US 11,655,238 B2Granted

MMPL3 inhibitors, compositions and uses thereof

AssigneeShanghaitech University

InventorsZihe Rao, Jun Li, Bing Zhang, Haitao Yang

Life of this patent

Estimating the term…

Abstract

The present disclosure relates generally to inhibitors of mycobacterial membrane protein MmpL3, compositions comprising the inhibitors, and methods of preparation and use thereof.

Claims28

Dependent claims

A compound of the below Formula III:

or a pharmaceutically acceptable salt, tautomer, isotopically enriched analog, stereoisomer, or mixture of stereoisomers thereof,
wherein:
X1, X2, and X3 are C;
X4 and X5 are N;
L1 is *—N(R1b)CO—, *—(CH2)k—N(R1b)CO—, *—(CH2)n—N(R1c)—(CH2)k—N(R1b)CO—, *—(CH2)n-(O(CH2)m)p—O(CH2)k—N(R1b)CO—, *—(CH2)m—CO-L1a-CO—, *—(CH2)m-L1a-CO—, *—(CH2)n—NHCONH—(CH2)m—, *—(CH2)n—N(R1c)—(CH2)k—N(R1b)—(CH2)m—, *—(CH2)n—CON(R1b)—(CH2)m—, *—(CH2)p—N(R1c)—(CH2)n—CON(R1b)—(CH2)m—, *—(CH2)p—N(R1c)—(CH2)n—SO2N(R1b)—(CH2)m—, *—(CH2)n—SO2N(R1b)—(CH2)m—, *—(CH2)n—OCO—, *—(CH2)n-L1a-(CH2)m—, *—N(R1c)—(CH2)m—N(R1b)—(CH2)m—, or —N(R1c)—(CH2)n—N(R1b)—N(R1b)—(CO)—;
wherein
* represents the point of connection with R1;
L1a is 5-, 6- or 7-membered heterocyclylene;
each R1b is independently H or C1-3 alkyl;
each R1c is independently H or C1-3 alkyl;
k is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
and
each m, n and p is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
R1 is adamantly substituted with one to ten R1a, bicyclo[2.2.1]heptyl substituted with one to ten R1a or unsubstituted adamantyl;
each R1a is independently selected from —CN, —NO2, C1-3 alkyl, C1-3 haloalkyl, —OR6, —SR6, —N(R6)2, —C(O)R6, —C(O)OR6, —S(O)R6, —S(O)2R6, —C(O)N(R6)2, —NR6C(O)R6, —NR6C(O)OR6, —NR6C(O)N(R6)2, —NHS(O)R6, —S(O)(NH)R6, cycloalkyl, aryl, heterocyclyl, heteroaryl, or a combination thereof;
R2 is C1-3 alkyl;
each R3b and R3c is independently H or R3a;
and
each R4b and R4c is independently H or R4a;
R3a and R4a is independently selected form halo and C1-3 alkyl;
R5 is absent;
each R6 is independently hydrogen, C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, aryl, heteroaryl, or heterocyclyl.

19 more elements

A compound, or a pharmaceutically acceptable salt, solvate, tautomer, isotopically enriched analog, stereoisomer, or mixture of stereoisomers thereof, wherein the compound is selected from any one of the following compounds:

Comp
No.
Structure
Name
1
1-((1r,3r,5r,7r)-adamantan-2- yl)-3-(5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl- 1H-pyrazol-3-yl)urea
2
1-((1r,3r,5r,7r)-adamantan-2- yl)-3-((5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl- 1H-pyrazol-3-yl)methyl)urea
3
1-(((1r,3r,5r,7r)-adamantan-2- yl)methyl)-3-((5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazol-3-yl)- methyl)urea
4
1-(2-((1r,3r,5r,7r)-adamantan- 2-yl)ethyl)-3-((5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazol-3-yl)- methyl)urea
5
1-(3-((1r,3r,5r,7r)-adamantan- 2-yl)propyl)-3-((5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazol-3-yl)- methyl)urea
6
1-(4-((1r,3r,5r,7r)-adamantan- 2-yl)butyl)-3-((5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazol-3-yl)- methyl)urea
7
1-(5-((1r,3r,5r,7r)-adamantan- 2-yl)pentyl)-3-((5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazol-3-yl)- methyl)urea
8
1-(6-((1r,3r,5r,7r)-adamantan- 2-yl)hexyl)-3-((5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazol-3-yl)- methyl)urea
9
1-((3s,5s,7s)-adamantan-1-yl)- 3-(5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H- pyrazol-3-yl)urea
10
1-((3s,5s,7s)-adamantan-1-yl)- 3-((5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H- pyrazol-3-yl)methyl)urea
11
1-(((3r,5r,7r)-adamantan-1-yl)- methyl)-3-((5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazol-3-yl)- methyl)urea
12
1-(2-((3r,5r,7r)-adamantan-1- yl)ethyl)-3-((5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazol-3-yl)- methyl)urea
13
1-(3-((3r,5r,7r)-adamantan-1- yl)propyl)-3-((5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazol-3-yl)- methyl)urea
14
1-(4-((3r,5r,7r)-adamantan-1- yl)butyl)-3-((5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazol-3-yl)- methyl)urea
15
1-(5-((3r,5r,7r)-adamantan-1- yl)pentyl)-3-((5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazol-3-yl)- methyl)urea
16
1-(6-((3r,5r,7r)-adamantan-1- yl)hexyl)-3-((5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazol-3-yl)- methyl)urea
17
N-(2-(((1r,3r,5r,7r)-adamantan- 2-yl)amino)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazole-3- carboxamide
18
N-(3-(((1r,3r,5r,7r)-adamantan- 2-yl)amino)propyl)-5-(4- chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
19
N-(4-(((1r,3r,5r,7r)-adamantan- 2-yl)amino)butyl)-5-(4- chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
20
N-(5-(((1r,3r,5r,7r)-adamantan- 2-yl)amino)pentyl)-5-(4- chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
21
N-(6-(((1r,3r,5r,7r)-adamantan- 2-yl)amino)hexyl)-5-(4- chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
22
N-(7-(((1r,3r,5r,7r)-adamantan- 2-yl)amino)heptyl)-5-(4- chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
23
(5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-N-(2- (((1r,3R,5S,7r)-3,5-dimethyl- adamantan-1-yl)amino)ethyl)- 4-methyl-1H-pyrazole-3- carboxamide
24
N-(3-(((3s,5s,7s)-adamantan- 1-yl)amino)propyl)-5-(4- chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
25
N-(4-(((3s,5s,7s)-adamantan- 1-yl)amino)butyl)-5-(4- chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
26
N-(5-(((3s,5s,7s)-adamantan- 1-yl)amino)pentyl)-5-(4- chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
27
N-(6-(((3s,5s,7s)-adamantan- 1-yl)amino)hexyl)-5-(4- chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
28
N-(7-(((3s,5s,7s)-adamantan- 1-yl)amino)heptyl)-5-(4- chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
29
(4-((1r,3r,5r,7r)-adamantan- 2-yl)piperazin-1-yl)-(5-(4- chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazol-3-yl)methanone
30
4-(((1r,3r,5r,7r)-adamantan- 2-yl)methyl)piperazin-1-yl)- (5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazol-3-yl)methanone
31
(4-(2-((1r,3r,5r,7r)-adamantan- 2-yl)ethyl)piperazin-1-yl)(5- (4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazol-3-yl)methanone
32
(4-(3-((1r,3r,5r,7r)-adamantan- 2-yl)propyl)piperazin-1-yl)- (5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazol-3-yl)methanone
33
(4-(4-(1r,3r,5r,7r)-adamantan- 2-yl)butyl)piperazin-1-yl)- (5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazol-3-yl)methanone
34
(4-(5-(1r,3r,5r,7r)-adamantan- 2-yl)pentyl)piperazin-1-yl)- (5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazol-3-yl)methanone
35
(4-(6-((1r,3r,5r,7r)-adamantan- 2-yl)hexyl)piperazin-1-yl)- (5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazol-3-yl)methanone
36
(4-((3s,5s,7s)-adamantan-1- yl)piperazin-1-yl)(5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazol-3-yl)- methanone
37
(4-(((3r,5r,7r)-adamantan-1- yl)methyl)piperazin-1-yl)(5- (4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazol-3-yl)methanone
38
(4-(2-((3r,5r,7r)-adamantan-1- yl)ethyl)piperazin-1-yl)(5-(4- chlorophenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H-pyrazol- 3-yl)methanone
39
(4-(3-((3r,5r,7r)-adamantan-1- yl)propyl)piperazin-1-yl)(5-(4- chlorophenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H-pyrazol- 3-yl)methanone
40
(4-(4-((3r,5r,7r)-adamantan-1- yl)butyl)piperazin-1-yl)(5-(4- chlorophenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H-pyrazol- 3-yl)methanone
41
(4-(5-((3r,5r,7r)-adamantan-1- yl)pentyl)piperazin-1-yl)(5-(4- chlorophenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H-pyrazol- 3-yl)methanone
42
(4-(6-((3r,5r,7r)-adamantan-1- yl)hexyl)piperazin-1-yl)(5-(4- chlorophenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H-pyrazol- 3-yl)methanone
43
N-((1r,3r,5r,7r)-adamantan-2- yl)-5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H- pyrazole-3-carboxamide
44
N-(((1r,3r,5r,7r)-adamantan-2- yl)methyl)-5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carbox- amide
45
N-(2-((1r,3r,5r,7r)-adamantan- 2-yl)ethyl)-5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carbox- amide
46
N-(3-((1r,3r,5r,7r)-adamantan- 2-yl)propyl)-5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carbox- amide
47
N-(4-((1r,3r,5r,7r)-adamantan- 2-yl)butyl)-5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carbox- amide
48
N-(5-((1r,3r,5r,7r)-adamantan- 2-yl)pentyl)-5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carbox- amide
49
N-(6-((1r,3r,5r,7r)-adamantan- 2-yl)hexyl)-5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carbox- amide
50
N-(7-((1r,3r,5r,7r)-adamantan- 2-yl)heptyl)-5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carbox- amide
51
N-(8-((1r,3r,5r,7r)-adamantan- 2-yl)octyl)-5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carbox- amide
52
N-((3s,5s,7s)-adamantan-1-yl)- 5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
53
N-(((3r,5r,7r)-adamantan-1- yl)methyl)-5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carbox- amide
54
N-(2-((3r,5r,7r)-adamantan-1- yl)ethyl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
55
N-(3-((3r,5r,7r)-adamantan-1- yl)propyl)-5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carbox- amide
56
N-(4-((3r,5r,7r)-adamantan-1- yl)butyl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
57
N-(5-((3r,5r,7r)-adamantan-1- yl)pentyl)-5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carbox- amide
58
N-(6-((3r,5r,7r)-adamantan-1- yl)hexyl)-5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carbox- amide
59
N-(7-((3r,5r,7r)-adamantan-1- yl)heptyl)-5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carbox- amide
60
N-(8-((3r,5r,7r)-adamantan-1- yl)octyl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
61
N-(2-(((1r,3r,5r,7r)-adamantan- 2-yl)oxy)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazole-3- carboxamide
62
N-(2-(((1r,3r,5r,7r)-adamantan- 2-yl)methoxy)ethyl)-5-(4- chlorophenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H-pyrazole- 3-carboxamide
63
N-(2-(2-((1r,3r,5r,7r)- adamantan-2-yl)ethoxy)ethyl)- 5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
64
N-(2-(2-(((1r,3r,5r,7r)- adamantan-2-yl)oxy)ethoxy)- ethyl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
65
N-(2-(2-(((1r,3r,5r,7r)- adamantan-2-yl)methoxy)- ethoxy)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H- pyrazole-3-carboxamide
66
N-(2-(2-(2-((1r,3r,5r,7r)- adamantan-2-yl)ethoxy)- ethoxy)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H- pyrazole-3-carboxamide
67
N-(2-(((3s,5s,7s)-adamantan- 1-yl)oxy)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H- pyrazole-3-carboxamide
68
N-(2-(((3r,5r,7s)-adamantan-1- yl)methoxy)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazole-3- carboxamide
69
N-(2-(2-((3r,5r,7r)-adamantan- 1-yl)ethoxy)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazole-3- carboxamide
70
N-(2-(2-(((3s,5s,7s)- adamantan-1-yl)oxy)ethoxy)- ethyl)-5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carbox- amide
71
N-(2-(2-(((3r,5r,7r)- adamantan-1-yl)methoxy)- ethoxy)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H- pyrazole-3-carboxamide
72
N-(2-(2-(2-((3r,5r,7r)- adamantan-1-yl)ethoxy)- ethoxy)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H- pyrazole-3-carboxamide
73
N-(2-(((1r,3r,5r,7r)-adamantan- 2-yl)(methyl)amino)ethyl)- 5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
74
N-(2-(((1r,3r,5r,7r)- adamantan-2-yl)amino)ethyl)- 5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-N,4-dimethyl- 1H-pyrazole-3-carboxamide
75
N-(2-(((1r,3r,5r,7r)- adamantan-2-yl)(methyl)- amino)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-N,4-dimethyl-1H- pyrazole-3-carboxamide
76
N-(2-(((1r,3r,5r,7r)-adamantan- 2-yl)amino)ethyl)-5-(4-chloro- phenyl)-1-(2,4-difluorophenyl)- 4-methyl-1H-pyrazole-3- carboxamide
77
N-(2-(((1r,3r,5r,7r)-adamantan- 2-yl)amino)ethyl-5-(4-chloro- phenyl)-1-(2,4-dimethylphenyl)- 4-methyl-1H-pyrazole-3- carboxamide
78
5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-N- (2-(((1S,2S,4S)-1,7,7-trimethyl- bicyclo[2.2.1]heptan-2-yl)oxy)- ethyl)-1H-pyrazole-3-carbox- amide
79
5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-N- (3-(((1S,2S,4S)-1,7,7-trimethyl- bicyclo[2.2.1]heptan-2-yl)oxy)- propyl)-1H-pyrazole-3-carbox- amide
80
5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-N- (2-(((1S,2S,4S)-1,7,7-trimethyl- bicyclo[2.2.1]heptan-2-yl)- amino)ethyl)-1H-pyrazole-3- carboxamide
81
5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-N- (3-(((1S,2S,4S)-1,7,7-trimethyl- bicyclo[2.2.1]heptan-2-yl)- amino)propyl)-1H-pyrazole- 3-carboxamide
82
N-(2-(((1r,3r,5r,7r)-adamantan- 2-yl)amino)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-(trifluoromethyl)-1H- pyrazole-3-carboxamide
83
N-(2-(((1r,3r,5r,7r)-adamantan- 2-yl)amino)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-isopropyl-1H-pyrazole-3- carboxamide
84
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-ethyl-1H-pyrazole-3-carbox- amide
85
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-4-chloro- 5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-1H-pyrazole- 3-carboxamide
86
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-4-cyclopropyl-1-(2,4- dichlorophenyl)-1H-pyrazole- 3-carboxamide
87
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 1H-pyrazole-3-carboxamide
88
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(2,4- dichlorophenyl)-4-methyl- 5-phenyl-1H-pyrazole-3- carboxamide
89
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(2,4- dichlorophenyl)-5-(4-methoxy- phenyl)-4-methyl-1H-pyrazole- 3-carboxamide
90
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(2,4- dichlorophenyl)-4-methyl- 5-(p-tolyl)-1H-pyrazole-3- carboxamide
91
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(2,4- dichlorophenyl)-5-(4-ethyl- phenyl)-4-methyl-1H-pyrazole- 3-carboxamide
92
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(2,4- dichlorophenyl)-5-(3,4- dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
93
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1,5-bis(2,4- dichlorophenyl)-4-methyl-1H- pyrazole-3-carboxamide
94
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(2,4- dichlorophenyl)-4-methyl-5- (pyridin-3-yl)-1H-pyrazole- 3-carboxamide
95
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(2,4- dichlorophenyl)-5-(6-methoxy- pyridin-3-yl)-4-methyl-1H- pyrazole-3-carboxamide
96
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(3-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazole-3- carboxamide
97
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-cyano- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazole-3- carboxamide
98
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(2,4- dichlorophenyl)-4-methyl-5- (tetrahydro-2H-pyran-4-yl)- 1H-pyrazole-3-carboxamide
99
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(2,4- dichlorophenyl)-4-methyl-5- morpholino-1H-pyrazole-3- carboxamide
100
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(2,4- dichlorophenyl)-4-methyl-5- (4-methylpiperazin-1-yl)-1H- pyrazole-3-carboxamide
101
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(2,4- dichlorophenyl)-4-methyl-5- (pyrrolidin-1-yl)-1H-pyrazole- 3-carboxamide
102
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-cyclo- propyl-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazole-3- carboxamide
103
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(2,4- dichlorophenyl)-5-isopropyl- 4-methyl-1H-pyrazole-3- carboxamide
104
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(2,4- dichlorophenyl)-5-(3,4- dimethylphenyl)-4-methyl- 1H-pyrazole-3-carboxamide
105
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1,5-bis(4- chlorophenyl)-4-methyl-1H- pyrazole-3-carboxamide)
106
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(2-chloro- phenyl)-5-(4-chlorophenyl)-4- methyl-1H-pyrazole-3-carbox- amide
107
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dimethoxy- phenyl)-4-methyl-1H- pyrazole-3-carboxamide
108
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-4-methyl-1-(p-tolyl)- 1H-pyrazole-3-carboxamide
109
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(2-chloro- 4-fluorophenyl)-5-(4-chloro- phenyl)-4-methyl-1H- pyrazole-3-carboxamide
110
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(4-chloro- 2-methylphenyl)-5-(4-chloro- phenyl)-4-methyl-1H-pyrazole- 3-carboxamide
111
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(4-cyano-2-methyl- phenyl)-4-methyl-1H-pyrazole- 3-carboxamide
112
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(4-cyanophenyl)-4- methyl-1H-pyrazole-3-carbox- amide
113
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-4-methyl-1-(pyridin- 3-yl)-1H-pyrazole-3-carbox- amide
114
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(6-methoxypyridin- 3-yl)-4-methyl-1H-pyrazole-3- carboxamide
115
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(6-methoxy-5- (trifluoromethyl)pyridin-3- yl)-4-methyl-1H-pyrazole-3- carboxamide
116
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-4-methyl-1-(pyridin- 2-yl)-1H-pyrazole-3-carbox- amide
117
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-4-methyl-1-(pyrimidin- 4-yl)-1H-pyrazole-3-carbox- amide
118
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(3,5-dimethyl- phenyl)-4-methyl-1H- pyrazole-3-carboxamide
119
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(3,5-dichloro- phenyl)-4-methyl-1H- pyrazole-3-carboxamide
120
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(3,4-dimethyl- phenyl)-4-methyl-1H- pyrazole-3-carboxamide
121
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(3,4-dichloro- phenyl)-4-methyl-1H- pyrazole-3-carboxamide
122
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(4-chloro- 3-methoxyphenyl)-5-(4- chlorophenyl)-4-methyl-1H- pyrazole-3-carboxamide
123
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(4-isopropylphenyl)- 4-methyl-1H-pyrazole-3- carboxamide
124
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(3,5-dimethoxy- phenyl)-4-methyl-1H- pyrazole-3-carboxamide
125
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1,4-dimethyl-1H- pyrazole-3-carboxamide
126
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-isopropyl-4-methyl- 1H-pyrazole-3-carboxamide
127
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-cyclopropyl-4- methyl-1H-pyrazole-3-carbox- amide
128
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-ethyl-4-methyl-1H- pyrazole-3-carboxamide
129
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-cyclopentyl-4- methyl-1H-pyrazole-3-carbox- amide
130
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-4-methyl-1-propyl-1H- pyrazole-3-carboxamide
131
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H-pyrrole- 3-carboxamide
132
N-(3-((1r,3r,5r,7r)-adamantan- 2-ylamino)propyl)-5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H-pyrrole- 3-carboxamide
133
1-(3-((1r,3r,5r,7r)-adamantan- 2-yl)propyl)-3-((5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrrol-3-yl)- methyl)urea
134
1-((3r,5r,7r)-adamantan-1- ylmethyl)-3-((5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H-pyrrol- 3-yl)methyl)urea
135
1-(2-((3r,5r,7r)-adamantan-1- yl)ethyl)-3-((5-(4-chloro- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrrol-3-yl)- methyl)urea
136
N-(2-((3s,5s,7s)-adamantan- 1-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H-pyrrole- 3-carboxamide
137
5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-N-(2- (((1r,3R,5S,7r)-3,5-dimethyl- adamantan-1-yl)amino)ethyl)- 4-methyl-1H-pyrrole-3- carboxamide
138
5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- N-(3-(((1S,2S,4S)-1,7,7- trimethylbicyclo[2.2.1]heptan- 2-yl)amino)propyl)-1H- pyrrole-3-carboxamide
139
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(2,4- dichlorophenyl)-4-methyl-5- phenyl-1H-pyrrole-3-carbox- amide
140
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-cyano- phenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrrole-3-carbox- amide)
141
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(2,4- dichlorophenyl)-4-methyl-5- (pyridin-3-yl)-1H-pyrrole-3- carboxamide
142
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1,5-bis(4- chlorophenyl)-4-methyl-1H- pyrrole-3-carboxamide
143
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(3,4-dichlorophenyl)- 4-methyl-1H-pyrrole-3-carbox- amide
144
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(3,5-dichlorophenyl)- 4-methyl-1H-pyrrole-3-carbox- amide
145
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(4-chloro- phenyl)-2-(2,4-dichlorophenyl)- 5-methyl-1H-imidazole-4- carboxamide
146
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(4-chloro- phenyl)-2-(2,4-dichloro- phenyl)-1H-imidazole-4- carboxamide
147
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-4-(4-chloro- phenyl)-3-(2,4-dichloro- phenyl)-1H-pyrazole-1- carboxamide
148
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-4-(4-chloro- phenyl)-3-(2,4-dichloro- phenyl)-5-methyl-1H-pyrazole- 1-carboxamide
149
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-3-(4-chloro- phenyl)-4-(2,4-dichloro- phenyl)-1H-pyrazole-1- carboxamide
150
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-2-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-1H-imidazole-4- carboxamide
151
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(4-chloro- phenyl)-5-(2,4-dichloro- phenyl)-1H-pyrazole-3- carboxamide
152
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(4-chloro- phenyl)-5-(2,4-dichloro- phenyl)-4-methyl-1H-pyrazole- 3-carboxamide
153
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-2-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-5-methyl-1H- imidazole-4-carboxamide
154
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(4-chloro- phenyl)-5-(2,4-dichloro- phenyl)-2-methyl-1H-pyrrole- 3-carboxamide
155
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-3-(4-chloro- phenyl)-4-(2,4-dichloro- phenyl)-2-methyl-1H-pyrrole- 1-carboxamide
156
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-1-(4-chloro- phenyl)-5-(2,4-dichloro- phenyl)-4-methyl-1H-pyrrole- 3-carboxamide
157
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-2,4-dimethyl-1H- pyrrole-3-carboxamide
158
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-4-(4-chloro- phenyl)-5-(2,4-dichloro- phenyl)-3-methyl-1H-pyrrole- 2-carboxamide
159
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-4-(2,4-dichloro- phenyl)-3H-pyrrole-2-carbox- amide
160
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-4-(4-chloro- phenyl)-5-(2,4-dichloro- phenyl)-3-methylthiophene- 2-carboxamide
161
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-4-(2,4-dichloro- phenyl)thiophene-2-carbox- amide
162
N-(2-((1r,3r,5r,7r)-adamantan- 2-ylamino)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-1H-1,2,4-triazole-3- carboxamide)
163
N-(2-(((3s,5s,7s)-adamantan- 1-yl)amino)ethyl)-5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H- pyrazole-3-carboxamide
164
N1-((1r,3r,5r,7r)-adamantan- 2-yl)-N3-((5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H-pyrazol- 3-yl)methyl)propane-1,3- diamine
165
N1-((1r,3r,5r,7r)-adamantan- 2-yl)-N2-((5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H- pyrazol-3-yl)methyl)-N2- methylethane-1,2-diamine
166
N1-((1r,3r,5r,7r)-adamantan- 2-yl)-N2-((5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazol-3-yl)- methyl)ethane-1,2-diamine
167
N1-((1r,3r,5r,7r)-adamantan- 2-yl)-N4-((5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazol-3-yl)- methyl)butane-1,4-diamine
168
N-((5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H- pyrazol-3-yl)methyl)-2- (((1r,3R,5S,7r)-3,5-dimethyl- adamantan-1-yl)amino)ethane- 1-sulfonamide
169
N-((5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H- pyrazol-3-yl)methyl)-2- (((1r,3R,5S,7r)-3,5-dimethyl- adamantan-1-yl)amino)- acetamide
170
((3r,5r,7r)-adamantan-1-yl)(4- (5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H- pyrazole-3-carbonyl)piperazin- 1-yl)methanone
171
1,7,7-trimethylbicyclo[2.2.1]- heptan-2-yl 5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carbox- ylate
172
(1S,2S,4S)-1,7,7-trimethyl- bicyclo[2.2.1]heptan-2-yl 5- (4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxylate
173
(1R,2S,4R)-1,7,7-trimethyl- bicyclo[2.2.1]heptan-2-yl 5- (4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxylate
174
1-((1r,3r,5r,7r)-adamantan-2- yl)-4-((5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl- 1H-pyrazol-3-yl)methyl)- piperazine
175
1-(((3r,5r,7r)-adamantan-1- yl)methyl)-4-((5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H-pyrazol- 3-yl)methyl)piperazine
176
1-((1r,3r,5r,7r)-adamantan-2- yl)-4-(2-(5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazol-3-yl)- ethyl)piperazine
177
1-(((3r,5r,7r)-adamantan-1- yl)methyl)-4-(2-(5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H-pyrazol- 3-yl)ethyl)piperazine
178
N1-((1r,3r,5r,7r)-adamantan- 2-yl)-N2-(2-(5-(4-chloro- phenyl)-1-(2,4-dichloro- phenyl)-4-methyl-1H-pyrazol- 3-yl)ethyl)ethane-1,2-diamine
179
N-((3s,5s,7s)-adamantan-1-yl)- 2-(2-(5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl- 1H-pyrazole-3-carbonyl)- hydrazinyl)acetamide.

359 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/295,227Filed 20 Nov 2019
Priority: WO PCT/CN2018/11635020 Nov 2018
Published: US 2022/0017492 A120 Jan 2022
Granted: 23 May 2023
Term ends: Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07D 403/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
A61P 31/06
Antibacterial agents: for tuberculosis
C07D 207/327
With substituted hydrocarbon radicals directly attached to the ring nitrogen atom: radicals substituted by carbon atoms having three bonds to…

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US 2022/0017492 A1Pre-grant publication · published 20 Jan 2022
US 11,655,238 B2This patent

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Abstract

The present disclosure relates generally to inhibitors of mycobacterial membrane protein MmpL3, compositions comprising the inhibitors, and methods of preparation and use thereof.

Facts

Application

17/295,227Filed 20 Nov 2019

Priority

WO PCT/CN2018/11635020 Nov 2018

Published

US 2022/0017492 A120 Jan 2022

Granted

23 May 2023

Term ends

Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07D 403/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
A61P 31/06
Antibacterial agents: for tuberculosis
C07D 207/327
With substituted hydrocarbon radicals directly attached to the ring nitrogen atom: radicals substituted by carbon atoms having three bonds to…