US2020048276A9PendingUtilityA9
Myc modulators and uses thereof
Assignee: MASSACHUSETTS INST TECHNOLOGYPriority: Dec 10, 2014Filed: Jun 11, 2018Published: Feb 13, 2020
Est. expiryDec 10, 2034(~8.4 yrs left)· nominal 20-yr term from priority
A61P 43/00A61P 35/02A61P 35/00C07D 417/14C07D 495/04C07D 405/12C07D 417/12C07D 471/04C07D 405/14
45
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Claims
Abstract
The present disclosure provides compounds of Formula (I-a), Formula (I), and Formula (II). The compounds described herein may be Myc modulators (e.g., Myc inhibitors) and may be useful in treating in a subject in need thereof diseases associated with Myc and proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including a compound described herein.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound of Formula (I-a):
or a pharmaceutically acceptable salt thereof, wherein:
each instance of R A is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR a , —N(R a ) 2 , —SR a , —CN, —SCN, —C(═NR a )R a , —C(═NR a )OR a , —C(═NR a )N(R a ) 2 , —C(═O)R a , —C(═O)OR a , —C(═O)N(R a ) 2 , —NO 2 , —N(R a )C(═O)R a , —N(R a )C(═O)OR a , —N(R a )C(═O)N(R a ) 2 , —N(R a )S(═O)R a , —N(R a )S(═O)OR a , —N(R a )S(═O)N(R a ) 2 , —N(R a )S(═O) 2 R a , —N(R a )S(═O) 2 OR a , —N(R a )S(═O) 2 N(R a ) 2 , —OC(═O)R a , —OC(═O)OR a , or —OC(═O)N(R a ) 2 , or two instances of R A are joined to form a substituted or unsubstituted, carbocyclic ring, substituted or unsubstituted, heterocyclic ring, substituted or unsubstituted, aryl ring, or substituted or unsubstituted, heteroaryl ring;
k is 0, 1, 2, or 3;
L is —N—, —O—, —S—, or a bond;
X a is —NR B —, —O—, or —S—;
W a is —C(R A )═, or —N═;
R B is hydrogen, substituted or unsubstituted C 1-6 alkyl, or a nitrogen protecting group;
R D is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR d1 , —N(R d1 ) 2 , —NO 2 , —NR d1 C(═O)R d1 , —NR d1 C(═O)OR d1 , —NR d1 C(═O)N(R d1 ) 2 , —OC(═O)R d1 , —OC(═O)OR d1 , —OC(═O)N(R d1 ) 2 , —C(═O)R d1 , —C(═O)OR d1 , —C(═O)N(R d1 ) 2 , —CH 2 N(R d1 ) 2 , or —CH 2 OR d1 ;
each instance of R a is independently hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of R a are joined to form a substituted or unsubstituted carbocyclyl ring, substituted or unsubstituted, heterocyclic ring, substituted or unsubstituted aryl ring, or substituted or unsubstituted, heteroaryl ring;
each instance of R d1 is independently hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of R d1 are joined to form a substituted or unsubstituted carbocyclyl ring, substituted or unsubstituted, heterocyclic ring, substituted or unsubstituted aryl ring, or substituted or unsubstituted, heteroaryl ring; and
Ring A is a substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.
2 . The compound of claim 1 , wherein the compound is of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
each instance of R A is independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR a , —N(R a ) 2 , —SR a , —CN, —SCN, —C(═NR a )R a , —C(═NR a )OR a , —C(═NR a )N(R a ) 2 , —C(═O)R a , —C(═O)OR a , —C(═O)N(R a ) 2 , —NO 2 , —N(R a )C(═O)R a , —N(R a )C(═O)OR a , —N(R a )C(═O)N(R a ) 2 , —N(R a )S(═O)R a , —N(R a )S(═O)OR a , —N(R a )S(═O)N(R a ) 2 , —N(R a )S(═O) 2 R a , —N(R a )S(═O) 2 OR a , —N(R a )S(═O) 2 N(R a ) 2 , —OC(═O)R a , —OC(═O)OR a , or —OC(═O)N(R a ) 2 , or two instances of R A are joined to form a substituted or unsubstituted, carbocyclic ring, substituted or unsubstituted, heterocyclic ring, substituted or unsubstituted, aryl ring, or substituted or unsubstituted, heteroaryl ring;
each instance of R a is independently H, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of R a are joined to form a substituted or unsubstituted, heterocyclic ring, or substituted or unsubstituted, heteroaryl ring;
k is 0, 1, 2, 3, or 4;
R B is hydrogen, substituted or unsubstituted C 1-6 alkyl, or a nitrogen protecting group;
X is —O— or —S—;
the double bond labeled with “a” is in the (E)- or (Z)-configuration; and
R C is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —C(═O)R a , —C(═O)OR a , —C(═O)N(R a ) 2 , or a nitrogen protecting group.
3 . The compound of claim 1 , wherein W a is —N═.
4 . The compound of claim 1 , wherein the compound is not of the formula:
or a pharmaceutically acceptable salt thereof.
5 . The compound of claim 1 , wherein the compound is not of the formula:
6 . The compound of any one of claims 1 - 5 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
7 . The compound of any one of claims 1 - 5 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
8 . The compound of any one of claims 1 - 5 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
9 . The compound of any one of claims 1 - 5 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
10 . The compound of any one of claims 1 - 5 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
11 . The compound of any one of claims 1 - 5 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
12 . The compound of any one of claims 1 - 11 , wherein at least one instance of R A is halogen, —OR a , —N(R a ) 2 , —NO 2 , —C(═O)R a , —C(═O)OR a , —C(═O)N(R a ) 2 , —N(R a )C(═O)R a , —N(R a )C(═O)N(R a ) 2 , or —N(R a )S(═O) 2 R a .
13 . The compound of claim 12 , wherein at least one instance of R A is Cl, —OMe, —OCF 3 , —NH 2 , —NHMe, —NMe 2 , —NO 2 , —C(═O)Me, —C(═O)OH, —C(═O)OMe, —C(═O)NH 2 , —C(═O)NHMe, —C(═O)NHPh, —C(═O)-(1-morpholinyl), —NHC(═O)Me, —NHC(═O)Ph, —NHC(═O)NH(i-Pr), —NHC(═O)NHPh, —NHS(═O) 2 Me, or —NHS(═O) 2 Ph.
14 . The compound of any one of claims 1 - 11 , wherein at least one instance of R A is substituted or unsubstituted alkyl.
15 . The compound of claim 14 , wherein at least one instance of R A is Me.
16 . The compound of claim 14 , wherein at least one instance of R A is —CF 3 , —CH 2 OH, or i-Pr.
17 . The compound of any one of claims 1 - 5 , 8 and 11 , wherein k is 0.
18 . The compound of any one of claims 1 - 5 , 8 , and 11 - 16 , wherein k is 1.
19 . The compound of any one of claims 1 - 5 , 8 , and 11 - 16 , wherein k is 2.
20 . The compound of any one of claims 1 - 10 and 12 - 19 , wherein R B is hydrogen.
21 . The compound of any one of claims 1 - 10 and 12 - 19 , wherein R B is substituted or unsubstituted C 1-6 alkyl.
22 . The compound of claim 21 , wherein R B is of the formula: —(CH 2 ) a N(R a1 ) 2 , wherein:
a is independently 1, 2, 3, or 4; and
each instance of R a1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.
23 . The compound of claim 22 , wherein:
a is 3; and each instance of R a1 is hydrogen.
24 . The compound of claim 1 , wherein R B is of the formula: —(CH 2 ) a NHC(═O)(CH 2 ) b R b1 , wherein:
R b1 is H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or —N(R b2 )C(═O)R b3 ;
each instance of a and b is independently 1, 2, 3, or 4; and
each instance of R b2 and R b3 is independently H, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.
25 . The compound of claim 24 , wherein R b1 is a bicyclic heterocycle.
26 . The compound of claim 25 , wherein R b1 is of the formula:
or a pharmaceutically acceptable salt thereof.
27 . The compound of claim 1 , wherein R B is of the formula: —(CH 2 ) a C(═O)NHR c1 , wherein:
R c1 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.
28 . The compound of claim 27 , wherein:
R c1 is of the formula: —(CH 2 ) d O(CH 2 ) e O(CH 2 )C(═O)NHR e1 , wherein: R e1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl; and each instance of d, e, or f is independently 1, 2, 3, 4, 5, or 6.
29 . The compound of claim 28 , wherein:
R e1 is of the formula:
30 . The compound of claim 1 , wherein R B is of the formula: —(CH 2 ) a NHC(═O)R f1 , wherein R f1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.
31 . The compound of claim 30 , wherein R f1 is substituted phenyl.
32 . The compound of claim 30 , wherein R f1 is of the formula:
33 . The compound of claim 27 , wherein:
R c1 is of the formula:
34 . The compound of claim 27 , wherein R b1 is of the formula:
35 . The compound of claim 22 , wherein R b1 is of the formula:
36 . The compound of claim 1 , wherein R B is Me or —(CH 2 ) 3 NH 2 .
37 . The compound of any one of claims 1 - 7 and 12 - 36 , wherein X is —O—.
38 . The compound of any one of claims 1 - 7 and 12 - 36 , wherein X is —S—.
39 . The compound of any one of claims 1 - 7 and 12 - 38 , wherein the double bond labeled with “a” is in the (E)-configuration.
40 . The compound of any one of claims 1 - 7 and 12 - 38 , wherein the double bond labeled with “a” is in the (Z)-configuration.
41 . The compound of any one of claims 1 - 40 , wherein R C is substituted or unsubstituted C 1-6 alkyl.
42 . The compound of claim 38 , wherein R C is i-Pr.
43 . The compound of claim 38 , wherein R C is sec-Bu.
44 . The compound of claim 38 , wherein R C is —CH 2 —CO 2 H, —CH 2 —CO 2 Me, —CH 2 —CO 2 (t-Bu), —CH(Me)-CO 2 Me, —CH(Me)-CO 2 Et,
45 . The compound of claim 38 , wherein R C is —(CH 2 ) 3 —NH 2 , —(CH 2 ) 3 —NHC(═O)NHEt, —(CH 2 ) 3 —NHC(═O)NHPh, or
46 . The compound of any one of claims 1 - 38 , wherein R C is substituted or unsubstituted phenyl.
47 . The compound of claim 1 , wherein Ring A is of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
W is —NH—, —O— or —S—.
48 . The compound of claim 1 , wherein Ring A is a monocyclic or bicyclic heteroaryl ring.
49 . The compound of claim 1 , wherein Ring A is of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
Y is —O— or —S—.
50 . The compound of claim 47 , wherein when W is —O—, then k is 1, 2, 3, or 4, and no instance of R A is Me.
51 . The compound of claim 47 , wherein when W is —O—, and k is 1, then no instance of R A is Me.
52 . The compound of claim 1 , wherein R D is of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
X 1 is —S—, or —NR C —, —CH 2 —; and
R C is H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —C(═O)R a , —C(═O)OR a , —C(═O)N(R a ) 2 , or a nitrogen protecting group.
53 . The compound of claim 52 , wherein R D is of the formula:
or a pharmaceutically acceptable salt thereof.
54 . The compound of claim 1 , wherein R D is of the formula: —CH 2 OR F , —C(═O)OR F , —C(═O)N(R g1 ) 2 , or —CH 2 N(R g1 ) 2 ;
R F is H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl; and
R g1 is H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or two instances of R g1 are joined to form a substituted or unsubstituted, carbocyclic ring, substituted or unsubstituted, heterocyclic ring, substituted or unsubstituted, aryl ring, or substituted or unsubstituted, heteroaryl ring.
55 . The compound of claim 1 , wherein R D is of the formula:
or a pharmaceutically acceptable salt thereof.
56 . The compound of claim 1 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
57 . The compound of claim 1 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
58 . The compound of claim 1 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
59 . The compound of claim 1 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
60 . The compound of claim 1 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
61 . A compound of Formula (II):
or a pharmaceutically acceptable salt thereof, wherein:
the double bond labeled with “a” is in the (E)- or (Z)-configuration;
R C is hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —C(═O)R a , —C(═O)OR a , —C(═O)N(R a ) 2 , or a nitrogen protecting group;
each instance of R a is independently hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of R a are joined to form a substituted or unsubstituted, heterocyclic ring, or substituted or unsubstituted, heteroaryl ring; and
R E is a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.
62 . The compound of claim 61 , wherein R E is of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
X is —O— or —S—; and
Ring B is a substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.
63 . The compound of claim 61 , wherein R E is of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
X is —O— or —S— and
Ring B is a substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.
64 . The compound of claim 61 , wherein Ring B is of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
W 1 and Y 1 are independently —N—, or —NR W —, as valency permits; and
R W is H, substituted or unsubstituted alkyl, substituted or unsubstituted acyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a nitrogen protecting group.
65 . The compound of claim 61 , wherein Ring B is of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
Z is —N— or —CH—; and R G is hydrogen, or substituted or unsubstituted alkyl.
66 . The compound of claim 63 or 64 , wherein Ring B is of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
Y 1 and Z 1 are independently —NR g —, —CH—, or —O—; and
R g is hydrogen, or substituted or unsubstituted alkyl.
67 . The compound of claim 61 , wherein R E is of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
X is —O— or —S—; and
R X is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted acyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.
68 . The compound of claim 61 , wherein R E is of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
R f is hydrogen, or substituted or unsubstituted alkyl.
69 . The compound of claim 61 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
70 . A pharmaceutical composition comprising a compound of any one of claims 1 - 69 , or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable excipient.
71 . The pharmaceutical composition of claim 70 further comprising an additional pharmaceutical agent.
72 . A method of treating a disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of any one of claims 1 - 69 , or a pharmaceutical composition of claim 70 or 72 , wherein the disease is associated with Myc.
73 . The method of claim 72 , wherein the disease is associated with increased activity of Myc.
74 . The method of claim 72 or 73 , wherein the disease is associated with a mutant form of Myc.
75 . The method of any one of claims 72 - 74 , wherein the disease is associated with somatic amplification of Myc.
76 . The method of any one of claims 72 - 75 , wherein the disease is associated with a chromosomal translocation.
77 . The method of any one of claims 72 - 76 , wherein the disease is associated with overexpression of Myc.
78 . The method of any one of claims 72 - 77 , wherein the disease is associated with enhanced translation of Myc.
79 . The method of any one of claims 72 - 78 , wherein the disease is associated with increased stability of Myc.
80 . A method of treating a disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of any one of claims 1 - 69 , or a pharmaceutical composition of claim 70 or 71 , wherein the disease is a proliferative disease.
81 . The method of any one of claims 72 - 80 , wherein the disease is cancer.
82 . The method of 81 , wherein the disease is lung cancer, cervical cancer, breast cancer, or colorectal cancer.
83 . The method of 81 , wherein the disease is ovarian cancer, pancreatic cancer, gastric cancer, or uterine cancer.
84 . The method of 81 , wherein the disease is hematological malignancy.
85 . The method of 81 , wherein the disease is lymphoma.
86 . The method of any one of claims 70 - 78 , wherein the disease is benign neoplasm.
87 . The method of any one of claims 70 - 78 , wherein the disease is pathological angiogenesis.
88 . A method of modulating the activity of Myc in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 - 69 , or a pharmaceutical composition of claim 70 or 71 .
89 . The method of any one of claims 70 - 88 , wherein the Myc is c-Myc, L-Myc, or N-Myc.
90 . The method of any one of claims 70 - 88 , wherein the subject is a human.
91 . A method of inducing apoptosis of a cell, the method comprising contacting the cell with an effective amount of a compound of any one of claims 1 - 69 , or a pharmaceutical composition of claim 70 or 71 .
92 . The method of claim 91 , wherein the cell is in vitro.
93 . The method of claim 91 , wherein the cell is in vivo.
94 . A kit comprising:
a compound of any one of claims 1 - 69 , or a pharmaceutical composition of claim 70 or 71 ; and instructions for using the compound or pharmaceutical composition.Join the waitlist — get patent alerts
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