PYRROLOPYRIDAZINES AS POTASSIUM ION CHANNEL INHIBITORS

A compound of formula (I) wherein A, R 1 , R 3 , and R 24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment of arrhythmia, I Kur -associated disorders, and other disorders mediated by ion channel function.

CYCLOALKYL INHIBITORS OF POTASSIUM CHANNEL FUNCTION

Novel cycloalkyl compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1 subfamily of voltage gated K+ channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K+ current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.

Quinazolines as potassium ion channel inhibitors

A compound of formula I wherein A, X, Y, Z, R1and R24are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

QUINAZOLINES AS POTASSIUM ION CHANNEL INHIBITORS

A compound of formula I 2. A pharmaceutical composition comprising a therapeutically effective amount of the compound of or salt thereof.3. The pharmaceutical composition of claim 2 , further comprising at least one other therapeutic agent claim 2 , wherein the other therapeutic agent is selected from anti-arrhythmic agents claim 2 , calcium channel blockers claim 2 , anti-platelet agents claim 2 , anti-hypertensive agents claim 2 , anti thrombotic/anti thrombolytic agents claim 2 , anti-coagulants claim 2 , HMG-CoA reductase inhibitors claim 2 , anti diabetic agents claim 2 , thyroid mimetics claim 2 , mineralocorticoid receptor antagonists claim 2 , and cardiac glycosides.4. A method of treating arrhythmia comprising administering to a patient in need thereof an effective amount of the compound of .5. A method of controlling heart rate comprising administering to a patient in need thereof an effective amount of the compound of .7. A pharmaceutical composition comprising a therapeutically effective amount of the compound of or salt thereof.8. The pharmaceutical composition of claim 7 , further comprising at least one other therapeutic agent claim 7 , wherein the other therapeutic agent is selected from anti-arrhythmic agents claim 7 , calcium channel blockers claim 7 , anti-platelet agents claim 7 , anti-hypertensive agents claim 7 , anti thrombotic/anti thrombolytic agents claim 7 , anti-coagulants claim 7 , HMG-CoA reductase inhibitors claim 7 , anti diabetic agents claim 7 , thyroid mimetics claim 7 , mineralocorticoid receptor antagonists claim 7 , and cardiac glycosides.9. A method of treating arrhythmia comprising administering to a patient in need thereof an effective amount of the compound of .10. A method of controlling heart rate comprising administering to a patient in need thereof an effective amount of the compound of .12. A pharmaceutical composition comprising a therapeutically effective amount of the compound of or salt thereof.13. The ...

Pyrrolinone carboxamide compounds useful as endothelial lipase inhibitors

The present invention provides compounds of Formula (I): (I), as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments.

PYRIDINEDIONE CARBOXAMIDE INHIBITORS OF ENDOTHELIAL LIPASE

The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments.

HETEROCYCLIC CETP INHIBITORS

Compounds of formula Ia and Ib wherein A, B, C and R1 are described herein.

Heterocyclic dihydropyrimidines as potassium channel inhibitors

Pyrrolopyridazines as potassium ion channel inhibitors

A compound of formula (I) wherein A, R 1 , R 3 , and R 24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment of arrhythmia, I Kur -associated disorders, and other disorders mediated by ion channel function.

QUINAZOLINES AS POTASSIUM ION CHANNEL INHIBITORS

A compound of formula I 2. A pharmaceutical composition comprising a therapeutically effective amount of the compound of or salt thereof.3. The pharmaceutical composition of claim 2 , further comprising at least one other therapeutic agent claim 2 , wherein the other therapeutic agent is selected from anti-arrhythmic agents claim 2 , calcium channel blockers claim 2 , anti-platelet agents claim 2 , anti-hypertensive agents claim 2 , anti-thrombotic/anti thrombolytic agents claim 2 , anti-coagulants claim 2 , HMG-CoA reductase inhibitors claim 2 , anti-diabetic agents claim 2 , thyroid mimetics claim 2 , mineralocorticoid receptor antagonists claim 2 , and cardiac glycosides.4. A method of treating arrhythmia comprising administering to a patient in need thereof an effective amount of the compound of .5. A method of controlling heart rate comprising administering to a patient in need thereof an effective amount of the compound of .7. A pharmaceutical composition comprising a therapeutically effective amount of the compound of or salt thereof.8. The pharmaceutical composition of claim 7 , further comprising at least one other therapeutic agent claim 7 , wherein the other therapeutic agent is selected from anti-arrhythmic agents claim 7 , calcium channel blockers claim 7 , anti-platelet agents claim 7 , anti-hypertensive agents claim 7 , anti-thrombotic/anti thrombolytic agents claim 7 , anti-coagulants claim 7 , HMG-CoA reductase inhibitors claim 7 , anti-diabetic agents claim 7 , thyroid mimetics claim 7 , mineralocorticoid receptor antagonists claim 7 , and cardiac glycosides.9. A method of treating arrhythmia comprising administering to a patient in need thereof an effective amount of the compound of .10. A method of controlling heart rate comprising administering to a patient in need thereof an effective amount of the compound of . This application is a continuation of U.S. application Ser. No. 16/243,400, filed Jan. 9, 2019 (allowed), which is a continuation of U ...

2-(benzothiazol-2-yl)-2-cyano-acetamide derivatives and their use as endothelial lipase inhibitors

The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicament.

6-HYDROXY-5-(PHENYL/HETEROARYLSULFONYL)PYRIMIDIN-4(1H)-ONE AS APJ AGONISTS

The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments. 14. A compound according to claim 1 , wherein the compound is selected from the exemplified examples or a stereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt thereof.15. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 , or a stereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt thereof.16. A method of treating cardiovascular diseases claim 15 , comprising administering to a patient in need there of a therapeutically effective amount of the pharmaceutical composition of .17. The method of wherein said cardiovascular diseases are coronary heart disease claim 16 , stroke claim 16 , heart failure claim 16 , systolic heart failure claim 16 , diastolic heart failure claim 16 , diabetic heart failure claim 16 , heart failure with preserved ejection fraction claim 16 , cardiomyopathy claim 16 , myocardial infarction claim 16 , left ventricular dysfunction claim 16 , left ventricular dysfunction after myocardial infarction claim 16 , cardiac hypertrophy claim 16 , myocardial remodeling claim 16 , myocardial remodeling after infarction or after cardiac surgery and valvular heart diseases. This application is entitled to priority pursuant to 35 U.S.C. § 119(e) to U.S. provisional patent application No. 62/349,692, filed Jun. 14, 2016, which is incorporated herein in its entirety.The present invention provides novel phenylsulfonyl- or heteroarylsulfonyl-substituted pyrimidine compounds, and their analogues thereof, which are APJ agonists, compositions containing them, and methods of using them, for example, for the treatment or prophylaxis of heart failure, atherosclerosis, ischemic heart disease and related conditions.Heart ...

Quinazolines as potassium ion channel inhibitors

A compound of formula I wherein A, X, Y, Z, R1and R24are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase

The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments.

Heterocyclic CETP inhibitors

Compounds of formula Ia and Ib wherein A, B, C and R 1 are described herein.

HETEROCYCLIC CETP INHIBITORS

Compounds of formula Ia and Ib wherein A, B, C and R1 are described herein.

Heterocyclic dihydropyrimidine compounds

Novel heterocyclic dihydropyrimidine compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1 subfamily of voltage gated K<+> channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K<+> current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.

Cycloalkyl inhibitors of potassium channel function

Novel cycloalkyl compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1 subfamily of voltage gated K+ channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K+ current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.

HETEROARYLHYDROXYPYRIMIDINONES AS AGONISTS OF THE APJ RECEPTOR

The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments, in particular for treating cardiovascular disorders. 14. A pharmaceutical composition claim 1 , comprising a pharmaceutically acceptable carrier and a compound according to claim 1 , or a stereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt thereof.15. A method of treating cardiovascular diseases claim 14 , comprising administering to a patient in need there of a therapeutically effective amount of the pharmaceutical composition according to .16. The method according to wherein said cardiovascular diseases are coronary heart disease claim 15 , stroke claim 15 , heart failure claim 15 , systolic heart failure claim 15 , diastolic heart failure claim 15 , diabetic heart failure claim 15 , heart failure with preserved ejection fraction claim 15 , cardiomyopathy claim 15 , myocardial infarction claim 15 , left ventricular dysfunction claim 15 , left ventricular dysfunction after myocardial infarction claim 15 , cardiac hypertrophy claim 15 , myocardial remodeling claim 15 , myocardial remodeling after infarction or after cardiac surgery and valvular heart diseases. This application is entitled to priority pursuant to 35 U.S.C. § 119(e) to U.S. provisional patent application No. 62/267,997, filed Dec. 16, 2015, which is incorporated herein in its entirety.The present invention provides substituted heteroarylhydroxypyrimidinones, and their analogues thereof, which are APJ agonists, compositions containing them, and methods of using them, for example, for the treatment or prophylaxis of heart failure, atherosclerosis, ischemic heart disease and related conditions.Heart failure (HF) and related complications constitute major health burden in developed countries with an estimated prevalence of 5,700,000 in the ...

QUINAZOLINES AS POTASSIUM ION CHANNEL INHIBITORS

A compound of formula I 2. A pharmaceutical composition comprising a therapeutically effective amount of the compound of or salt thereof.3. The pharmaceutical composition of claim 2 , further comprising at least one other therapeutic agent claim 2 , wherein the other therapeutic agent is selected from anti-arrhythmic agents claim 2 , calcium channel blockers claim 2 , anti-platelet agents claim 2 , anti-hypertensive agents claim 2 , anti thrombotic/anti thrombolytic agents claim 2 , anti-coagulants claim 2 , HMG-CoA reductase inhibitors claim 2 , anti diabetic agents claim 2 , thyroid mimetics claim 2 , mineralocorticoid receptor antagonists claim 2 , and cardiac glycosides.4. A method of treating arrhythmia comprising administering to a patient in need thereof an effective amount of the compound of .5. A method of controlling heart rate comprising administering to a patient in need thereof an effective amount of the compound of .7. A pharmaceutical composition comprising a therapeutically effective amount of the compound of or salt thereof.8. The pharmaceutical composition of claim 7 , further comprising at least one other therapeutic agent claim 7 , wherein the other therapeutic agent is selected from anti-arrhythmic agents claim 7 , calcium channel blockers claim 7 , anti-platelet agents claim 7 , anti-hypertensive agents claim 7 , anti thrombotic/anti thrombolytic agents claim 7 , anti-coagulants claim 7 , HMG-CoA reductase inhibitors claim 7 , anti diabetic agents claim 7 , thyroid mimetics claim 7 , mineralocorticoid receptor antagonists claim 7 , and cardiac glycosides.9. A method of treating arrhythmia comprising administering to a patient in need thereof an effective amount of the compound of .10. A method of controlling heart rate comprising administering to a patient in need thereof an effective amount of the compound of .12. A pharmaceutical composition comprising a therapeutically effective amount of the compound of or salt thereof.13. The ...

Heterocyclo inhibitors of potassium channel function

Novel heterocyclo compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1 subfamily of voltage gated K+ channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K+ current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.

Quinazolines as potassium ion channel inhibitors

A compound of formula I wherein A, X, Y, Z, R1and R24are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

PYRROLOTRIAZINES AS POTASSIUM ION CHANNEL INHIBITORS

A compound of formula (I), wherein A, R, R, and Rare described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, I-associated disorders, and other disorders mediated by ion channel function. 3. The compound claim 2 , of claim 2 , or salt thereof wherein:{'sup': 13', '14', '14', '14', '14', '14', '14', '14', '14', '14', '14', '14', '14b', '14b', '14', '14', '14', '14', '14', '4', '14', '14a, 'sub': 1-6', '1-6', '1-6', '3-6', '2', '2', 'm', '2', '2', '2', 'm', '2', '2', '2', '2', '2, 'R, at each occurrence, is independently H, —OH, F, Cl, Br, I, Calkyl, Calkoxy, haloCalkyl, Ccycloalkyl, phenyl, a 4- to 12-membered heteroaryl, wherein the heteroaryl is selected from tetrazolyl, —CN, —NO, —(CH)—SOR, —NRSOR, —CONRR, —(CH)—SONRR, —NRCONRR, NRCONRR, —NRCOR, —NRCOR, —COR, or —NRR, wherein the alkyl, cycloalkyl, phenyl, and heteroaryl may be substituted with 0-2 R, and the heteroaryl and heterocyclyl consist of carbon atoms and 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of N, S, or O;'}{'sup': 14', '14a, 'sub': 1-6', '3-6, 'R, at each occurrence, is independently selected from hydrogen, Calkyl, Ccycloalkyl, or phenyl, wherein the alkyl, cycloalkyl, and phenyl, may be substituted with 0-3 R; or'}{'sup': '14b', 'sub': '1-6', "alternatively, two R's are taken together with the atoms to which they are attached to form a cyclic ring, wherein the cyclic ring is morpholinyl, piperidinyl, or piperazinyl, and may be substituted with 0-1 Calkyl; and"}{'sup': '14a', 'sub': 1-6', '1-6', '3-6, 'R, at each occurrence, is independently selected from F, Cl, Br, I, Calkyl, haloCalkyl, phenyl, or Ccycloalkyl.'}4. The compound of claim 3 , or salt thereof wherein:{'sub': 2', 'm', '2', '2', 'n-1', '2', 'n-1', '2', '2', 'n-1', '2, 'sup': 2', '26', '2', '25', '2', '26', '2', '25', '2, 'A is —(CH)—R, —CH(R)—R, —(CH)—O—R, —(CH)—NR—R, —CH(R)—CO—R, or —(CH)—NR—CO—R;'}{'sup': 2', '2a, 'Ris ...

PYRROLINONE CARBOXAMIDE COMPOUNDS USEFUL AS ENDOTHELIAL LIPASE INHIBITORS

The present invention provides compounds of Formula (I): (I), as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments. 3. A compound according to claim 2 , wherein:{'sup': 2', '6, 'Ris OR;'}{'sup': 3', 'a', 'b', 'c, 'sub': 1-6', '2', 'n', '3-6', '2', 'n, 'Ris independently selected from the group consisting of: H, Calkyl substituted with R, —(CH)—Ccycloalkyl substituted with 0-3 R, and —(CH)-phenyl substituted with 0-3 R; and'}{'sup': '4', 'Ris H.'}8. (canceled)14. A compound according to claim 1 , wherein the compound is selected from the exemplified examples claim 1 , or a stereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt thereof.15. A pharmaceutical composition claim 1 , comprising: a pharmaceutically acceptable carrier and a compound of .16. A pharmaceutical composition claim 5 , comprising: a pharmaceutically acceptable carrier and a compound of .17. A pharmaceutical composition claim 11 , comprising: a pharmaceutically acceptable carrier and a compound of . The present application claims priority benefit of U.S. provisional application Ser. No. 61/539,643, filed Sep. 27, 2011, which is incorporated by reference herein.The present invention provides novel pyrrolinone carboxamide compounds and analogues, which are endothelial lipase (EL) inhibitors, compositions containing them, and methods of using them, for example, for the treatment and/or prophylaxis of dyslipidemias and the sequelae thereof.Cardiovascular disease is a major health risk throughout the industrialized world. Atherosclerosis, the most prevalent of cardiovascular diseases, is the principal cause of heart attack, and stroke, and thereby the principal cause of death in the United States.Atherosclerosis is a complex disease involving many cell types and molecular factors (for a detailed review, see Ross, Nature, 362(80):1-809 (1993)). Results from ...

Quinazolines as potassium ion channel inhibitors

A compound of formula I wherein A, X, Y, Z, R 1 and R 24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, I Kur -associated disorders, and other disorders mediated by ion channel function.

Pyrrolinone carboxamide compounds useful as endothelial lipase inhibitors

The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments. The disclosure also provides a novel method of treating diseases or conditions related to the activity of endothelial lipase by use of compounds according to Formula (II): as defined in the specification and compositions comprising any of the compounds.

Heterocyclo inhibitors of potassium channel function

Novel heterocyclo compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1 subfamily of voltage gated K+ channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K+ current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.

Heterocyclic dihydropyrimidine compounds

Novel heterocyclic dihydropyrimidine compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1 subfamily of voltage gated K+ channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K+ current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.

Heterocyclic CETP inhibitors

Compounds of formula Ia and Ib wherein A, B, C and R1 are described herein.

Apelin receptor agonists and methods of use

The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.

2-(BENZOTHIAZOL-2-YL)-2-CYANO-ACETAMIDE DERIVATIVES AND THEIR USE AS ENDOTHELIAL LIPASE INHIBITORS

The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicament. 3. The compound according to claim 1 , wherein Ris phenyl claim 1 , pyridinyl claim 1 , pyrrolidinonyl claim 1 , or pyridinonyl claim 1 , each of which is independently substituted with 0 claim 1 , 1 claim 1 , 2 claim 1 , or 3 R.4. The compound according to claim 1 , wherein{'sup': 3', '7', '7', 'e', '4, 'sub': 2', 'Y', '3-6', '2', 'Y', '2', 'Y, 'Ris —(CH)—CONH(Ccarbocyclyl substituted with 0, 1, or 2 R), —(CH)—CONH(4- to 6-membered heterocyclyl substituted with 0, 1, or 2 R), or —(CH)—CONRR;'}Y is 1 or 2; and{'sup': e', '4', '5, 'Rand R, taken together with the atoms to which they are attached, form a 5- or 6-membered azacyclyl, which is substituted with 0, 1, or 2 R.'}5. The compound according to claim 4 , wherein{'sup': 3', '7', '7', 'e', '4, 'sub': 2', 'Y', '3-6', '2', 'Y', '2', 'Y, 'Ris —(CH)—CONH(Ccycloalkyl substituted with 0, 1, or 2 R), —(CH)—CONH(4- to 6-membered heterocycloalkyl substituted with 0, 1, or 2 R), or —(CH)—CONRR;'}Y is 1; and{'sup': e', '4', '5, 'Rand R, taken together with the atoms to which they are attached, form azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl, each of which is substituted with 0, 1, or 2 R.'}6. The compound according to claim 1 , wherein{'sup': 6', '6', 'g', 'h', 'i, 'sub': 1-6', '1-4', '1-4', '2, 'Ris not present or Ris OH, halogen, Calkyl, Calkoxy, Chaloalkyl, NH, NHR, and —CONRR;'}{'sup': g', 'm', 'p', 'n', 'p, 'sub': 1-4', '2, 'Ris Calkyl, COR, CONHR, or CONRR;'}{'sup': h', 'i', 'h', 'i', 'a', '9, 'sub': 1-4', '1-4', '1-4', '1-4', 'Z, 'Rand Rare independently hydrogen, Calkyl, Calkoxy, Chaloalkyl, Chaloalkoxy; or alternatively, Rand R, taken together with the atoms to which they are attached, form a 5- or 6-membered azacyclyl comprising one or more carbon atoms and 1 to 4 ...

6-HYDROXY-4-OXO-1,4-DIHYDROPYRIMIDINE-5-CARBOXAMIDES AS APJ AGONISTS

The present invention provides compounds of Formula (I): 7. A compound according to claim 1 , or a stereoisomer claim 1 , an enantiomer claim 1 , a diastereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': 1', 'a', 'a', 'a', 'a, 'sub': 2', '3', '3', '3', '2', '3', '2', '3', '3', '2, 'R, at each occurrence, is independently selected from —CHOH, —OCH, —OCH, —OCF, OCHPh, —C(═O)NRR, —NRR, CH, CHCH, CH(CH), and cyclopropyl;'}{'sup': 2', 'e', 'e', 'e, 'sub': 1-4', '3-6', '2', '2', '1-3, 'Ris independently selected from Calkyl substituted with 0-3 R; C2-4 alkenyl, phenyl substituted with 0-3 R, 5- to 6-membered heteroaryl substituted with 0-3 R, Ccycloalkyl, and CHO(CH)CH3;'}{'sup': '3', 'sub': '1-4', 'Ris independently selected from H and Calkyl{'sup': 4', '7', '6', '6', '6', '6, 'sub': 1-4', '2', '2', '1-3', '2', '0-3, 'Ris independently selected from —(CHR)—R, —(CH)1-30R, —(CH)NHR, and —(CH)NHC(═O)R;'}{'sup': 6', '7', '7', '7', '7', '7', '7', '8, 'sub': n', 'n', '3-6', 'n, 'R, at each occurrence, is independently selected from —(CRR)-aryl, —(CRR)—Ccycloalkyl, and —(CRR)-heteroaryl, each substituted with 0-3 R;'}{'sup': '7', 'sub': '1-4', 'R, at each occurrence, is independently selected from H, Calkyl, and aryl;'}{'sup': 8', 'b', 'a', 'a', 'e', 'e', 'e, 'sub': '1-4', 'R, at each occurrence, is independently selected from H, F, Cl, —OR, —NRR, Calkyl substituted with 0-3 R, phenyl substituted with 0-3 R, and heterocyclyl substituted with 0-3 R;'}{'sup': a', 'e', 'e', 'e, 'sub': 1-6', '2', 'n', '2', 'n, 'R, at each occurrence, is independently selected from H, Calkyl substituted with 0-5 R, —(CH)—phenyl substituted with 0-5 R, and —(CH)-heteroaryl substituted with 0-5 R;'}{'sup': b', 'e', 'e', 'e, 'sub': 1-6', '2', 'n', '3-10', '2', 'n, 'R, at each occurrence, is independently selected from H, Calkyl substituted with 0-5 R, —(CH)—Ccarbocyclyl substituted with 0-5 R, and —(CH)-heterocyclyl substituted with 0-5 R ...

QUINAZOLINES AS POTASSIUM ION CHANNEL INHIBITORS

A compound of formula I 2. A pharmaceutical composition comprising a therapeutically effective amount of the compound of or salt thereof.3. The pharmaceutical composition of claim 2 , further comprising at least one other therapeutic agent claim 2 , wherein the other therapeutic agent is selected from anti-arrhythmic agents claim 2 , calcium channel blockers claim 2 , anti-platelet agents claim 2 , anti-hypertensive agents claim 2 , anti thrombotic/anti thrombolytic agents claim 2 , anti-coagulants claim 2 , HMG-CoA reductase inhibitors claim 2 , anti diabetic agents claim 2 , thyroid mimetics claim 2 , mineralocorticoid receptor antagonists claim 2 , and cardiac glycosides.4. A method of treating arrhythmia comprising administering to a patient in need thereof an effective amount of the compound of .5. A method of controlling heart rate comprising administering to a patient in need thereof an effective amount of the compound of .7. A pharmaceutical composition comprising a therapeutically effective amount of the compound of or salt thereof.8. The pharmaceutical composition of claim 7 , further comprising at least one other therapeutic agent claim 7 , wherein the other therapeutic agent is selected from anti-arrhythmic agents claim 7 , calcium channel blockers claim 7 , anti-platelet agents claim 7 , anti-hypertensive agents claim 7 , anti thrombotic/anti thrombolytic agents claim 7 , anti-coagulants claim 7 , HMG-CoA reductase inhibitors claim 7 , anti diabetic agents claim 7 , thyroid mimetics claim 7 , mineralocorticoid receptor antagonists claim 7 , and cardiac glycosides.9. A method of treating arrhythmia comprising administering to a patient in need thereof an effective amount of the compound of .10. A method of controlling heart rate comprising administering to a patient in need thereof an effective amount of the compound of .12. A pharmaceutical composition comprising a therapeutically effective amount of the compound of or salt thereof.13. The ...

Sulfone amide linked benzothiazole inhibitors of endothelial lipase

The present invention provides compounds of Formula (I) as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used medicaments.

ACYCLIC IKUR INHIBITORS

A compound of formula I 2. The compound of claim 1 , wherein Ris a monocylic aryl ring claim 1 , which may be optionally substituted with one or more R's.3. The compound of claim 1 , wherein Ris a monocylic heterocyclic ring claim 1 , which may be optionally substituted with one or more R's.6. The compound of claim 4 , wherein T is O claim 4 , S claim 4 , C═O claim 4 , NRor CR; and U claim 4 , V claim 4 , and W are C(R)p.7. The compound of claim 6 , wherein T is O claim 6 , S claim 6 , C═O or NR.12. The compound of wherein the compound is selected from the group of compounds set forth in the examples.13. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of and a pharmaceutically acceptable vehicle or carrier thereof.14. A method of treating or preventing arrhythmia comprising administering to a patient in need thereof an effective amount of at least one compound of claim 1 , or a stereoisomer or a tautomer or a pharmaceutically acceptable salt thereof15. A method of controlling heart rate comprising administering to a patient in need thereof an effective amount of at least one compound of claim 1 , or a stereoisomer or a tautomer or a pharmaceutically acceptable salt thereof. This application is a Divisional of patent application U.S. Ser. No. 11/518,483 filed Sep. 8, 2006 which claims the benefit of U.S. Provisional Application No. 60/715,679, filed on Sep. 9, 2005, incorporated herein by reference in its entirety.The present invention provides for acyclic compounds useful as inhibitors of potassium channel function (especially inhibitors of the K1 subfamily of voltage gated K channels, more especially inhibitors of K1.5 (which have been linked to the ultra-rapidly activating delayed rectifier K current I), and/or K1.3 channels, and/or K1.1 channels) and to pharmaceutical compositions containing such compounds. The present invention further provides for methods of using such compounds in the treatment and prevention ...

Acyclic IKur inhibitors

A compound of formula I wherein R1, R2, R3, R4 and R5 are described herein.

Potassium channel inhibitors and method

Indanes, benzopyrans and analogues thereof are potassium channel inhibitors and blockers of IKur and have the structure where A, B, D, Q, X1, R, R1, X2 and R2 are as defined herein. These compounds are useful as antiarrhythmic agents. In addition, a method is provided for preventing cardiac arrhythmia employing the above compounds.

PYRROLINONE CARBOXAMIDE COMPOUNDS USEFUL AS ENDOTHELIAL LIPASE INHIBITORS

The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments. The disclosure also provides a novel method of treating diseases or conditions related to the activity of endothelial lipase by use of compounds according to Formula (II): as defined in the specification and compositions comprising any of the compounds. 2. A compound according claim 1 , wherein:{'sub': 2', '2', '2', '2', '3', '2', '4', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '4', '3', '2', '2', '2', '2', '2', '2, 'L is —CH—, —(CH)—, —(CH)—, —(CH)—, —(CH)CH(Me)—, —(CH)CH(Et)-, —(CH)CH(i-Pr)—, —(CH)CH(Ph)-, —O(CH)—, —O(CH)—, —O(CH)—, —OCH(CH)CH—, —O(CH)CH(Me)—, and —CH—O—(CH)—.'}5. A pharmaceutical composition claim 1 , comprising: a pharmaceutically acceptable carrier and a compound of .6. A pharmaceutical composition claim 2 , comprising: a pharmaceutically acceptable carrier and a compound of .7. A pharmaceutical composition claim 3 , comprising: a pharmaceutically acceptable carrier and a compound of .8. A pharmaceutical composition claim 4 , comprising: a pharmaceutically acceptable carrier and a compound of . The present application claims priority benefit of U.S. provisional application Ser. No. 61/539,633, filed Sep. 27, 2011, which is incorporated by reference herein.The present invention provides novel pyrrolinone carboxamide compounds and analogues, which are endothelial lipase (EL) inhibitors, compositions containing them, and methods of using them, for example, for the treatment and/or prophylaxis of dyslipidemias and the sequelae thereof.Cardiovascular disease is a major health risk throughout the industrialized world. Atherosclerosis, the most prevalent of cardiovascular diseases, is the principal cause of heart attack, and stroke, and thereby the principal cause of death in the United States. ...

Heterocyclo inhibitors of potassium channel function

Novel heterocyclo compounds useful as inhibitors of potassium channel function (especially inhibitors of the K_v1 subfamily of voltage gated K⁺ channels, especially inhibitors K_v1.5 which has been linked to the ultra-rapidly activating delayed rectifier K⁺ current I_Kur), methods of using such compounds in the prevention and treatment of arrhythmia and I_Kur-associated conditions, and pharmaceutical compositions containing such compounds.

QUINAZOLINES AS POTASSIUM ION CHANNEL INHIBITORS

A compound of formula I 6. The compound claim 1 , enantiomer claim 1 , diastereomer claim 1 , tautomer claim 1 , or salt thereof claim 1 , of claim 1 , wherein X and Y are H.7. The compound claim 1 , enantiomer claim 1 , diastereomer claim 1 , tautomer claim 1 , or salt thereof claim 1 , of claim 1 , wherein X claim 1 , Y and Z are H.8. The compound claim 1 , enantiomer claim 1 , diastereomer claim 1 , tautomer claim 1 , or salt thereof claim 1 , of claim 1 , wherein Ris F claim 1 , Cl claim 1 , Br or I.9. The compound claim 1 , enantiomer claim 1 , diastereomer claim 1 , tautomer claim 1 , or salt thereof claim 1 , of claim 1 , wherein Ris Cl.10. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of .11. The pharmaceutical composition of claim 10 , further comprising at least one other therapeutic agent.12. A method of treating or preventing arrhythmia comprising administering to a patient in need thereof an effective amount of at least one compound of .13. A method of controlling heart rate comprising administering to a patient in need thereof an effective amount of at least one compound of .14. A method of treating an I-associated condition comprising administering to a patient in need thereof an effective amount of at least one compound of . This application is a continuation of U.S. application Ser. No. 13/393,328 filed Feb. 29, 2012, which was the National Stage of International Application No. PCT/US2010/047430, filed on Sep. 1, 2010, which claims the benefit of U.S. Provisional Application No. 61/239,452, filed on Sep. 3, 2009, each incorporated herein by reference in its entirety.The present invention provides for quinazolines useful as inhibitors of potassium channel function (especially inhibitors of the K1 subfamily of voltage gated K channels, more especially inhibitors of K1.5 (which have been linked to the ultra-rapidly activating delayed rectifier K current I), and/or K1.3 channels, and/or K1.1 ...

Heterocyclic dihydropyrimidine compounds

Novel heterocyclic dihydropyrimidine compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1 subfamily of voltage gated K+ channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K+ current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.

Acyclic Ikur inhibitors

A compound of formula I wherein R1, R2, R3, R4 and R5 are described herein.

Phthalazines as potassium ion channel inhibitors

A compound of formula (I) wherein A, R1, R3, and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

6-hydroxy-4-oxo-1,4-dihydropyrimidine-5-carboxamides as APJ agonists

The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.

Quinazolines as potassium ion channel inhibitors

A compound of formula I wherein A, X, Y, Z, R1and R24are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

2,4-DIHYDROXY-NICOTINAMIDES AS APJ AGONISTS

The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, O and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments. 7. A compound according to claim 3 , or a stereoisomer claim 3 , an enantiomer claim 3 , a diastereoisomer claim 3 , a tautomer claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein:{'sup': 1', 'a', 'a', 'a', 'a, 'sub': 2', '3', '3', '2', '3', '2', '3', '3', '2, 'Ris independently selected from: —CHOH, —OCH, —OCF, OCHPh, —C(═O)NRR, —NRR, CH, CHCH, CH(CH), and cyclopropyl;'}{'sup': 2', 'e', 'e', 'e, 'sub': 1-5', '1-5', '3-6', '2', '2', '1-3', '3, 'Ris independently selected from: Calkyl substituted with 0-3 R; Calkenyl, phenyl substituted with 0-3 R, 6-membered heteroaryl substituted with 0-3 R, Ccycloalkyl and CHO(CH)CH;'}{'sup': 3', '4', '6', '6', '6, 'sub': 1-5', '2', 'n', '3-6', '2', 'n, 'Rand Rare independently selected from: Calkyl substituted with 0-3 R; —(CH)—Ccarbocyclyl substituted with 0-3 R, and —(CH)-heterocyclyl substituted with 0-3 R;'}{'sup': 6', 'b', 'a', 'a', 'a', 'a', 'a', 'b', 'a', 'b', 'a', 'a', 'b', 'a', 'a', 'a', 'a', 'a', 'e', 'e', 'e, 'sub': 2', 'n', '2', 'n', '2', 'n', '2', 'n', '2', 'n', '2', 'n', '2', 'n', '2', 'n', 'p', '2', 'n', 'p', '1-5, 'Ris independently selected from: H, halogen, —(CH)OR, —(CH)NRR, —(CH)C(═O)NRR, —(CH)NRC(═O)R, —(CH)NRC(═O)OR, —(CH)OC(═O)NRR, —(CH)C(═O)OR, (CH)S(O)NRR, —(CH)NRS(O)NRR, Calkyl substituted with 0-3 R, phenyl substituted with 0-3 R, and heterocyclyl substituted with 0-3 R;'}{'sup': a', 'e', 'e', 'e, 'sub': 1-6', '2', 'n', '2', 'n, 'R, at each occurrence, is independently selected from H, Calkyl substituted with 0-5 R, —(CH)-phenyl substituted with 0-5 R, and —(CH)-heteroaryl substituted with 0-5 R;'}{'sup': b', 'e', 'e', 'e, 'sub': 1-6', '2', 'n', '3-10', '2', 'n, 'R, at each occurrence, is independently selected from H, Calkyl substituted with 0 ...

QUINAZOLINES AS POTASSIUM ION CHANNEL INHIBITORS

A compound of formula (I) wherein A, X, Y, Z, Rand Rare described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, Iassociated disorders, and other disorders mediated by ion channel function. 7. The compound claim 6 , enantiomer claim 6 , diastereomer claim 6 , tautomer claim 6 , or salt thereof claim 6 , of claim 6 , wherein:{'sub': 1-10', '1-10', '2', '1', '11', '12, 'X is H, F, Cl, Br, I, Calkoxy, haloCalkyl, —CORor —NRR;'}{'sub': 1-10', '1-10', '2', '11', '11', '12, 'Y is H, F, Cl, Br, I, Calkoxy, haloCalkyl, —CORor —NRR;'}{'sub': 1-10', '1-10', '11', '12, 'Z is H, Cl, Br, I, Calkoxy, haloCalkyl or —NRR;'}{'sub': 11', '12', '1-10', '1-10', '3-10', '6-10', '13, "Rand R, at each occurrence, are independently selected from H, Calkyl, haloCalkyl, Ccycloalkyl, Caryl, a 4- to 12-membered heteroaryl and a 4- to 12-membered heterocyclyl, wherein the alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl may be optionally substituted with one or more R's and the heteroaryl and heterocyclyl consist of carbon atoms and 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of N, S, or O;"}{'sub': 13a', '1-10', '2-10', '1-10', '3-10', '2-12', '6-10', '1-10', '2', 'm', '2', '14', '14', '2', '14', '14', '14', '2', 'm', '14', '2', '14', '2', 'm', '14', '2', '14', '14', '14', '2', '14', '14', '2', '14', '14', '14', '2', '14', '14', '14', '14', '2', '14', '14', '14', '14a, "Ris independently H, —OH, F, Cl, Br, I, Calkyl, Calkoxy, haloCalkyl, Ccycloalkyl, Calkenyl, Caryl, a 4- to 12-membered heteroaryl, a 4- to 12-membered heterocyclyl, a 4- to 12-membered heteroaryl-Calkyl, —CN, —(CH)—SOR, —NRSOR, —CONRR, —(CH)—NRSOR, —(CH)—NRSONRR, —NRSONRR, —CONRR, —NRCONRR, —NRCOR, —CORor —NRR, wherein the alkyl, cycloalkyl, alkenyl, alkoxy, aryl, heteroaryl and heterocyclyl may be optionally substituted with one or more R's and the heteroaryl and heterocyclyl consist of carbon atoms and 1, 2, 3, ...

4-HYDROXY-3-SULFONYLPYRIDIN-2(1H)-ONES AS APJ RECEPTOR AGONISTS

The present invention provides compounds of Formula (I) wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.

HETEROCYCLIC CETP INHIBITORS

Compounds of formula Ia and Ib wherein A, B, C and R1 are described herein.

Heterocyclic dihydropyrimidine compounds

Novel heterocyclic dihydropyrimidine compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1 subfamily of voltage gated K+ channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K+ current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.

SULFONE AMIDE LINKED BENZOTHIAZOLE INHIBITORS OF ENDOTHELIAL LIPASE

The present invention provides compounds of Formula (I) as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used medicaments. 10. A compound according to claim 1 , wherein the compound is selected from any one of Examples 1 to 612 or a stereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt thereof.11. A pharmaceutical composition claim 1 , comprising a pharmaceutically acceptable carrier and a compound according to claim 1 , or a stereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt thereof. The present invention provides novel sulfone amide linked benzothiazole compounds and analogues, which are endothelial lipase (EL) inhibitors, compositions containing them, and methods of using them, for example, for the treatment and/or prophylaxis of dyslipidemias and the sequelae thereof.Cardiovascular disease is a major health risk throughout the industrialized world. Atherosclerosis, the most prevalent of cardiovascular diseases, is the principal cause of heart attack, and stroke, and thereby the principal cause of death in the United States.Atherosclerosis is a complex disease involving many cell types and molecular factors (for a detailed review, see Ross, R., 362(6423):801-809 (1993)). Results from epidemiologic studies have clearly established an inverse relationship between levels of high density lipoprotein (HDL), which transports endogenous cholesterol from tissues to the liver as well as mediating selective cholesteryl ester delivery to steroidogenic tissues, and the risk for atherosclerosis (Gordon, D. J. et al., 321(19):1311-1316 (1989)).The metabolism of HDL is influenced by several members of the phospholipase and triacylglycerol (TG) lipase family of proteins, which hydrolyze triglycerides, phospholipids (PL), and cholesteryl esters (CE), generating fatty acids to facilitate intestinal absorption, energy ...

ISOQUINOLINES AS POTASSIUM ION CHANNEL INHIBITORS

A compound of formula (I) (I) wherein A, R1, R1a, R3 and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

6-hydroxy-5-(phenyl/heteroarylsulfonyl)pyrimidin-4(1H)-one as APJ agonists

The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.

Heterocyclo inhibitors of potassium channel function

Novel heterocyclo compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1 subfamily of voltage gated K+ channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K+ current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.

Heteroarylhydroxypyrimidinones as agonists of the APJ receptor

The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments, in particular for treating cardiovascular disorders.

PYRROLINONE CARBOXAMIDE COMPOUNDS USEFUL AS ENDOTHELIAL LIPASE INHIBITORS

The present invention provides compounds of Formula (I) or Formula (III): 3. A compound according to claim 2 , wherein:{'sup': '1', 'sub': '1-4', 'Ris Calkyl;'}{'sup': '3', 'Ris H;'}{'sup': '5', 'Ris phenyl optionally substituted with one, two, or three halogen atoms;'}{'sup': 8', 'a, 'sub': 1-4', '2', '3', '2', '2', '2', '2', '3', '2', '2, 'Ris selected from the group consisting of: H, Calkyl substituted with 0-1 R, cyclopropyl, phenyl, benzyl, (3,4-diCl-phenyl)-(CH)—, (tetrahydrofuran-2-yl)-CH—, (1-Me-pyrrolidin-2-yl)-(CH)—, (piperidin-1-yl)-(CH)—, and (pyrid-4-yl)-(CH)—; and'}{'sub': 2', '3', '2', '4, 'L is —(CH)— or —(CH)—.'}4. A compound according to claim 2 , wherein:{'sup': '1', 'Ris ethyl;'}{'sup': '3', 'Ris H;'}{'sup': '5', 'Ris 3,4-diCl-phenyl;'}{'sup': '8', 'sub': 2', '3', '2', '2', '2', '3', '2', '2', '3', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2, 'Ris H, methyl, —CHCF, —(CH)OCHCH, —(CH)OCH(CH), cyclopropyl, phenyl, benzyl, (3,4-diCl-phenyl)-(CH)—, (tetrahydrofuran-2-yl)-CH—, (1-Me-pyrrolidin-2-yl)-(CH)—, (piperidin-1-yl)-(CH)—, and (pyrid-4-yl)-(CH)—; and'}{'sub': 2', '3, 'L is —(CH)—.'}6. A compound according to claim 5 , wherein:{'sup': '1', 'sub': '1-4', 'Ris Calkyl;'}{'sup': 5', 'd, 'Ris independently selected from the group consisting of: cyclohexyl, indazolyl, chromanyl, and quinolinyl; and wherein each moiety is substituted with 0-2 R;'}{'sup': '5', 'sub': 3', '2', '2, 'alternatively, Ris phenyl substituted with OCFor SONH; and'}{'sub': 2', '3', '2', '4, 'L is independently —(CH)—, or —(CH)—.'}7. A compound according to claim 5 , wherein:{'sup': 1', 'a', 'a', 'c', 'f', 'b', 'e', 'c, 'sub': 1-6', '2-6', '2', '2', 'n', '3-6', '2', 'n', '2', 'm', '2', 'n', '2', 'n', 'p, 'Ris independently selected from the group consisting of: H, Calkyl substituted with 0-3 R, Calkenyl substituted with 0-3 R, —SO(phenyl), —(CH)—(Ccycloalkyl substituted with 0-3 R), —(CH)(CHR)(CH)-phenyl, —(CH)-(phenyl substituted with 0-3 R), and —(CH)-(5- to 6-membered ...

6-hydroxy-4-oxo-1,4-dihydropyrimidine-5-carboxamides as APJ agonists

The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.

Heterocyclic dihydropyrimidine compounds

Novel heterocyclic dihydropyrimidine compounds useful as inhibitors of potassium channel function (especially inhibitors of the K v 1 subfamily of voltage gated K + channels, especially inhibitors K v 1.5 which has been linked to the ultra-rapidly activating delayed rectifier K + current I Kur ), methods of using such compounds in the prevention and treatment of arrhythmia and I Kur -associated conditions, and pharmaceutical compositions containing such compounds.

Acyclic IKur inhibitors

A compound of formula I wherein R1, R2, R3, R4 and R5 are described herein.

Pyrrolotriazines as potassium ion channel inhibitors

A compound of formula (I), wherein A, R1, R3, and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

HETEROCYCLIC CETP INHIBITORS

Compounds of formula Ia and Ib wherein A, B, C and R1 are described herein.

Heterocyclic CETP inhibitors

Compounds of formula Ia and Ib wherein A, B, C and R 1 are described herein.

Potassium channel inhibitors and method

Indanes, benzopyrans and analogues thereof are potassium channel inhibitors and blockers of IKur and have the structure where A, B, D, Q, X1, R, R1, X2 and R2 are as defined herein. These compounds are useful as antiarrhythmic agents. In addition, a method is provided for preventing cardiac arrhythmia employing the above compounds.

HETEROCYCLO INHIBITORS OF POTASSIUM CHANNEL FUNCTION

Novel heterocyclo compounds useful as inhibitors of potassium channel function (especially inhibitors of the K v 1 subfamily of voltage gated K + channels, especially inhibitors K v 1.5 which has been linked to the ultra-rapidly activating delayed rectifier K + current I Kur ), methods of using such compounds in the prevention and treatment of arrhythmia and I Kur -associated conditions, and pharmaceutical compositions containing such compounds.

Quinazolines as potassium ion channel inhibitors

A compound of formula (I) wherein A, X, Y, Z, R1 and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

2,4-dihydroxy-nicotinamides as APJ agonists

The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.

Pyrrolinone carboxamide compounds useful as endothelial lipase inhibitors

The present invention provides compounds of Formula (I) or Formula (III): as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments.

Sulfonyl containing benzothiazole inhibitors of endothelial lipase

The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments.

Cycloalkyl inhibitors of potassium channel function

Novel cycloalkyl compounds useful as inhibitors of potassium channel function (especially inhibitors of the K_v1 subfamily of voltage gated K⁺ channels, especially inhibitors K_v1.5 which has been linked to the ultra-rapidly activating delayed rectifier K⁺ current I_Kur), methods of using such compounds in the prevention and treatment of arrhythmia and I_Kur-associated conditions, and pharmaceutical compositions containing such compounds.

APELIN RECEPTOR AGONISTS AND METHODS OF USE

The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments. 11. A compound according claim 1 , wherein the compound is selected from the exemplified examples or a stereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt thereof.12. A pharmaceutical composition claim 1 , comprising a pharmaceutically acceptable carrier and a compound of claim 1 , or a stereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt thereof.13. A method of treating cardiovascular diseases claim 12 , comprising administering to a patient in need there of a therapeutically effective amount of the pharmaceutical composition of .14. The method of wherein said cardiovascular diseases are coronary heart disease claim 13 , stroke claim 13 , heart failure claim 13 , systolic heart failure claim 13 , diastolic heart failure claim 13 , diabetic heart failure claim 13 , heart failure with preserved ejection fraction claim 13 , cardiomyopathy claim 13 , myocardial infarction claim 13 , left ventricular dysfunction claim 13 , left ventricular dysfunction after myocardial infarction claim 13 , cardiac hypertrophy claim 13 , myocardial remodeling claim 13 , myocardial remodeling after infarction or after cardiac surgery and valvular heart diseases. This application is entitled to priority pursuant to 35 U.S.C. § 119(e) to U.S. provisional patent application No. 62/263,106, filed Dec. 4, 2015, which is incorporated herein in its entirety.The present invention provides substituted hydroxypyrimidinones, and their analogues thereof, which are APJ agonists, compositions containing them, and methods of using them, for example, for the treatment or prophylaxis of heart failure, atherosclerosis, ischemic heart disease and related conditions.Heart failure (HF) and related complications ...

PHTHALAZINES AS POTASSIUM ION CHANNEL INHIBITORS

A compound of formula (I) 3. The compound claim 2 , of claim 2 , wherein:{'sup': 13', '14', '14', '14', '14', '14', '14', '14', '14', '14', '14', '14', '14b', '14b', '14', '14', '14', '14', '14', '14', '14', '14a, 'sub': 1-6', '1-6', '1-6', '3-6', '2', '2', 'm', '2', '2', '2', 'm', '2', '2', '2', '2', '2, 'R, at each occurrence, is independently H, —OH, F, Cl, Br, I, Calkyl, Calkoxy, haloCalkyl, Ccycloalkyl, phenyl, a 4- to 12-membered heteroaryl, wherein the heteroaryl is selected from tetrazolyl, —CN, —NO, —(CH)—SOR, —NRSOR, —CONRR, —(CH)—SONRR, —NRCONRR, —NRCONRR, —NRCOR, —NRCOR, —COR, or —NRR, wherein the alkyl, cycloalkyl, phenyl, and heteroaryl may be substituted with 0-2 R, and the heteroaryl and heterocyclyl consist of carbon atoms and 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of N, S, or O;'}{'sup': 14', '14a, 'sub': 1-6', '3-6, 'R, at each occurrence, is independently selected from hydrogen, Calkyl, Ccycloalkyl, phenyl, wherein the alkyl, cycloalkyl, and phenyl, may be substituted with 0-3 R; or'}{'sup': '14b', 'sub': '1-6', "alternatively, two R's are taken together with the atoms to which they are attached to form a cyclic ring, wherein the cyclic ring is morpholinyl, piperidinyl, or piperazinyl, and may be substituted with 0-1 Calkyl;"}{'sup': '14a', 'sub': 1-6', '1-6', '3-6, 'R, at each occurrence, is independently selected from F, Cl, Br, I, Calkyl, haloCalkyl, phenyl, Ccycloalkyl.'}4. The compound of claim 3 , wherein:{'sub': 2', 'm', '2', '2', 'n−1', '2', '2', 'n−1', '2', '2', '2', 'n−1', '2, 'sup': 2', '26', '25', '26', '2', '25', '2, 'A is —(CH)—R, —CH(R)—R, —(CH)—O—R, —(CH)—NR—R, —CH(R)—CO—R, or —(CH)—NR—CO—R;'}{'sup': 2', '2a, 'Ris phenyl, pyridinyl, pyrazinyl, pyrimidinyl, piperidinyl, or pyridinone, any of which are substituted with 0-2 R; or'}{'sup': 2a', '14', '14, 'sub': 1-6', '1-6', '2, 'R, at each occurrence, is independently H, —OH, F, Calkyl, Calkoxy, 6-SONRR.'}6. The compound of claim 5 , wherein:{'sup ...

6-HYDROXY-4-OXO-1,4-DIHYDROPYRIMIDINE-5-CARBOXAMIDES AS APJ AGONISTS

The present invention provides compounds of Formula (I): 7. A compound according to claim 1 , or a stereoisomer claim 1 , an enantiomer claim 1 , a diastereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': 1', 'a', 'a', 'a', 'a, 'sub': 2', '3', '3', '3', '2', '3', '2', '3', '3', '2, 'R, at each occurrence, is independently selected from —CHOH, —OCH, —OCH, —OCF, OCHPh, —C(═O)NRR, —NRR, CH, CHCH, CH(CH), and cyclopropyl;'}{'sup': 2', 'e', 'e', 'e, 'sub': 1-4', '2-4', '3-6', '2', '2', '1-3', '3, 'Ris independently selected from Calkyl substituted with 0-3 R; Calkenyl, phenyl substituted with 0-3 R, 5- to 6-membered heteroaryl substituted with 0-3 R, Ccycloalkyl, and CHO(CH)CH;'}{'sup': '3', 'sub': '1-4', 'Ris independently selected from H and Calkyl{'sup': 4', '7', '6', '6', '6', '6, 'sub': 1-4', '2', '1-3', '2', '1-3', '2', '0-3, 'Ris independently selected from —(CHR)—R, —(CH)OR, —(CH)NHR, and —(CH)NHC(═O)R;'}{'sup': 6', '7', '7', '7', '7', '7', '7', '8, 'sub': n', 'n', '3-6', 'n, 'R, at each occurrence, is independently selected from —(CRR)-aryl, —(CRR)—Ccycloalkyl, and —(CRR)-heteroaryl, each substituted with 0-3 R;'}{'sup': '7', 'sub': '1-4', 'R, at each occurrence, is independently selected from H, Calkyl, and aryl;'}{'sup': 8', 'b', 'a', 'a', 'e', 'e', 'e, 'sub': '1-4', 'R, at each occurrence, is independently selected from H, F, Cl, —OR, —NRR, Calkyl substituted with 0-3 R, phenyl substituted with 0-3 R, and heterocyclyl substituted with 0-3 R;'}{'sup': a', 'e', 'e', 'e, 'sub': 1-6', '2', 'n', '2', 'n, 'R, at each occurrence, is independently selected from H, Calkyl substituted with 0-5 R, —(CH)-phenyl substituted with 0-5 R, and —(CH)-heteroaryl substituted with 0-5 R;'}{'sup': b', 'e', 'e', 'e, 'sub': 1-6', '2', 'n', '3-10', '2', 'n, 'R, at each occurrence, is independently selected from H, Calkyl substituted with 0-5 R, —(CH)—Ccarbocyclyl substituted with 0-5 R, and —(CH)-heterocyclyl substituted ...

Cycloalkyl inhibitors of potassium channel function

Novel cycloalkyl compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1 subfamily of voltage gated K+ channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K+ current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.

Heterocyclic CETP inhibitors

Compounds of formula Ia and Ib and wherein A, B, C and R1 are described herein.

SULFONYL CONTAINING BENZOTHIAZOLE INHIBITORS OF ENDOTHELIAL LIPASE

The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments.

Potassium channel inhibitors and method

Indanes, benzopyrans and analogues thereof are potassium channel inhibitors and blockers of IKur and have the structure where A, B, D, Q, X1, R, R1, X2 and R2 are as defined herein. These compounds are useful as antiarrhythmic agents. In addition, a method is provided for preventing cardiac arrhythmia employing the above compounds.

Heterocyclic dihydropyrimidine compounds

Novel heterocyclic dihydropyrimidine compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1 subfamily of voltage gated K+ channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K+ current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.

Isoquinolines as potassium ion channel inhibitors

A compound of formula (I) (I) wherein A, R1, R1a, R3 and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

4-hydroxy-3-sulfonylpyridin-2(1H)-ones as APJ receptor agonists

The present invention provides compounds of Formula (I) wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.

Pyrrolotriazines as potassium ion channel inhibitors

A compound of formula (I) wherein A, R1, R3, and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment of arrhythmia, maintaining normal sinus rhythm, IKur-associated disorders, and other disorders mediated by ion channel function.

AMIDE, UREA OR SULFONE AMIDE LINKED BENZOTHIAZOLE INHIBITORS OF ENDOTHELIAL LIPASE

The present invention provides compounds of Formula (I): 15. A compound selected from the exemplified examples or a stereoisomer , a tautomer , or a pharmaceutically acceptable salt thereof.16. A pharmaceutical composition claim 1 , comprising: a pharmaceutically acceptable carrier and a compound of claim 1 , or a stereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt thereof. The present invention provides novel amide, urea or sulfone amide linked benzothiazole compounds and analogues, which are endothelial lipase (EL) inhibitors, compositions containing them, and methods of using them, for example, for the treatment and/or prophylaxis of dyslipidemias and the sequelae thereof.Cardiovascular disease is a major health risk throughout the industrialized world. Atherosclerosis, the most prevalent of cardiovascular diseases, is the principal cause of heart attack, and stroke, and thereby the principal cause of death in the United States.Atherosclerosis is a complex disease involving many cell types and molecular factors (for a detailed review, see Ross, R., 362(6423):801-809 (1993)). Results from epidemiologic studies have clearly established an inverse relationship between levels of high density lipoprotein (HDL), which transports endogenous cholesterol from tissues to the liver as well as mediating selective cholesteryl ester delivery to steroidogenic tissues, and the risk for atherosclerosis (Gordon, D. J. et al., 321(19):1311-1316 (1989)).The metabolism of HDL is influenced by several members of the phospholipase and triacylglycerol (TG) lipase family of proteins, which hydrolyze triglycerides, phospholipids (PL), and cholesteryl esters (CE), generating fatty acids to facilitate intestinal absorption, energy production, or storage. Of the TG lipases, lipoprotein lipase (LPL) influences the metabolism of HDL cholesterol by hydrolyzing triglycerides in triglyceride-rich lipoproteins, resulting in the transfer of lipids and apolipoproteins ...

PYRROLINONE CARBOXAMIDE COMPOUNDS USEFUL AS ENDOTHELIAL LIPASE INHIBITORS

The present invention provides compounds of Formula (I) or Formula (III): [INSERT CHEMICAL STRUCTURE HERE] (I) [INSERT CHEMICAL STRUCTURE HERE] (III) as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments. 3. A compound according to claim 2 , wherein:{'sup': '1', 'sub': '1-4', 'Ris Calkyl;'}{'sup': '3', 'Ris H;'}{'sup': '5', 'Ris phenyl optionally substituted with one, two, or three halogen atoms;'}{'sup': 8', 'a, 'sub': 1-4', '2', '3', '2', '2', '2', '2', '3', '2', '2, 'Ris selected from the group consisting of: H, Calkyl substituted with 0-1 R, cyclopropyl, phenyl, benzyl, (3,4-diCl-phenyl)-(CH)—, (tetrahydrofuran-2-yl)-CH—, (1-Me-pyrrolidin-2-yl)-(CH)—, (piperidin-1-yl)-(CH)—, and (pyrid-4-yl)-(CH)—; and'}{'sub': 2', '3', '2', '4, 'L is —(CH)— or —(CH)—.'}4. A compound according to claim 2 , wherein:{'sup': '1', 'Ris ethyl;'}{'sup': '3', 'Ris H;'}{'sup': '5', 'Ris 3,4-diCl-phenyl;'}{'sup': '8', 'sub': 2', '3', '2', '2', '2', '3', '2', '2', '3', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2, 'Ris H, methyl, —CHCF, —(CH)OCHCH, —(CH)OCH(CH), cyclopropyl, phenyl, benzyl, (3,4-diCl-phenyl)-(CH)—, (tetrahydrofuran-2-yl)-CH—, (1-Me-pyrrolidin-2-yl)-(CH)—, (piperidin-1-yl)-(CH)—, and (pyrid-4-yl)-(CH)—; and'}{'sub': 2', '3, 'L is —(CH)—.'}6. A compound according to claim 5 , wherein:{'sup': '1', 'sub': '1-4', 'Ris Calkyl;'}{'sup': 5', 'd, 'Ris independently selected from the group consisting of: cyclohexyl, indazolyl, chromanyl, and quinolinyl; and wherein each moiety is substituted with 0-2 R;'}{'sup': '5', 'sub': 3', '2', '2, 'alternatively, Ris phenyl substituted with OCFor SONH; and'}{'sub': 2', '3', '2', '4, 'L is independently —(CH)—, or —(CH)—.'}7. A compound according to claim 5 , wherein:{'sup': 1', 'a', 'a', 'c', 'f', 'b', 'e', 'c, 'sub': 1-6', '2-6', '2', '2', 'r', '3-6', '2', 'n', '2', 'm', '2', 'n', '2', 'n', 'p, 'Ris independently selected ...

PYRROLOTRIAZINES AS POTASSIUM ION CHANNEL INHIBITORS

A compound of formula (I)

KETONE LINKED BENZOTHIAZOLE INHIBITORS OF ENDOTHELIAL LIPASE

The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicament. 8. A compound according to claim 1 , wherein the compound is selected from the exemplified examples or a stereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt thereof.9. A pharmaceutical composition claim 1 , comprising a pharmaceutically acceptable carrier and a compound of claim 1 , or a stereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt thereof. The present invention provides novel ketone linked benzothiazole compounds and analogues, which are endothelial lipase (EL) inhibitors, compositions containing them, and methods of using them, for example, for the treatment and/or prophylaxis of dyslipidemias and the sequelae thereof.Cardiovascular disease is a major health risk throughout the industrialized world. Atherosclerosis, the most prevalent of cardiovascular diseases, is the principal cause of heart attack, and stroke, and thereby the principal cause of death in the United States.Atherosclerosis is a complex disease involving many cell types and molecular factors (for a detailed review, see Ross, R., 362(6423):801-809 (1993)). Results from epidemiologic studies have clearly established an inverse relationship between levels of high density lipoprotein (HDL), which transports endogenous cholesterol from tissues to the liver as well as mediating selective cholesteryl ester delivery to steroidogenic tissues, and the risk for atherosclerosis (Gordon, D. J. et al., 321(19):1311-1316 (1989)).The metabolism of HDL is influenced by several members of the triacylglycerol (TG) lipase family of proteins, which hydrolyze triglycerides, phospholipids, and cholesteryl esters, generating fatty acids to facilitate intestinal absorption, energy production, or storage. Of the TG lipases, ...

Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase

Heteroarylhydroxypyrimidinones as agonists of the apj receptor.

La presente invención proporciona compuestos de la Fórmula (I): (ver Fórmula) en donde todas las variables son como se definen en la descripción, y composiciones que comprenden cualquiera de tales compuestos novedosos. Estos compuestos son agonistas de APJ que se pueden usar como medicamentos.

Heterocyclic dihydropyrimidines as potassium channel inhibitors

Novel heterocyclic dihydropyrimidine compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1 subfamily of voltage gated K+ channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K+ current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur- associated conditions, and pharmaceutical compositions containing such compounds.

Heteroarylhydroxypyrimidinones as agonists of the APJ receptor

The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments, in particular for treating cardiovascular disorders.

6-HYDROXY-4-OXO-1,4-DIHYDROPYRIMIDINE-5-CARBOXAMIDES AS APJ INHIBITORS

Heterocyclic CETP inhibitors

Compounds of formula Ia and Ib wherein A, B, C and R are described herein.

Potassium channel inhibitors and method

Indanes, benzopyrans and analogues thereof are potassium channel inhibitors and blockers of IKur and have structure (I) where A, B, D, Q, X1, R, R1, X2 and R2 are as defined herein. These compounds are useful as antiarrhythmic agents. In addition, a method is provided for preventing cardiac arrythmia employing the above compounds.

QUINAZOLINES AS INHIBITORS OF POTASSIUM ION CHANNELS

REFERIDA A UN COMPUESTO DE FORMULA I, DONDE X ES H, OH, F, Cl, ALQUILO C1-C10, HALOALQUILO C1-C10, ENTRE OTROS; Y ES H, F, Cl, Br, ALQUILO C1-C10, CICLOALQUILO C3-C10, HETEROARILO DE 4-12 MIEMBROS, CN, ENTRE OTROS; Z ES H, Cl, Br, ALQUILO C1-C10, CICLOALQUILO C3-C10, HETEROARILO DE 6-12 MIEMBROS, NO2, ENTRE OTROS; A ES 2-ILMETIL-PIRIDINA, BENZAMIDA, 2-TIAZOL, ENTRE OTROS; R1 ES OH, F, Cl, I, ALQUILO C1-C10, CN, CICLOALQUILO C3-C10, ENTRE OTROS; R24 ES H, CICLOALQUILO C3-C10, ARILO C6-C10, HETEROARILO DE 4-12 MIEMBROS, ENTRE OTROS. SON COMPUESTOS PREFERIDOS: 5-FENIL-N-(PIRIDIN-2-ILMETIL)-2-(PIRIMIDIN-5-IL)QUINAZOLIN-4-AMINA; 5-(5-FENIL-4-(PIRIDIN-2-ILMETILAMINO)QUINAZOLIN-2-IL)NICOTINAMIDA; 4-((5-FENIL-2-(PIRIMIDIN-5-IL)QUINAZOLIN-4-ILAMINO)METIL)BENZAMIDA; ENTRE OTROS. DICHOS COMPUESTOS SON INHIBORES DE LA FUNCION DE LOS CANALES DE POTASIO, UTILES EN EL TRATAMIENTO Y PREVENCION DE ARRITMIA, TRASTONOS ASOCIADOS CON Ikur Y OTROS TRASTORNOS MEDIADOS POR LA FUNCION DE LOS CANALES IONICOS REFERRING TO A COMPOUND OF FORMULA I, WHERE X IS H, OH, F, Cl, C1-C10 ALKYL, C1-C10 HALOALKYL, AMONG OTHERS; Y IS H, F, Cl, Br, C1-C10 ALKYL, C3-C10 CYCLOALKYL, 4-12-MEMBER HETEROARYL, CN, AMONG OTHERS; Z IS H, Cl, Br, C1-C10 ALKYL, C3-C10 CYCLOALKYL, 6-12 MEMBER HETEROARYL, NO2, AMONG OTHERS; A IS 2-ILMETHYL-PYRIDINE, BENZAMIDE, 2-THIAZOLE, AMONG OTHERS; R1 IS OH, F, Cl, I, C1-C10 ALKYL, CN, C3-C10 CYCLOALKYL, AMONG OTHERS; R24 IS H, C3-C10 CYCLOALKYL, C6-C10 ARYL, 4-12 MEMBER HETEROARYL, AMONG OTHERS. PREFERRED COMPOUNDS ARE: 5-PHENYL-N- (PYRIDIN-2-ILMETHYL) -2- (PYRIMIDIN-5-IL) QUINAZOLIN-4-AMINE; 5- (5-PHENYL-4- (PYRIDIN-2-ILMETHYLAMINE) QUINAZOLIN-2-IL) NICOTINAMIDE; 4 - ((5-PHENYL-2- (PYRIMIDIN-5-IL) QUINAZOLIN-4-ILAMINO) METHYL) BENZAMIDE; AMONG OTHERS. SAID COMPOUNDS ARE INHIBITORS OF THE FUNCTION OF POTASSIUM CHANNELS, USEFUL IN THE TREATMENT AND PREVENTION OF ARRHYTHMIA, TRASTONS ASSOCIATED WITH Ikur AND OTHER DISORDERS MEDIATED BY THE FUNCTION OF THE ION CHANNELS

Pyrrolinone carboxamide compounds useful as endothelial lipase inhibitors

The present invention provides compounds of Formula (I): (I), as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments.

Heterocyclic cetp inhibitors

Compounds of formula (Ia) and (Ib) wherein A, B, C and R1 are described herein. The compounds (Ia) and (Ib) are useful as CETP inhibitors.

Homo- and heterocyclic compounds suitable as cetp inhibitors

apelin receptor agonists and methods of use

a presente invenção fornece compostos da fórmula (i): (i) em que todas as variáveis são como definido no relatório descritivo e composições que compreendem qualquer um destes compostos. estes compostos são agonistas de apj que podem ser utilizados como medicamentos. The present invention provides compounds of formula (I): (i) wherein all variables are as defined in the specification and compositions comprising any of these compounds. These compounds are apj agonists which may be used as medicaments.

Quinazolines as potassium ion channel inhibitors

A compound of formula I wherein A, X, Y, Z, R 1 and R 24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, I Kur -associated disorders, and other disorders mediated by ion channel function.

Heterocyclic cetp inhibitors

Quinazolines as potassium ion channel inhibitors

A compound of formula (I) wherein A, X, Y, Z, R and R are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, I-associated disorders, and other disorders mediated by ion channel function.

QUINAZOLINAS AS INHIBITORS OF THE IONIC CHANNELS OF POTASSIUM AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

Los compuestos son utiles como inhibidores de la funcion de los canales de potasio y en el tratamiento y prevencion de arritmia, trastornos asociados con IKur y otros trastornos mediados por la funcion de los canales ionicos. Reivindicacion 1: Un compuesto, caracterizado porque tiene la formula (1) o un enantiomero, diastereomero, tautomero o sales del mismo, en la que: X es H, -OH, F, Cl, Br, I, alquilo C1-10, alcoxi C1-10, haloalquilo C1-10, alquenilo C2-12 alquinilo C2-12, cicloalquilo C3-10, un heteroarilo de 4 a 12 miembros, heterociclilo de 4 a 12 miembros, -CN, -NO2, -NR11SO2R12, -SO2NR11R12, -CONR11R12, -NR11CONR11R12, -NCOR11, -NR11SO2NR11R12, -OCONR11R12, -CO2R11 o -NR11R12; Y es H, F, Cl, Br, I, alquilo C1-10, alcoxi C1-10, haloalquilo C1-10, alquenilo C2-12, alquinilo C2-12, cicloalquilo C3-10, un heteroarilo de 4 a 12 miembros, heterociclilo de 4 a 12 miembros, -CN, -NO2, -SO2NR11R12, -CONR11R12, -NR11CONR11R12, -NCOR11, -NR11SO2NR11R12, -OCONR11R12, -CO2R11 o -NR11R12; Z es H, Cl, Br, I, alquilo C1-10, alcoxi C1-10, haloalquilo C1-10, alquenilo C2-12, alquinilo C2-12, cicloalquilo C3-10, un heteroarilo de 6 a 12 miembros, heterociclilo de 4 a 12 miembros, -NO2, -NR11SO2R12, -SO2NR11R12, -NR11CONR11R12, -NCOR11, -NR11SO2NR11R12, -OCONR11R12, -CO2R11 o -NR11R12; A es -(CH2)m-R2, -CH(R25)(R26), -CH(R26)CO2-R2a o -(CH2)n-1-NR25-CO2-R24; m es 0 a 4; n es 1 a 4; n-1 es 2 a 4; R1 es -OH, F, Cl, Br, I, alquilo C1-10, haloalquilo C1-10, alquenilo C2-12, cicloalquilo C3-10, -CN, -(CH2)n-SO2NR11R12, -(CH2)n-CO2R11 o -(CH2)n-NR11SO2R12, pudiendo estar el alquenilo y cicloalquilo opcionalmente sustituidos con uno o más R13; o R1 se selecciona del grupo de formulas (2); o R1 es el resto de formula (3); R2 es alquilo C1-10, ciclopropilo opcionalmente sustituido con uno o más R13; cicloalquilo C4-10 opcionalmente sustituido con uno o más R13bb; cicloalquenilo C3-10 opcionalmente sustituido con uno o más R13b; o -NR14R14; con la condicion de que R2 no sea -NR14R14 ...

Quinazolines as inhibitors of potassium ion channels

Una composición farmacéutica para administración oral, que comprende un compuesto de fórmulas (Ib) o (Ic) o un enantiómero, un diastereómero, un tautómero o una sal del mismo, y un vehículo o un diluyente farmacéuticamente aceptables: **(Ver fórmula)** en las que: X es H, F, Cl, Br, I, alcoxi C1-10 o haloalquilo C1-10; Y es H, F, Cl, Br, I, alcoxi C1-10 o haloalquilo C1-10; Z es H, Cl, Br, I, alcoxi C1-10 o haloalquilo C1-10; R13a es independientemente H, -OH, F, Cl, Br, I, alquilo C1-10, alcoxi C2-10, haloalquilo C1-10, cicloalquilo C3-10, alquenilo C2-12, arilo C6-10, un heteroarilo de 4 a 12 miembros, un heterociclilo de 4 a 12 miembros, un heteroaril de 4 a 12 miembros-alquilo C1-10, -CN, -(CH2)m-SO2R14, -NR14SO2R14, -CONR14R14, -(CH2)m-NR14SO2R14, -(CH2)n- NR14SO2NR14R14, -CO2R14 o -NR14R14 en donde el alquilo, el cicloalquilo, el alquenilo, el alcoxi, el arilo, el heteroarilo y el heterociclilo pueden estar opcionalmente sustituidos con uno o más R14a y el heteroarilo y el heterociclilo consisten en átomos de carbono y 1, 2, 3 o 4 heteroátomos independientemente seleccionados del grupo que consiste en N, S u O; R13a-2 es independientemente H, -OH, F, Br, I, alquilo C1-10, alcoxi C1-10, haloalquilo C1-10, cicloalquilo C3-10, alquenilo C2-12, arilo C6-10, un heteroarilo de 4 a 12 miembros, un heterociclilo de 4 a 12 miembros, un heteroaril de 4 a 12 miembros-alquilo C1-10, -(CH2)m-SO2R14, -NR14SO2R14, -CONR14R14, -(CH2)m-SO2NR14R14, -(CH2)m-NR14SO2R14, - (CH2)n-NR14SO2NR14R14, -NR14SO2NR14R14, -CO2R14 o -NR14R14, en donde el alquilo, el cicloalquilo, el alquenilo, el alcoxi, el arilo, el heteroarilo y el heterociclilo pueden estar opcionalmente sustituidos con uno o más R14a y el heteroarilo y el heterociclilo consisten en átomos de carbono y 1, 2, 3 o 4 heteroátomos independientemente seleccionados del grupo que consiste en N, S u O; R13b es independientemente H, F, Cl, Br, I, alquilo C1-10, alcoxi C1-10, haloalquilo C1-10, cicloalquilo C3-10, alquenilo C2-12, ...

Quinazolines as potassium ion channel inhibitors

A compound of formula I wherein A, X, Y, Z, R 1 and R 24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, I Kur -associated disorders, and other disorders mediated by ion channel function.

Heterocyclo inhibitors of calcium channel function

Det er beskrevet nye heterosykloforbindelser som er nyttige som inhibitorer av kaliumkanalfunksjonen (spesielt inhibitorer av Kv 1-subfamilien av strømførte K+-kanaler, spesielt inhibitorene Kv 1.5 som er blitt koblet til ultra-hurtig aktiverende forsinket rectifier K+-strøm IKur), fremgangsmåter for anvendelse av slike forbindelser for forebygging og behandling av arytmi og IKur-assosierte tilstander, og farmasøytiske sammensetninger inneholdende slike forbindelser.

Quinazolines as potassium ion channel inhibitors

Compuestos derivados de 2,4-dihidroxi-nicotinamidas, agonistas del receptor de apelina (apj); composicion farmaceutica que los comprende; uso en el tratamiento de enfermedades cardiovasculares.

La presente invención proporciona compuestos de la Fórmula (I), en donde todas las variables son como se definen en la memoria descriptiva, y composiciones que comprenden cualquiera de tales compuestos novedosos. Estos compuestos son agonistas de APJ que se pueden usar como medicamentos. The present invention provides compounds of the Formula (I), wherein all variables are as defined in the specification, and compositions comprising any such novel compounds. These compounds are APJ agonists that can be used as medications.

Quinazolines as potassium ion channel inhibitors

apelin receptor agonists and methods of use

a presente invenção fornece compostos da fórmula (i): (i) em que todas as variáveis são como definido no relatório descritivo e composições que compreendem qualquer um destes compostos. estes compostos são agonistas de apj que podem ser utilizados como medicamentos.

BENZOTIAZOLES LINKED TO AMIDA, UREA OR SULFONAMIDE AS INHIBITORS OF THE ENDOTELIAL LIPASE

Composición farmacéutica. Reivindicación 1: Un compuesto caracterizado por la fórmula (1), o un estereoisómero, un tautómero o una sal de aquel aceptable desde el punto de vista farmacéutico, en donde: R¹ se selecciona independientemente de halógeno, CN, CO₂(alquilo C₁₋₄), -CO-Rʲ, -CONH-(CH₂)ₘ-Rʲ, un resto del grupo de fórmulas (2), (fenilo sustituido con 0 - 3 Rᵃ) y (un heteroarilo de 5 a 6 miembros que comprende átomos de carbono y 1 - 4 heteroátomos seleccionados de N, NRᶜ, O y S(O)ₚ; en donde el heteroarilo se sustituye con 0 - 3 Rᵃ); R² se selecciona independientemente, en cada caso, de halógeno, OH, alquilo C₁₋₄, alcoxi C₁₋₄, haloalquilo C₁₋₄, haloalcoxi C₁₋₄, CN, NH₂, NO₂, NH(alquilo C₁₋₄), N(alquilo C₁₋₄)₂, CO₂H, CO₂(alquilo C₁₋₄) y CONH₂; R³ se selecciona independientemente de: -SO₂R⁵ y -NHCOR⁶; R⁴ se selecciona independientemente de: los restos de fórmula (3) y (4); R⁵ se selecciona independientemente de: alquilo C₁₋₆ sustituido con 0 - 1 R⁹, alquenilo C₂₋₆, haloalquilo C₁₋₆, alcoxi C₁₋₆, -(CH₂)ₘ-(O)ₙ-(carbociclo C₃₋₆ sustituido con 0 - 3 Rᵇ) y -(CH₂)ₘ-(O)ₙ-(heterociclo de 5 a 6 miembros que comprende átomos de carbono y 1 - 4 heteroátomos seleccionados de N, NRᶜ, O y S(O)ₚ; en donde el heterociclo se sustituye con 0 - 2 Rᵇ); R⁶ se selecciona independientemente de: alquilo C₁₋₆, alquenilo C₂₋₆, alcoxi C₁₋₆, haloalquilo C₁₋₄, -(CH₂)ₘ-(carbociclo C₃₋₆ sustituido con 0 - 3 Rᵇ), -(CH₂)ₘ-(piridilo sustituido con 0 - 2 Rᵇ), -NH(alquilo C₁₋₄), -NHCH₂CO₂(alquilo C₁₋₄), -NH(4-halo-Ph), -NHBn y un resto de fórmula (5); R⁷ se selecciona independientemente de: CONH₂, CONH(alquilo C₁₋₄), CON(alquilo C₁₋₄)₂, SO₂NHSO₂(alquilo C₁₋₄), SO₂NH(CH₂)₂₋₄CO₂(alquilo C₁₋₄), NHSO₂NH₂, NHSO₂(alquilo C₁₋₄), N(alquilo C₁₋₄)SO₂NH₂, N(CO₂-alquilo C₁₋₄)SO₂(alquilo C₁₋₄), SO₂R¹⁰ y el resto de fórmula (6); R⁸ se selecciona independientemente de: el grupo de fórmulas (7), fenilo y un heteroarilo de 5 a 6 miembros que comprende átomos de carbono y 1 - 4 heteroátomos seleccionados de N, NRᶜ, ...

Heterocyclic dihydropyrimidine compounds

NOVEL HETEROCYCLIC DIHYDROPYRIMIDINE COMPOUNDS USEFUL AS INHIBITORS OF POTASSIUM CHANNEL FUNCTION (ESPECIALLY INHIBITORS OF THE Kv1 SUBFAMILY OF VOLTAGE GATED K⁺ CHANNELS, ESPECIALLY INHIBITORS Kv1.5 WHICH HAS BEEN LINKED TO THE ULTRA-RAPIDLY ACTIVATING DELAYED RECTIFIER K+ CURRENT Ikur), METHODS OF USING SUCH COMPOUNDS IN THE PREVENTION AND TREATMENT OF ARRHYTHMIA AND Ikur-ASSOCIATED CONDITIONS, AND PHARMACEUTICAL COMPOSITIONS CONTAINING SUCH COMPOUNDS.

Heteroarylhydroxypyrimidinones as apeline receptor agonists (apj)

LA PRESENTE INVENCIÓN PROPORCIONA COMPUESTOS DE LA FÓRMULA (I), EN DONDE TODAS LAS VARIABLES SON COMO SE DEFINEN EN LA MEMORIA DESCRIPTIVA, Y COMPOSICIONES QUE COMPRENDEN CUALQUIERA DE TALES COMPUESTOS NOVEDOSOS. ESTOS COMPUESTOS SON AGONISTAS DE APJ QUE SE PUEDEN USAR COMO MEDICAMENTOS, EN PARTICULAR PARA EL TRATAMIENTO DE TRASTORNOS CARDIOVASCULARES. THE PRESENT INVENTION PROVIDES COMPOUNDS OF THE FORMULA (I), WHERE ALL THE VARIABLES ARE AS DEFINED IN THE DESCRIPTIVE MEMORY, AND COMPOSITIONS THAT INCLUDE ANY OF SUCH NOVELTY COMPOUNDS. THESE COMPOUNDS ARE APJ AGONISTS THAT CAN BE USED AS MEDICINES, IN PARTICULAR FOR THE TREATMENT OF CARDIOVASCULAR DISORDERS.

Cycloalkyl inhibitors of potassium channel function

Novel cycloalkyl compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1subfamily of voltage gated K+ channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K+ current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.

Sulfone amide linked benzothiazole inhibitors of endothelial lipase

The present invention provides compounds of Formula (I) as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used medicaments.

2,4-dihydroxy-nicotinamides as APJ agonists

The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.

Heterocyclo inhibitors of potassium channel function

Novel heterocyclo compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1 subfamily of voltage gated K+ channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K+ current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.

6-hydroxy-4-oxo-1,4-dihydropyrimidine-5-carboxamides as apj agonists

Heteroarylhydroxypyrimidinones as agonists of the apj receptor

The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments, in particular for treating cardiovascular disorders.

6-hydroxy-4-oxo-1,4-dihydropyrimidine-5-carboxamides as apj agonists

Cycloalkyl inhibitors of potassium channel function

Heterocyclo inhibitors of potassium channel function

Novel heterocyclo compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1 subfamily of voltage gated K+ channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K+ current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.

Heterocyclische dihydropyrimidine als kaliumkanalhemmer

Agonistas de rxfp1

La descripción se refiere a compuestos de la fórmula (1), que son agonistas del receptor RXFP1, composiciones que los contienen y métodos para usarlos, por ejemplo, en el tratamiento de insuficiencia cardíaca, enfermedades fibróticas y enfermedades relacionadas, tales como enfermedad pulmonar (p. ej., fibrosis pulmonar idiopática), enfermedad renal (p. ej., enfermedad renal crónica) o enfermedad hepática (p. ej., esteatohepatitis no alcohólica e hipertensión portal). Reivindicación 18: Una composición farmacéutica caracterizada porque comprende un compuesto de la reivindicación 1 o una sal farmacéuticamente aceptable del mismo y un vehículo farmacéuticamente aceptable. Reivindicación 19: Un método para tratar una enfermedad asociada a relaxina caracterizado porque comprende administrar una cantidad terapéuticamente efectiva de la composición farmacéutica de la reivindicación 18 a un paciente que lo necesite.

Sulfonyl containing benzothiazole inhibitors of endothelial lipase

The present invention provides compounds of Formula (I) as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments.

Rxfp1 agonists

The disclosure relates to compounds of Formula (I), which are RXFP1 receptor agonists, compositions containing them, and methods of using them, for example, in the treatment of heart failure, fibrotic diseases, and related diseases such as lung disease (e.g., idiopathic pulmonary fibrosis), kidney disease (e.g., chronic kidney disease), or hepatic disease (e.g., non-alcoholic steatohepatitis and portal hypertension).

Compounds and methods useful for stabilizing phenylalanine hydroxylase mutations

The disclosure relates to compounds of Formula I or a pharmaceutically acceptable salt thereof, wherein, m, R 1 -R 5 , R 5A , and L are defined herein. These compounds are useful in methods for stabilizing a mutant PAH protein or reducing blood phenylalanine concentration in a subject suffering from phenylketonuria. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, or V388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation.

Als cetp-hemmer geeignete homo- und heterocyclische verbindungen

Quinazolines as potassium ion channel inhibitors

A compound of formula Iwherein A, X, Y, Z, R1 and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

Heterocyclo-hemmer der kaliumkanalfunktion

Pyrrolotriazines as potassium ion channel inhibitors

A compound of formula (I), wherein A, R1, R3, and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

Compounds and methods useful for stabilizing phenylalanine hydroxylase mutations

The disclosure relates to compounds of Formula I or a pharmaceutically acceptable salt thereof, wherein, m, R1-R5, R5A, and L are defined herein. These compounds are useful in methods for stabilizing a mutant PAH protein or reducing blood phenylalanine concentration in a subject suffering from phenylketonuria. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, or V388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation.

Rxfp1 agonists

The disclosure relates to compounds of Formula (I), which are RXFP1 receptor agonists, compositions containing them, and methods of using them, for example, in the treatment of heart failure, fibrotic diseases, and related diseases such as lung disease (e.g., idiopathic pulmonary fibrosis), kidney disease (e.g., chronic kidney disease), or hepatic disease (e.g., non-alcoholic steatohepatitis and portal hypertension).

Agonistas de rxfp1

La descripción se refiere a compuestos de la Fórmula (I), que son agonistas del receptor RXFP1, composiciones que los contienen y métodos para usarlos, por ejemplo, en el tratamiento de insuficiencia cardíaca, enfermedades fibróticas y enfermedades relacionadas, tales como enfermedad pulmonar (p. ej., fibrosis pulmonar idiopática), enfermedad renal (p. ej., enfermedad renal crónica) o enfermedad hepática (p. ej., esteatohepatitis no alcohólica e hipertensión portal). (I)

Compounds and methods useful for stabilizing phenylalanine hydroxylase mutations

The disclosure relates to compounds of Formula I or a pharmaceutically acceptable salt thereof, wherein, m, R1-R5, R5A, and L are defined herein.These compounds are useful in methods for stabilizing a mutant PAH protein or reducing blood phenylalanine concentration in a subject suffering from phenylketonuria. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, or V388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation.

Compounds and methods useful for stabilizing phenylalanine hydroxylase mutations

The disclosure relates to compounds of Formula I or a pharmaceutically acceptable salt thereof, wherein, m, R 1 -R 5 , R 5A , and L are defined herein. These compounds are useful in methods for stabilizing a mutant PAH protein or reducing blood phenylalanine concentration in a subject suffering from phenylketonuria. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, or V388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation.

Rxfp1 agonists

Compuestos y métodos útiles para estabilizar mutaciones de fenilalanina hidroxilasa

La divulgación se refiere a compuestos de fórmula (1) o una sal farmacéuticamente aceptable de estos, en donde, m, R¹ - R⁵, R⁵A y L se definen en el presente documento. Estos compuestos son útiles en métodos para estabilizar una proteína PAH mutante o reducir la concentración de fenilalanina en sangre en un sujeto que padece fenilcetonuria. En algunas realizaciones, la proteína PAH mutante contiene al menos una mutación R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, o V388M. En otras realizaciones, la proteína PAH mutante contiene al menos una mutación R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, o L48S.

Κιναζολινες ως αναστολεις διαυλων ιοντων καλιου

Φαρμακευτικές συνθέσεις για εκ του στόματος χορήγηση που περιλαμβάνουν μία ένωση του χημικού τύπου (Ib) ή (Ic) ή ένα εναντιομερές, διαστερεομερές, ταυτομερές, ή άλας εξ αυτής, και μία φαρμακευτικώς αποδεκτή ουσία-όχημα ή αραιωτικό:

Pyridinedione carboxamide inhibitors of endothelial lipase

The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments.

Phthalazines as potassium ion channel inhibitors

A compound of formula (I), wherein A, R1, R3, and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

Potassium channel inhibitors and method

Rxfp1 agonists

The disclosure relates to compounds of Formula (I), which are RXFP1 receptor agonists, compositions containing them, and methods of using them, for example, in the treatment of heart failure, fibrotic diseases, and related diseases such as lung disease (e.g., idiopathic pulmonary fibrosis), kidney disease (e.g., chronic kidney disease), or hepatic disease (e.g., non-alcoholic steatohepatitis and portal hypertension).

Agonistas del receptor 1 de peptidos de la familia de la relaxina (rxfp1).

La descripción se refiere a compuestos de la Fórmula (I), que son agonistas del receptor RXFP1, composiciones que los contienen y métodos para usarlos, por ejemplo, en el tratamiento de insuficiencia cardíaca, enfermedades fibróticas y enfermedades relacionadas, tales como enfermedad pulmonar (p. ej., fibrosis pulmonar idiopática), enfermedad renal (p. ej., enfermedad renal crónica) o enfermedad hepática (p. ej., esteatohepatitis no alcohólica e hipertensión portal). (ver Fórmula).

Compuestos y métodos útiles para estabilizar mutaciones de la fenilalanina hidroxilasa

La descripción se relaciona con compuestos de la Fórmula I o una sal farmacéuticamente aceptable de estos, en donde, m, R1 -R5 , R5A y L se definen en la presente descripción. I Estos compuestos son útiles en métodos para estabilizar una proteína PAH mutante o reducir la concentración sanguínea de fenilalanina en un sujeto que padece fenilcetonuria. En algunas modalidades, la proteína PAH mutante contiene al menos un R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, o mutación V388M. En otras modalidades, la proteína PAH mutante contiene al menos un R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, o mutación L48S. Por la presente certifico que el documento adjunto es traducción fiel al idioma español de las partes pertinentes del documento adjunto redactado en idioma inglés al cual me remito en la Ciudad de Buenos Aires a los 11 días del mes de marzo de 2023.

Compounds and methods useful for stabilizing phenylalanine hydroxylase mutations

The disclosure relates to compounds of Formula I or a pharmaceutically acceptable salt thereof, wherein, m, R

Compuestos y métodos útiles para estabilizar mutaciones de la fenilalanina hidroxilasa.

La descripción se relaciona con compuestos de la Fórmula I o una sal farmacéuticamente aceptable de estos, en donde, m, R1 -R5, R5A y L se definen en la presente descripción. (ver formula I) Estos compuestos son útiles en métodos para estabilizar una proteína PAH mutante o reducir la concentración sanguínea de fenilalanina en un sujeto que padece fenilcetonuria. En algunas modalidades, la proteína PAH mutante contiene al menos una mutación R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, o V388M. En otras modalidades, la proteína PAH mutante contiene al menos una mutación R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, o L48S.