PCSK9 antagonists bicyclo-compounds

A compound of the Formula I:

• wherein:
• R4 is:
• (a) linear, branched or cyclic alkyl of up to 6 carbon atoms;
• (b) —(CH2)x—R13B, wherein:
• x is 1-4, and R13B is —NH2 or —N+H3;
• (c) —(CH2)x—R13C, wherein:
• x is 1-4, and R13C is —N(R13D)2 or —N(R13D)3 wherein R13D is a linear or branched alkyl of up to 4 carbon atoms;
• (d) —CH2NH—C(O)—O—C(CH3)3;
• or
• (e) —CH2—NH—C(O)—[(CH2)2—O—]y—(CH2)2—R13E, wherein, y is 1 to 4 and R13E is —NH2, —N+H3, or —N+(CH3)3;
• R8 is a moiety of the formula:
• wherein R8a is —H, or a linear, branched or cyclic alkyl of up to four carbon atoms;
• A is (a) —CH2—;
• or
• (b) a moiety of the formula:
• wherein R3 is:
• (i) linear, branched or cyclic alkyl of up to 6 carbon atoms;
• (ii) —(CH2)z—R14A, wherein:
• z is 1-4, and R14A is —NH2 or —N+H3;
• (iii) —(CH2)z—R14B, wherein:
• z is 1-4, and R14B is —N(CH3)2 or —N+(CH3)3;
• or
• (iv) —CH2—NH—C(O)—[(CH2)y—O—]2—(CH2)2—R14C wherein, y′ is 1 to 6, and R14C is —NH2, —N+H3, or —N+(CH3)3;
• B is:
• (a) a moiety of the formula:
• wherein:
• R1 is —H or —NH—C(O)—CH3;
• R2 is —H or —C(O)—R15A, wherein R15A is —NH2, —N+H3, or —N+(CH3)3;
• and
• C1 is —CH2— or —(CH2)2—O—;
• or
• (b) a moiety of the formula:
• D is:
• (a) a moiety of the formula:
• or
• (b) a moiety of the formula:
• wherein R12 is —H or —CH3;
• and
• E is:
• (a) a moiety of the formula:
• or
• (b) a moiety of the formula:
• or a pharmaceutically acceptable salt thereof.