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US 2003/0125365 A1Published application
Hydroxypropylamines
AssigneePharmacia & Upjohn Company
InventorsJed F. Fisher, Jon S. Jacobs, Brian Sherer
Life of this patent
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Abstract
Disclosed are compounds of formula I: 1 and the pharmaceutically acceptable salts thereof wherein the variables RN, R1, R2, R3, RP and RC are defined herein. These compounds are useful in treating Alzheimer's disease and other similar diseases. These compounds include inhibitors of the beta-secretase enzyme that are useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal. The compounds of the invention are useful in pharmaceutical compositions and methods of treatment to reduce A beta peptide formation.
Claims24
A compound of the formula:
- 14
- or a pharmaceutically acceptable salts thereof wherein
- R1 is —(CH2)1-2—S(O)0-2-(C1-C6 alkyl), or
- C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, —OH, ═O, —SH, —C≡N, —CF3, —C1-C3 alkoxy, amino, mono- or dialkylamino, —N(R)C(O)R′—, —OC(═O)-amino and —OC(═O)-mono- or dialkylamino, or
- C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, amino, and mono- or dialkylamino, or
- aryl, heteroaryl, heterocyclyl, aryl-(C1-C6)alkyl-, heteroaryl-(C1-C6)alkyl-, or heterocyclyl-(C1-C6)alkyl-, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, —OH, —SH, —C≡N, —NO2, —NR105R′105, —CO2R, —N(R)COR′, —N(R)SO2R′, —C (═O)—(C1-C4) alkyl, —SO2-amino, —SO2-monoalkylamino, —SO2-dialkylamino, —C(═O)-amino, —C(═O)-monoalkylamino, —C(═O)-dialkylamino, —SO2—(C1-C4) alkyl,
- C1-C6 alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen,
- C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, amino, —C1-C6 alkyl and mono- or dialkylamino,
- C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, —OH, —SH, —C═N. —CF3, —C1-C3 alkoxy, amino, mono- or dialkylamino and —C1-C3 alkyl, and
- C2-C10 alkenyl or C2-C10 alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, amino, C1-C6 alkyl and mono- or dialkylamino;
- and the heterocyclyl group is optionally further substituted with oxo;
- R and R′ independently are hydrogen, C1-C10 alkyl, C1-C10 alkylaryl or C1-C10 alkylheteroaryl;
- R2 is —H, or is C1-C6 alkyl, optionally substituted with one, two or three substituents independently selected from the group consisting of C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —CON, —CF3, C1-C3 alkoxy, —NRR′;
- R3 is —H or is C1-C6 alkyl, optionally substituted with one, two or three substituents independently selected from the group consisting of C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, SH, —CON, —CF3, C1-C3 alkoxy, —NRR′;
- or
- R2 and R3 together with the carbon atom to which they are attached form a carbocycle of three, four, five, six, or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO2—, —NR105—;
- RP is a hydrogen or a protecting group;
- RN is R′100, —SO2R′100, —(CRR′)1-6R′100, —C(═O)—(CRR′)1-6R100, —C(═O)—(CRR′)1-6—O—R′100, —C (═O)—(CRR′)1-6—S—R′100, —C (═O)—(CRR′)1-6—C(═O)—R100, —C(═O)—(CRR′)1-6—SO2—R100 or —C(═O)—(CRR′)1-6—NR100—R′100;
- R100 and R′100 independently represent aryl, heteroaryl, heterocyclyl, -aryl-W-aryl, -aryl-W-heteroaryl, -aryl-W-heterocyclyl, -heteroaryl-W-aryl, -heteroaryl-W-heteroaryl, -heteroaryl-W-heterocyclyl, -heterocyclyl-W-aryl, -heterocyclyl-W-heteroaryl, -heterocyclyl-W-heterocyclyl, —CH[(CH2)0-2—O—R150]-(CH2)0-2-aryl, —CH[(CH2)0-2-O—R150]-(CH2)0-2-heterocyclyl or —CH[(CH2)0-2—O—R150]-(CH2)0-2-heteroaryl, where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from
- —OR, —NO2, C1-C6 alkyl, halogen, —C≡N, —OCF3, —CF3, —(CH2)0-4—O—P (═O)(OR)(OR′), —(CH2)0-4—CO—NR105R′105, —(CH2)0-4—O—(CH2)0-4—CONR102R102′, —(CH2)0-4—CO—(C1-C12 alkyl), —(CH2)0-4—CO—(C2-C12 alkenyl), —(CH2)0-4—CO—(C2-C12 alkynyl), —(CH2)0-4—CO—(CH2)0-4 (C3-C7 cycloalkyl), —(CH2)0-4—R110, —(CH2)0-4—R120, —(CH2)0-4—R130, —(CH2)0-4—CO—R110, —(CH2)0-4—CO—R120, —(CH2)0-4—CO—R130, —(CH2)0-4—CO—R140, —(CH2)0-4—CO—O—R150, —(CH2)0-4—SO2—NR105R′105, —(CH2)0-4—SO—(C1-C8 alkyl), —(CH2)0-4—SO2—(C1-C12 alkyl), —(CH2)0-4—SO2—(CH2)0-4—(C3-C7 cycloalkyl), —(CH2)0-4—N(R150)—CO—O—R150, —(CH2)0-4—N(R150)—CO—N(R150)2, —(CH2)0-4—N(R150)—CS—N(R150)2, —(CH2)0-4—N(R150)—CO—R105, —(CH2)0-4—NR105R′105, —(CH2)0-4—R140, —(CH2)0-4—O—CO—(C1-C6 alkyl), —(CH2)0-4—O—P(O)—(O—R110)2, —(CH2)0-4—O—CO—N(R150)2, —(CH2)0-4—O—CS—N(R150)2, —(CH2)0-4—O—(R150) —(CH2)0-4—O—R150′—COOH, —(CH2)0-4—S—(R150) —(CH2)0-4—N(R150) —SO2—R105, —(CH2)0-4—C3-C7 cycloalkyl, (C2-C10)alkenyl, and (C2-C10)alkynyl, or
- R100 is C1-C10 alkyl optionally substituted with 1, 2, or 3 R115 groups, or
- R100 is —(C1-C6 alkyl)-O—(C1-C6 alkyl) or —(C1-C6 alkyl)-S—(C1-C6 alkyl), each of which is optionally substituted with 1, 2, or 3 R115 groups, or
- R100 is C3-C8 cycloalkyl optionally substituted with 1, 2, or 3 R115 groups;
- W is —(CH2)0-4—, —O—, —S(O)0-2—, —N(R135)—, —CR(OH)— or —C(O)—;
- R102 and R102′ independently are hydrogen, or
- C1-C10 alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, aryl or —R110;
- R105 and R′105 independently represent —H, —R110, —R120, C3-C7 cycloalkyl, —(C1-C2 alkyl)-(C3-C7 cycloalkyl), —(C1-C6 alkyl)-O—(C1-C3 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, or C1-C6 alkyl chain with one double bond and one triple bond, or
- C1-C6 alkyl optionally substituted with —OH or —NH2;
- or,
- C1-C6 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, or
- R105 and R′105 together with the atom to which they are attached form a 3 to 7 membered carbocylic ring, where one member is optionally a heteratom selected from —O—, —S(O)0-2—, —N(R135)—, the ring being optionally substituted with 1, 2 or 3 independently selected R140 groups;
- R115 at each occurrence is independently halogen, —OH, —CO2R102, —C1-C6 thioalkoxy, —CO2-phenyl, —NR105R′135, —SO2—(C1-C8 alkyl), —C-(═O)R180, R180, —CONR105R′105, —SO2NR105R′105, —NH—CO—(C1-C6 alkyl), —NH—C (═O) —OH, —NH—C (═O) —OR, —NH—C (═O) —O-phenyl, —O—C-(═O)—(C1-C6 alkyl), —O—C-(═O)-amino, —O—C (═O)-mono- or dialkylamino, —O—C-(═O)-phenyl, —O—(C1-C6 alkyl)-CO2H, —NH—SO2—(C1-C6 alkyl), C1-C6 alkoxy or C1-C6 haloalkoxy;
- R135 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, —(CH2)0-2-(aryl), —(CH2)0-2-(heteroaryl), or —(CH2)0-2-(heterocyclyl);
- R140 is heterocyclyl optionally substituted with 1, 2, 3, or 4 groups independently selected from C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, cyano, nitro, amino, mono(C1-C6)alkylamino, di(C1-C6)alkylamino, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, amino(C1-C6)alkyl, mono(C1-C6)alkylamino(C1-C6)alkyl, di(C1-C6)alkylamino(C1-C6)alkyl, and ═O;
- R150 is hydrogen, C3-C7 cycloalkyl, —(C1-C2 alkyl)-(C3-C7 cycloalkyl), C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl with one double bond and one triple bond, —R110, —R120, or
- C1-C6 alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from —OH, —NH2, C1-C3 alkoxy, R110, and halogen;
- R150′ is C3-C7 cycloalkyl, —(C1-C3 alkyl)-(C3-C7 cycloalkyl), C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl with one double bond and one triple bond, —R110, —R120, or
- C1-C6 alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from —OH, —NH2, C1-C3 alkoxy, R110, and halogen;
- R180 is selected from morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl, each of which is optionally substituted with 1, 2, 3, or 4 groups independently selected from C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, cyano, nitro, amino, mono(C1-C6)alkylamino, di(C1-C6)alkylamino, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, amino(C1-C6)alkyl, mono(C1-C6)alkylamino(C1-C6)alkyl, di(C1-C6)alkylamino(C1-C6)alkyl, and ═O;
- R110 is aryl optionally substituted with 1 or 2 R125 groups;
- R125 at each occurrence is independently halogen, amino, mono- or dialkylamino, —OH, —C≡N, —SO2—NH2, —SO2—NH—C1-C6 alkyl, —SO2—N(C1-C6 alkyl)2, —SO2—(C1-C4 alkyl), —CO—NH2, —CO—NH—C1-C6 alkyl, or —CO—N(C1-C6 alkyl)2, or
- C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups that are independently selected from C1-C3 alkyl, halogen, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, amino, and mono- and dialkylamino, or
- C1-C6 alkoxy optionally substituted with one, two or three of halogen;
- R120 is heteroaryl, which is optionally substituted with 1 or 2 R125 groups;
- and
- R130 is heterocyclyl optionally substituted with 1 or 2 R125 groups;
- RC is hydrogen, —(CR245R250)0-4-aryl, —(CR245R250)0-4-heteroaryl, (CR245R250)0-4-heterocyclyl, —(CR245R250)0-4-aryl-heteroaryl, (CR245R250)0-4-aryl-heterocyclyl, —(CR245R250)0-4-aryl-aryl, —(CR245R250)0-4-heteroaryl-aryl, —(CR245R250)0-4-heteroaryl-heterocyclyl, —(CR245R250)0-4-heteroaryl-heteroaryl, —(CR245R250)0-4-heterocyclyl-heteroaryl, —(CR245R250)0-4-heterocyclyl-heterocyclyl, —(CR245R250)0-4-heterocyclyl-aryl, —[C(R255) (R260)]1-3—CO—N—(R255)2, —CH (aryl)2, —CH (heteroaryl)2, —CH(heterocyclyl)2, —CH(aryl) (heteroaryl), —(CH2)0-1—CH((CH2)0-6-OH)—(CH2)0-1-aryl, —(CH2)0-1—CH((CH2)0-6—OH—(CH2)0-1-heteroaryl, —CH (-aryl or -heteroaryl) —CO—O(C1-C4 alkyl), —CH (—CH2—OH) —CH(OH)-phenyl-NO2, (C1-C6 alkyl) —O—(C1-C6 alkyl) —OH;
- —CH2—NH—CH2—CH (—O—CH2—CH3)2, —(CH2)0-6—C(═NR235)(NR235R240), or
- C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, —OC═ONR235R240, —S (═O)0-2 (C1-C6 alkyl), —SH, —NR235C═ONR235R240, —C═ONR235R240, and —S (═O)2NR235R240, or —(CH2)0-3-(C3-C8) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, —CO2H, and —CO2—(C1-C4 alkyl), or
- cyclopentyl, cyclohexyl, or cycloheptyl ring fused to aryl, heteroaryl, or heterocyclyl wherein one, two or three carbons of the cyclopentyl, cyclohexyl, or cycloheptyl is optionally replaced with a heteroatom independently selected from NH, NR215, 0, or S(═O)0-2, and wherein the cyclopentyl, cyclohexyl, or cycloheptyl group can be optionally substituted with one or two groups that are independently R205, ═O, —CO—NR235R240, or —SO2—(C1-C4 alkyl), or
- C2-C10 alkenyl or C2-C10 alkynyl, each of which is optionally substituted with 1, 2, or 3 R205 groups, wherein
- each aryl and heteroaryl is optionally substituted with 1, 2, or 3 R200, and wherein each heterocyclyl is optionally substituted with 1, 2, 3, or 4 R210;
- R200 at each occurrence is independently selected from —OH, —NO2, halogen, —CO2H, C≡N, —(CH2)0-4—CO—NR220R225, —(CH2)0-4—CO—(C1-C12 alkyl), —(CH2)0-4—CO—(C2-C12 alkenyl), —(CH2)0-4—CO—(C2-C12 alkynyl), —(CH2)0-4-CO—(C3-C7 cycloalkyl), —(CH2)0-4—CO-aryl, —(CH2)0-4—CO-heteroaryl, —(CH2)0-4—CO-heterocyclyl, —(CH2)0-4—CO—O—R215, —(CH2)0-4—SO2—NR220R225, —(CH2)0-4—SO—(C1-C8 alkyl), —(CH2)0-4—SO2 (C1-C12 alkyl), —(CH2)0-4—SO2—(C3-C7 cycloalkyl), —(CH2)0-4—N(H or R215)—CO—O—R215, —(CH2)0-4—N(H or R215) —CO—N(R215)2, —(CH2)0-4—N—CS—N(R215)2, —(CH2)0-4—N (—H or R215) —CO—R220, —(CH2)0-4—NR220R225, —(CH2)0-4—O—CO—(C1-C6 alkyl), —(CH2)0-4—O—P(O)—(OR240)2, —(CH2)0-4—O—CO—N(R215)2, —(CH2)0-4—O—CS—N(R215)2, —(CH2)0-4—O—(R215), —(CH2)0-4—O—(R215) —COOH, —(CH2)0-4—S—(R215), —(CH2)0-4—O—(C1-C6 alkyl optionally substituted with 1, 2, 3, or 5 —F), C3-C7 cycloalkyl, —(CH2)0-4—N(H or R215)—SO2—R220, —(CH2)0-4—C3-C7 cycloalkyl, or
- C1-C10 alkyl optionally substituted with 1, 2, or 3 R205 groups, or
- C2-C10 alkenyl or C2-C10alkynyl, each of which is optionally substituted with 1 or 2 R205 groups, wherein
- the aryl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 groups that are independently R205, R210, or
- C1-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein
- the heterocyclyl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R210;
- R205 at each occurrence is independently selected from C1-C6 alkyl, halogen, —OH, —O-phenyl, —SH, —C≡N, —CF3, C1-C6 alkoxy, NH2, NH(C1-C6 alkyl) or N-(C1-C6 alkyl) (C1-C6 alkyl);
- R210 at each occurrence is independently selected from halogen, C1-C6 alkoxy, C1-C6 haloalkoxy, —NR220R225, OH, C≡N, —CO—(C1-C4 alkyl), SO2—NR235R240, —CO—NR235R240, —SO2—(C1-C4 alkyl), ═O, or
- C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 R205 groups;
- R215 at each occurrence is independently selected from C1-C6 alkyl, —(CH2)0-2-(aryl), C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, and —(CH2)0-2-(heteroaryl), —(CH2)0-2-(heterocyclyl), wherein
- the aryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein
- the heterocyclyl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 R210;
- R220 and R225 at each occurrence are independently selected from —H, —C3-C7 cycloalkyl, —(C1-C2 alkyl)-(C3-C7 cycloalkyl), —(C1-C6 alkyl)-O—(C1-C3 alkyl), —C2-C6 alkenyl, —C2-C6 alkynyl, —C1-C6 alkyl chain with one double bond and one triple bond, -aryl, -heteroaryl, and -heterocyclyl, or
- —C1-C10 alkyl optionally substituted with —OH, —NH2 or halogen, wherein
- the aryl, heterocyclyl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 R270 groups
- R235 and R240 at each occurrence are independently H, or C1-C6 alkyl;
- R245 and R250 at each occurrence are independently selected from —H, C1-C4 alkyl, C1-C4 alkylaryl, C1-C4 alkylheteroaryl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, —(CH2)0-4-C3-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, and phenyl;
- or
- R245 and R250 are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms, where one carbon atom is optionally replaced by a heteroatom selected from —O—, —S—, —SO2—, and —NR220—;
- R255 and R260 at each occurrence are independently selected from —H, —(CH2) l-2-S(O)0-2—(C1-C6 alkyl), —(C1-C4 alkyl)-aryl, —(C1-C4 alkyl)-heteroaryl, —(C1-C4 alkyl)-heterocyclyl, -aryl, -heteroaryl, -heterocyclyl, —(CH2)1-4—R265—(CH2)0-4-aryl, —(CH2)1-4—R265—(CH2)0-4-heteroaryl, —(CH2)1-4—R265—(CH2)0-4-heterocyclyl, or
- C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or —(CH2)0-4—C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 R205 groups, wherein
- each aryl or phenyl is optionally substituted with 1, 2, or 3 groups that are independently R205, R210, or
- C1-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein
- each heterocyclyl is optionally substituted with 1, 2, 3, or 4 R210;
- R265 at each occurrence is independently —O—, —S— or —N(C1-C6 alkyl)-;
- and
- R270 at each occurrence is independently R205, halogen C1-C6 alkoxy, C1-C6 haloalkoxy, NR235R240, —OH, —C≡N, —CO—(C1-C4 alkyl), SO2—NR235R240, —CO—NR235R240, —SO2—(C1-C4 alkyl), ═O, or
- C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or —(CH2)0-4—C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 R205 groups.
77 more elements
A compound of the formula 5:
- 15
- R1 is —(CH2)1-2—S(O)0-2-(C1-C6 alkyl), or
- C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, —OH, ═O, —SH, —C≡N, —CF3, —C1-C3 alkoxy, amino, mono- or dialkylamino, —N(R)C(O)R′—, —OC (═O)-amino and —OC(═O)-mono- or dialkylamino, or
- C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, amino, and mono- or dialkylamino, or
- aryl, heteroaryl, heterocyclyl, aryl-(C1-C6)alkyl-, heteroaryl-(C1-C6)alkyl-, or heterocyclyl-(C1-C6)alkyl-, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, —OH, —SH, —C≡N, —NO2, —NR105R′105, —CO2R, —N(R)COR′, —N(R)SO2R′, —C(═O)—(C1-C4) alkyl, —SO2-amino, —SO2-monoalkylamino, —SO2-dialkylamino, —C(═O)-amino, —C(═O)-monoalkylamino, —C(═O)-dialkylamino, —SO2—(C1-C4) alkyl,
- C1-C6 alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen,
- C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, amino, —C1-C6 alkyl and mono- or dialkylamino,
- C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, —OH, —SH, —C≡N, —CF3, —C1-C3 alkoxy, amino, mono- or dialkylamino and —C1-C3 alkyl, and
- C2-C10 alkenyl or C2-C10 alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, amino, C1-C6 alkyl and mono- or dialkylamino;
- and the heterocyclyl group is optionally further substituted with oxo;
- R and R′ independently are hydrogen, C1-C10 alkyl, C1-C10 alkylaryl or C1-C10 alkylheteroaryl;
- RP is a hydrogen or a protecting group;
- R105 and R′105 independently represent —H, —R110, —R120, C3-C7 cycloalkyl, —(C1-C2 alkyl)-(C3-C7 cycloalkyl), —(C1-C6 alkyl)-O—(C1-C3 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, or C1-C6 alkyl chain with one double bond and one triple bond, or
- C1-C6 alkyl optionally substituted with —OH or —NH2;
- or,
- C1-C6 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, or
- R105 and R′105 together with the atom to which they are attached form a 3 to 7 membered carbocylic ring, where one member is optionally a heteratom selected from —O—, —S(O)0-2—, N(R135)—, the ring being optionally substituted with 1, 2 or 3 independently selected R140 groups;
- R140 is heterocyclyl optionally substituted with 1, 2, 3, or 4 groups independently selected from C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, cyano, nitro, amino, mono(C1-C6)alkylamino, di(C1-C6)alkylamino, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, amino(C1-C6)alkyl, mono(C1-C6)alkylamino(C1-C6)alkyl, di(C1-C6)alkylamino(C1-C6)alkyl, and ═O;
- R110 is aryl optionally substituted with 1 or 2 R125 groups;
- R125 at each occurrence is independently halogen, amino, mono- or dialkylamino, —OH, —C≡N, —SO2—NH2, —SO2—NH—C1-C6 alkyl, —SO2—N(C1-C6 alkyl)2, —SO2—(C1-C4 alkyl), —CO—NH2, —CO—NH—C1-C6 alkyl, or —CO—N(C1-C6 alkyl)2, or
- C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups that are independently selected from C1-C3 alkyl, halogen, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, amino, and mono- and dialkylamino, or
- C1-C6 alkoxy optionally substituted with one, two or three of halogen;
- R120 is heteroaryl, which is optionally substituted with 1 or 2 R125 groups;
- and
- RC is hydrogen, —(CR245R250)0-4-aryl, —(CR245R250)0-4-heteroaryl, —(CR245R250)0-4-heterocyclyl, —(CR245R250)0-4-aryl-heteroaryl, —(CR245R250)0-4-aryl-heterocyclyl, —(CR245R250)0-4-aryl-aryl, —(CR245R250)0-4-heteroaryl-aryl, —(CR245R250)0-4-heteroaryl-heterocyclyl, —(CR245R250)0-4-heteroaryl-heteroaryl, —(CR245R250)0-4-heterocyclyl-heteroaryl, —(CR245R250)0-4-heterocyclyl-heterocyclyl, —(CR245R250)0-4-heterocyclyl-aryl, —[C(R255) (R260)]1-3—CO—N—(R255)2, —CH (aryl)2, —CH(heteroaryl)2, —CH(heterocyclyl)2, —CH(aryl)(heteroaryl), —(CH2)0-1—CH ((CH2)0-6—OH)—(CH2)0-1-aryl, —(CH2)0-1—CH((CH2)0-6—OH—(CH2)0-1-heteroaryl, —CH(-aryl or -heteroaryl)-CO—O(C1-C4 alkyl), —CH(—CH2—OH) —CH(OH)-phenyl-NO2, (C1-C6 alkyl) —O—(C1-C6 alkyl)-OH;
- —CH2—NH—CH2—CH(—O—CH2—CH3)2, —(CH2)0-6—C—(═NR235) (NR235R240), or
- C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, —OC═ONR235R240, —S(═O)0-2(C1-C6 alkyl), —SH, —NR235C═ONR235R240, —C═ONR235R240, and —S(═O)2NR235R240, or
- —(CH2)0-3-(C3-C8) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, —CO2H, and —CO2—(C1-C4 alkyl), or
- cyclopentyl, cyclohexyl, or cycloheptyl ring fused to aryl, heteroaryl, or heterocyclyl wherein one, two or three carbons of the cyclopentyl, cyclohexyl, or cycloheptyl is optionally replaced with a heteroatom independently selected from NH, NR215, O, or S(═O)0-2, and wherein the cyclopentyl, cyclohexyl, or cycloheptyl group can be optionally substituted with one or two groups that are independently R205, ═O, —CO—NR235R240, or —SO2—(C1-C4 alkyl), or
- C2-C10 alkenyl or C2-C10alkynyl, each of which is optionally substituted with 1, 2, or 3 R205 groups, wherein
- each aryl and heteroaryl is optionally substituted with 1, 2, or 3 R200, and wherein each heterocyclyl is optionally substituted with 1, 2, 3, or 4 R210;
- R200 at each occurrence is independently selected from —OH, —NO2, halogen, —CO2H, C≡N, —(CH2)0-4—CO—NR220R225, —(CH2)0-4-CO—(C1-C12 alkyl), —(CH2)0-4—CO—(C2-C12 alkenyl), —(CH2)0-4-CO—(C2-C12 alkynyl), —(CH2)0-4—CO—(C3-C7 cycloalkyl), —(CH2)0-4—CO-aryl, —(CH2)0-4—CO-heteroaryl, —(CH2)0-4—CO-heterocyclyl, —(CH2)0-4—CO—O—R215, —(CH2)0-4—SO2—NR220R225, —(CH2)0-4—SO—(C1-C8 alkyl), —(CH2)0-4—SO2—(C1-C12 alkyl), —(CH2)0-4—SO2—(C3-C7 cycloalkyl), —(CH2)0-4—N(H or R215) —CO—O—R215, —(CH2)0-4—N(H or R215) —CO—N(R215)2, —(CH2)0-4—N—CS—N(R215)2, —(CH2)0-4—N (—H or R215)—CO—R220, —(CH2)0-4—NR220R225, —(CH2)0-4—O—CO—(C1-C6 alkyl), —(CH2)0-4—O—P(O)—(OR240)2, —(CH2)0-4—O—CO—N(R215)2, —(CH2)0-4—O—CS—N(R215)2, —(CH2)0-4—O—(R215), —(CH2)0-4—O—(R215) —COOH, —(CH2)0-4—S—(R215), —(CH2)0-4—O—(C1-C6 alkyl optionally substituted with 1, 2, 3, or 5 —F), C3-C7 cycloalkyl, —(CH2)0-4—N(H or R215)—SO2—R220, —(CH2)0-4—C3-C7 cycloalkyl, or
- C1-C10 alkyl optionally substituted with 1, 2, or 3 R205 groups, or
- C2-C10alkenyl or C2-C10 alkynyl, each of which is optionally substituted with 1 or 2 R205 groups, wherein
- the aryl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 groups that are independently R205, R210, or
- C1-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein
- the heterocyclyl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R210;
- R205 at each occurrence is independently selected from C1-C6 alkyl, halogen, —OH, —O-phenyl, —SH, —C≡N, —CF3, C1-C6 alkoxy, NH2, NH(C1-C6 alkyl) or N—(C1-C6 alkyl) (C1-C6 alkyl);
- R210 at each occurrence is independently selected from halogen, C1-C6 alkoxy, C1-C6 haloalkoxy, —NR220R225, OH, C≡N, —CO—(C1-C4 alkyl), SO2—NR235R240, —CO—NR235R240, —SO2—(C1-C4 alkyl) ═O, or
- C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 R205 groups;
- R215 at each occurrence is independently selected from C1-C6 alkyl, —(CH2)0-2-(aryl), C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, and —(CH2)0-2-(heteroaryl), —(CH2)0-2-(heterocyclyl), wherein
- the aryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein
- the heterocyclyl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 R210;
- R220 and R225 at each occurrence are independently selected from —H, —C3-C7 cycloalkyl, —(C1-C2 alkyl)-(C3-C7 cycloalkyl), —(C1-C6 alkyl) —O—(C1-C3 alkyl), —C2-C6 alkenyl, —C2-C6 alkynyl, —C1-C6 alkyl chain with one double bond and one triple bond, -aryl, -heteroaryl, and -heterocyclyl, or —C1-C10 alkyl optionally substituted with —OH, —NH2 or halogen, wherein
- the aryl, heterocyclyl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 R270 groups
- R235 and R240 at each occurrence are independently H, or C1-C6 alkyl;
- R245 and R250 at each occurrence are independently selected from —H, C1-C4 alkyl, C1-C4 alkylaryl, C1-C4 alkylheteroaryl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, —(CH2)0-4—C3-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, and phenyl;
- or
- R245 and R250 are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms, where one carbon atom is optionally replaced by a heteroatom selected from —O—, —S—, —SO2—, and —NR220—;
- R255 and R260 at each occurrence are independently selected from —H, —(CH2)1-2—S(O)0-2-(C1-C6 alkyl), —(C1-C4 alkyl)-aryl, —(C1-C4 alkyl)-heteroaryl, —(C1-C4 alkyl)-heterocyclyl, -aryl, -heteroaryl, -heterocyclyl, —(CH2)1-4—R265—(CH2)0-4-aryl, —(CH2)1-4—R265—(CH2)0-4-heteroaryl, —(CH2) 1-4—R265—(CH2)0-4-heterocyclyl, or
- C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or —(CH2)0-4—C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 R205 groups, wherein
- each aryl or phenyl is optionally substituted with 1, 2, or 3 groups that are independently R205, R210, or
- C1-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein
- each heterocyclyl is optionally substituted with 1, 2, 3, or 4 R210;
- R265 at each occurrence is independently —O—, —S— or —N(C1-C6 alkyl)-;
- and
- R270 at each occurrence is independently R205, halogen C1-C6 alkoxy, C1-C6 haloalkoxy, NR235R240, —OH, —C≡N, —CO—(C1-C4 alkyl), —SO2—NR235R240, —CO—NR235R240, —SO2—(C1-C4 alkyl), ═O, or
- C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or —(CH2)0-4—C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 R205 groups.
55 more elements
A compound of the formula 4:
- 16
- R1 is —(CH2)1-2-S(O)0-2—(C1-C6 alkyl), or
- C1-C1-0 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, —OH, ═O, —SH, —C≡N, —CF3, —C1-C3 alkoxy, amino, mono- or dialkylamino, —N(R)C(O)R′—, —OC(═O)-amino and —OC(═O)-mono- or dialkylamino, or
- C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, amino, and mono- or dialkylamino, or
- aryl, heteroaryl, heterocyclyl, aryl-(C1-C6)alkyl-, heteroaryl-(C1-C6)alkyl-, or heterocyclyl-(C1-C6)alkyl-, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, —OH, —SH, —C≡N, —NO2, —NR105R′105, —CO2R, —N(R)COR′, —N(R)SO2R′, —C(═O) —(C1-C4) alkyl, —SO2-amino, —SO2-monoalkylamino, —SO2-dialkylamino, —C (═O)-amino, —C (═O)-monoalkylamino, —C(═O)-dialkylamino, —SO2—(C1-C4) alkyl,
- C1-C6 alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen,
- C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, —OH, —SH, —CE-N, —CF3, C1-C3 alkoxy, amino, —C1-C6 alkyl and mono- or dialkylamino,
- C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, —OH, —SH, —C≡N, —CF3, —C1-C3 alkoxy, amino, mono- or dialkylamino and —C1-C3 alkyl, and
- C2-C10alkenyl or C2-C10alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, amino, C1-C6 alkyl and mono- or dialkylamino;
- and the heterocyclyl group is optionally further substituted with oxo;
- R and R′ independently are hydrogen, C1-C10alkyl, C1-C10 alkylaryl or C1-C10 alkylheteroaryl;
- RP is a hydrogen or a protecting group;
- R105 and R′105 independently represent —H, —R110, —R120, C3-C7 cycloalkyl, —(C1-C2 alkyl)-(C3-C7 cycloalkyl), —(C1-C6 alkyl)-O—(C1-C3 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, or C1-C6 alkyl chain with one double bond and one triple bond, or
- C1-C6 alkyl optionally substituted with —OH or —NH2;
- or,
- C1-C6 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, or
- R105 and R′105 together with the atom to which they are attached form a 3 to 7 membered carbocylic ring, where one member is optionally a heteratom selected from —O—, —S(O)0-2—, —N(R135)-, the ring being optionally substituted with 1, 2 or 3 independently selected R140 groups;
- R140 is heterocyclyl optionally substituted with 1, 2, 3, or 4 groups independently selected from C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, cyano, nitro, amino, mono(C1-C6)alkylamino, di(C1-C6)alkylamino, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, amino(C1-C6)alkyl, mono(C1-C6)alkylamino(C1-C6)alkyl, di(C1-C6) alkylamino (C1-C6) alkyl, and ═O;
- R110 is aryl optionally substituted with 1 or 2 R125 groups;
- R125 at each occurrence is independently halogen, amino, mono- or dialkylamino, —OH, —C≡N, —SO2—NH2, —SO2—NH—C1-C6 alkyl, —SO2—N(C1-C6 alkyl)2, —SO2—(C1-C4 alkyl), —CO—NH2, —CO—NH—C1-C6 alkyl, or —CO—N(C1-C6 alkyl)2, or
- C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups that are independently selected from C1-C3 alkyl, halogen, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, amino, and mono- and dialkylamino, or
- C1-C6 alkoxy optionally substituted with one, two or three of halogen;
- R120 is heteroaryl, which is optionally substituted with 1 or 2 R125 groups;
- and
- RC is hydrogen, —(CR245R250)0-4-aryl, —(CR245R250)0-4-heteroaryl, —(CR245R250)0-4-heterocyclyl, —(CR245R250)0-4-aryl-heteroaryl, —(CR245R250)0-4-aryl-heterocyclyl, —(CR245R250)0-4-aryl-aryl, —(CR245R250)0-4-heteroaryl-aryl, —(CR245R250)0-4-heteroaryl-heterocyclyl, —(CR245R250)0-4-heteroaryl-heteroaryl, —(CR245R250)0-4-heterocyclyl-heteroaryl, —(CR245R250)0-4-heterocyclyl-heterocyclyl, —(CR245R250)0-4-heterocyclyl-aryl, —[C(R255) (R260)]1-3-CO—N—(R255)2, —CH (aryl)2, —CH(heteroaryl)2, —CH(heterocyclyl)2, —CH(aryl)(heteroaryl), —(CH2)0-1—CH ((CH2)0-6—OH)—(CH2)0-1-aryl, —(CH2)0-1—CH ((CH2)0-6—OH—(CH2)0-1-heteroaryl, —CH(-aryl or -heteroaryl) —CO—C(C1-C4 alkyl), —CH (—CH2—OH) —CH(OH)-phenyl-NO2, (C1-C6 alkyl) —O—(C1-C6 alkyl) —OH;
- —CH2—NH—CH2—CH (—O—CH2—CH3)2, —(CH2)0-6—C(═NR235) (NR235R240), or
- C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, —OC═ONR235R240, —S (═O)0-2 (C1-C6 alkyl), —SH, —NR235C═ONR235R240, —C═ONR235R240, and —S(═O)2NR235R240, or
- —(CH2)0-3—(C3-C8) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, —CO2H, and —CO2—(C1-C4 alkyl), or
- cyclopentyl, cyclohexyl, or cycloheptyl ring fused to aryl, heteroaryl, or heterocyclyl wherein one, two or three carbons of the cyclopentyl, cyclohexyl, or cycloheptyl is optionally replaced with a heteroatom independently selected from NH, NR215, O, or S(═O)0-2, and wherein the cyclopentyl, cyclohexyl, or cycloheptyl group can be optionally substituted with one or two groups that are independently R205, ═O, —CO—NR235R240, or —SO2—(C1-C4 alkyl), or
- C2-C10 alkenyl or C2-C10 alkynyl, each of which is optionally substituted with 1, 2, or 3 R205 groups, wherein
- each aryl and heteroaryl is optionally substituted with 1, 2, or 3 R200, and wherein each heterocyclyl is optionally substituted with 1, 2, 3, or 4 R210;
- R200 at each occurrence is independently selected from —OH, —NO2, halogen, —CO2H, C≡N, —(CH2)0-4—CO—NR220R225, —(CH2)0-4—CO—(C1-C12 alkyl), —(CH2)0-4—CO—(C2-C12 alkenyl), —(CH2)0-4—CO—(C2-C12 alkynyl), —(CH2)0-4—CO—(C3-C7 cycloalkyl), —(CH2)0-4—CO-aryl, —(CH2)0-4—CO-heteroaryl, —(CH2)0-4—CO-heterocyclyl, —(CH2)0-4—CO—O—R215, —(CH2)0-4—SO2—NR220R225, —(CH2)0-4—SO—(C1-C8 alkyl), —(CH2)0-4—SO2 (C1-C12 alkyl), —(CH2)0-4—SO2—(C3-C7 cycloalkyl), —(CH2)0-4—N(H or R215) —CO—O—R215, —(CH2)0-4—N(H or R215) —CO—N(R215)2—(CH2)0-4—N—CS—N(R215)2, —(CH2)0-4—N (—H or R215)—CO—R220, —(CH2)0-4—NR220R225, —(CH2)0-4—O—CO—(C1-C6 alkyl), —(CH2)0-4—O—P(O)—(OR240)2, —(CH2)0-4—O—CO—N(R215)2—(CH2)0-4—O—CS—N(R215)2, —(CH2)0-4—O—(R215), —(CH2)0-4—O—(R215) —COOH, —(CH2)0-4—S—(R215), —(CH2)0-4—O—(C1-C6 alkyl optionally substituted with 1, 2, 3, or 5 —F), C3-C7 cycloalkyl, —(CH2)0-4—N(H or R215)—SO2—R220, —(CH2)0-4—C3-C7 cycloalkyl, or
- C1-C10 alkyl optionally substituted with 1, 2, or 3 R205 groups, or
- C2-C10alkenyl or C2-C10 alkynyl, each of which is optionally substituted with 1 or 2 R205 groups, wherein
- the aryl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 groups that are independently R205, R210, or
- C1-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein
- the heterocyclyl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R210;
- R205 at each occurrence is independently selected from C1-C6 alkyl, halogen, —OH, —O-phenyl, —SH, —C≡N, —CF3, C1-C6 alkoxy, NH2, NH(C1-C6 alkyl) or N-(C1-C6 alkyl) (C1-C6 alkyl);
- R210 at each occurrence is independently selected from halogen, C1-C6 alkoxy, C1-C6 haloalkoxy, —NR220R225, OH, C≡N, —CO—(C1-C4 alkyl), SO2—NR235R240, —CO—NR235R240, —SO2—(C1-C4 alkyl) ═O, or
- C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 R205 groups;
- R215 at each occurrence is independently selected from C1-C6 alkyl, —(CH2)0-2-(aryl), C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, and —(CH2)0-2-(heteroaryl), —(CH2)0-2-(heterocyclyl), wherein
- the aryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein
- the heterocyclyl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 R210;
- R220 and R225 at each occurrence are independently selected from —H, —C3-C7 cycloalkyl, —(C1-C2 alkyl)-(C3-C7 cycloalkyl), —(C1-C6 alkyl) —O—(C1-C3 alkyl), —C2-C6 alkenyl, —C2-C6 alkynyl, —C1-C6 alkyl chain with one double bond and one triple bond, -aryl, -heteroaryl, and -heterocyclyl, or —C1-C10 alkyl optionally substituted with —OH, —NH2 or halogen, wherein
- the aryl, heterocyclyl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 R270 groups
- R235 and R240 at each occurrence are independently H, or C1-C6 alkyl;
- R245 and R250 at each occurrence are independently selected from —H, C1-C4 alkyl, C1-C4 alkylaryl, C1-C4 alkylheteroaryl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, —(CH2)0-4-C3-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, and phenyl;
- or
- R245 and R250 are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms, where one carbon atom is optionally replaced by a heteroatom selected from —O—, —S—, —SO2—, and —NR220-;
- R255 and R260 at each occurrence are independently selected from —H, —(CH2)1-2-S(O)0-2—(C1-C6 alkyl), —(C1-C4 alkyl)-aryl, —(C1-C4 alkyl)-heteroaryl, —(C1-C4 alkyl)-heterocyclyl, -aryl, -heteroaryl, -heterocyclyl, —(CH2)1-4—R265—(CH2)0-4-aryl, —(CH2)1-4—R265—(CH2)0-4-heteroaryl, —(CH2)1-4—R265—(CH2)0-4-heterocyclyl, or
- C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or —(CH2)0-4—C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 R205 groups, wherein
- each aryl or phenyl is optionally substituted with 1, 2, or 3 groups that are independently R205, R210, or
- C1-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein
- each heterocyclyl is optionally substituted with 1, 2, 3, or 4 R210;
- R265 at each occurrence is independently —O—, —S— or —N(C1-C6 alkyl)-;
- and
- R270 at each occurrence is independently R205, halogen C1-C6 alkoxy, C1-C6 haloalkoxy, NR235R240, —OH, —C≡N, —CO—(C1-C4 alkyl), —SO2—NR235R240, —CO—NR235R240, —SO2—(C1-C4 alkyl), ═O, or
- C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or —(CH2)0-4—C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 R205 groups.
55 more elements
Dependencies are inferred from the claim text.