SGC STIMULATORS OR SGC ACTIVATORS IN COMBINATION WITH PDE5 INHIBITORS FOR THE TREATMENT OF ERECTILE DYSFUNCTION
The present invention relates to soluble guanylate cyclase (sGC) and to phosphodiesterases (PDEs) and the pharmacology of sGC stimulators, sGC activators and PDE inhibitors. More particularly, the invention relates to the use of sGC stimulators and sGC activators in combination with PDE5 inhibitors for preparation of medicaments for the treatment of male erectile dysfunction (MED) in particular for the MED treatment of difficult to treat patients and patients not or not fully responding to PDE5 inhibitors.
1 . A pharmaceutical Combination comprising at least one sGC stimulator or activator selected from 2-[1(2 fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-(4-morpholinyl)-4,6-pyrimidinediamine (1), 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-(4-pyridinyl)-4-pyrimidinamine (2), methyl-4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl(methyl)carbamate (3), methyl-4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinylcarbamate (4), 5-chloro-2-(5-chlorothiophene-2-sulfonylamino-N-(4-(morpholine-4-sulfonyl)-phenyl)-benzamide sodium salt (6), 2-(4-chloro-phenylsulfonylamino)-4,5-dimethoxy-N-(4-(thiomorpholine-4-sulfonyl)-phenyl)-benzamide (7), or 4-({(4-carboxybutyl)[2-(2-{[4-(2-phenylethyl)benzyl]oxy}phenyl)ethyl]amino}methyl)benzoic acid (5) and a PDE5 inhibitor selected from Vardenafil, Sildenafil, Tadalafil, Udenafil, Dasantafil, Avanafil, Mirodenafil, Lodenafil, UK 369.003, UK 371.800, SLx2101 or LAS34179, in which the combination comprises 0.1 to 1 mg of the sGC stimulator or activator and 2.5 to 20 mg of the PDE5 inhibitor.
2 . The pharmaceutical Combination according to claim 1 in which the sGC stimulator is methyl-4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl(methyl)carbamate (3) or methyl-4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinylcarbamate (4).
3 . The pharmaceutical Combination according to claim 1 in which the PDE5 inhibitor is Vardenafil or Sildenafil.
4 . (canceled)
5 . A method of treating Male Sexual Dysfunction (MED) comprising the step of administering the pharmaceutical combination according to claim 1 to a patient in need thereof.
6 . (canceled)
7 . A method of treating Male Sexual Dysfunction (MED) in cases where the patient suffers from a PDE5 inhibitor resistance comprising the step of administering the pharmaceutical combination according to claim 1 .
8 . (canceled)
9 . A Pharmaceutical formulation comprising the pharmaceutical combination according to claim 1 .
10 - 11 . (canceled)