sGC STIMULATORS

Abstract

Compounds of Formula IA and Formula IB are described. They are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds may be useful for treating, preventing or managing various disorders that are herein disclosed.

We claim: 
     
         1 - 82 . (canceled) 
     
     
         83 . A method of treating a disease, health condition or disorder in a subject, comprising administering a therapeutically effective amount of a compound of Formula IA or Formula IB, or a pharmaceutically acceptable salt thereof, to the subject in need of the treatment, wherein the disease, health condition or disorder is
 (a) a peripheral or cardiac vascular disorder or health condition selected from:
 pulmonary hypertension, pulmonary arterial hypertension, and associated pulmonary vascular remodeling, localized pulmonary thrombosis, right heart hypertrophy, pulmonary hypertonia, primary pulmonary hypertension, secondary pulmonary hypertension, familial pulmonary hypertension, sporadic pulmonary hypertension, pre-capillary pulmonary hypertension, idiopathic pulmonary hypertension, thrombotic pulmonary artheriopathy, plexogenic pulmonary artheriopathy; pulmonary hypertension associated with or related to: left ventricular dysfunction, hypoxemia, mitral valve disease, constrictive pericarditis, aortic stenosis, cardiomyopathy, mediastinal fibrosis, pulmonary fibrosis, anomalous pulmonary venous drainage, pulmonary venooclusive disease, pulmonary vasculitis, collagen vascular disease, congenital heart disease, pulmonary venous hypertension, interstitial lung disease, sleep-disordered breathing, apnea, alveolar hypoventilation disorders, chronic exposure to high altitude, neonatal lung disease, alveolar-capillary dysplasia, sickle cell disease, other coagulation disorders, chronic thromboembolism, pulmonary embolism, connective tissue disease, lupus, schitosomiasis, sarcoidosis, chronic obstructive pulmonary disease, emphysema, chronic bronchitis, pulmonary capillary hemangiomatosis; histiocytosis X, lymphangiomatosis and compressed pulmonary vessels; 
   (b) a health disorder related to high blood pressure and decreased coronary blood flow selected from:
 increased acute and chronic coronary blood pressure, arterial hypertension, vascular disorder resulting from heart disease, stroke, cerebral ischemia, or renal failure, congestive heart failure, thromboembolic disorders, ischemias, myocardial infarction, stroke, transient ischemic attacks, stable or unstable angina pectoris, arrhythmias, diastolic dysfunction, coronary insufficiency; 
   (c) atherosclerosis, restenosis, percutaneous transluminal coronary angioplasties or inflammation;   (d) liver cirrhosis, hepatic fibrosis, hepatic stellate cell activation, hepatic fibrous collagen and total collagen accumulation, liver disease of necro-inflammatory and/or of immunological origin; or   (e) a urogenital system disorder selected from renal fibrosis, renal failure resulting from chronic kidney diseases or insufficiency, prostate hypertrophy, erectile dysfunction, female sexual dysfunction and incontinence;   
       wherein the compound of Formula IA or Formula IB is: 
       
         
           
           
               
               
           
         
         the symbol with the encircled letter B represents ring B, and ring B is a phenyl or a 6-membered heteroaryl ring, having 1 or 2 nitrogen ring atoms; 
         n is an integer selected from 0 to 3; 
         each J B  is independently selected from halogen, —CN, —NO 2 , a C 1-6  aliphatic, —OR B  or a C 3-8  cycloaliphatic group; wherein each said C 1-6  aliphatic and each said C 3-8  cycloaliphatic group is optionally and independently substituted with up to 3 instances of R 3 ; 
         each R B  is independently selected from hydrogen, a C 1-6  aliphatic or a C 3-8  cycloaliphatic; wherein each said C 1-6  aliphatic and each said C 3-8  cycloaliphatic ring is optionally and independently substituted with up to 3 instances of R 3 ; 
         each R 3  is independently selected from halogen, —CN, C 1-4  alkyl, C 1-4  haloalkyl, —O(C 1-4  alkyl) or —O(C 1-4  haloalkyl); 
         wherein ring D is the 5-membered ring heteroaryl of Formula IB or the 6-membered heteroaryl ring of Formula IA that is substituted by m instances of J D ; 
         X is selected from N or C; 
         each Y is independently selected from C, N, O or S; wherein a minimum of 0 and maximum of 3 instances of Y can be N, O or S simultaneously and the remaining instance or instances of Y are C; 
         m is an integer selected from 0 to 3; 
         each J D  that is a substituent on a carbon ring atom of Formula IA or Formula IB is independently selected from halogen, —NO 2 , —OR D , —SR D , —C(O)R D , —C(O)OR D , —C(O)N(R D ) 2 , —CN, —N(R D ) 2 , —N(R d )C(O)R D , —N(R d )C(O)OR D , —SO 2 R D , —SO 2 N(R D ) 2 , —N(R d )SO 2 R D , a C 1-6  aliphatic, —(C 1-6  aliphatic)-R D , a C 3-8  cycloaliphatic ring, a 6 to 10-membered aryl ring, a 4 to 8-membered heterocyclic ring or a 5 to 10-membered heteroaryl ring; wherein each said 4 to 8-membered heterocylic ring and each said 5 to 10-membered heteroaryl ring contains between 1 and 3 heteroatoms independently selected from O, N or S; and wherein each said C 1-6  aliphatic, each said C 3-8  cycloaliphatic ring, each said 6 to 10-membered aryl ring, each said 4 to 8-membered heterocyclic ring and each said 5 to 10-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of R 5 ; 
         each J D  that is a substituent on a nitrogen ring atom of Formula IB is independently selected from —C(O)R D , —C(O)OR D , —C(O)N(R D ) 2 , —SO 2 R D , —SO 2 N(R D ) 2 , a C 1-6  aliphatic, —(C 1-6  aliphatic)-R D , a C 3-8  cycloaliphatic ring, a 6 to 10-membered aryl ring, a 4 to 8-membered heterocyclic ring or a 5 to 10-membered heteroaryl ring; wherein each said 4 to 8-membered heterocylic ring and each said 5 to 10-membered heteroaryl ring has between 1 and 3 heteroatoms independently selected from O, N or S; and wherein each said C 1-6  aliphatic, each said C 3-8  cycloaliphatic ring, each said 6 to 10-membered aryl ring, each said 4 to 8-membered heterocyclic ring and each said 5 to 10-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of R 5 ; 
         each R D  is independently selected from hydrogen, a C 1-6  aliphatic, —(C 1-6  aliphatic)-R f , a C 3-8  cycloaliphatic ring, a 4 to 8-membered heterocyclic ring, phenyl or a 5 to 6-membered heteroaryl ring; wherein each said 4 to 8-membered heterocylic ring and each said 5 to 6-membered heteroaryl ring has between 1 and 3 heteroatoms independently selected from O, N or S; and wherein each said C 1-6  aliphatic, each said C 3-8  cycloaliphatic ring, each said 4 to 8-membered heterocyclic ring, each said phenyl and each said 5 to 6-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of R 5 ; 
         each R d  is independently selected from hydrogen, a C 1-6  aliphatic, —(C 1-6  aliphatic)-R f , a C 3-8  cycloaliphatic ring, a 4 to 8-membered heterocyclic ring, phenyl or a 5 to 6-membered heteroaryl ring; wherein each said heterocylic ring and each said heteroaryl ring has between 1 and 3 heteroatoms independently selected from O, N or S; and wherein each said C 1-6  aliphatic, each said C 3-8  cycloaliphatic ring, each said 4 to 8-membered heterocyclic ring, each said phenyl and each said 5 to 6-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R 5 ; 
         each R f  is independently selected from a C 3-8  cycloaliphatic ring, a 4 to 8-membered heterocyclic ring, phenyl or a 5 to 6-membered heteroaryl ring; wherein each said heterocylic ring and each said heteroaryl ring has between 1 and 3 heteroatoms independently selected from O, N or S; and wherein each said C 1-6  aliphatic, each said C 3-8  cycloaliphatic ring, each said 4 to 8-membered heterocyclic ring, each said phenyl and each said 5 to 6-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R 5 ; 
         alternatively, two instances of R D  linked to the same nitrogen atom of J D , together with said nitrogen atom of J D , form a 4 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally has up to 2 additional heteroatoms independently selected from N, O or S, and wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R 5 ; or 
         alternatively, one instance of R D  linked to a carbon, oxygen or sulfur atom of J D  and one instance of R d  linked to a nitrogen atom of the same J D , together with said carbon, oxygen or sulfur and said nitrogen atom of that same J D , form a 4 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally has up to 2 additional heteroatoms independently selected from N, O or S, and wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R 5 ; 
         each R 5  is independently selected from halogen, —CN, —NO 2 , C 1-4  alkyl, a C 7-12  aralkyl, C 3-8  cycloalkyl ring, C 1-4  haloalkyl, C 1-4  cyanoalkyl, —OR 6 , —SR 6 , —COR 6 , —C(O)OR 6 , —C(O)N(R 6 ) 2 , —N(R 6 )C(O)R 6 , —N(R 6 ) 2 , —SO 2 R 6 , —SO 2 N(R 6 ) 2 , —N(R 6 )SO 2 R 6 , phenyl or an oxo group; wherein each said phenyl group is optionally and independently substituted with up to 3 instances of halogen, —OH, —NH 2 , —NH(C 1-4  alkyl), —N(C 1-4  alkyl) 2 , —NO 2 , —CN, C 1-4  alkyl, C 1-4  haloalkyl, —O(C 1-4  alkyl) or —O(C 1-4  haloalkyl); and wherein each said C 7-12  aralkyl and each said cycloalkyl group is optionally and independently substituted with up to 3 instances of halogen; 
         each R 6  is independently selected from hydrogen, a C 1-4  alkyl, phenyl, a C 7-12  aralkyl or a C 3-8  cycloalkyl ring; wherein each of said C 1-4  alkyl, each said phenyl, each said C 7-12  aralkyl and each said cycloalkyl group is optionally and independently substituted with up to 3 instances of halogen; 
         alternatively, two instances of R 6  linked to the same nitrogen atom of R 5 , together with said nitrogen atom of R 5 , form a 5 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 5 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally has up to 2 additional heteroatoms independently selected from N, O or S; or 
         alternatively, one instance of R 6  linked to a nitrogen atom of R 5  and one instance of R 6  linked to a carbon or sulfur atom of the same R 5 , together with said nitrogen and said carbon or sulfur atom of the same R 5 , form a 5 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 5 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally has up to 2 additional heteroatoms independently selected from N, O or S; 
         or, alternatively, two J D  groups attached to two vicinal ring D atoms, taken together with said two vicinal ring D atoms, form a 5 to 7-membered heterocycle resulting in a fused ring D wherein said 5 to 7-membered heterocycle has from 1 to 3 heteroatoms independently selected from N, O or S; and wherein said 5 to 7-membered heterocycle is optionally and independently substituted by up to 3 instances of halogen, —OH, —NH 2 , —NH(C 1-4  alkyl), —N(C 1-4  alkyl) 2 , —CN, C 1-4  alkyl, C 1-4  haloalkyl, —O(C 1-4  alkyl), —O(C 1-4  haloalkyl) or oxo; 
         R C  is selected from halo, —CN, C 1-6  alkyl or a ring C; 
         ring C is a phenyl ring, a monocyclic 5 or 6-membered heteroaryl ring, a bicyclic 8 to 10-membered heteroaryl ring, a monocyclic 3 to 10-membered cycloaliphatic ring, or a monocyclic 4 to 10-membered heterocycle; wherein said monocyclic 5 or 6-membered heteroaryl ring, said bicyclic 8 to 10-membered heteroaryl ring, or said monocyclic 4 to 10-membered heterocycle has between 1 and 4 heteroatoms selected from N, O or S; and wherein said phenyl, monocyclic 5 to 6-membered heteroaryl ring, bicyclic 8 to 10-membered heteroaryl ring, or monocyclic 4 to 10-membered heterocycle is optionally and independently substituted with up to 3 instances of J C ; 
         each J C  is independently selected from halogen, —CN, —NO 2 , a C 1-6  aliphatic, —OR H , —SR H , —N(R H ) 2 , a C 3-8  cycloaliphatic ring or a 4 to 8-membered heterocyclic ring; wherein said 4 to 8-membered heterocyclic ring has 1 or 2 heteroatoms independently selected from N, O or S; wherein each said C 1-6  aliphatic, each said C 3-8  cycloaliphatic ring and each said 4 to 8-membered heterocyclic ring, is optionally and independently substituted with up to 3 instances of R 7 ; or alternatively, two J C  groups attached to two vicinal ring C atoms, taken together with said two vicinal ring C atoms, form a 5 to 7-membered heterocycle resulting in a fused ring C; wherein said 5 to 7-membered heterocycle has from 1 to 2 heteroatoms independently selected from N, O or S; 
         each R H  is independently selected from hydrogen, a C 1-6  aliphatic, a C 3-8  cycloaliphatic ring or a 4 to 8-membered heterocyclic ring; wherein each said 4 to 8-membered heterocylic ring has between 1 and 3 heteroatoms independently selected from O, N or S; and wherein each said C 1-6  aliphatic, each said C 3-8  cycloaliphatic ring, each said 4 to 8-membered heterocyclic ring, is optionally and independently substituted with up to 3 instances of R 7 ; 
         alternatively, two instances of R H  linked to the same nitrogen atom of J C , together with said nitrogen atom of J C , form a 4 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally has up to 2 additional heteroatoms independently selected from N, O or S, and wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R 7 ; or 
         each R 7  is independently selected from halogen, —CN, —NO 2 , C 1-4  alkyl, C 1-4  haloalkyl, C 3-8  cycloalkyl ring, —OR 8 , —N(R 8 ) 2 , or an oxo group; wherein each said cycloalkyl group is optionally and independently substituted with up to 3 instances of halogen; 
         each R 8  is independently selected from hydrogen, a C 1-4  alkyl, C 1-4  haloalkyl or a C 3-8  cycloalkyl ring; wherein each said cycloalkyl group is optionally and independently substituted with up to 3 instances of halogen; and 
         alternatively, two instances of R 8  linked to the same nitrogen atom of R 7 , together with said nitrogen atom of R 7 , form a 5 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 5 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally has up to 2 additional heteroatoms independently selected from N, O or S. 
       
     
     
         84 . The method of  claim 83 , wherein the disease, health condition or disorder is
 (a) a peripheral or cardiac vascular disorder or health condition selected from:
 pulmonary hypertension, pulmonary arterial hypertension, and associated pulmonary vascular remodeling, localized pulmonary thrombosis, right heart hypertrophy, pulmonary hypertonia, primary pulmonary hypertension, secondary pulmonary hypertension, familial pulmonary hypertension, sporadic pulmonary hypertension, pre-capillary pulmonary hypertension, idiopathic pulmonary hypertension, thrombotic pulmonary artheriopathy, plexogenic pulmonary artheriopathy; pulmonary hypertension associated with or related to: left ventricular dysfunction, hypoxemia, mitral valve disease, constrictive pericarditis, aortic stenosis, cardiomyopathy, mediastinal fibrosis, pulmonary fibrosis, anomalous pulmonary venous drainage, pulmonary venooclusive disease, pulmonary vasculitis, collagen vascular disease, congenital heart disease, pulmonary venous hypertension, interstitial lung disease, sleep-disordered breathing, apnea, alveolar hypoventilation disorders, chronic exposure to high altitude, neonatal lung disease, alveolar-capillary dysplasia, sickle cell disease, other coagulation disorders, chronic thromboembolism, pulmonary embolism, connective tissue disease, lupus, schitosomiasis, sarcoidosis, chronic obstructive pulmonary disease, emphysema, chronic bronchitis, pulmonary capillary hemangiomatosis; histiocytosis X, lymphangiomatosis or compressed pulmonary vessels; 
   (b) liver cirrhosis, or   (c) a urogenital system disorder selected from renal fibrosis, renal failure resulting from chronic kidney diseases or insufficiency, erectile dysfunction or female sexual dysfunction.   
     
     
         85 . The method of  claim 84 , wherein the disease, health condition or disorder is pulmonary hypertension, pulmonary arterial hypertension, and associated pulmonary vascular remodeling, localized pulmonary thrombosis, right heart hypertrophy, pulmonary hypertonia, primary pulmonary hypertension, secondary pulmonary hypertension, familial pulmonary hypertension, sporadic pulmonary hypertension, pre-capillary pulmonary hypertension, idiopathic pulmonary hypertension, thrombotic pulmonary arteriopathy, plexogenic pulmonary arteriopathy or chronic obstructive pulmonary disease, liver cirrhosis, renal fibrosis, renal failure resulting from chronic kidney diseases or insufficiency, erectile dysfunction or female sexual dysfunction. 
     
     
         86 . The method of  claim 85 , wherein the disease, health condition or disorder is pulmonary hypertension, pulmonary arterial hypertension, and associated pulmonary vascular remodeling, pulmonary hypertonia, primary pulmonary hypertension, secondary pulmonary hypertension, familial pulmonary hypertension, sporadic pulmonary hypertension, pre-capillary pulmonary hypertension or idiopathic pulmonary hypertension. 
     
     
         87 . The method of  claim 83 , further comprising administering an effective amount of one or more additional therapeutic agents to the subject. 
     
     
         88 . The method of  claim 87 , wherein the one or more additional therapeutic agents are selected from edothelium-derived releasing factor, NO donors, substances that enhance cGMP concentrations, nitric oxide synthase substrates, compounds which enhance eNOS transcription, NO-independent heme-independent sGC activators, heme-dependent sGC stimulators; inhibitors of cGMP degradation, calcium channel blockers, endothelin receptor antagonists, prostacyclin derivatives, antihyperlipidemics, anticoagulants, antiplatelet drugs, ACE inhibitors, supplemental oxygen, beta blockers, antiarrhythmic agents, diuretics, exogenous vasodilators, bronchodilators, corticosteroids, dietary supplements, PGD2 receptor antagonists, immunosuppressants, non-steroidal antiasthmatics, non-steroidal anti-inflammatory agents, cyclooxygenase-2 inhibitors or anti-diabetic agents. 
     
     
         89 . (canceled) 
     
     
         90 . A method of treating a disease, health condition or disorder in a subject, comprising administering a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         to the subject in need of the treatment, wherein the disease, health condition or disorder is 
         (a) a peripheral or cardiac vascular disorder or health condition selected from:
 pulmonary hypertension, pulmonary arterial hypertension, and associated pulmonary vascular remodeling, localized pulmonary thrombosis, right heart hypertrophy, pulmonary hypertonia, primary pulmonary hypertension, secondary pulmonary hypertension, familial pulmonary hypertension, sporadic pulmonary hypertension, pre-capillary pulmonary hypertension, idiopathic pulmonary hypertension, thrombotic pulmonary artheriopathy, plexogenic pulmonary artheriopathy; pulmonary hypertension associated with or related to: left ventricular dysfunction, hypoxemia, mitral valve disease, constrictive pericarditis, aortic stenosis, cardiomyopathy, mediastinal fibrosis, pulmonary fibrosis, anomalous pulmonary venous drainage, pulmonary venooclusive disease, pulmonary vasculitis, collagen vascular disease, congenital heart disease, pulmonary venous hypertension, interstitial lung disease, sleep-disordered breathing, apnea, alveolar hypoventilation disorders, chronic exposure to high altitude, neonatal lung disease, alveolar-capillary dysplasia, sickle cell disease, other coagulation disorders, chronic thromboembolism, pulmonary embolism, connective tissue disease, lupus, schitosomiasis, sarcoidosis, chronic obstructive pulmonary disease, emphysema, chronic bronchitis, pulmonary capillary hemangiomatosis; histiocytosis X, lymphangiomatosis and compressed pulmonary vessels; 
 
         (b) a health disorder related to high blood pressure and decreased coronary blood flow selected from:
 increased acute and chronic coronary blood pressure, arterial hypertension, vascular disorder resulting from heart disease, stroke, cerebral ischemia, or renal failure, congestive heart failure, thromboembolic disorders, ischemias, myocardial infarction, stroke, transient ischemic attacks, stable or unstable angina pectoris, arrhythmias, diastolic dysfunction, coronary insufficiency; 
 
         (c) atherosclerosis, restenosis, percutaneous transluminal coronary angioplasties or inflammation; 
         (d) liver cirrhosis, hepatic fibrosis, hepatic stellate cell activation, hepatic fibrous collagen and total collagen accumulation, liver disease of necro-inflammatory and/or of immunological origin; or 
         (e) a urogenital system disorder selected from renal fibrosis, renal failure resulting from chronic kidney diseases or insufficiency, prostate hypertrophy, erectile dysfunction, female sexual dysfunction and incontinence. 
       
     
     
         91 . The method of  claim 90 , wherein the disease, health condition or disorder is
 (a) a peripheral or cardiac vascular disorder or health condition selected from:
 pulmonary hypertension, pulmonary arterial hypertension, and associated pulmonary vascular remodeling, localized pulmonary thrombosis, right heart hypertrophy, pulmonary hypertonia, primary pulmonary hypertension, secondary pulmonary hypertension, familial pulmonary hypertension, sporadic pulmonary hypertension, pre-capillary pulmonary hypertension, idiopathic pulmonary hypertension, thrombotic pulmonary artheriopathy, plexogenic pulmonary artheriopathy; pulmonary hypertension associated with or related to: left ventricular dysfunction, hypoxemia, mitral valve disease, constrictive pericarditis, aortic stenosis, cardiomyopathy, mediastinal fibrosis, pulmonary fibrosis, anomalous pulmonary venous drainage, pulmonary venooclusive disease, pulmonary vasculitis, collagen vascular disease, congenital heart disease, pulmonary venous hypertension, interstitial lung disease, sleep-disordered breathing, apnea, alveolar hypoventilation disorders, chronic exposure to high altitude, neonatal lung disease, alveolar-capillary dysplasia, sickle cell disease, other coagulation disorders, chronic thromboembolism, pulmonary embolism, connective tissue disease, lupus, schitosomiasis, sarcoidosis, chronic obstructive pulmonary disease, emphysema, chronic bronchitis, pulmonary capillary hemangiomatosis; histiocytosis X, lymphangiomatosis or compressed pulmonary vessels; 
   (b) liver cirrhosis, or   (c) a urogenital system disorder selected from renal fibrosis, renal failure resulting from chronic kidney diseases or insufficiency, erectile dysfunction or female sexual dysfunction.   
     
     
         92 . The method of  claim 91 , wherein the disease, health condition or disorder is pulmonary hypertension, pulmonary arterial hypertension, and associated pulmonary vascular remodeling, localized pulmonary thrombosis, right heart hypertrophy, pulmonary hypertonia, primary pulmonary hypertension, secondary pulmonary hypertension, familial pulmonary hypertension, sporadic pulmonary hypertension, pre-capillary pulmonary hypertension, idiopathic pulmonary hypertension, thrombotic pulmonary arteriopathy, plexogenic pulmonary arteriopathy or chronic obstructive pulmonary disease, liver cirrhosis, renal fibrosis, renal failure resulting from chronic kidney diseases or insufficiency, erectile dysfunction or female sexual dysfunction. 
     
     
         93 . The method of  claim 92 , wherein the disease, health condition or disorder is pulmonary hypertension, pulmonary arterial hypertension, and associated pulmonary vascular remodeling, pulmonary hypertonia, primary pulmonary hypertension, secondary pulmonary hypertension, familial pulmonary hypertension, sporadic pulmonary hypertension, pre-capillary pulmonary hypertension or idiopathic pulmonary hypertension. 
     
     
         94 . The method of  claim 90 , further comprising administering an effective amount of one or more additional therapeutic agents to the subject. 
     
     
         95 . The method of  claim 94 , wherein the one or more additional therapeutic agents are selected from edothelium-derived releasing factor, NO donors, substances that enhance cGMP concentrations, nitric oxide synthase substrates, compounds which enhance eNOS transcription, NO-independent heme-independent sGC activators, heme-dependent sGC stimulators; inhibitors of cGMP degradation, calcium channel blockers, endothelin receptor antagonists, prostacyclin derivatives, antihyperlipidemics, anticoagulants, antiplatelet drugs, ACE inhibitors, supplemental oxygen, beta blockers, antiarrhythmic agents, diuretics, exogenous vasodilators, bronchodilators, corticosteroids, dietary supplements, PGD2 receptor antagonists, immunosuppressants, non-steroidal antiasthmatics, non-steroidal anti-inflammatory agents, cyclooxygenase-2 inhibitors or anti-diabetic agents. 
     
     
         96 . The method of  claim 83 , wherein the disease is a health disorder related to high blood pressure and decreased coronary blood flow selected from: increased acute and chronic coronary blood pressure, arterial hypertension, vascular disorder resulting from heart disease, stroke, cerebral ischemia, or renal failure, congestive heart failure, thromboembolic disorders, ischemias, myocardial infarction, stroke, transient ischemic attacks, stable or unstable angina pectoris, arrhythmias, diastolic dysfunction, coronary insufficiency. 
     
     
         97 . The method of  claim 83 , wherein the disease is a health disorder related to high blood pressure and decreased coronary blood flow selected from: stroke, cerebral ischemia, thromboembolic disorders or transient ischemic attacks. 
     
     
         98 . The method of  claim 83 , wherein the disease is selected from liver cirrhosis, hepatic fibrosis, hepatic stellate cell activation, hepatic fibrous collagen and total collagen accumulation or liver disease of necro-inflammatory and/or of immunological origin. 
     
     
         99 . The method of  claim 83 , wherein the disease a urogenital system disorder selected from renal fibrosis or renal failure resulting from chronic kidney diseases or insufficiency. 
     
     
         100 . The method of  claim 90 , wherein the disease is a health disorder related to high blood pressure and decreased coronary blood flow selected from: increased acute and chronic coronary blood pressure, arterial hypertension, vascular disorder resulting from heart disease, stroke, cerebral ischemia, or renal failure, congestive heart failure, thromboembolic disorders, ischemias, myocardial infarction, stroke, transient ischemic attacks, stable or unstable angina pectoris, arrhythmias, diastolic dysfunction, coronary insufficiency. 
     
     
         101 . The method of  claim 90 , wherein the disease is a health disorder related to high blood pressure and decreased coronary blood flow selected from: stroke, cerebral ischemia, thromboembolic disorders or transient ischemic attacks. 
     
     
         102 . The method of  claim 90 , wherein the disease is selected from liver cirrhosis, hepatic fibrosis, hepatic stellate cell activation, hepatic fibrous collagen and total collagen accumulation or liver disease of necro-inflammatory and/or of immunological origin. 
     
     
         103 . The method of  claim 90 , wherein the disease a urogenital system disorder selected from renal fibrosis or renal failure resulting from chronic kidney diseases or insufficiency.