Substituted hydroxyethylamine aspartyl protease inhibitors

A method of preventing or treating at least one condition which benefits from inhibition of at least one aspartyl-protease, comprising:

• administering to a host a composition comprising a therapeutically effective amount of at least one compound of formula (I),
• or pharmaceutically acceptable salts thereof, wherein
• R1 is selected from
• wherein
• X, Y, and Z are independently, selected from
• —C(H)0-2—,
• —O—,
• —C(O)—,
• —NH—, and
• —N—,
• wherein at least one bond of the (IIf) ring may optionally be a double bond;
• L is selected from
• —O—,
• —C(O)—,
• —C(R55)(R60)—, and
• —CH(NR55R60)—;
• R55 and R60 are each independently selected from hydrogen and alkyl;
• R50, R50a, and R50b are independently selected from
• —H
• -halogen,
• —OH,
• —C(O)H,
• —C(O)CH3,
• —CH2OH,
• —SH,
• —S(O)0-2CH3,
• —CN,
• —NO2,
• —NH2,
• —NHCH3,
• —N(CH3)2
• —C1—C2 alkyl,
• —OCH3,
• —OCF3, and
• —CF3;
• R2 is selected from
• —H,
• wherein when R1 is benzyl, and RC is 6-Isopropyl-2,2-dioxo-2λ6-isothiochroman-4-yl, R2 is not —H;
• wherein, when R1 is 3,5-difluorobenzyl, and RC is 6-Ethyl-2,2-dioxo-2λ6-isothiochroman-4-yl, R2 is not —H;
• wherein when R1 is 3,5-difluorobenzyl, and RC is 7-ethyl-1,2,3,4-tetrahydro-naphthalen-1-yl, R2 is not —H;
• —OH,
• —O-alkyl, optionally substituted with at least one group independently selected from R200;
• —O-aryl, optionally substituted with at least one group, independently selected from R200;
• -alkyl, optionally substituted with at least one group independently selected from R200;
• —NH-alkyl, optionally substituted with at least one group independently selected from R200;
• -heterocycloalkyl, (wherein at least one carbon is optionally replaced with a group independently selected from —(CR245R250)—, —O—, —C(O)—, —C(O)C(O)—, —N(R200)0-1, and —S(O)0-2—, and wherein the heterocycloalkyl is optionally substituted with at least one group independently selected from R200);
• —NH-heterocycloalkyl, wherein at least one carbon is optionally replaced with a group independently selected from —(CR245R250)—, —O—, —C(O)—, —C(O)C(O)—, —N(R200)0-2—, and —S(O)0-2—, and wherein the heterocycloalkyl is optionally substituted with at least one group Independently selected from R200;
• —C(O)—N(R315)(R320),
• wherein R315 and R320 are each independently selected from —H, -alkyl, and phenyl,
• wherein when R1 is 3,5-difluorobenzyl, and RC is 7-ethyl-1,2,3,4-tetrahydro-naphthalen-1-yl, R2 is not methylcarbamoyl;
• —O—C(O)—N(R315)(R320),
• —NH—R400,
• —R400,
• —NH—R500,
• —R500
• —NH—R600,
• —R600, and
• —NH—R700,
• R400 is
• wherein R405 is selected from —H, —N(R515)2, and O-alkyl;
• R500 is a heteroaryl selected from III(a) and III(b),
• wherein
• M1 and M4 are independently selected from
• —C(R505)—,
• —N—,
• —N(R515)—,
• —S—, and
• —O—;
• M2 and M3 are independently selected from
• —C(R510)—,
• —N—,
• —N(R520)—,
• —S—, and
• —O—;
• M5 is selected from —C— and —N—;
• R505 is independently selected from
• —H,
• -alkyl,
• -halogen,
• —NO2,
• —CN,
• —R200, and
• phenyl;
• R510 is independently selected from
• —H,
• -alkyl,
• -halogen,
• -amino,
• —CF3,
• —R200, and
• -phenyl;
• R515 is independently selected from
• —H,
• -alkyl, and
• -phenyl;
• R520 is independently selected from
• —H,
• -alkyl,
• —(CH2)0-2-phenyl, and
• —C(Ph)3;
• R600 is a monocyclic, bicyclic, or tricyclic heteroaryl ring system of 6, 7, 8, 9, 10, 11, 12, 13, or 14 atoms, optionally substituted with at least one group independently selected from R605;
• R605 is selected from -hydrogen, -halogen, -alkyl, -phenyl, alkyl-O—C(O)—, -nitro, —CN, -amino, —NR220R225, -thioalkyl, —CF3, —OH, —O-alkyl, and -heterocycloalkyl;
• wherein when R1 is 3,5-difluoro-benzyl, and RC is 6-ethyl-2,2-dioxo-2λ6-isothiochroman-4-yl, R2 is not Benzothiazol-2-ylamino, or Benzooxazol-2-ylamino;
• wherein when R1 is 3,5-difluoro-benzyl, and RC is 3-methoxy-benzyl, R2 is not 3-methyl-5-nitro-3H-imidazol-4-ylamino, Benzooxazol-2-ylamino, 1-phenyl-1H-tetrazol-5-ylamino, Benzothiazol-2-ylamino;
• or 2,5-dimethyl-4-nitro-2H-pyrazol-3-ylamino;
• R700 is aryl optionally substituted with at least one R205;
• RC is selected from
• —(CH2)0-3-cycloalkyl wherein the cycloalkyl is optionally substituted with at least one group independently selected from —R205 and —CO2-(alkyl),
• -alkyl optionally substituted with at least one group independently selected from R205,
• —(CR245R250)0-4—RX, wherein at least one —(CR245R250)— is optionally replaced with a group independently selected from —O—, —N(R215)—, —C(O)1-2—, —C(O)N(R215)—, and —S(O)0-2—, and
• -formulae (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), and (IVg);
• RX is selected from
• -hydrogen,
• -aryl,
• -heteroaryl,
• -cycloalkyl,
• -heterocycloalkyl, and
• —RXa—RXb, wherein RXa and RXb are independently selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl;
• wherein each aryl or heteroaryl group attached directly or indirectly to —(CR245R250)0-4— is optionally substituted with at least one group independently selected from R200;
• wherein each cycloalkyl or heterocycloalkyl group attached directly or indirectly to —(CR245R250)0-4— is optionally substituted with at least one group independently selected from R210 and —(CR245R250)0-4—R200;
• wherein at least one atom of the heteroaryl or heterocycloalkyl group attached directly or indirectly to —(CR245R250)0-4— is independently optionally replaced with a group selected from —O—, —C(O)—, —N(R215)0-1—, and —S(O)0-2—;
• wherein at least one heteroatom of the heteroaryl or heterocycloalkyl group attached directly or indirectly to —(CR245R250)0-4— is independently optionally substituted with a group selected from
• —(CO)0-1R215,
• —(CO)0-1R220,
• —S(O)0-2R200, and
• —N(R200)—S(O)0-2R200;
• R245 and R250 at each occurrence are independently selected from
• —H,
• —(CH2)0-4C(O)—OH,
• —(CH2)0-4C(O)—O-alkyl,
• —(CH2)0-4C(O)-alkyl,
• -alkyl,
• -hydroxyalkyl,
• —O-alkyl,
• -haloalkoxy,
• —(CH2)0-4-cycloalkyl,
• —(CH2)0-4-aryl,
• —(CH2)0-4-heteroaryl, and
• —(CH2)0-4-heterocycloalkyl;
• or
• R245 and R250 are taken together with the. carbon to which they are attached to form a monocyclic or bicyclic ring system of 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms,
• wherein at least one bond in the monocyclic or bicyclic ring system is optionally a double bond,
• wherein the bicyclic ring system is optionally a fused or spiro ring system,
• wherein at least one carbon atom in the monocyclic or bicyclic ring system is optionally replaced by a group independently selected from
• —O—,
• —C(O)—,
• —S(O)0-2—,
• —(═N—R255)—,
• —N—,
• —NR220—,
• —NR((CO)0-1R200)—, and
• —N(SO2R200)—;
• wherein the aryl, heteroaryl, and heterocycloalkyl groups included in R245 and R250 are optionally substituted with at least one group independently selected from -halogen, -alkyl, —N(R220)(R225), —CN, and —OH;
• wherein the monocyclic and bicyclic groups included in R245 and R250 are optionally substituted with at least one group independently selected from halogen, —(CH2)0-2—OH, —O-alkyl, alkyl, —(CH2)0-2—S-alkyl, —CF3, aryl, —N(R220)(R225), —CN, —(CH2)0-2—NH2, —(CH2)0-2—NH(alkyl), —NHOH, —NH—O-alkyl, —N(alkyl)(alkyl), —NH—C(O)-alkyl, and —NHS(O2)-alkyl;
• formula (IVa) is
• wherein Q1 is selected from (—CH2—)0-1, —CH(R200)—, —C(R200)2—, and —C(O)—;
• Q2 and Q3 each are independently selected from (—CH2—)0-1, —CH(R200)—, —C(R200)2—, —O—, —C(O)—, —S—, —S(O)2—, —NH—, and —N(R7)—;
• Q4 is selected from a bond, (—CH2—)0-1, —CH(R200)—, 13 C(R200)2—, —O—, —C(O)—, —S—, —S(O)2—, —NH—, and —N(R7);
• and
• P1, P2, P3, and P4 each are independently selected from —CH—, —C(R200)—, and —N—;
• formula (IVb) is
• wherein R4 is selected from —H and -alkyl, and
• P1, P2, P3, and P4 at each occurrence are independently selected from —CH—, —C(R200)—, and —N—;
• formula (IVc) is
• wherein R4 is selected from —H and -alkyl;
• and
• P1, P2, P3, and P4 at each occurrence are independently selected from —CH—, —CR200—, and —N—;
• formula (IVd) is
• wherein m is 0, 1, 2, 3, 4, 5, or 6;
• Y′ is selected from —H, —CN, —OH, —O-alkyl, —CO2H, —C(O)OR215, -amino, -aryl, and -heteroaryl;
• and
• P1 and P2 at each occurrence are independently selected from —CH—, —C(R200)—, and —N—,
• or P1 and P2 are optionally taken together to form a monocyclic or bicyclic ring system of 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms,
• P3 and P4 at each occurrence are independently selected from —CH—, —C(R200)—, and —N—,
• or P3 and P4 are optionally taken together to form a monocyclic or bicyclic ring system of 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms,
• P5 at each occurrence is independently selected from —CH—, —C(R200)—, and —N—,
• wherein at least one bond in the monocyclic or bicyclic ring system included in P1 and P2 or P3 and P4 is optionally a double bond,
• wherein the bicyclic ring system included in P1 and P2 or P3 and P4 is optionally a fused or spiro ring system,
• wherein at least one carbon atom in the monocyclic or bicyclic ring system included in P1 and P2 or P3 and P4 is optionally replaced by a group independently selected from
• —O—,
• —C(O)—,
• —S(O)0-2—,
• —C(═N—R255)—,
• —N—,
• —NR220—,
• —N((CO)0-1R200)—, and
• —N(SO2R200)—;
• formula (IVe) is
• wherein
• U is selected from —CH2—CR100R101—, —CH2—S—, —CH2—S(O)—, —CH2—S(O)2—, —CH2—N(R100)—, —CH2—C(O)—, —CH2—O—, —C(O)—C(R100)(R101)—, —SO2—N(R100)—, —C(O)—N(R55)—, —N(R55)—C(O)—N(R55)—, —O—C(O)—O—, —N(R55)—C(O)—O—, and —C(O)—O—;
• wherein R100 and R101 at each occurrence are independently selected from —H, -alkyl, -aryl, —C(O)-alkyl, —(CO)0-1R215, —(CO)0-1R220, and —S(O)2-alkyl;
• formula (IVf) is
• wherein the B ring is optionally substituted with at least one group independently selected from -alkyl, -halogen, —OH, —SH, —CN, —CF3, —O-alkyl, —N(R5)C(O)H, —C(O)H, —C(O)N(R5)(R6), —NR5R6, R280, R285, -aryl, and -heteroaryl;
• wherein R280 and R285, and the carbon to which they are attached form a C3—C7 spirocycle which is optionally substituted with at least one group independently selected from -alkyl, —O-alkyl, -halogen, —CF3, and —CN;
• wherein the A ring is aryl or heteroaryl, each optionally substituted with at least one group independently selected from R290 and R295;
• wherein R290 and R295 at each occurrence are independently selected from -alkyl optionally substituted with at least one group selected from -alkyl, -halogen, —OH, —SH, —CN, —CF3, —O-alkyl, and —NR5R6,
• —OH,
• —NO2,
• -halogen,
• —CO2H,
• —CN,
• —(CH2)0-4—C(O)—NR21R22,
• —(CH2)0-4—CO2R20,
• —(CH2)0-4—SO2NR21R22,
• —(CH2)0-4S(O)-alkyl),
• —(CH2)0-4—S(O)2-(alkyl),
• —(CH2)0-4—S(O)2-(cycloalkyl),
• —(CH2)0-4—N(H or R20)—C(O)—O—R20,
• —(CH2)0-4—N(H or R20)—C(O)—N(R20)2,
• —(CH2)0-4—N—C(S)—N(R20)2,
• —(CH2)0-4—N(H or R20)—CO—R21,
• —(CH2)0-4—NR21R22,
• —(CH2)0-4—R11,
• —(CH2)0-4—O—C(O)-(alkyl),
• —(CH2)0-4—O—P(O)—(OR5)2,
• —(CH2)0-4—O—C(O)—N(R20)2,
• —(CH2)0-4—O—C(S)—N(R20)2,
• —(CH2)0-4—O—(R20)2,
• —(CH2)0-4—O—(R20)—CO2H,
• —(CH2)0-4—S—(R20),
• —(CH2)0-4—O-(alkyl optionally substituted with at least one halogen),
• -cycloalkyl,
• —(CH2)0-4—N(H or R20)—S(O)2—R21, and
• —(CH2)0-4-cycloalkyl;
• formula (IVg) is
• wherein
• a is 0 or 1;
• b is 0 or 1;
• S′ is selected from —C(O)— and —CO2—;
• T′ is —(CH2)0-4—;
• U′ is —(CR245R250)—;
• V′ is selected from -aryl- and -heteroaryl-;
• W′ is selected from
• -a bond,
• -alkyl-substituted with at least one group independently selected from R205,
• —(CH2)0-4—(CO)0-1—N(R220)—,
• —(CH2)0-4—(CO)0-1—,
• —(CH2)0-4—CO2—,
• —(CH2)0-4—SO2—N(R220)—,
• —(CH2)0-4—N(H or R215)—CO2—,
• —(CH2)0-4—N(H or R215)—SO2—,
• —(CH2)0-4—N(H or R215)—C(O)—N(R215)—,
• —(CH2)0-4—N(H or R215)—C(O)—,
• —(CH2)0-4—N(R220)—,
• —(CH2)0-4—O—, and
• —(CH2)0-4—S—;
• X′ is selected from aryl and heteroaryl;
• wherein each cycloalkyl included in formula (IVg) is optionally substituted with at least one group independently selected from R205;
• wherein each aryl or heteroaryl group included in formula (IVg) is optionally substituted with at least one group independently selected from R200;
• wherein at least one heteroatom of the heteroaryl group included within formula (IVg) is optionally substituted with a group selected from
• —(CO)0-1R215,
• —(CO)0-1R220, and
• —S(O)0-2R200;
• R21 and R22 each independently are selected from
• —H,
• -alkyl optionally substituted with at least one group independently selected from —OH, amino, -halogen, -alkyl, -cycloalkyl, -(alkyl-cycloalkyl), -alkyl-O-alkyl, —R17, and —R18,
• —(CH2)0-4—C(O)-(alkyl),
• —(CH2)0-4—C(O)-(cycloalkyl),
• —(CH2)0-4—C(O)—R17,
• —(CH2)0-4—C(O)—R18,
• —(CH2)0-4—C(O)—R19, and
• —(CH2)0-4—C(O)—R11;
• R17 at each occurrence is aryl optionally substituted with at least one group independently selected from
• -alkyl optionally substituted with at least one group independently selected from -alkyl, -halogen, —OH, —SH, —NR5R6, —CN, —CF3, and —O-alkyl,
• -halogen,
• —O-alkyl optionally substituted with at least one group independently selected from halogen, —NR21R22, —OH, —CN, and -cycloalkyl optionally substituted with at least one group independently selected from -halogen, —OH, —SH, —CN, —CF3, —O-alkyl, and —NR5R6,
• —C(O)-(alkyl),
• —S(O)—O—NR5R6,
• —C(O)—NR5R6, and
• —S(O)2-(alkyl);
• R18 at each occurrence is heteroaryl optionally substituted with at least one group independently selected from
• -alkyl optionally substituted with at least one group independently selected from -alkyl, -halogen, —OH, —SH, —CN, —CF3, —O-alkyl, and —NR5R6,
• -halogen,
• —O-alkyl optionally substituted with at least one group independently selected from -halogen, —NR21R22, —OH, and —CN,
• -cycloalkyl optionally substituted with at least one group independently selected from -halogen, —OH, —SH, —CN, CF3, —O-alkyl, and —NR5R6,
• —C(O)-alkyl),
• —S(O)2—NR5R6,
• —C(O)—NR5R6, and
• —S(O)2-(alkyl);
• R19 at each occurrence is heterocycloalkyl wherein at least one carbon is optionally replaced with —C(O)—, —S(O)—, and —S(O)2—, wherein the heterocycloalkyl is optionally substituted with at least one group independently selected from
• -alkyl optionally substituted with at least one group independently selected from -alkyl, -halogen, —OH, —SH, —CN, —CF3, —O-alkyl, and —NR5R6,
• -halogen,
• —O-alkyl optionally substituted with at least one group independently selected from -halogen, —OH, —CN, —NR21R22, and -cycloalkyl optionally substituted with at least one group independently selected from -halogen, —OH, —SH, —CN, —CF3, —O-alkyl, and —NR5R6,
• —C(O)-(alkyl),
• —S(O)2—NR5R6,
• —C(O)—NR5R6, and
• —S(O)2-(alkyl);
• R11 at each occurrence is heterocycloalkyl
• wherein at least one carbon of the heterocycloalkyl is optionally replaced with —C(O)—, —S—(O)—, and —S(O)2—,
• wherein the heterocycloalkyl is optionally substituted with at least one group independently selected from -alkyl, —O-alkyl, and -halogen;
• R20 is selected from -alkyl, -cycloalkyl, —(CH2)0-2—(R17), and —(CH2)0-2—(R18);
• R200 at each occurrence is independently selected from
• -alkyl optionally substituted with at least one group independently selected from R205,
• —OH,
• —NO2,
• —NH2,
• -halogen,
• —CN,
• —CF3,
• —OCF3,
• —(CH2)0-4—C(O)H,
• —(CO)0-1R215,
• —(CO)0-1R220,
• —(CH2)0-4—C(O)—NR220R225,
• —(CH2)0-4—(C(O))0-1—R215,
• —(CH2)0-4—(C(O))0-1—R220,
• —(CH2)0-4—C(O)-alkyl,
• —(CH2)0-4—(C(O))0-1-cycloalkyl,
• —(CH2)0-4—(C(O))0-1-heterocycloalkyl,
• —(CH2)0-4—C(O)0-1-aryl,
• —(CH2)0-4—(C(O)0-1-heteroaryl,
• —(CH2)0-4—C(O)—O—R215,
• —(CH2)0-4—S(O)0-2—NR220R225,
• —(CH2)0-4—S(O)0-2-alkyl,
• —(CH2)0-4S(O)0-2-cycloalkyl,
• —(CH2)0-4—N(H or R215)—C(O)—O—R215,
• —(CH2)0-4—N(H or R215)—S(O)1-2—R220,
• —(CH2)0-4—N(H or R215)—C(O)—N(R215)2,
• —(CH2)0-4—N(H or R215)—C(O)—R220,
• —(CH2)0-4—NR220R225,
• —(CH2)0-4—O—C(O)-alkyl,
• —(CH2)0-4—O—(R215),
• —(CH2)0-4—S—(R215),
• —(CH2)0-4—C(O)H,
• —(CH2)0-4—O-(alkyl optionally substituted with at least one halogen), and
• -adamantane,
• wherein each aryl and heteroaryl group included within R200 is optionally substituted with at least one group independently selected from
• —R205,
• —R210, and
• -alkyl optionally substituted with at least one group independently selected from R205 and R210;
• wherein each cycloalkyl or heterocycloalkyl group included within R200 is optionally substituted with at least one group independently selected from
• —R205,
• —R210, and
• -alkyl optionally substituted with at least one group independently selected from R205 and R210;
• R205 at each occurrence is independently selected from
• -alkyl,
• -heteroaryl,
• -heterocycloalkyl,
• -aryl,
• -haloalkoxy,
• —(CH2)0-3-cycloalkyl,
• -halogen,
• —(CH2)0-6—OH,
• —O-phenyl,
• —SH,
• —(CH2)0-4—C(O)CH3
• —(CH2)0-4—C(O)H
• —(CH2)0-4—CO2H,
• —(CH2)0-6—CN,
• —(CH2)0-6—C(O)—NR235R240,
• —(CH2)0-6—C(O)—R235,
• —(CH2)0-4—N(H or R215)—SO2—R235,
• —CF3,
• —CN,
• —OCF3,
• —C(O)2-benzyl,
• —O-alkyl,
• —C(O)2-alkyl, and
• —NR235R240;
• R210 at each occurrence is independently selected from
• —OH,
• —CN,
• —(CH2)0-4—C(O)H,
• -alkyl wherein a carbon atom is optionally replaced with —C(O)—, and a carbon atom is optionally substituted with at least one group independently selected from R205,
• —S-alkyl,
• -halogen,
• —O-alkyl,
• -haloalkoxy,
• —NR220R225,
• -cycloalkyl optionally substituted with at least one group independently selected from R205,
• —C(O)-alkyl,
• —S(O)2—NR235R240,
• —C(O)—NR235R240, and
• —S(O)2-alkyl;
• R215 at each occurrence is independently selected from
• -alkyl,
• —(CH2)0-2-aryl,
• —(CH2)0-2-cycloalkyl,
• —(CH2)0-2-heteroaryl, and
• —(CH2)0-2-heterocycloalkyl;
• wherein the aryl groups included within R215 are optionally substituted with at least one group independently selected from R205 or R210;
• wherein the heterocycloalkyl and heteroaryl groups included within R215 are optionally substituted with at least one group independently selected from R210;
• R220 and R225 at each occurrence are independently selected from
• —H,
• —OH,
• -alkyl,
• —(CH2)0-4—C(O)H,
• -alkyl-OH,
• —(CH2)0-4CO2-alkyl, wherein alkyl is optionally substituted with at least one group independently selected from R205,
• -aminoalkyl,
• —S(O)2-alkyl,
• —(CH2)0-4—C(O)-alkyl, wherein alkyl is optionally substituted with at least one group independently selected from R205,
• —(CH2)0-4—C(O)—NH2,
• —(CH2)0-4—C(O)—NH(alkyl), wherein alkyl is optionally substituted with at least one group independently selected from R205,
• —(CH2)0-4—C(O)—N(alkyl)(alkyl),
• -haloalkyl,
• —(CH2)0-2-cycloalkyl,
• -alkyl-O-alkyl,
• —O-alkyl,
• -aryl,
• -heteroaryl, and
• -heterocycloalkyl;
• wherein the aryl, heteroaryl and heterocycloalkyl groups included within R220 and R225 are each optionally substituted with at least one group independently selected from R270;
• R270 at each occurrence is independently selected from
• —R205,
• -alkyl optionally substituted with at least one group independently selected from R205,
• -phenyl,
• -halogen,
• —O-alkyl,
• -haloalkoxy,
• —NR235R240,
• —OH,
• —CN,
• -cycloalkyl optionally substituted with at least one group independently selected from R205,
• —C(O)-alkyl,
• —S(O)2—NR235R240,
• —CO—NR235R240,
• —S(O)2-alkyl, and
• —(CH2)0-4—C(O)H;
• R235 and R240 at each occurrence are independently selected from
• —H,
• -alkyl,
• —C(O)-alkyl,
• —OH,
• —CF3,
• —OCH3,
• —NH—CH3,
• —N(CH3)2,
• —(CH2)0-4—C(O)—(H or alkyl),
• —SO2-alkyl, and
• -phenyl;
• R255 is selected from -hydrogen, —OH, —N(R220)(R225), and —O-alkyl;
• R5 and R6 are independently selected from —H and -alkyl, or
• R5 and R6, and the nitrogen to which they are attached, form a 5 or 6 membered heterocycloalkyl ring;
• and
• R7 is independently selected from
• —H,
• -alkyl optionally substituted with at least one group independently selected from —OH, amino, and halogen,
• -cycloalkyl, and
• -alkyl-O-alkyl.