Methods for treating hypertension

A method for treating pre-hypertension in a subject in need of treatment thereof, the method comprising the step of:

• administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein said compound comprises the formula:
• wherein R1 and R2 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C1-C10 alkyl group, an unsubstituted or substituted C1-C10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, a phenylsulfinyl group or a cyano (—CN) group;
• wherein R3 and R4 are each independently a hydrogen or A, B, C or D as shown below:
• wherein T connects A, B, C or D to the aromatic ring shown above at R1, R2, R3 or R4.
• wherein R5 and R6 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C1-C10 alkyl group, an unsubstituted or substituted C1-C10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, COO-Glucoronide or COO-Sulfate;
• wherein R7 and R8 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C1-C10 alkyl group, an unsubstituted or substituted C1-C10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, COO-Glucoronide or COO-Sulfate;
• wherein R9 is an unsubstituted pyridyl group or a substituted pyridyl group;
• and
• wherein R10 is a hydrogen or a lower alkyl group, a lower alkyl group substituted with a pivaloyloxy group and in each case, R10 bonds to one of the nitrogen atoms in the 1,2,4-triazole ring shown above.

A method for treating hypertension in a subject in need of treatment thereof, the method comprising the step of:

• administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein said compound comprises the formula:
• wherein R1 and R2 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C1-C10 alkyl group, an unsubstituted or substituted C1-C10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, a phenylsulfinyl group or a cyano (—CN) group;
• wherein R3 and R4 are each independently a hydrogen or A, B, C or D as shown below:
• wherein T connects A, B, C or D to the aromatic ring shown above at R1, R2, R3 or R4.
• wherein R5 and R6 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C1-C10 alkyl group, an unsubstituted or substituted C1-C10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, COO-Glucoronide or COO-Sulfate;
• wherein R7 and R8 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C1-C10 alkyl group, an unsubstituted or substituted C1-C10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, COO-Glucoronide or COO-Sulfate;
• wherein R9 is an unsubstituted pyridyl group or a substituted pyridyl group;
• and
• wherein R10 is a hydrogen or a lower alkyl group, a lower alkyl group substituted with a pivaloyloxy group and in each case, R10 bonds to one of the nitrogen atoms in the 1,2,4-triazole ring shown above.

A method of lowering blood pressure in a subject, the method comprising the step of:

• administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof wherein said compound comprises the formula:
• wherein R1 and R2 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C1-C10 alkyl group, an unsubstituted or substituted C1-C10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, a phenylsulfinyl group or a cyano (—CN) group;
• wherein R3 and R4 are each independently a hydrogen or A, B, C or D as shown below:
• wherein T connects A, B, C or D to the aromatic ring shown above at R1, R2, R3 or R4.
• wherein R5 and R6 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C1-C10 alkyl group, an unsubstituted or substituted C1-C10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, COO-Glucoronide or COO-Sulfate;
• wherein R7 and R8 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C1-C10 alkyl group, an unsubstituted or substituted C1-C10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, COO-Glucoronide or COO-Sulfate;
• wherein R9 is an unsubstituted pyridyl group or a substituted pyridyl group;
• and
• wherein R10 is a hydrogen or a lower alkyl group, a lower alkyl group substituted with a pivaloyloxy group and in each case, R10 bonds to one of the nitrogen atoms in the 1,2,4-triazole ring shown above.

A method of decreasing elevated blood pressure in a subject, the method comprising the step of:

• administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein said compound comprises the formula:
• wherein R1 and R2 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C1-C10 alkyl group, an unsubstituted or substituted C1-C10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, a phenylsulfinyl group or a cyano (—CN) group;
• wherein R3 and R4 are each independently a hydrogen or A, B, C or D as shown below:
• wherein T connects A, B, C or D to the aromatic ring shown above at R1, R2, R3 or R4.
• wherein R5 and R6 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C1-C10 alkyl group, an unsubstituted or substituted C1-C10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, COO-Glucoronide or COO-Sulfate;
• wherein R7 and R8 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C1-C10 alkyl group, an unsubstituted or substituted C1-C10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, COO-Glucoronide or COO-Sulfate;
• wherein R9 is an unsubstituted pyridyl group or a substituted pyridyl group;
• and
• wherein R10 is a hydrogen or a lower alkyl group, a lower alkyl group substituted with a pivaloyloxy group and in each case, R10 bonds to one of the nitrogen atoms in the 1,2,4-triazole ring shown above.

A method of normalizing blood pressure in a subject having a history of hypertension, the method comprising the step of:

• administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein said compound comprises the formula:
• wherein R1 and R2 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C1-C10 alkyl group, an unsubstituted or substituted C1-C10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, a phenylsulfinyl group or a cyano (—CN) group;
• wherein R3 and R4 are each independently a hydrogen or A, B, C or D as shown below:
• wherein T connects A, B, C or D to the aromatic ring shown above at R1, R2, R3 or R4.
• wherein R5 and R6 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C1-C10 alkyl group, an unsubstituted or substituted C1-C10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, COO-Glucoronide or COO-Sulfate;
• wherein R7 and R8 are each independently a hydrogen, a hydroxyl group, a COOH group, an unsubstituted or substituted C1-C10 alkyl group, an unsubstituted or substituted C1-C10 alkoxy, an unsubstituted or substituted hydroxyalkoxy, COO-Glucoronide or COO-Sulfate;
• wherein R9 is an unsubstituted pyridyl group or a substituted pyridyl group;
• and
• wherein R10 is a hydrogen or a lower alkyl group, a lower alkyl group substituted with a pivaloyloxy group and in each case, R10 bonds to one of the nitrogen atoms in the 1,2,4-triazole ring shown above.

A method for treating pre-hypertension in a subject in need of treatment thereof, the method comprising the step of:

• administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein said compound comprises the formula:
• wherein R11 and R12 are each independently a hydrogen, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted phenyl, or R11 and R12 may together form a four- to eight-membered carbon ring together with the carbon atom to which they are attached;
• wherein R13 is a hydrogen or a substituted or unsubstituted lower alkyl group;
• wherein R14 is one or two radicals selected from a group consisting of a hydrogen, a halogen, a nitro group, a substituted or unsubstituted lower alkyl, a substituted or unsubstituted phenyl, —OR16 and —SO2NR17R17′, wherein R16 is a hydrogen, a substituted or unsubstituted lower alkyl, a phenyl-substituted lower alkyl, a carboxymethyl or ester thereof, a hydroxyethyl or ether thereof, or an allyl;
• R17 and R17′ are each independently a hydrogen or a substituted or unsubstituted lower alkyl;
• wherein R15 is a hydrogen or a pharmaceutically active ester-forming group;
• wherein A is a straight or branched hydrocarbon radical having one to five carbon atoms;
• wherein B is a halogen, an oxygen, or a ethylenedithio;
• wherein Y is an oxygen, a sulfur, a nitrogen or a substituted nitrogen;
• wherein Z is an oxygen, a nitrogen or a substituted nitrogen;
• and
• the dotted line refers to either a single bond, a double bond, or two single bonds.

A method for treating hypertension in a subject in need of treatment thereof, the method comprising the step of:

• administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein said compound comprises the formula:
• wherein R11 and R12 are each independently a hydrogen, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted phenyl, or R11 and R12 may together form a four- to eight-membered carbon ring together with the carbon atom to which they are attached;
• wherein R13 is a hydrogen or a substituted or unsubstituted lower alkyl group;
• wherein R14 is one or two radicals selected from a group consisting of a hydrogen, a halogen, a nitro group, a substituted or unsubstituted lower alkyl, a substituted or unsubstituted phenyl, —OR16 and —SO2NR17R17′, wherein R16 is a hydrogen, a substituted or unsubstituted lower alkyl, a phenyl-substituted lower alkyl, a carboxymethyl or ester thereof, a hydroxyethyl or ether thereof, or an allyl;
• R17 and R17 are each independently a hydrogen or a substituted or unsubstituted lower alkyl;
• wherein R15 is a hydrogen or a pharmaceutically active ester-forming group;
• wherein A is a straight or branched hydrocarbon radical having one to five carbon atoms;
• wherein B is a halogen, an oxygen, or a ethylenedithio;
• wherein Y is an oxygen, a sulfur, a nitrogen or a substituted nitrogen;
• wherein Z is an oxygen, a nitrogen or a substituted nitrogen;
• and
• the dotted line refers to either a single bond, a double bond, or two single bonds.

A method of lowering blood pressure in a subject, the method comprising the step of:

• administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof wherein said compound comprises the formula:
• wherein R11 and R12 are each independently a hydrogen, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted phenyl, or R11 and R12 may together form a four- to eight-membered carbon ring together with the carbon atom to which they are attached;
• wherein R13 is a hydrogen or a substituted or unsubstituted lower alkyl group;
• wherein R14 is one or two radicals selected from a group consisting of a hydrogen, a halogen, a nitro group, a substituted or unsubstituted lower alkyl, a substituted or unsubstituted phenyl, —OR16 and —SO2NR17R7′, wherein R16 is a hydrogen, a substituted or unsubstituted lower alkyl, a phenyl-substituted lower alkyl, a carboxymethyl or ester thereof, a hydroxyethyl or ether thereof, or an allyl;
• R17 and R17′ are each independently a hydrogen or a substituted or unsubstituted lower alkyl;
• wherein R15 is a hydrogen or a pharmaceutically active ester-forming group;
• wherein A is a straight or branched hydrocarbon radical having one to five carbon atoms;
• wherein B is a halogen, an oxygen, or a ethylenedithio;
• wherein Y is an oxygen, a sulfur, a nitrogen or a substituted nitrogen;
• wherein Z is an oxygen, a nitrogen or a substituted nitrogen;
• and
• the dotted line refers to either a single bond, a double bond, or two single bonds.

A method of decreasing elevated blood pressure in a subject, the method comprising the step of:

• administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein said compound comprises the formula:
• wherein R11 and R12 are each independently a hydrogen, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted phenyl, or R11 and R12 may together form a four- to eight-membered carbon ring together with the carbon atom to which they are attached;
• wherein R13 is a hydrogen or a substituted or unsubstituted lower alkyl group;
• wherein R14 is one or two radicals selected from a group consisting of a hydrogen, a halogen, a nitro group, a substituted or unsubstituted lower alkyl, a substituted or unsubstituted phenyl, —OR16 and -SO2NR17R17′, wherein R16 is a hydrogen, a substituted or unsubstituted lower alkyl, a phenyl-substituted lower alkyl, a carboxymethyl or ester thereof, a hydroxyethyl or ether thereof, or an allyl;
• R17 and R17′ are each independently a hydrogen or a substituted or unsubstituted lower alkyl;
• wherein R15 is a hydrogen or a pharmaceutically active ester-forming group;
• wherein A is a straight or branched hydrocarbon radical having one to five carbon atoms;
• wherein B is a halogen, an oxygen, or a ethylenedithio;
• wherein Y is an oxygen, a sulfur, a nitrogen or a substituted nitrogen;
• wherein Z is an oxygen, a nitrogen or a substituted nitrogen;
• and
• the dotted line refers to either a single bond, a double bond, or two single bonds.

A method of normalizing blood pressure in a subject having a history of hypertension, the method comprising the step of:

• administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein said compound comprises the formula:
• wherein R11 and R12 are each independently a hydrogen, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted phenyl, or R11 and R12 may together form a four- to eight-membered carbon ring together with the carbon atom to which they are attached;
• wherein R13 is a hydrogen or a substituted or unsubstituted lower alkyl group;
• wherein R14 is one or two radicals selected from a group consisting of a hydrogen, a halogen, a nitro group, a substituted or unsubstituted lower alkyl, a substituted or unsubstituted phenyl, —OR16 and —SO2NR17R17′, wherein R16 is a hydrogen, a substituted or unsubstituted lower alkyl, a phenyl-substituted lower alkyl, a carboxymethyl or ester thereof, a hydroxyethyl or ether thereof, or an allyl;
• R17 and R17 are each independently a hydrogen or a substituted or unsubstituted lower alkyl;
• wherein R15 is a hydrogen or a pharmaceutically active ester-forming group;
• wherein A is a straight or branched hydrocarbon radical having one to five carbon atoms;
• wherein B is a halogen, an oxygen, or a ethylenedithio;
• wherein Y is an oxygen, a sulfur, a nitrogen or a substituted nitrogen;
• wherein Z is an oxygen, a nitrogen or a substituted nitrogen;
• and
• the dotted line refers to either a single bond, a double bond, or two single bonds.