- METHODS AN COMPOSITIONS FOR TREATMENT OF AN INTERSTITIAL LUNG DISEASE
-
Provided herein are methods of treatment of an interstitial lung disease (ILD) by administering an endothelin antagonist, such as sitaxsentan or a pharmaceutically acceptable salt thereof.
- -
-
Page/Page column 39-40
(2008/12/07)
-
- SUBSTITUTED THIOPHENES
-
Disclosed herein are substituted pyrimidine-based endothelin modulators of Formula I, processes of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
- -
-
Page/Page column 66
(2008/12/04)
-
- Formulations of sitaxsentan sodium
-
Provided herein are stable lyophilized and oral formulations of sitaxsentan sodium. In certain embodiments the lyophilized formulations provided herein have improved stability upon reconstitution. Also provided are methods of making and using the formulations.
- -
-
Page/Page column 11
(2008/06/13)
-
- Methods and compositions for treatment of sleep apnea
-
Provided herein are methods of treatment of sleep apnea by administering an endothelin antagonist, such as sitaxsentan or a pharmaceutically acceptable salt thereof to a patient in need of the treatment.
- -
-
Page/Page column 15-16
(2008/06/13)
-
- PROCESSES FOR THE PREPARATION OF 4-CHLORO-3-METHYL-5-(2-(2-(6-METHYLBENZO[D][1,3]DIOXOL-5-YL)ACETYL)-3-THIENYLSULFONAMIDO) ISOXAZOLE
-
Provided are processes for the preparation of 4-chloro-3-methyl-5-(2-(2-(6- methylbenzo[d][1,3Jdioxol-5-yl)acetyl)-3-thienylsulfonamido)isoxazole of formula (I), a compound useful for the treatment of endothelin-mediated disorders.
- -
-
Page/Page column 12
(2008/06/13)
-
- METHODS AND COMPOSITIONS FOR TREATMENT OF DIASTOLIC HEART FAILURE
-
Provided herein are methods of treatment of diastolic heart failure (DHF) by administering an endothelin antagonist, such as sitaxsentan or a pharmaceutically acceptable salt thereof.
- -
-
-
- POLYMORPHS OF N-(4-CHLORO-3-METHYL-5-ISOXAZOLYL)2-[2-METHYL-4,5-(METHYLENEDIOXY) PHENYLACETYL]THIOPHENE-3-SULFONAMIDE, SODIUM SALT
-
N-(4-chloro-3-methyl-5-isoxazolyl)-2-[2-methyl-4,5-(methylenedioxy)phenyl- acetyl]thiophene-3-sulfonamide,, sodium salt, is provided herein in the form of three polymorphs (Forms A, B and C). Forms A, B and C are specified by the peaks in their X-ray powder diffraction patterns, their absorption peaks in their infrared absorption spectra, their peaks in their Raman spectra and their melting points.
- -
-
Page/Page column 63
(2008/06/13)
-
- CRYSTALLINE N-(4-CHLORO-3-METHYL-5-ISOXAZOLYL)-2-[2-METHYL-4,5-(METHYLENEDIOXY)PHENYLACETYL]-THIOPHENE-3-SULFONAMIDE
-
Provided herein are polymorphs of N-(4-chloro-3-methyl-5-isoxazolyl)-2-[2-methyl-4,5-(methylenedioxy)phenylacetyl]thiophene-3-sulfonamide and pharmaceutical compositions thereof. Also provided are methods of treatment of endothelin-mediated disorders by administering a polymorph N-(4-chloro-3-methyl-5-isoxazolyl)-2-[2-methyl-4,5-(methylenedioxy)phenylacetyl]thiophene-3-sulfonamide or pharmaceutical compositions thereof.
- -
-
Page/Page column 42
(2008/06/13)
-
- N-aryl thienyl-, furyl-, and pyrrolyl-sulfonamides and derivatives thereof that 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.
- -
-
Page column 126
(2010/01/30)
-
- Sulfonamides for treatment of endothelin-mediated disorders
-
Thienylsulfonamides and their pharmaceutically acceptable derivatives, pharmaceutical compositions, articles of manufacture, combinations, lyophilized powders and methods for the treatment of endothelin diseases using these formulations and sulfonamides a
- -
-
-
- Biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin
-
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.
- -
-
-
- Sulfonamides for treatment of endothelin-mediated disorders
-
Thienyl-, furyl- and pyrrolyl-sulfonamides, pharmaceutically-acceptable salts of sulfonamides, formulations of salts and the sulfonamides, and methods for modulating or altering the activity of the endothelin family of peptides using the formulations and
- -
-
-
- Formulation of sulfonamides for treatment of endothelin-mediated disorders
-
Formulations of pharmaceutically-acceptable salts of thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides using the formulations are provided. In particular, formulations of so
- -
-
-
- Discovery of TBC11251, a potent, long acting, orally active endothelin receptor-A selective antagonist
-
Previously we reported the discovery of amidothiophenesulfonamides as endothelin receptor-A antagonists with high potency and selectivity. Replacement of an amide group in this class of compounds with an acetyl group maintained the in vitro binding affinity and in vivo activity while providing a compound with oral bioavailability and longer duration of action. The optimal compound discovered during these studies, 15q (TBC11251), binds competitively to human ET(A) receptors with a K(i) of 0.43 ± 0.03 nM and an IC50 of 1.4 nM (IC50 for ET(B) = 9800 nM). This compound inhibits ET-1- induced stimulation of phosphoinositide turnover with a K(i) of 0.686 nM and a pA2 of 8.0. The compound has a serum half-life in the rat and the dog of 6-7 h and 60-100% oral bioavailability. This compound is one of the most selective ET(A) antagonists reported and therefore is suitable for additional pharmacological and clinical investigation of the role of ET(A) receptors in diseases.
- Wu, Chengde,Chan, Ming F.,Stavros, Fiona,Raju,Okun, Ilya,Mong, Seymour,Keller, Karin M.,Brock, Tommy,Kogan, Timothy P.,Dixon, Richard A. F.
-
p. 1690 - 1697
(2007/10/03)
-
