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1. (WO1997018209) ALPHA 1a ADRENERGIC RECEPTOR ANTAGONISTS
Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

WHAT IS CLAIMED IS:
1. A compound of the formula:


wherein

W is selected from unsubstituted, mono or di-substituted: phenyl, pyridyl, thienyl, furanyl or naphthyl where the substituents on the phenyl, pyridyl, thienyl, furanyl or naphthyl are independently selected from CF3, phenyl, OR4, halogen, C1 -4 alkyl or C3-8 cycloalkyl;

R1 and R2 are each independently selected from hydrogen, cyano, CONR4R5, CO2R4 or SO2R4;

R3 is selected from

or ;




R4 and R5 are each independently selected from hydrogen, C1 -8 alkyl or C3-8 cycloalkyl; and

R6 is selected from hydrogen or chloro;

R7 is selected from C1 -8 alkyl,

or
, ;





T, U, X, Y and Z are each independently selected from hydrogen, halogen, C1-8 alkyl, C3-8 cycloalkyl or OR8;

A is selected from CH or N;

G is selected from H2, O or S;

E is selected from CH2, O or NR8;

R8 is selected from hydrogen, C1 -8 alkyl or C3-8 cycloalkyl, (CH2)mCO2R4 or (CH2)mCONH2;

each m is independently an integer of from zero to three; and n is an integer of from two to six;
and the pharmaceutically acceptable salts thereof.

2. The compound of Claim 1 wherein

R3 is selected from


and the pharmaceutically acceptable salts thereof.

3. The compound of Claim 2, wherein
W is selected from unsubstituted or mono-substituted phenyl where the substituent on the phenyl is C1 -4 alkyl or halogen; 2-, 3- or 4-pyridyl; 2- or 3-thienyl; 2- or 3-furanyl; or unsubstituted, mono- or di-substituted naphthyl where the substituent on the naphthyl is selected from CF3, phenyl, OR4, halogen, C1-4 alkyl or C3-8 cycloalkyl;

R3 is selected from



and the pharmaceutically acceptable salts thereof.

4. The compound of Claim 3, wherein
R3 is


and the pharmaceutically acceptable salts thereof.

5. The compound of Claim 4, of the formula



wherein
R1 is selected from hydrogen or cyano; and
W is selected from unsubstituted or mono-substituted phenyl where the substituent on phenyl is selected from methyl or halogen;
and the pharmaceutically acceptable salts thereof.

6. The compound of Claim 5, of the formula



wherein W is selected from phenyl, 2-methylphenyl or 2-chlorophenyl; and the pharmaceutically acceptable salts thereof.

7. The compound of Claim 3, selected from
4-(4-saccarylbutyl)-2-cyano-1-phenylpiperazine or
4-(propyl-ditolylacetamide)-2-cyano-1-phenylpiperazine;
and the pharmaceutically acceptable salts thereof.

8. A pharmaceutical composition comprising a therapeutically effective amount of the compound of Claim 1 and a pharmaceutically acceptable carrier.

9. The composition of Claim 8 further comprising a therapeutically effective amount of a testosterone 5-alpha reductase inhibitor.

10. The composition of Claim 9, wherein the testosterone

5-alpha reductase inhibitor is a type 1 , a type 2, both a type 1 and a type 2 or a dual type 1 and type 2 testosterone 5-alpha reductase inhibitor.

11. The composition of Claim 10, wherein the
testosterone 5-alpha reductase inhibitor is a type 2 testosterone 5-alpha reductase inhibitor.

12. The composition of Claim 11, wherein the
testosterone 5-alpha reductase inhibitor is finasteride.

13. A method of treating benign prostatic hyperplasia in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the compound of Claim 1.

14. The method of Claim 13, wherein the compound additionally does not cause a fall in blood pressure at dosages effective to alleviate benign prostatic hypertophy.

15. The method of Claim 13, wherein the compound is administered in combination with a testosterone 5 -alpha reductase inhibitor.

16. The method of Claim 15, wherein the testosterone 5-alpha reductase inhibitor is finasteride.

17. A method of treating benign prostatic hyperplasia in a subject in need thereof which comprises administering a therapeutically effective amount of the composition of Claim 8.

18. The method of Claim 17, wherein the composition further comprises a therapeutically effective amount of a testosterone 5-alpha reductase inhibitor.

19. A method of relaxing urethral smooth muscle in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the compound of Claim 1.

20. The method of Claim 19, wherein the compound additionally does not cause a fall in blood pressure at dosages effective to relax urethral smooth muscle.

21. The method of Claim 19, wherein the compound is administered in combination with a testosterone 5 -alpha reductase inhibitor.

22. The method of Claim 21 , wherein the testosterone 5-alpha reductase inhibitor is finasteride.

23. A method of treating a disease which is susceptible to treatment by antagonism of the alpha la receptor which comprises administering to a subject in need thereof an amount of the compound of Claim 1 effective to treat the disease.

24. A compound of the formula



wherein R1 is selected from cyano, CONR4R5, CO2R4 or SO2R4;

R4 and R5 are each independently selected from hydrogen, C1-8 alkyl or C3-8 cycloalkyl; and

R9 is selected from hydrogen, CF3, phenyl, OR4, halogen, C1 -4 alkyl or C3-8 cycloalkyl;
and the pharmaceutically acceptable salts thereof.

25. The compound of Claim 24, wherein

R1 is cyano; and

R9 is selected from hydrogen, methyl or chloro;
and the pharmaceutically acceptable salts thereof.