Patent Application

App. No. 16/157,225

Abstract

Claims (52)

1 . A method of treating or preventing endothelial dysfunction in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of a compound of the formula:

or a pharmaceutically acceptable salt or tautomer thereof,

wherein the patient has been identified as not having at least one of the following characteristics:

(a) a history of left-sided myocardial disease;

(b) an elevated B-type natriuretic peptide (BNP) level; and

(c) an elevated albumin/creatinine ratio (ACR).

2 - 62 . (canceled)

63 . A method of treating or preventing pulmonary hypertension in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of a compound of the formula:

or a pharmaceutically acceptable salt or tautomer thereof.

64 - 112 . (canceled)

113 . The method of claim 63 , wherein the pulmonary hypertension is pulmonary arterial hypertension.

114 - 172 . (canceled)

173 . A method of treating or preventing a cardiovascular disease in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of a compound of the formula:

or a pharmaceutically acceptable salt or tautomer thereof,

wherein the patient has been identified as not having at least one of the following characteristics:

(a) a history of left-sided myocardial disease;

(b) an elevated B-type natriuretic peptide (BNP) level; and

(c) an elevated albumin/creatinine ratio (ACR).

174 . The method of claim 173 , wherein the cardiovascular disease is atherosclerosis, restenosis, or thrombosis.

175 - 272 . (canceled)

273 . A method of treating or preventing chronic kidney disease in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of a compound of the formula:

or a pharmaceutically acceptable salt or tautomer thereof,

wherein the patient has been identified as not having at least one of the following characteristics:

(a) a history of left-sided myocardial disease;

(b) an elevated B-type natriuretic peptide (BNP) level; and

(c) an elevated albumin/creatinine ratio (ACR).

274 . The method of claim 273 , wherein the patient does not have stage 4 CKD.

275 . The method of claim 273 , wherein the patient does not have a history of left-sided myocardial disease.

276 . The method of claim 273 , wherein the patient does not have a history of heart failure.

277 . The method of claim 273 , wherein the patient does not have an elevated BNP level.

278 . The method of claim 277 , wherein the patient does not have a BNP level greater than 200 pg/mL.

279 . The method of claim 273 , wherein the patient does not have an elevated ACR.

280 . The method of claim 279 , wherein the patient does not have an ACR greater than 300 mg/g.

281 . The method of claim 273 , wherein the patient's estimated glomerular filtration rate (eGFR) is greater than or equal to 30 mL/min/1.73 m 2 .

282 . The method of claim 281 , wherein the patient's eGFR is greater than or equal to 45 mL/min/1.73 m 2 .

283 . The method of claim 282 , wherein the patient's eGFR is greater than or equal to 60 mL/min/1.73 m 2 .

284 . The method of claim 273 , wherein at least a portion of the compound is present as an amorphous form having an X-ray diffraction pattern (CuKα) with a halo peak at approximately 13.5° 2θ, substantially as shown in FIG. 1C , and a transition glass temperature (T g ).

285 . The method of claim 284 , wherein the T g value is in the range of about 120° C. to about 135° C.

286 . The method of claim 285 , wherein the T g value is in the range of about 125° C. to about 130° C.

287 . The method of claim 273 , wherein the pharmaceutically effective amount is a daily dose from about 0.1 mg to about 300 mg of the compound.

288 . The method of claim 287 , wherein the daily dose is from about 0.5 mg to about 200 mg of the compound.

289 . The method of claim 273 , wherein the compound is administered orally, intraarterially or intravenously.

290 . The method of claim 273 , wherein the compound is formulated as a hard or soft capsule or a tablet.

291 . The method of claim 273 , wherein the compound is formulated as a solid dispersion comprising (i) the compound and (ii) an excipient.

292 . The method of claim 291 , wherein the excipient is a methacrylic acid ethyl acrylate copolymer.

293 . The method of claim 292 , wherein the copolymer comprises methacrylic acid and ethyl acrylate at a 1:1 ratio.

294 . A method for treating or preventing a disorder for which endothelial dysfunction is a significant contributing factor in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of a compound of the formula:

or a pharmaceutically acceptable salt or tautomer thereof,

wherein the patient has been identified as not having at least one of the following characteristics:

(a) a history of left-sided myocardial disease;

(b) an elevated B-type natriuretic peptide (BNP) level; and

(c) an elevated albumin/creatinine ratio (ACR).

Assignments (8)