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US 2003/0119887 A1Published application
Lactacystin analogs
AssigneePresident and Fellows of Harvard College
InventorsStuart L. Schreiber, Robert F. Standaert, Gabriel Fenteany, Timothy F. Jamison
Life of this patent
Estimating the term…
Abstract
Described herein are compounds related to lactacystin and lactacystin β-lactone, pharmaceutical compositions containing the compounds, and methods of use.
Claims59
A compound having the formula
- 65
- wherein Z1 is O, S, SO2, NH, or NRa, Ra being C1-6 alkyl;
- X1 is O, S, CH2, two singly bonded H, CH(Rb) in the E or Z configuration, or C(Rb)(Rc) in the E or Z configuration, each of Rb and Rc, independently, being C1-6 alkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 h eterocyclic radical, or halogen, X1 being two singly bonded H when Z1 is SO2;
- Z2 is O, S, NH, NRd, CHR1, or CHOR1 in the (R) or (S) configuration, wherein Rd is C1-6 alkyl and R1 is H, halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, NRdRe (except where Z2 is CHOR1), or the side chain of any naturally occurring α-amino acid, or R1 and R2 taken together are a bivalent moiety, provided that when R1 and R2 are taken together, Z1 is NH or NRa and Z2 is CHR1;
- Re being H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-6 alkynyl, and the bivalent moiety forming a C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or C6-12 aryl, where the H in CHR1 is deleted when R1 and R2 taken together form a C3-8 heteroaryl or C6-12 aryl;
- R2 is C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, azido, C2-6 alkynyl, halogen, ORf, SRf, NRfRg, —ONRfRg, —NRg(ORf), or —NRg(SRf) (each of Rf and Rg, independently, being H, C1-6, alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-6 alkynyl), or R1 and R2 taken together are a bivalent moiety, the bivalent moiety forming a C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or C6-12 aryl, where the H in CHR1 is deleted when R1 and R2 taken together form a C3-8 heteroaryl or C6-12 aryl;
- and when R1 and R2 are taken together, Z2 is CR1, and one of A1 and Lo is (C1-4 alkyl)oxycarbonyl or carboxyl, the other of A1 and Lo has a fragment formula weight of at least 20;
- A1 is the side chain of any naturally occurring α-amino acid, or is of the following formula,
- —(CH2)m—y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh, NRiRi′, —NRi(ORh), or —NRi (NRiRi′) wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-10 acyl, C1-6 alkylsulfonyl, and C6-10 arylsulfonyl;
- and each of Ri and Ri′ independently is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxycarbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid;
- and
- LO is —(C═X2)—L1, —(C═X2)—L2, or —C(L2)—CH2—O, where — in X2 is O or S;
- L2 is H, C1-6 haloalkyl, C1-6 alkyl, or C6-14 aryl, and L1 is a moiety having 0 to 25 carbon atoms, 0 to 10 heteroatoms, and 0 to 6 halogen atoms, L1 being linked by an oxygen or sulfur atom to the carbon atom bonded to X2, where A1 is C5-20 alkyl when Lo is carboxyl or (C1-4 alkyl)-oxy-carbonyl and A1 is alkyl;
- where only one of A1 and Lo is selected from carboxyl and (C1-4 alkyl)oxycarbonyl;
- where L1 has at least 3 carbon atoms when Z1 and Z2 are both NH, and A1 is methoxy;
- and when Z1 is NH and Z2 is (R) CHR1, L1 has between 0 and 3 nonaromatic acyclic carbon atoms when there are 5 heteroatoms, L1 has between 6 and 15 nonaromatic acyclic carbon atoms when there is only one oxygen atom, L1 has 0, 1, 3, or 5 nonaromatic carbon atoms when there are three halogen atoms.
17 more elements
A compound having the following formula
- 66
- wherein Z1 is O, S, SO2, NH, or NRa, Ra being C1-6 alkyl;
- X1 is O, S, CH2, two singly bonded H, CH(Rb) in the E or Z configuration, or C(Rb)(Rc) in the E or Z configuration, each of Rb and Rc, independently, being C1-6 alkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or halogen, provided that when Z1 is SO2, X1 is two singly bonded H;
- Z2 is CHR1 in the (R) or (S) configuration, wherein R1 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, hydroxyl, halogen, a side chain of a naturally occuring amino acid, ORd, SRd, or NRdRe (each of Rd and Re, independently, being H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-5 alkynyl);
- Z3 is O, S, NH, or NRj, Rj being C1-6 alkyl;
- X2 is O or S;
- and
- A1 is the side chain of any naturally occurring α-amino acid, or is of the following formula,
- —(CH2)m—Y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh, NRiRi′, —NRi—(ORh), or —NRi(NRiRi′), wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-10 acyl, C1-6 alkylsulfonyl, and C6-10 arylsulfonyl;
- each of Ri and Ri′, independently, is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxycarbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid;
- provided that R1 is H, OH or ORd when X4 is hydroxyl in the (S) configuration and —(CH2)n—R3X3 is isopropyl;
- and provided that the moiety —(CH2)n—R3X3 has between 5 and 20 carbon atoms when X4 is hydroxyl in the (R) configuration, m is 0, and R1 is C1-6 alkyl.
13 more elements
A compound having one of the following formulae
- 67
- wherein Z1 is NH or NRa, Ra being C1-6 alkyl;
- X1 is O, S, CH2, two singly bonded H, CH(Rb) in the E or Z configuration, or C(Rb)(Rc) in the E or Z configuration, each of Rb and Rc, independently, being C1-6 alkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or halogen;
- Z2 is O, S, NH, or NRi, Rj being C1-6 alkyl;
- R1 is in the (R) or (S) configuration, and is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, hydroxyl, halogen, a side chain of a naturally occuring α-amino acid, ORd, SRd, or NRdRe (each of Rd and Re, independently, being H, C1-6 alkyl, C1-6 haloalkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or halogen);
- X2 is O or S;
- and
- A1 is the side chain of any naturally occurring α-amino acid, or is of the following formula,
- —(CH2)m—Y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh, NRiRi′, —NRi(ORh), or —NRi(NRiRi′), wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, and each of R1 and Ri′, independently is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxycarbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid;
- when X1 is 2 singly bonded H and R1 has only one oxygen, then the fragment formula weight of R1 is at least 30 atomic mass units;
- when X1 is 2 singly bonded H and R1 is 2 H, and A1 is alkyl, then A1 has at least 3 carbon atoms;
- A1, R1 and X1 taken together have at least one carbon atom, halogen, or heteroatom;
- when X1 is two singly bonded H, and R1 is H, X2 is O, and Rh is alkyl, then Rh is C4-6 alkyl;
- and when n is 2, Rh is C1-6 haloalkyl.
15 more elements
A compound having the following formula
- 68
- wherein Z2 is O, S, NH or NRj, Rj being C1-6 alkyl;
- X1 is O or S;
- R1 is in the (R) or (S) configuration, and is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, hydroxyl, halogen, a side chain of a naturally occuring α-amino acid, ORd, SRd, or NRdRe (each of Rd and Re, independently, being H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-5 alkynyl);
- R2 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-12 aryl, C3-8 heteroaryl, or halogen;
- X2 is O or S;
- and
- A1 is H, the side chain of any naturally occurring α-amino acid, or is of the following formula,
- —(CH2)m—Y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh, NRiRi′, —NRi(ORh), or —NRi(NRiRi′), wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, and each of Ri and Ri′, independently is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxycarbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid.
10 more elements
A compound having the following formula
- 69
- wherein Z1 is O, S, NH or NRj, Rj being C1-6 alkyl;
- X1 is O or S;
- R1 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, hydroxyl, halogen, a side chain of a naturally occuring α-amino acid, ORd, SRd, or NRdRe (each of Rd and Re, independently, being C1-6 alkyl, C1-6 haloalkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or halogen);
- R2 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-12 aryl, C3-8 heteroaryl, or halogen;
- Ra is C1-6 alkyl;
- and
- A1 is H, the side chain of any naturally occurring α-amino acid, or is of the following formula,
- —(CH2)m—Y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh, NRiNRi′(ORh), or —NRi(NRiRi′), wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, an d each of Ri and Ri′, independently is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxycarbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid.
10 more elements
A compound having the formula
- 70
- wherein X1 is O, S, CH2, two singly bonded H, CH(Rb) in the E or Z configuration, or C(Rb)(Rc) in the E or Z configuration, each of Rb and Rc, independently, being C1-6 alkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or halogen;
- Z1 is O, S, NH, or NRa, Ra being C1-6 alkyl;
- R1 H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, hydroxyl, halogen, a side chain of any naturally occuring α-amino acid, ORd, SRd, or NRdRe (each of Rd and Re, independently, being H, C1-6 alkyl, C1-6 haloalkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or halogen);
- or R1 and R2 taken together are a bivalent moiety which forms a C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or C6-12 aryl;
- R2 is C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, azido, C2-6 alkynyl, halogen, ORf, SRf, NRfRg, —ONRfRg, NRg (ORf), or NRg(SRf) (each of Rf and Rg, independently, being H, C1-6, alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-6 alkynyl), or R1 and R2 taken together are a bivalent moiety, the bivalent moiety forming a C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or C6-12 aryl;
- X2 is O or S;
- and
- A1 is in the (R) or (S) configuration, and each of A1 and A2 is independently H, the side chain of any naturally occurring amino α-acid, or is of the following formula,
- —(CH2)m—Y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh, NRiRi′, —NRi(ORh), or —NRi(NRiRi′), wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, and each of Ri and Ri′, independently is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxycarbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid.
11 more elements
A compound having the following formula
- 71
- wherein Z1 is NH or NRa, NRa being C1-6 alkyl;
- X1 is O. S, CH21 two singly bonded H, CH(Rb) in the E or Z configuration, or C(Rb)(Rc) in the E or Z configuration, each of Rb and Rc, independently, being C1-6 alkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or halogen;
- Z2 is O, S, NH, or NRj, Rj being C1-6 alkyl;
- R1 is in the (R) or (S) configuration, and is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, hydroxyl, halogen, a side chain of any naturally occurring amino acid, ORd, SRd, or NRdRe (each of Rd and Re, independently, being H, C1-6 alkyl, C1-6 haloalkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or halogen);
- or R1 and R2 taken together are a bivalent moiety which forms a C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or C6-12 aryl;
- R2 is C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, azido, C2-6 alkynyl, halogen, ORf, SRf, NRfRg, —ONRfRg, —NRg(ORf), or NRg(SRf) (each of Rf and Rg, independently, being H, C1-6, alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-6 alkynyl), or R1 and R2 taken together are a bivalent moiety, the bivalent moiety forming a C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or C6-12 aryl;
- X2 is O or S;
- and
- each of A1 and A2 is independently in the (R) or (S) configuration, and is independently H, the side chain of any naturally occurring α-amino acid, or is of the following formula,
- —(CH2)m—Y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh, NRiRi′, —NRi(ORh), or —NRi(NRiRi′), wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, and each of Ri and Ri′, independently is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxycarbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid.
12 more elements
A compound of the formula
- 72
- wherein Z1 is O, NH, or NRa, NRa being C1-6 alkyl;
- X1 is O, S, CH2, or two singly bonded H;
- each of A1 and A2 is independently H, the side chain of any naturally occurring α-amino acid, or is of the following formula,
- —(CH2)m—Y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh, NRiRi′, —NRi(ORh), or —NRi(NRiRi′), wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, and each of Ri and Ri′, independently is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxycarbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid;
- and
- R12 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-6 alkynyl;
- where A1, A2, R2, and X1 taken together have at least one carbon atom and one heteroatom.
9 more elements
A compound having the formula
- 73
- wherein Z is NH, or NRa, NRa being C1-6 alkyl;
- each of X1 and X2, independently, is O or S;
- each of A1 and A2 is independently in the (R) or (S) configuration, and is independently H, the side chain of any naturally occurring α-amino acid, or is of the following formula,
- —(CH2)m—Y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh, NRiRi′, —NRi(ORh), or —NRi(NRiRi′), wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, and each of Ri and Ri′, independently is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxycarbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid.
6 more elements
A pharmaceutical composition comprising a compound having the formula
- 76
- wherein Z1 is O, S, SO2, NH, or NRa, Ra being C1-6 alkyl;
- X1 is O, S, CH2, two singly bonded H, CH(Rb) in the E or Z configuration, or C(Rb)(Rc) in the E or Z configuration, each of Rb and Rc, independently, being C1-6 alkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or halogen, X1 being two singly bonded H when Z1 is SO2;
- Z2 is O, S, NH, NRd, CHR1, or CHOR1 in the (R) or (S) configuration, wherein Rd is C1-6 alkyl and R1 is H, halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, NRdRe (except where Z2 is CHOR1), or the side chain of any naturally occurring α-amino acid, or R1 and R2 taken together are a bivalent moiety, provided that when R1 and R2 are taken together, Z1 is NH or NRa and Z2is CHR1;
- Re being H, C1-6 alkyl, C;6 haloalkyl, C2-6 alkenyl, or C2-6 alkynyl, and the bivalent moiety forming a C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or C6-12 aryl, where the H in CHR1 is deleted when R1 and R2 taken together form a C3-8 heteroaryl or C6-12 aryl;
- R2 is C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, azido, C2-6 alkynyl, halogen, ORf, SRf, NRfRg, —ONRfRg, —NRg(ORf), or —NRg(SRf) (each of Rf and Rg, independently, being H, C1-6, alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-6 alkynyl), or R1 and R2 taken together are a bivalent moiety, the bivalent moiety forming a C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or C6-12 aryl, where the H in CHR1 is deleted when R1 and R2 taken together form a C3-8 heteroaryl or C6-12 aryl;
- A1 is H, the side chain of any naturally occurring α-amino acid, or is of the following formula,
- —(CH2)m—Y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh, NRiRi′, —NRi(ORh), or —NRi(NRiRi′), wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-10 acyl, C1-6 alkylsulfonyl, and C6-10 arylsulfonyl, and each of Ri and Ri′, independently is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxycarbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid;
- and
- LO is H or an organic moiety having 1 to 25 carbon atoms, 0 to 10 heteroatoms, and 0 to 6 halogen atoms;
- and
- a pharmaceutically acceptable carrier.
13 more elements
A pharmaceutical composition comprising a compound having the following formula
- 78
- wherein Z1is O, S, SO2, NH, or NRa, Ra being C1-6 alkyl;
- X1 is O, S, SO2, two singly bonded H, CH(Rb) in the E or Z configuration, or C(Rb)(Rc) in the E or Z configuration, each of Rb and Rc, independently, being C1-6 alkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or halogen, provided that when Z1 is SO2, X1 is two singly bonded H;
- Z2 is CHR1 in the (R) (S) configuration, R1 being H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, hydroxyl, halogen, a side chain of a naturally occuring α-amino acid, ORd, SRd, or NRdRe (each of Rd and Re, independently, being H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-5 alkynyl);
- Z3 is O, S, NH, or NRj, wherein Rj is C1-6 alkyl;
- X2 is O or S;
- and
- A1 is H, the side chain of any naturally occurring, α-amino acid, or is of the following formula,
- —(CH2)m—Y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh, NRiRi′, —NRi(ORh), or —NRi(NRiRi′), wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-10 acyl, C1-6 alkylsulfonyl, and C6-10 arylsulfonyl;
- and each of Ri and Ri′, independently is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxycarbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid;
- and
- a pharmaceutically acceptable carrier.
13 more elements
A pharmaceutical composition comprising a compound having a formula selected from:
- 79
- wherein Z1 is NH or NRa, Ra being C1-6 alkyl;
- X1 is O, S, CH2, two singly bonded H, CH(Rb) in the E or Z configuration, or C(Rb)(Rc) in the E or Z configuration, each of Rb and Rc, independently, being C1-6 alkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or halogen;
- Z2 is O, S, NH, or NRi, wherein Ri is C1-6 alkyl;
- R1 is in the (R) or (S) configuration, and is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, hydroxyl, halogen, a side chain of a naturally occurring α-amino acid, ORd, SRd, or NRdRe (each of Rd and Re, independently, being H, C1-6 alkyl, C1-6 haloalkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or halogen);
- X2 is O or S;
- and
- A1 is H, the side chain of any naturally occurring α-amino acid, or is of the following formula,
- —(CH2)m—Y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh, NRiRi′, —NRi(ORh), or —NRi(NRiRi′), wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, and each of Ri and Ri′ independently is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxycarbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid;
- and
- a pharmaceutically acceptable carrier.
12 more elements
A pharmaceutical composition comprising a compound having the following formula
- 80
- wherein Z1 is O, S, NH or NRj, Rj being C1-6 alkyl;
- X1 is O or S;
- R is in the (R) or (S) configuration, and is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, hydroxyl, halogen, a side chain of a naturally occuring α-amino acid, ORd, SRd, or NRdRe (each of Rd and Re, independently, being H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-5 alkynyl);
- R2 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-16 alkynyl, C6-12 aryl, C3-8 heteroaryl, or halogen;
- X2 is O or S;
- and
- A1 is H, the side chain of any naturally occurring α-amino acid, or is of the following formula,
- —(CH2)m—Y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh, NRiRi′, —NRi(ORh), or —NRi(NRiRi′), wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, and each of Ri and Ri′, independently is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxycarbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid;
- and
- a pharmaceutically acceptable carrier.
12 more elements
A pharmaceutical composition comprising a compound having the following formula
- 81
- wherein Z1 is O, S, NH or NRj, Rj being C1-6 alkyl;
- X1 is O or S;
- R1 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, hydroxyl, halogen, a side chain of a naturally occuring α-amino acid, ORd, SRd, or NRdRe (each of Rd and Re, independently, being C1-6 alkyl, C1-6 haloalkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or halogen);
- R2 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-12 aryl, C3-8 heteroaryl, or halogen;
- Ra is C1-6 alkyl;
- and
- A1 is H, the side chain of any naturally occurring α-amino acid, or is of the following formula,
- —(CH2)m—Y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh NRiRi′, —NRi(ORh), or —NRi(NRiRi′), wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, and each of Ri and Ri′, independently is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxy-carbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid;
- and
- a pharmaceutically acceptable carrier.
12 more elements
A pharmaceutical composition comprising a compound having the formula
- 82
- wherein X1 is O, S, CH2, two singly bonded H, CH(Rb) in the E or Z configuration, or C(Rb)(Rc) in the E or Z configuration, each of Rb and Rc, independently, being C1-6 alkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or halogen;
- Z1 is O, S, NH, or NRa, Ra being C1-6 alkyl;
- R1 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, hydroxyl, halogen, a side chain of any naturally occuring α-amino acid, ORd, SRd, or NRdRe (each of Rd and Re, independently, being H, C1-6 alkyl, C1-6 haloalkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or halogen);
- or R1 and R2 taken together are a bivalent moiety which forms a C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or C6-12 aryl;
- R2 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, azido, C2-6 alkynyl, halogen, ORf, SRf, NRfRg, —ONRfRg, —NRg—(ORf), or —NRg(SRf) (each of Rf and Rg, independently, being H, C16, alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-6 alkynyl), or R1 and R2 taken together are a bivalent moiety, the bivalent moiety forming a C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or C6-12 aryl;
- X2 is O or S;
- and
- A1 is in the (R) or (S) configuration, and each of A1 and A2 is independently H, the side chain of any naturally occurring amino α-acid, or is of the following formula,
- —(CH2)m—Y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh, NRiRi′, —NRi(ORh), or —NRi(NRiRi′), wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, and each of Ri and Ri′, independently is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxycarbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid;
- and
- a pharmaceutically acceptable carrier.
13 more elements
A pharmaceutical composition comprising a compound having the following formula
- 83
- wherein Z1 is NH or NRa, NRa being C1-6 alkyl;
- X1 is O, S, CH2, two singly bonded H, CH(Rb) in the E or Z configuration, or C(Rb)(Rc) in the E or Z configuration, each of Rb and Rc, independently, being C1-6 alkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or halogen;
- Z2 is O, S, NH, or NRj, Rj being C1-6 alkyl;
- R1 is in the (R) or (S) configuration, and is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, hydroxyl, halogen, a side chain of any naturally occuring amino acid, ORd, SRd, or NRdRe (each of Rd and Re, independently, being H, C1-6 alkyl, C1-6 haloalkyl, C6-12 aryl, C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or halogen);
- or R1 and R2 taken together are a bivalent moiety which forms a C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or C6-12 aryl;
- R2 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, azido, C2-6 alkynyl, halogen, ORf, SRf, NRfRg, ONRfRg, NRg—(ORf), or NRg(SRf) (each of Rf and Rg, independently, being H, C1-6, alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-6 alkynyl), or R1 and R2 taken together are a bivalent moiety, the bivalent moiety forming a C3-8 cycloalkyl, C3-8 heteroaryl, C3-8 heterocyclic radical, or C6-12 aryl;
- X2 is O or S;
- and
- each of A1 and A2 is independently in the (R) or (S) configuration, and is independently H, the side chain of any naturally occurring α-amino acid, or is of the following formula,
- —(CH2)m—Y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh, NRiRi′, —NRi(ORh), or —NRi(NRiRi′), wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, and each of Ri and Ri′, independently is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxycarbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid;
- and
- a pharmaceutically acceptable carrier.
14 more elements
A pharmaceutical composition comprising a compound of the formula
- 84
- wherein Z1 is O, NH, or NRa, NRa being C1-6 alkyl;
- X1 is O, S, CH2, or two singly bonded H;
- each of A1 and A2 is independently H, the side chain of any naturally occurring α-amino acid, or is of the following formula,
- —(CH2)m—Y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh, NRiRi′, —NRi(ORh), or —NRi(NRiRi′), wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, and each of Ri and Ri′ independently is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxycarbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid;
- and
- R12 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-6 alkynyl;
- and a pharmaceutically acceptable carrier.
9 more elements
A pharmaceutical composition comprising a compound having the formula
- 85
- wherein Z1 is NH, or NRa, NRa being C1-6 alkyl;
- each of X1 and X2, independently, is O or S;
- each of A1 and A2 is independently in the (R) or (S), configuration, and is independently H, the side chain of any naturally occurring amino acid, or is of the following formula,
- —(CH2)m—Y—(CH2)n—R3X3
- wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NORh, —C═NNRiRi′, sulfonyl, methylene, CHX4 in the (R) or (S) configuration, or deleted, X4 being halogen, methyl, halomethyl, ORh, SRh, NRiRi′, —NRi(ORh), or —NRi(NRiRi′), wherein Rh is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, and each of Ri and Ri′, independently is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-10 acyl;
- m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3;
- and R3 is straight chain or branched C1-8 alkylidene, straight chain or branched C1-8 alkylene, C3-10 cycloalkylidene, C3-10 cycloalkylene, phenylene, C6-14 arylalkylidene, C6-14 arylalkylene, or deleted, and X3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C1-6 alkyl)oxycarbonyl, (C7-14 arylalkyl)oxycarbonyl, or C6-14 aryl;
- or R3 and X3 taken together are the side chain of any naturally occurring α-amino acid;
- and a pharmaceutically acceptable carrier.
7 more elements
Dependencies are inferred from the claim text.