R.sup.5 is hydrogen, cycloalkyl, C.sub.6 -C.sub.12 aryl substituted cycloalkyl, substituted C.sub.6 -C.sub.12 aryl, alkyl or alkyl substituted with one or more substituents selected from the group consisting of: alkoxy, acyloxy, aryloxy, amino, N-acylamino, oxo, hydroxy, --C(O)OR.sup.6, --S(O).sub.n R.sup.7, nitro, cyano, cycloalkyl, substituted cycloalkyl, halogen, C.sub.6 -C.sub.12 aryl, substituted C.sub.6 -C.sub.12 aryl and protected --OH, where R.sup.6 is hydrogen or alkyl, n is 0-2 and R.sup.7 is hydrogen or alkyl; or a pharmaceutically acceptable salt, hydrate, solvate or ester thereof.

2. A method of enhancing leukocyte production in a subject which comprises administering to the subject a therapeutically effective amount of a compound of claim 1.

3. A method of treating neutropenia in a subject which comprises administering to the subject a therapeutically effective amount of a compound of claim 1.

4. The method of claim 1 wherein the G-CSF receptor is the human G-CSF receptor.

5. The method of claim 2 wherein the subject is a human.

6. The method of claim 3 wherein the subject is a human.
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