Texas Biotechnology Corporation

Axys Pharmaceuticals, Inc.

Encysive Pharmaceuticals, Inc.

Immunopharmaceutics, Inc.

Erik Joel Verner

Ming Fai Chan

Adam Kois

Vitukudi Narayanaiyengar Balaji

Chengde Wu

Bore G Raju

Rosario Silvestre Castillo

Venkatachalapathi Yalamoori

Timothy P Kogan

Wendy B Young

Kalyanaraman Ramnarayan

Paul Ross Fatheree

Martin Sheringham Linsell

Thomas E Jenkins

Aleksandr Kolesnikov

Sean Gary Trapp

William Dvorak Shrader

Roopa Rai

Richard L Mackman

Darin A Allen

Jason M Hataye

Witold N Hruzewicz

Yalamoori Venkatachalapathi

Spencer R Jeffrey

Venkatachalapathi Yalamorri

The present invention provides novel compounds of the Formula (I): A-B, its prodrug forms, or pharmaceutically acceptable salts thereof, wherein A represents a saturated, unsaturated, or a partially unsaturated bicyclic heterocyclic ring structure, and B represents an aryl or a heteroaryl group. Preferred compounds of the present invention comprise a benzimidazole or indole nucleus. The compounds of this invention are inhibitors of serine proteases, Urokinase (uPA), Factor Xa (FXa), and/or Factor VIIa (FVIIa), and have utility as anti cancer agents and/or as anticoagulants for the treatment or prevention of thromboembolic disorders in mammals.

(Hetero)aryl-bicyclic heteroaryl derivatives, their preparation and their use as protease inhibitors

Biphenylsulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, bicyclic or tricyclic carbon or heterocyclic ring biphenylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

Biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin

Method of treating glaucoma

N-(5-isoxazolyl)benzenesulfonamides and N-(3-isoxazolyl)benzenesulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(5-isoxazolyl)biphenylsulfonamides and N-(3-isoxazolyl)biphenylsulfonamides and methods for inhibiting the binding of an endothelin peptide to an endothelin receptor or increasing the activity of endothelin peptides by contacting the receptor with a sulfonamide are provided. N-isoxzolyl-4-biphenylsulfonamides are particularly preferred. These compounds exhibit activity as endothelin receptor B antagonists. Methods for treating endothelin-mediated disorders, particularly inflammatory diseases, such as asthma, by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

Benzenesulfonamides and the use thereof to modulate the activity of endothelin

Phosphoramidates, phosphinic amides and related compounds and the use thereof to modulate the activity of endothelin

Thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

N-aryl thienyl-, furyl-, and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin

N-alkyl, N-alkenyl, N-alkynyl, N-aryl and N-fused bicyclo or tricyclo thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, (phenyl) and (phenoxy)thienylsulfonamides, (phenyl) and (phenoxy)furylsulfonamides, and (phenyl) and (phenoxy)pyrrolylsulfonamides and methods of using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

N-Alkyl, N-Alkenyl, N-Alkynyl, N-Aryl and N-fused bicyclo or tricyclo thienyl-, furyl-,and Pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin

Methods, compositions, and compounds for modulating the activity of an endothelin peptide are provided. The methods use compositions that contain compounds that include those of the formula:

Use of thieno-pyridine sulfonamides derivatives thereof and related compounds that modulate the activity of endothelin

The present invention relates to novel biheterocyclic derivatives which are factor Xa inhibitors; the pharmaceutically acceptable salts and N-oxides thereof; their uses as therapeutic agents and the methods of their making.

Compounds and compositions as anticoagulants

N-(5-isoxazolyl)benzenesulfonamides and N-(3-isoxazolyl) benzene-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(5-isoxazolyl)-biphenylsulfonamides and N-(3-isoxazolyl)biphenylsulfonamides and methods for inhibiting the binding of an endothelin peptide to an endothelin receptor or increasing the activity of endothelin peptides by contacting the receptor with a sulfonamide are provided. N-isoxzolyl-4-biphenylsulfonamides are particularly preferred. These compounds exhibit activity as endothelin receptor B antagonists. Methods for treating endothelin-mediated disorders, particularly inflammatory diseases, such as asthma, by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

Benzenesulfonamides and the use thereof to modulate the activity of

Methods, compositions, and compounds for modulating the activity of an endothelin pepuide are provided. The methods use compositions that contain compounds that include those of the formula: ##STR1## where X is selected from groups that include O, S, and NH; Y is selected from O.sup.+ and N, and R.sup.1 and R.sup.2 are each selected independently from among alkyl, lower allkenyl, lower alkynyl, lower haloalkyl, halide, pseudohalide or H, except that R.sup.2 is not halide. R.sup.3, R.sup.4 and R.sup.5 are selected from among groups that include hydrogen, halide, alkoxy, alkyl, haloalkyl; and R.sup.7 is selected from groups that include (CH.sub.2).sub.r R.sup.18, in which r is 0 to 6 and R.sup.18 is selected from groups that include aryl, particularly pyrimidinyl and phenyl. The methods are effected by contacting endothelin receptors with one or more of the compounds or with compositions containing one or more of the compounds prior to, simultaneously with, or subsequent to contacting the receptors with an endothelin peptide.

Thieno-pyridine sulfonamides derivatives thereof and related compounds

Thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)-furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

Thienyl-, furyl- and pyrrolyl-sulfonamides and derivatives thereof that

Phosphoramidates and phosphinic amides and related compounds are provided. Also provided are methods that use the compounds for modulating the activity of the endothelin family of peptides are provided. In particular, compounds having formula: ##STR1## in which A, B, R.sup.1 and R.sup.2 are as described are provided. Also provided are methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these compounds or prodrugs thereof. Methods for elucidating the physiological and pathophysiological roles of endothelin, as well as isolating endothelin receptors are also provided.

Phosphoramidates, phosphinic amides and related compounds and the use

Methods, compositions, and compounds for modulating the activity of an endothelin peptide are provided. The methods use compositions that contain compounds that include those of the formula: ##STR1## where X is selected from groups that include O, S, and NH; Y is selected from O.sup.+ and N, and R.sup.1 and R.sup.2 are each selected independently from among alkyl, lower alkenyl, lower alkynyl, lower haloalkyl, halide, pseudohalide or H, except that R.sup.2 is not halide. R.sup.3, R.sup.4 and R.sup.5 are selected from among groups that include hydrogen, halide, alkoxy, alkyl, haloalkyl; and R.sup.7 is selected from groups that include (CH.sub.2).sub.r R.sup.18, in which r is 0 to 6 and R.sup.18 is selected from groups that include aryl, particularly pyrmidinyl and phenyl. The methods are effected by contacting endothelin receptors with one or more of the compounds or with compositions containing one or more of the compounds prior to, simultaneously with, or subsequent to contacting the receptors with an endothelin peptide.

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Foster City, CA, United States of America

Erik Joel Verner