Compositions for preventing or treating pulmonary arterial hypertension

A pharmaceutical composition for preventing or treating pulmonary arterial hypertension, comprising a compound represented by formula I below, optical isomers thereof or pharmaceutically acceptable salts thereof as an active ingredient:

• in formula I,
• wherein L1, L2 or L3 are each independently a bond or —(C1-C2 alkylene)-;
• R1 is —CX2H or —CX3;
• R2 is —NRARB, —ORC,
• wherein, at least one H of
• may be substituted with —X, —OH, —O(C1-C4 alkyl), —NRDRE, —(C1-C4 alkyl), —CF3, —CF2H, —CN, -aryl, -heteroaryl, —(C1-C4 alkyl)-aryl or —(C1-C4 alkyl)-heteroaryl, [wherein at least one H of the -aryl, -heteroaryl, —(C1-C4 alkyl)-aryl or —(C1-C4 alkyl)-heteroaryl may be substituted with —X, —OH, —CF3 or —CF2H];
• R3 is —H, —(C1-C4 alkyl), —(C1-C4 alkyl)-O(C1-C4 alkyl), —(C1-C4 alkyl)-C(═O)—O(C1-C4 alkyl), —(C3-C7 cycloalkyl), —(C2-C6 cycloheteroalkyl), -aryl, -heteroaryl, -adamantyl,
• wherein, at least one H of —(C1-C4 alkyl) may be substituted with —X or —OH,
• at least one H of -aryl or -heteroaryl each independently may be substituted with —X, —OH, —O(C1-C4 alkyl), —OCF3, —O-aryl, —NRDRE, —(C1-C4 alkyl), —CF3, —CF2H, —C(═O)—(C1-C4 alkyl), —C(═O)—O(C1-C4 alkyl), —C(═O)—NRDRE, —S(═O)2—(C1-C4 alkyl), aryl, heteroaryl,
• wherein, at least one H of
• may be substituted with —X, —(C1-C4 alkyl), —NRDRE, —CF3 or —CF2H,
• at least one H of —(C3-C7 cycloalkyl), —(C2-C6 cycloheteroalkyl), adamantyl,
• may be each independently substituted with —X, —OH or —(C1-C4 alkyl);
• Y1, Y2 and Y4 are each independently —CH2—, —NRF—, —O—, —C(═O)— or —S(═O)2—;
• Y3 is —CH— or —N—;
• Z1 to Z4 are each independently N or CRZ, wherein at least three of Z1 to Z4 may not be simultaneously N, and RZ is —H, —X or —O(C1-C4 alkyl);
• Z5 and Z6 are each independently —CH2— or —O—;
• Z7 and Z8 are each independently ═CH— or ═N—;
• Z9 is —NRG— or —S—;
• RA and RB are each independently —H, —(C1-C4 alkyl), —(C1-C4 alkyl)-OH, —(C1-C4 alkyl)-NRDRE, -aryl, —(C1-C4 alkyl)-aryl, -heteroaryl, —(C1-C4 aryl)-heteroaryl, —(C3-C7 cycloalkyl), —(C2-C6 heterocycloalkyl) or
• wherein, at least one H of the —(C1-C4 alkyl), —(C1-C4 alkyl)-OH or —(C1-C4 alkyl)-NRDRE may be substituted with —X,
• at least one H of the -aryl, —(C1-C4 alkyl)-aryl, -heteroaryl, —(C1-C4 alkyl)-heteroaryl, —(C3-C7 cycloalkyl) or —(C2-C6 heterocycloalkyl) may be substituted with —X, —OH, —O(C1-C4 alkyl), —(C1-C4 alkyl), —CF3, —CF2H or —CN,
• at least one H of
• may be substituted with n-X, —OH, —O(C1-C4 alkyl), —(C1-C4 alkyl), —CF3, —CF2H, —CN, —(C2-C6 heterocycloalkyl), -aryl, —(C1-C4 alkyl)-aryl, -heteroaryl or -heteroaryl-(C1-C4 alkyl);
• RC is —(C1-C4 alkyl), -aryl, —(C1-C4 alkyl)-aryl, -heteroaryl or —(C1-C4 alkyl)-heteroaryl, wherein, at least one H of —(C1-C4 alkyl) may be substituted with —X or —OH, at least one H of -aryl, —(C1-C4 alkyl)-aryl, -heteroaryl or —(C1-C4 alkyl)-heteroaryl may be substituted with —X, —OH, —CF3 or —CF2H;
• RD and RE are each independently —H, —(C1-C4 alkyl), -aryl or —(C1-C4 alkyl)-aryl, wherein, at least one H of —(C1-C4 alkyl) may be substituted with —X or —OH, at least one H of -aryl or —(C1-C4 alkyl)-aryl may be substituted with —X, —OH, —CF3 or —CF2H;
• RF is —H, —(C1-C6 alkyl), —(C1-C4 alkyl)-OH, —(C1-C4 alkyl)-O—(C1-C4 alkyl), —C(═O)—(C1-C4 alkyl), —C(═O)-0 (C1-C4 alkyl), —(C1-C4 alkyl)-C(═O)—O(C1-C4 alkyl), —(C1-C4 alkyl)-NRDRE, —S(═O)2—(C1-C4 alkyl), -aryl, —(C1-C4 alkyl)-aryl, —(C2-C4 alkenyl)-aryl, -heteroaryl, —(C1-C4 alkyl)-heteroaryl, —C(═O)—(C3-C7cycloalkyl), —(C2-C6 heterocycloalkyl) or —(C1-C4 alkyl)-C(═O)—(C2-C6 heterocycloalkyl)
• wherein at least one H of —(C1-C4 alkyl), —(C1-C4 alkyl)-OH, —(C1-C4 alkyl)-O—(C1-C4 alkyl), —C(═O)—(C1-C4 alkyl), —C(═O)—O(C1-C4 alkyl), —(C1-C4 alkyl)-C(═O)—O(C1-C4 alkyl), —(C1-C4 alkyl)-NRDRE or —S(═O)2—(C1-C4 alkyl) may be substituted with —X,
• at least one H of -aryl, —(C1-C4alkyl)-aryl, —(C2-C4 alkenyl)-aryl, -heteroaryl, —(C1-C4 alkyl)-heteroaryl, —C(═O)—(C3-C7 cycloalkyl), —C2-C6 heterocycloalkyl or —(C1-C4alkyl)-C(═O)—(C2-C6heterocycloalkyl) may be substituted with —X, —OH, —CF3 or —CF2H;
• RG is —H or —(C1-C4 alkyl);
• Q is —O— or a bond;
• is a single bond or double bond, provided that, is a double bond, Y1 is ═CH—;
• a to e are each independently an integer of 0, 1, 2, 3 or 4 provided that, a and b may not be simultaneously 0, and c and d may not be simultaneously 0;
• X is each independently F, Cl, Br or I.