Treprostinil derivative compounds and methods of using same

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.

Treprostinil derivatives and compositions and uses thereof

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

Treprostinil derivatives and compositions and uses thereof

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

Treprostinil derivative compounds and methods of using same

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable dosage. Transdermal applications can be used.

Treprostinil derivative compounds and methods of using same

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.

Treprostinil derivatives and compositions and uses thereof

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

TREPROSTINIL DERIVATIVES AND COMPOSITIONS AND USES THEREOF

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension. 120-. (canceled)22. The pharmaceutical composition of claim 21 , which is formulated for transdermal delivery of the compound.23. The pharmaceutical composition of claim 22 , which is configured as a transdermal patch.25. The method of claim 24 , wherein the medical condition is selected from the group consisting of pulmonary hypertension claim 24 , pulmonary fibrosis claim 24 , ischemic diseases claim 24 , peripheral vascular disease claim 24 , peripheral ischemic lesions on the skin claim 24 , critical limb ischemia claim 24 , heart failure claim 24 , atherogenesis claim 24 , inflammatory diseases claim 24 , diabetic neuropathic foot ulcer claim 24 , kidney malfunction and failure claim 24 , tumors claim 24 , cancers claim 24 , and pain associated with each of the preceding conditions.26. The method of claim 25 , wherein the medical condition is pulmonary hypertension.27. The method of claim 26 , wherein the medical condition is pulmonary arterial hypertension.28. The method of claim 24 , wherein the compound is administered topically.29. The method of claim 28 , wherein the compound is administered transdermally.30. The method of claim 29 , wherein the compound is administered via a transdermal patch.31. The method of claim 28 , wherein the compound is administered pulmonarily by oral inhalation.32. The method of claim 24 , wherein the compound is administered orally.33. The method of claim 24 , wherein the compound is administered parenterally.34. The method of claim 33 , wherein the compound is administered subcutaneously or intravenously.35. The method of claim 24 , further comprising administering an additional therapeutic agent.36. The method of claim 35 , wherein the additional ...

Treprostinil derivatives and compositions and uses thereof

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

TREPROSTINIL DERIVATIVES AND COMPOSITIONS AND USES THEREOF

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension. 124-. (canceled)26. A pharmaceutical composition comprising the compound of claim 25 , or a pharmaceutically acceptable salt claim 25 , solvate claim 25 , hydrate claim 25 , clathrate claim 25 , polymorph or stereoisomer thereof claim 25 , and one or more pharmaceutically acceptable excipients or carriers.27. The pharmaceutical composition of claim 26 , which is formulated for oral administration of the compound.28. The pharmaceutical composition of claim 26 , which is formulated for parenteral administration of the compound.29. The pharmaceutical composition of claim 28 , which is formulated for intravenous or subcutaneous administration of the compound.30. The pharmaceutical composition of claim 26 , which is formulated for topical administration of the compound.31. The pharmaceutical composition of claim 30 , which is formulated for transdermal administration or pulmonary administration by inhalation of the compound.32. A method of treating a medical condition responsive to treatment with treprostinil claim 25 , comprising administering to a subject in need of treatment a therapeutically effective amount of the compound of claim 25 , or a pharmaceutically acceptable salt claim 25 , solvate claim 25 , hydrate claim 25 , clathrate claim 25 , polymorph or stereoisomer thereof.33. The method of claim 32 , wherein the medical condition is selected from the group consisting of pulmonary hypertension claim 32 , pulmonary arterial hypertension claim 32 , portopulmonary hypertension claim 32 , pulmonary fibrosis claim 32 , interstitial lung disease claim 32 , asthma claim 32 , cardiovascular disease claim 32 , heart failure claim 32 , congestive heart failure claim 32 , conditions requiring ...

TREPROSTINIL DERIVATIVE COMPOUNDS AND METHODS OF USING SAME

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used. 181-. (canceled)83. The compound of claim 82 , wherein Ris Pand Ris H.84. The compound of claim 82 , wherein Ris H and Ris P.85. The compound of claim 82 , wherein Ris Pand Ris P.88. The compound of claim 82 , wherein each of Rto Ris H.89. The compound of claim 82 , wherein at least one of Rto Ris deuterium.90. The compound of claim 82 , wherein Z is —OH claim 82 , —OR claim 82 , —N(R)Ror P.91. The compound of claim 82 , wherein Z is P.92. The compound of claim 82 , wherein Z is —OH.93. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers or excipients.94. The pharmaceutical composition of claim 93 , which is formulated for transdermal delivery claim 93 , optionally via a patch.95. A method of treating pulmonary hypertension claim 82 , comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof.96. The method of claim 95 , wherein the pulmonary hypertension is pulmonary arterial hypertension.97. The method of claim 95 , wherein the compound is administered orally claim 95 , topically or parenterally.98. The method of claim 97 , wherein the compound is administered transdermally claim 97 , optionally via a patch.99. The method of claim 95 , further comprising administering an additional therapeutic agent.100. The method of claim 99 , wherein the additional therapeutic agent is selected from the group consisting of vasoactive agents claim 99 , diuretics claim 99 , anticoagulants and cardiac glycosides. This application is ...

TREPROSTINIL DERIVATIVES AND COMPOSITIONS AND USES THEREOF

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

TREPROSTINIL DERIVATIVE COMPOUNDS AND METHODS OF USING SAME

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used. 181-. (canceled)83. The compound of claim 82 , wherein Ris H and Ris P.84. The compound of claim 82 , wherein Ris Pand Ris H.85. The compound of claim 82 , wherein Ris Pand Ris P.86. The compound of claim 82 , wherein Rand Rare each H.87. The compound of claim 82 , wherein each of Rto Ris H.88. The compound of claim 82 , wherein at least one of Rto Ris deuterium.89. A composition comprising at least one compound according to and at least one other component.90. The composition of claim 89 , which is formulated for transdermal delivery.91. The composition of claim 90 , which is formulated for transdermal delivery with a patch.92. The composition of claim 89 , further comprising at least one solvent.93. A method of treating pulmonary hypertension claim 82 , comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt claim 82 , solvate claim 82 , polymorph or enantiomer thereof.94. The method of claim 93 , wherein the pulmonary hypertension is pulmonary arterial hypertension.95. The method of claim 93 , wherein the compound is administered topically.96. The method of claim 95 , wherein the compound is administered transdermally.97. The method of claim 96 , wherein the compound is administered via a transdermal patch.98. The method of claim 93 , further comprising administering an additional therapeutic agent.99. The method of claim 98 , wherein the additional therapeutic agent is selected from the group consisting of vasoactive agents claim 98 , diuretics claim 98 , anticoagulants and cardiac glycosides. This application is a ...

TREPROSTINIL DERIVATIVE COMPOUNDS AND METHODS OF USING SAME

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used. 147-. (canceled)49. The compound of claim 48 , wherein R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , and Rare H.50. The compound of claim 48 , wherein at least one of R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , and Rare is deuterium.51. The compound of claim 48 , wherein Lis —O-alkylene-C(O)—.52. The compound of claim 48 , wherein Lis —O-alkylene-OC(O)—.53. The compound of claim 48 , wherein Lis a bond.54. The compound of claim 48 , wherein the alkylene group is a C-Calkylene group.55. The compound of claim 48 , wherein the alkylene group is a Calkylene group.56. (canceled)5863-. (canceled)66. A composition comprising a compound of claim 48 , or and one or more pharmaceutically acceptable excipients.67. The composition of claim 66 , which is formulated for transdermal delivery.6870-. (canceled)71. A method of treating pulmonary hypertension claim 66 , comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of claim 66 , or or a pharmaceutically acceptable salt thereof.72. The method of claim 71 , wherein the pulmonary hypertension is pulmonary arterial hypertension.73. The method of claim 71 , wherein the compound is administered transdermally. This application claims priority to U.S. provisional application 61/751,608 filed Jan. 11, 2013 ...

TREPROSTINIL DERIVATIVES AND COMPOSITIONS AND USES THEREOF

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension. 123-. (canceled)26. The transdermal patch of claim 25 , wherein both Rand Rare hydrogen.29. The transdermal patch of claim 24 , wherein —O—Z—COH is —O-cycloalkyl-COH claim 24 , —O—CH-cycloalkyl-COH claim 24 , —O-cycloalkyl-CH—COH claim 24 , or —O—CH-cycloalkyl-CH—COH claim 24 , and for each of the preceding moieties -cycloalkyl- is:1,2-cyclopropyl (cis or trans); or1,3-cyclobutyl (cis or trans) or 1,2-cyclobutyl (cis or trans); or1,3-cyclopentyl (cis or trans) or 1,2-cyclopentyl (cis or trans); or1,4-cyclohexyl (cis or trans), 1,3-cyclohexyl (cis or trans), or 1,2-cyclohexyl (cis or trans).31. The transdermal patch of claim 24 , further comprising a drug reservoir and a semi-permeable membrane.32. The transdermal patch of claim 24 , further comprising a drug/polymer matrix.33. The transdermal patch of claim 24 , further comprising a chemical permeation enhancer.36. The kit of claim 35 , wherein both Rand Rare hydrogen.39. The kit of claim 34 , wherein —O—Z—COH is —O-cycloalkyl-COH claim 34 , —O—CH-cycloalkyl-COH claim 34 , —O-cycloalkyl-CH—COH claim 34 , or —O—CH-cycloalkyl-CH—COH claim 34 , and for each of the preceding moieties -cycloalkyl- is:1,2-cyclopropyl (cis or trans); or1,3-cyclobutyl (cis or trans) or 1,2-cyclobutyl (cis or trans); or1,3-cyclopentyl (cis or trans) or 1,2-cyclopentyl (cis or trans); or1,4-cyclohexyl (cis or trans), 1,3-cyclohexyl (cis or trans), or 1,2-cyclohexyl (cis or trans).41. The kit of claim 34 , wherein the medical condition is selected from the group consisting of pulmonary hypertension claim 34 , pulmonary fibrosis claim 34 , ischemic diseases claim 34 , peripheral vascular disease claim 34 , peripheral ischemic lesions on the skin claim 34 , critical ...

TREPROSTINIL DERIVATIVE COMPOUNDS AND METHODS OF USING SAME

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used. 2. The compound of claim 1 , wherein Ris Pand Ris H.3. The compound of claim 1 , wherein Ris H and Ris P.4. The compound of claim 1 , wherein Ris Pand Ris P.615-. (canceled)16. The compound of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare H claim 1 , or wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare deuterium.17. (canceled)18. The compound of claim 1 , wherein Z is —OR claim 1 , —N(R)R claim 1 , or P.19. (canceled)20. The compound of claim 1 , wherein Z is —OH claim 1 , —OR claim 1 , —N(R)R claim 1 , or P.21. (canceled)22. The compound of claim 1 , wherein Z is not —OH and Ris not unsubstituted or substituted benzyl.25. The compound of claim 24 , wherein Z is —OR.26. The compound of claim 24 , wherein Z is —N(R)R.27. The compound of claim 24 , wherein Z is —SR.28. The compound of claim 24 , wherein Z is P.29. The compound of claim 24 , wherein Z is ORand Ris bicycloalkyl claim 24 , alkylcycloalkyl claim 24 , or alkylcycloheteroalkyl.30. The compound of claim 24 , wherein Ris haloalkyl.31. (canceled)32. The compound of claim 24 , wherein Ris hydrogen and Ris P.33. The compound of claim 24 , wherein Ris Pand Ris hydrogen.34. The compound of claim 24 , wherein Ris Pand Ris P.35. The compound of claim 24 , wherein Rand Rare each hydrogen.36. A compound according to claim ...

TREPROSTINIL DERIVATIVE COMPOUNDS AND METHODS OF USING SAME

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used. 157-. (canceled)60. The compound of claim 58 , wherein R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , and Rare H.61. The compound of claim 58 , wherein at least one of R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , and Ris deuterium.62. (canceled)64. (canceled)65. (canceled)66. A composition comprising a compound of or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers or excipients.67. The composition of claim 66 , which is formulated for transdermal delivery.68. The composition of claim 66 , which is formulated for transdermal delivery with a patch.6972-. (canceled)73. A method of treating pulmonary hypertension claim 58 , comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof.74. (canceled)75. (canceled)76. The method of claim 73 , wherein the compound is administered orally claim 73 , topically or parenterally.77. The method of claim 76 , wherein the compound is administered transdermally.78. The method of claim 73 , wherein the pulmonary hypertension is pulmonary arterial hypertension.79. The method of claim 73 , further comprising administering an additional therapeutic agent.80. The method of claim 79 , wherein the additional therapeutic agent is ...

TREPROSTINIL DERIVATIVE COMPOUNDS AND METHODS OF USING SAME

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.

Flavonoid compounds

The present invention relates to compounds, compositions, and methods for treatment of conditions related to mitochondrial function. In various aspects, the present invention comprises administering one or more epicatechin derivatives in an amount effective to stimulate mitochondrial function in cells. The compounds, compositions, and methods described herein provide for reducing infarct size in the heart following permanent ischemia or ischemia/reperfusion event or method for delaying, attenuating or preventing adverse cardiac remodeling, and can assist in prevention of impaired mitochondria biogenesis and thus prevention of the consequences of impaired mitochondrial biogenesis in various diseases and conditions, as well as provide for the active therapy of mitochondrial depletion that may have already occurred.

Treprostinil derivatives and compositions and uses thereof

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

USE OF NEUROKININ-1 ANTAGONISTS AS ANTITUSSIVES

The disclosure relates to the use of neurokinin-1 (NK-1) antagonists, such as serlopitant, MK-0303 or MK-8478, in alleviating or suppressing cough (including acute, subacute and chronic cough) and urge to cough. The cough can have an unknown cause (idiopathic cough) or can be associated with any type of medical condition, such as a respiratory disorder. The NK-1 antagonist can be delivered by oral inhalation for more rapid peripheral and central antitussive action. Another antitussive agent in addition to the NK-1 antagonist can optionally be administered for the treatment of the cough or urge to cough, or the cough-associated medical condition. 146-. (canceled)47. A method of treating cough or urge to cough , comprising orally administering serlopitant or a pharmaceutically acceptable salt , solvate , hydrate , clathrate , polymorph , prodrug , metabolite or stereoisomer thereof , to a subject in need of such treatment according to a schedule , said schedule comprising:a) first administering at least one loading dose; andb) second administering at least one therapeutically effective maintenance dose;wherein said maintenance dose comprises a dosage from about 1 to about 10 mg.48. The method according to claim 47 , wherein the loading dose is 1.5 claim 47 , 2 claim 47 , 3 claim 47 , 4 or 5 times the maintenance dose.49. The method according to claim 48 , wherein the loading dose is 3 times the maintenance dose.50. The method according to claim 47 , wherein the loading dose is administered on day 1 and the maintenance dose is administered on day 2 and thereafter.51. The method according to claim 47 , wherein the maintenance dose is administered in the morning.52. The method according to claim 47 , wherein the maintenance dose is administered without food at least two hours before or after a meal.53. The method according to claim 47 , wherein the maintenance dose is about 5 mg.54. The method according to claim 47 , wherein the maintenance dose is administered once a ...

Treprostinil derivatives and compositions and uses thereof

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

TREPROSTINIL DERIVATIVES AND COMPOSITIONS AND USES THEREOF

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension. 128-. (canceled)31. The compound of claim 29 , wherein Ris hydrogen and —ORis derivatized.32. The compound of claim 29 , wherein Ris hydrogen and —ORis derivatized.33. The compound of claim 29 , wherein both —ORand —ORare derivatized claim 29 , optionally with the same moiety.34. The compound of claim 33 , wherein both —ORand —ORare derivatized with the same moiety.36. The pharmaceutical composition of claim 35 , wherein Ris hydrogen and —ORis derivatized.37. The pharmaceutical composition of claim 35 , wherein Ris hydrogen and —ORis derivatized.38. The pharmaceutical composition of claim 35 , wherein both —ORand —ORare derivatized claim 35 , optionally with the same moiety.39. The pharmaceutical composition of claim 38 , wherein both —ORand —ORare derivatized with the same moiety.40. The pharmaceutical composition of claim 35 , which is formulated for transdermal delivery of the compound.41. The pharmaceutical composition of claim 40 , which is configured as a transdermal patch.43. The method of claim 42 , wherein Ris hydrogen and —ORis derivatized.44. The method of claim 42 , wherein Ris hydrogen and —ORis derivatized.45. The method of claim 42 , wherein both —ORand —ORare derivatized claim 42 , optionally with the same moiety.46. The method of claim 45 , wherein both —ORand —ORare derivatized with the same moiety.47. The method of claim 42 , wherein the medical condition is selected from the group consisting of pulmonary hypertension claim 42 , pulmonary fibrosis claim 42 , ischemic diseases claim 42 , peripheral vascular disease claim 42 , peripheral ischemic lesions on the skin claim 42 , critical limb ischemia claim 42 , heart failure claim 42 , atherogenesis claim 42 , inflammatory ...

Dermal and transdermal administration of treprostinil and salts thereof

The present disclosure provides methods, compositions, devices and systems for dermal and transdermal administration of treprostinil or salts thereof, and optionally an additional therapeutic agent. Treprostinil and salts thereof can be dermally or transdermally administered to treat any medical conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

TREPROSTINIL DERIVATIVE COMPOUNDS AND METHODS OF USING SAME

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used. 170-. (canceled)72. The compound of claim 71 , wherein Ris Pand Ris H.73. The compound of claim 71 , wherein Ris H and Ris P.74. The compound of claim 71 , wherein Ris Pand Ris P.75. The compound of claim 71 , wherein each of Rto Ris H.76. The compound of claim 71 , wherein at least one of Rto Ris deuterium.77. The compound of claim 71 , wherein Z is —OR.78. The compound of claim 71 , wherein Z is P.79. The compound of claim 71 , wherein Z is —N(R)R.80. The compound of claim 71 , wherein Z is —OH.82. A composition comprising a compound of or a pharmaceutically acceptable salt thereof and at least one other component.83. The composition of claim 82 , which is formulated for transdermal delivery.84. The composition of claim 83 , which is formulated for transdermal delivery with a patch.85. The composition of claim 82 , further comprising at least one solvent.86. A method of treating pulmonary hypertension claim 71 , comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof.87. The method of claim 86 , wherein the pulmonary hypertension is pulmonary arterial hypertension.88. The method of claim 86 , wherein the compound is administered transdermally.89. The method of claim 88 , wherein the compound is administered via a transdermal patch. This application claims priority to U.S. provisional application 61/751,608 filed Jan. 11, 2013 which is incorporated herein by reference in its entirety for all purposes.Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is a disease which can result in death and is ...

TREPROSTINIL DERIVATIVES AND COMPOSITIONS AND USES THEREOF

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension. 128-. (canceled)31. The method of claim 29 , wherein:{'sup': '3', 'sub': 1', '6, 'Rin each occurrence independently is C-Calkyl;'}{'sup': 4', '5', '4', '5, 'sub': 1', '3, 'Rand Rin each occurrence independently are hydrogen or C-Calkyl, or Rand Rand the carbon atom to which they are connected form a cyclopropyl ring;'}{'sup': 6', '3, 'Rin each occurrence independently is hydrogen or R;'}j in each occurrence independently is 0 or 1; andm in each occurrence independently is 1 or 2.32. The method of claim 31 , wherein:{'sup': '3', 'Rin each occurrence independently is methyl, ethyl, propyl, isopropyl, butyl, iso-butyl, sec-butyl or tert-butyl;'}{'sup': 4', '5, 'Rand Rin each occurrence independently are hydrogen, methyl, ethyl, propyl or isopropyl;'}{'sup': 6', '3, 'Rin each occurrence independently is hydrogen or R;'}j is 0; andm is 1.33. The method of claim 29 , wherein Ris hydrogen and —ORis derivatized.34. The method of claim 29 , wherein Ris hydrogen and —ORis derivatized.35. The method of claim 29 , wherein both —ORand —ORare derivatized.36. The method of claim 35 , wherein both —ORand —ORare derivatized with the same moiety.37. The method of claim 29 , wherein the medical condition is selected from the group consisting of pulmonary hypertension claim 29 , pulmonary fibrosis claim 29 , ischemic diseases claim 29 , peripheral vascular disease claim 29 , peripheral ischemic lesions on the skin claim 29 , critical limb ischemia claim 29 , heart failure claim 29 , atherogenesis claim 29 , inflammatory diseases claim 29 , diabetic neuropathic foot ulcer claim 29 , kidney malfunction and failure claim 29 , tumors claim 29 , cancers claim 29 , and pain associated with each of the preceding ...

TREPROSTINIL DERIVATIVES AND COMPOSITIONS AND USES THEREOF

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension. 4. The pharmaceutical composition of claim 3 , wherein both Rand Rare hydrogen claim 3 , and p is an integer from 1 to 9 or from 1 to 5 (or each occurrence of Rand Ris hydrogen claim 3 , and q is an integer from 0 to 8 or from 0 to 4).7. The pharmaceutical composition of claim 2 , wherein —O—Z—COH is —O-cycloalkyl-COH claim 2 , —O—CH-cycloalkyl-COH claim 2 , —O-cycloalkyl-CH—COH claim 2 , or —O—CH-cycloalkyl-CH—COH claim 2 , and for each of the preceding moieties -cycloalkyl- is:1,2-cyclopropyl (cis or trans); or1,3-cyclobutyl (cis or trans) or 1,2-cyclobutyl (cis or trans); or1,3-cyclopentyl (cis or trans) or 1,2-cyclopentyl (cis or trans); or1,4-cyclohexyl (cis or trans), 1,3-cyclohexyl (cis or trans), or 1,2-cyclohexyl (cis or trans).9. The pharmaceutical composition of claim 2 , which is configured for transdermal delivery of the compound.10. The pharmaceutical composition of claim 9 , which is configured as a transdermal patch.13. The method of claim 12 , wherein both Rand Rare hydrogen claim 12 , and p is an integer from 1 to 9 or from 1 to 5 (or each occurrence of Rand Ris hydrogen claim 12 , and q is an integer from 0 to 8 or from 0 to 4).16. The method of claim 11 , wherein —O—Z—COH is —O-cycloalkyl-COH claim 11 , —O—CH-cycloalkyl-COH claim 11 , —O-cycloalkyl-CH—COH claim 11 , or —O—CH-cycloalkyl-CH—COH claim 11 , and for each of the preceding moieties -cycloalkyl- is:1,2-cyclopropyl (cis or trans); or1,3-cyclobutyl (cis or trans) or 1,2-cyclobutyl (cis or trans); or1,3-cyclopentyl (cis or trans) or 1,2-cyclopentyl (cis or trans); or1,4-cyclohexyl (cis or trans), 1,3-cyclohexyl (cis or trans), or 1,2-cyclohexyl (cis or trans).18. The method of claim 11 , wherein the medical ...

Treprostinil derivatives and compositions and uses thereof

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

Treprostinil derivative compounds and methods of using same

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.

TREPROSTINIL DERIVATIVES AND COMPOSITIONS AND USES THEREOF

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension. 124-. (canceled)26. The compound of claim 25 , wherein:{'sup': 6', '3, 'Rin each occurrence independently is hydrogen or R;'}{'sup': '3', 'sub': 1', '6, 'Rin each occurrence independently is C-Calkyl;'}{'sup': 9', '10', '9', '10, 'sub': 1', '6, 'Rand Rin each occurrence independently are C-Calkyl, or Rand Rand the nitrogen atom to which they are connected form a 3- to 6-membered heterocyclic ring;'}j in each occurrence independently is 0 or 1; andt in each occurrence independently is 1 or 2.28. The compound of claim 25 , wherein Ris hydrogen and —ORis derivatized.29. The compound of claim 25 , wherein Ris hydrogen and —ORis derivatized.30. The compound of claim 25 , wherein both —ORand —ORare derivatized claim 25 , optionally with the same group.31. The method of claim 25 , wherein the compound is administered orally.32. The method of claim 25 , wherein the compound is administered parenterally.33. The method of claim 32 , wherein the compound is administered subcutaneously or intravenously.34. The method of claim 25 , wherein the compound is administered topically.35. The method of claim 34 , wherein the compound is administered transdermally or by oral inhalation.37. The method of claim 36 , wherein ring A is cyclopropyl and u is an integer from 0 to 9 or from 0 to 5.39. The method of claim 36 , wherein the compound is administered orally.40. The method of claim 36 , wherein the compound is administered parenterally.41. The method of claim 40 , wherein the compound is administered subcutaneously or intravenously.42. The method of claim 36 , wherein the compound is administered topically.43. The method of claim 42 , wherein the compound is administered transdermally or by oral inhalation. ...

Aminoadamantyl nitrate compounds and their use to treat cns disorders

The present disclosure provides adamantyl compounds having one or more amine groups and one or more nitrate groups. The aminoadamantyl nitrate compounds can be used to treat disorders of the central nervous system, including neurodegenerative and non-neurodegenerative diseases.

TREPROSTINIL DERIVATIVE COMPOUNDS AND METHODS OF USING SAME

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used. 170-. (canceled)72. The compound of claim 71 , wherein Ris Pand Ris H.73. The compound of claim 71 , wherein Ris H and Ris P.74. The compound of claim 71 , wherein Ris Pand Ris P.75. The compound of claim 71 , wherein each of Rto Ris H.76. The compound of claim 71 , wherein at least one of Rto Ris deuterium.77. The compound of claim 71 , wherein Z is —OR.78. The compound of claim 71 , wherein Z is P.79. The compound of claim 71 , wherein Z is —N(R)R.80. The compound of claim 71 , wherein Z is −OH.82. A composition comprising a compound of or a pharmaceutically acceptable salt thereof and at least one other component.83. The composition of claim 82 , which is formulated for transdermal delivery.84. The composition of claim 83 , which is formulated for transdermal delivery with a patch.85. The composition of claim 82 , further comprising at least one solvent.86. A method of treating pulmonary hypertension claim 71 , comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof.87. The method of claim 86 , wherein the pulmonary hypertension is pulmonary arterial hypertension.88. The method of claim 86 , wherein the compound is administered transdermally.89. The method of claim 88 , wherein the compound is administered via a transdermal patch. This application claims priority to U.S. provisional application 61/751,608 filed Jan. 11, 2013 which is incorporated herein by reference in its entirety for all purposes.Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is a disease which can result in death and is ...

Use of neurokinin-1 antagonists as antitussives

The disclosure relates to the use of neurokinin- 1 (NK- 1) antagonists, such as serlopitant, MK-0303 or MK-8478, in alleviating or suppressing cough (including acute, subacute and chronic cough) and urge to cough. The cough can have an unknown cause (idiopathic cough) or can be associated with any type of medical condition, such as a respiratory disorder. The NK- 1 antagonist can be delivered by oral inhalation for more rapid peripheral and central antitussive action. Another antitussive agent in addition to the NK-1 antagonist, such as an NMDA receptor antagonist, can optionally be administered for the treatment of the cough or urge to cough, or the cough-associated medical condition.

Treprostinil derivatives and compositions and uses thereof

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

Treprostinil derivative compounds and methods of using same

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.

Treprostinil derivatives and compositions and uses thereof

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

Dermal and transdermal administration of treprostinil and salts thereof

The present disclosure provides methods, compositions, devices and systems for dermal and transdermal administration of treprostinil or salts thereof, and optionally an additional therapeutic agent. Treprostinil and salts thereof can be dermally or transdermally administered to treat any medical conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

Aminoadamantyl nitrate compounds and their use to treat CNS disorders

The present disclosure provides adamantyl compounds having one or more amine groups and one or more nitrate groups. The aminoadamantyl nitrate compounds can be used to treat disorders of the central nervous system, including neurodegenerative and non- neurodegenerative diseases.

トレプロスチニルおよびその塩の皮膚投与および経皮投与方法

【課題】トレプロスチニルまたはその塩および任意で追加の治療剤を皮膚投与および経皮投与するための方法、組成物、装置、およびシステムを提供する。【解決手段】トレプロスチニルまたはその薬学的に許容される塩、溶媒和物、水和物、包接化合物、もしくは多形体、および１種または複数種の薬学的に許容される賦形剤または担体を含み、トレプロスチニルまたはその塩を対象に経皮送達するように製剤化または構成されている、経皮薬物送達システム(TDS)とする。【選択図】図１

Treprostinil derivative compounds and methods of using same

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.

トレプロスチニル誘導体ならびにその組成物および使用

【課題】トレプロスチニルのプロドラッグとして作用しうるトレプロスチニル誘導体を提供する。【解決手段】式（Ｉ）の化合物、またはその薬学的に許容される塩等。TIFF2024019523000135.tif33128（式中、Ｒ１およびＲ２は独立して、水素、アルキルカルボニル、アルコキシアルキルカルボニル等であり、但し、Ｒ１およびＲ２の両方が水素であることはなく、－ＯＲ１及び－ＯＲ２はいずれも酢酸エステル、安息香酸エステル等を形成しない。）【選択図】なし

Compounds, compositions and methods for treating inflammatory bowel disease

Protein-drug conjugates and variants thereof that treat inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. The protein-drug conjugates (PDC) have a fusion protein having a thioredoxin protein and an IL22 protein or variant/mutein thereof, wherein a drug laquinimod (or derivative thereof) is conjugated to the thioredoxin, and wherein the laquinimod is cleavable from the fusion protein upon being deposited within an intestinal epithelial cell or an intestinal epithelial stem cells.

Treprostinil derivatives and compositions and uses thereof

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

Treprostinil derivatives and compositions and uses thereof

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

Treprostinil derivative compounds and methods of using same

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.

Aminoadamantyl nitrate compounds and their use to treat cns disorders

The present disclosure provides adamantyl compounds having one or more amine groups and one or more nitrate groups. The aminoadamantyl nitrate compounds can be used to treat disorders of the central nervous system, including neurodegenerative and non- neurodegenerative diseases.

Aminoadamantyl nitrate compounds and their use to treat cns disorders

The present disclosure provides adamantyl compounds having one or more amine groups and one or more nitrate groups. The aminoadamantyl nitrate compounds can be used to treat disorders of the central nervous system, including neurodegenerative and non-neurodegenerative diseases.

Oral pyrophosphate for use in reducing calcification

The current invention relates to use of oral pyrophosphate wherein said pyrophosphate is selected from the group consisting of monoarginine pyrophosphate, monolysine pyrophosphate, dipotassium pyrophosphate, bisethanolamine pyrophosphate and bisammonium pyrophosphate for preventing and/or reducing tissue calcification, particularly soft tissue calcification, and/or diseases or disorders characterized by low plasma PPi levels, as, e.g., occurs in chronic kidney disease (CKD), end-stage renal disease (ESRD), N generalized arterial calcification of infancy (GACI), Pseudoxanthoma elasticum (PXE), Arterial Calcification Due to Deficiency of CD73 (ACDC), Ehlers-Danlos syndrome, arteriosclerosis obliterans, venous calcifications, crystal deposition disorders, calcification resulting from neurological disorders, calcinosis universalis, calcinosis circumscripta, scleroderma, dermatomyositis, systemic lupus erythematosus, hyperparathyroidism, neoplasms, milk-alkali syndrome, hypervitaminosis D, tumoral calcinosis, hypophosphatemic rickets, ossification of the posterior longitudinal ligament of the spine, myocardial ischemia, joint calcification, heterotropic ossification of traumatized muscle, angioid streaks, diabetes mellitus type I and II, cardiovascular disorder, calciphylaxis, calciphylaxis secondary to chronic kidney disease, calcific uremic arteriolopathy or atherosclerosis.

Treprostinil derivatives and compositions and uses thereof

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

Treprostinil derivatives and compositions and uses thereof

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

Flavonoid compounds

The present invention relates to compounds, compositions, and methods for treatment of conditions related to mitochondrial function. In various aspects, the present invention comprises administering one or more epicatechin derivatives in an amount effective to stimulate mitochondrial function in cells. The compounds, compositions, and methods described herein provide for reducing infarct size in the heart following permanent ischemia or ischemia/reperfusion event or method for delaying, attenuating or preventing adverse cardiac remodeling, and can assist in prevention of impaired mitochondria biogenesis and thus prevention of the consequences of impaired mitochondrial biogenesis in various diseases and conditions, as well as provide for the active therapy of mitochondrial depletion that may have already occurred.

Treprostinil derivatives and compositions and uses thereof

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

Aminoadamantyl nitrate compounds and their use to treat cns disorders

Aminoadamantyl nitrate compounds and their use to treat CNS disorders

The present disclosure provides adamantyl compounds having one or more amine groups and one or more nitrate groups. The aminoadamantyl nitrate compounds can be used to treat disorders of the central nervous system, including neurodegenerative and non-neurodegenerative diseases.

Treprostinil derivative compounds and methods of using same

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.