Systemix, Inc.

Pharmacyclics, Inc.

Prolinx Incorporated

Steven M Torkelson

Aleksandr Kolesnikov

Wendy B Young

Kieron E Wesson

William Dvorak Shrader

Roopa Rai

Kevin P Lund

Robert J Kaiser

Mark L Stolowitz

Mark L Stowolitz

Clarence N Ahlem

The present invention relates to novel inhibitors of Factors VIIa, IXa, Xa, XIa, in particular Factor VIIa, pharmaceutical compositions comprising these inhibitors, and methods for using these inhibitors for treating or preventing thromboembolic disorders, cancer or rheumatoid arthritis. Processes for preparing these inhibitors are also disclosed.

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2-(2-hydroxybiphenyl-3-yl)-1H-Benzoimidazole-5-carboxamidine derivatives as factor VIIA inhibitors

2-(2-hydroxybiphenyl-3-yl)-1H-benzoimidazole-5-carboxamidine derivatives as factor VIIA inhibitors

A class of sulforhodamine labeling reagents capable of binding with a biomolecular species to produce a conjugate with fluorescent properties. The sulforhodamine labeling reagents have the structure: ##STR1## The group X is selected from an alkyl, an olefin, a monocyclic aliphatic saturated hydrocarbon, an aryl, or nothing at all. The group Y is selected from an amide, a substituted amide, or nothing at all. The group Z is selected from a monocyclic aliphatic hydrocarbon, an aryl, or an alkyl, as defined with respect to group X, a polyethylene glycol chain of the general form (CH.sub.2 CH.sub.2 O).sub.n, or nothing at all. The alkyl or polyethylene glycol chain may further have inert intermediate amide, ether, or disulfide functionalities. The group X, group Y, and group Z cannot all be nothing at all or non-existent. The group R is an electrophilic moiety suitable for conjugation of the fluorescent labeling reagent with a biomolecular species. Also disclosed is a method of making the reagents.

Fluorescent labeling reagents

Boron compound complexing reagents, intermediate reagents of those reagents, and methods of synthesizing these reagents are disclosed. These reagents, including those shown as General Formula II may be used, after further reactions described herein, to complex with boronic compounds, such as phenylboronic acid or derivatives thereof. ##STR1## In one embodiment, group Z comprises a spacer selected from a saturated or unsaturated chain of up to about 6 carbon equivalents in length, an unbranched saturated or unsaturated chain from about 6 to 18 carbon equivalents in length with at least one intermediate amide or disulfide moieties, and a polyethylene glycol chain of from about 3 to 12 carbon equivalents in length; group R.sub.2 is one of an alkyl and a methylene group with an electronegative moiety; and BAS is a biologically active species.

Boronic compound complexing reagents and complexes

Boron compound complexing reagents, boron compound complexes, and methods of synthesizing these reagents and complexes are disclosed. These reagents and complexes include those shown in General Formula IV and General Formula VI. In one embodiment, the reagent of General Formula IV may be used to form a complex with a boron compound, such as a complex shown in General Formula VI. ##STR1## In one embodiment, group Z comprises a spacer selected from a saturated or unsaturated chain of up to about 6 carbon equivalents in length, an unbranched saturated or unsaturated chain of from about 6 to 18 carbon equivalents in length with at least one of intermediate amide or disulfide moieties, and a polyethylene glycol chain of from about 3 to 12 carbon equivalents in length; group R.sub.3 is selected from one of an H, an alkyl, and a methylene or ethylene moiety with an electronegative substituent; and BAS and BAS* are biologically active species.

Boron compound complexing reagents and methods of synthesizing these reagents are disclosed. These reagents, including those shown as General Formula I and General Formula II may be used, after further reactions described herein, to complex with boronic compounds, such as phenylboronic acid or derivatives thereof. ##STR1##

Boron compound complexing reagents, boron compound complexes, and methods of synthesizing these reagents and complexes are disclosed. These reagents and complexes include those shown in General Formula III, General Formula IV, and General Formula VI. In one embodiment, the reagents of General Formula III may be used to produce, after condensation with a bioactive species (BAS), the reagent of General Formula IV. The reagent of General Formula IV may be used to form a complex with a boron compound, such as a complex shown in General Formula VI. ##STR1##

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San Mateo, CA, United States of America

Steven M Torkelson