Tetrahydroisoquinoline compounds

A compound of Formula I, enantiomers and pharmaceutically acceptable salts thereof:

• wherein:
• R1 is (Ry)k1—(Y1)n1—(X1)m1—Rx, (Ry)k1—(X1)m1—(Y1)n1—Rx or halogen, such as ORx or Y1X1Rx, more particularly ORx,
• Y1 is C(O) or S(O)2, such as C(O),
• X1 is NH or O,
• Ry is C1-4 alkanediyl, C2-4 alkenediyl or C2-4 alkynediyl, such as —CH2—,
• Rx is C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, or H, such as CH3 or H;
• k1is 0 or 1,
• n1 is 0 or 1,
• m1 is 0 or 1,
• R2 is H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, halogen, OC1-4 alkyl, OC2-4 alkenyl, or OC2-4 alkynyl, such as H, CH3, or OCH3, particularly H or OCH3, more particularly H;
• R3 is —(CH2)n3—C(Y3)—(X3)m3—(CH2)k3—R3a,
• n3 is an integer in the range of 0 to 2, such as 0 or 2,
• Y3 is S or O, such as O,
• X3 is S, NH, or O, such as NH or O, particularly NH,
• m3 is 0 or 1,
• k3 is 0 or 1,
• R3a is C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, OC1-4 alkyl, OC2-4 alkenyl, OC2-4 alkynyl Het3, Ar3, HetCyc3 or Cyc3, such as C1-4 alkyl or Het3,
• Het3 is a 5- to 10-membered heteroaromatic ring or ring system containing one or more heteroatoms selected from the group consisting of N, O, and S, such as oxazolyl, thiazolyl, or pyridinyl, particularly oxazol-4-yl, thiazol-4-yl, or pyridin-4-yl,
• Ar3 is a 6- to 10-membered aromatic ring or ring system, such as phenyl or naphtyl,
• HetCyc3 is a 3- to 8-membered heterocyclyl containing one or more heteroatoms selected from the group consisting of N, O, and S, such as pyrrolidinyl, oxazolidinyl, morpholinyl,
• Cyc3 is a 3- to 8-membered cyclyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl;
• R4 is halogen, OC1-4 alkyl , OC2-4 alkenyl, OC2-4 alkynyl, C1-4 alkyl, C2-4 alkenyl or C2-4 alkynyl, such as halogen or C1-2 alkyl, particularly Cl, F, or C1-2 alkyl, more particularly, Cl, F, or CH3, even more particularly Cl or CH3, such as CH3;
• R5 is hydrogen, OC1-4 alkyl, OC2-4 alkenyl, OC2-4 alkynyl, OH, C1-4 alkyl, C2-4 alkenyl, or C2-4 alkynyl, each C1-4 alkyl, C2-4 alkenyl, or C2-4 alkynyl independently optionally substituted with 1 to 3 halogens, such as F, particularly H, C1-2 alkyl, or OC1-2 alkyl, more particularly C1-2 alkyl or OC1-2 alkyl, even more particularly CH3 or OCH3, such as CH3;
• R6 is H, OH, halogen, or NH2, such as H or OH, more particularly H;
• R7 is H, halogen, OH, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, OC1-4 alkyl, OC2-4 alkenyl, or OC2-4 alkynyl such as H, CH3, or OCH3, particularly H or OCH3, more particularly H;
• R8 is —(CH2)n8—(C(O))m8—R8a,
• n8 is an integer from 1 to 2, such as 2, m8 is an integer from 0 to 1, such as 0, and
• R8a is an aromatic or heteroaromatic ring having 5 or 6 ring members, optionally substituted with at least 1 substituent selected from the group consisting of OH, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, OC1-4 alkyl, OC2-4 alkenyl, OC2-4 alkynyl, CO2—C1-4 alkyl, CO2—C2-4 alkenyl, CO2—C2-4 alkynyl, halogen, CONH2, CN, COOH, —OCO—C1-4 alkyl, —OCO—C2-4 alkenyl, —OCO—C2-4 alkynyl, —NHCO—C1-4 alkyl, —NHCO—C2-4 alkenyl, —NHCO—C2-4 alkynyl, NH2, NHC1-4 alkyl, NHC2-4 alkenyl, NHC2-4 alkynyl, N(C1-4 alkyl)2, N(C2-4 alkenyl)2, N(C2-4 alkynyl)2, CONHC1-4 alkyl, CONHC2-4 alkenyl, CONHC2-4 alkynyl, CON(C1-4 alkyl)2, CON(C2-4 alkenyl)2, CON(C2-4 alkynyl)2, such as OH, OCH3, CO2CH3, halogen, CONH2, CN, and COOH, particularly OH, OCH3, CO2CH3, F, CONH2, CN, and COOH, more particularly, OH, OCH3, and F, even more particularly OH and F, such as OH;
• or R8a is an aromatic or heteroaromatic ring having 5 or 6 ring members fused with an additional optionally substituted cyclic, heterocyclic, aromatic, or heteroaromatic ring, such as an optionally substituted cyclic, heterocyclic, or heteroaromatic ring.