Polycyclic guanine phosphodiesterase V inhibitors

A compound having the formula (I.1) or (II.1):

• 194
• or a pharmaceutically acceptable salt or solvate thereof
• where,
• q=0 or 1;
• R1 is H, cycloalkyl, alkyl, R23-alkyl- or R26;
• Ra, Rb and Rc are, independently of one another, each H, alkyl, cycloalkyl, aryl, R22-aryl- or R24-alkyl-;
• or
• Ra and Rb, together with the carbon to which they are both attached, form a 4- to 7-membered ring, and R1 is H or alkyl;
• or
• Ra and Rc, together with the respective carbons to which they are attached, form a 4- to 7-membered ring, and Rb is H or alkyl;
• (i) X is a bond;
• Y is H, R26, cycloalkyl, alkyl, R25-alkyl- or —(CH2)tTCOR100, where t is 1 to 6, T is —O— or —NH—, and R100 is H, R26 alkyl or R26-alkyl-;
• and
• R2 is monohaloalkyl, polyhaloalkyl, provided that it is not trifluoromethyl, azido, cyano, oximino, cycloalkenyl, heteroaryl, R22-heteroaryl- or R27-alkyl-;
• (ii) X is a bond;
• Y is Q-V, where Q is a bond or C1-C8 alkyl, and V is:
• (a) aryl substituted with nitro, aminosulfonyl, cyano, monohaloalkyl, polyhaloalkyl, provided that it is not trifluoromethyl, thiol, alkylthio, cycloalkyl, cycloalkylalkyl, —OCF3 or acyloxy, and optionally further substituted with 1 to 3 additional substituents independently selected from the group consisting of R21;
• (b) R22-heteroaryl-;
• or
• (c) aryl or heteroaryl, each of which is independently substituted with 2 substituents on adjacent atoms of the group V, which are joined to form a fused non-aromatic 4- to 8-membered carbocyclic or heterocyclic ring, and optionally further substituted with 1 to 2 additional substituents independently selected from the group consisting of R21;
• and
• R2 is H, halo, —CONHR6, —CONR6R7, —CO2R6, monohaloalkyl, polyhaloalkyl, azido, cyano, —C═N—OR6, cycloalkyl, cycloalkylalkyl, R26, aminosulfonyl, alkyl or R23-alkyl-;
• (iii) X is —O— or —S—;
• Y is defined in section (i) above;
• and
• R2 is R26, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, cycloalkenyl or R28-alkyl-;
• (iv) X is —O— or —S—;
• Y is defined in section (ii) above;
• and
• R2 is alkyl, R26, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, cycloalkenyl or R28-alkyl-;
• (v) X is —SO— or —SO2—;
• Y is defined in section (i) or (ii) above;
• and
• R2 is alkyl, R26, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, cycloalkenyl or R28-alkyl-;
• (vi) X is —NR8—;
• Y is defined in section (i) above;
• and
• R2 is (R29)p-alkyl-, cycloalkyl, (R30)p-cycloalkyl-, cycloalkenyl, (R30)p-cycloalkenyl-, heterocycloalkyl or (R30)p-heterocycloalkyl-;
• (vii) X is —NR8—;
• Y is defined in section (ii) above;
• and
• R2 is alkyl, R26, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, cycloalkenyl or R31-alkyl-;
• or
• (viii) X is —C≡C—;
• Y is defined in section (i) or (ii) above;
• and
• R2 is alkyl, R26, cycloalkyl, cycloalkylalkyl or R23-alkyl-;
• where,
• R6 is H or R7;
• R7 is alkyl, cycloalkyl or cycloalkylalkyl;
• R8 is heterocycloalkyl or R6;
• R21 is 1-6 substituents each independently selected from the group consisting of halo, hydroxy, alkoxy, phenoxy, phenyl, nitro, aminosulfonyl, cyano, monohaloalkyl, polyhaloalkyl, thiol, alkylthio, cycloalkyl, cycloalkylalkyl, amino, alkylamino, acylamino, carboxyl, —C(O)OR34, carboxamido, —OCF3 and acyloxy;
• R22 is 1-6 substituents each independently selected from the group consisting of alkyl and R21;
• R23 is cycloalkoxy aryloxy, alkylthio, arylthio, cycloalkyl or R28;
• R24 is cycloalkyl or R26;
• R25 is hydroxy, alkoxy, amino, monoalkylamino, dialkylamino or R26;
• R26 is aryl, R22-aryl-, heteroaryl or R22-heteroaryl-;
• R27 is cycloalkoxy, aryloxy, alkylthio, arylthio, heteroaryl, R22-heteroaryl-, cycloalkyl, heterocycloalkyl, cycloalkenyl, cycloalkylamino or heterocycloalkylamino;
• R28 is cycloalkylamino, heterocycloalkylamino or R25;
• R29 is alkoxy, cycloalkylamino, heterocycloalkylamino or R26;
• R30 is halo, hydroxy, alkoxy, amino, aminosulfonyl, cyano, monohaloalkyl, polyhaloalkyl, thiol, alkylthio, alkyl, cycloalkyl, cycloalkylalkyl or acyloxy;
• R31 is cycloalkyl or R28;
• R34 is alkyl, aryl, aralkyl and heteroaryl;
• and
• p is 1 to 4