US2018051041A1PendingUtilityA1
Boronic acid derivatives and therapeutic uses thereof
Assignee: REMPEX PHARMACEUTICALS INCPriority: Mar 17, 2015Filed: Mar 16, 2016Published: Feb 22, 2018
Est. expiryMar 17, 2035(~8.7 yrs left)· nominal 20-yr term from priority
A61K 45/06C07F 5/025A61P 31/04A61K 31/69Y02A50/30
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Claims
Abstract
Disclosed herein are antimicrobial compounds compositions, pharmaceutical compositions, the use and preparation thereof. Some embodiments relate to boronic acid derivatives and their use as therapeutic agents.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound having the structure of the formula III′ or IV′:
or a pharmaceutically acceptable salt thereof, wherein:
A is a C 6-10 aryl or 5-10 membered heteroaryl;
m is 0, 1 or 2;
Y 7 is selected from the group consisting of —CH 2 —, —O—, —S— and —NR 1 —;
n 1 is 1, 2 or 3;
Q 1 and Q 2 are H;
each R 7 is independently selected from the group consisting of OH, optionally substituted —O—C 1-6 alkyl, —NR 1 R 2 , and —N(OR 1 )R 2 ; and
Y 4 is selected from the group consisting of —O—, —S—, and —NR 1 —;
Y 5 is selected from the group consisting of —OH, —SH, and —NHR 1 ;
Y 6 is selected from the group consisting of —OH, optionally substituted —O—C 1-6 alkyl, —NR 1 R 2 , and —N(OR 1 )R 2 ;
each R 1 , R 2 , R 3 and R 4 are independently selected from —H, halogen, optionally substituted C 1-4 alkyl, optionally substituted O—C 1-4 alkyl, optionally substituted C 3-7 carbocyclyl, optionally substituted 4-10 membered heterocyclyl, optionally substituted C 6-10 aryl, and optionally substituted 5-10 membered heteroaryl;
R 5 is present 1 to 5 times and each R 5 is independently selected from the group consisting of H, OH, halogen, —C(O)OR 1 ; —C(O)NR 1 R 2 ; —C(O)NR 1 OR 2 ; —C(═NR 1 )R 2 ; —C(═NR 1 )NR 2 R 3 ; —NR 1 C(O)R 2 ; —NR 1 C(O)NR 2 R 3 ; —NR 1 C(O)OR 2 ; —NR 1 S(O) 2 R 2 ; —NR 1 S(O) 2 NR 2 R 3 ; —NR 1 CR 2 (═NR 3 ); —NR 1 C(═NR 2 )NR 3 R 4 ; —S(O)(CH 2 ) 1-3 R 4 , —S(O) 2 NR 1 R 2 , —S(O) 2 NR 1 OR 3 , —NR 1 S(O) 2 NR 1 OR 3 , optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 7 carbocyclyl, optionally substituted 5-10 membered heterocyclyl, optionally substituted C 6-10 aryl, optionally substituted 5-10 membered heteroaryl, cyano, C 1 -C 6 alkoxy(C 1 -C 6 )alkyl, aryloxy, sulfhydryl (mercapto), and —(CH 2 ) p —Y 3 —(CH 2 ) q M′;
p and q are each independently 0, 1, or 2;
Y 3 is selected from the group consisting of —S—, —S(O)—, —S(O) 2 —, —O—, —CR 1 R 2 —, and —NR 1 —;
M′ is selected from the group consisting of halogen, cyano, —OH, —C(O)NR 1 R 2 ; —C(O)NR 1 OR 2 ; —NR 1 C(O)R 2 ; —NR 1 C(O)NR 2 R 3 ; —NR 1 C(O)OR 2 ; —NR 1 S(O) 2 R 2 ; —NR 1 S(O) 2 NR 2 R 3 ; —C(═NR 1 )R 2 ; —C(═NR 1 )NR 2 R 3 ; —NR 1 CR 2 (═NR 3 ); —NR 1 C(═NR 2 )NR 3 R 4 ; —S(O) 2 R 1 , —S(O) 2 NR 1 R 2 , —S(O) 2 NR 1 OR 3 , C 1-4 alkyl optionally substituted with 0-2 substituents selected from the group consisting of —OR 1 , —CN, —NR 1 R 2 , -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; C 2-4 alkenyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —(CH 2 ) 0-4 OR 1 , —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; C 2-4 alkynyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —(CH 2 ) 0-4 OR 1 , —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; C 6-10 aryl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —(CH 2 ) 0-4 OR 1 , —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; C 3-7 carbocyclyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —(CH 2 ) 0-4 OR 1 , —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; 5-10 membered heteroaryl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —(CH 2 ) 0-4 OR, —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; and 3-10 membered heterocyclyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —(CH 2 ) 0-4 OR 1 , —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ;
R 6 is selected from the group consisting of H, halogen, substituted —C 1-6 alkyl, —OH, —C(O)OR, —P(O)(OR) 2 , P(O)(OR)R 1 optionally substituted —O—C 1-6 alkyl, —NR 1 R 2 , —N(OR 1 )R 2 , optionally substituted —S—C 1-6 alkyl, —C(O)NR 1 R 2 , —S(O) 2 NR 1 R 2 , CN, optionally substituted —S(O)—C 1-6 alkyl, optionally substituted —S(O) 2 —C 1-6 alkyl, and a carboxylic acid isostere;
R is selected from —H, alkali metal, NH 4 + , —C 1-9 alkyl, —CR 10 R 11 OC(O)C 1-9 alkyl, —CR 10 R 11 OC(O)OC 1-9 alkyl, —CR 10 R 11 OC(O)C 6-10 aryl, —CR 10 R 11 OC(O)OC 6-10 aryl, —CR 10 R 11 OC(O)NR 10 C 1-9 -alkyl, —CR 10 R 11 OC(O)NR 10 C 6-10 aryl, and
R 10 and R 11 are independently selected from the group consisting of —H, optionally substituted C 1-4 alkyl, optionally substituted C 3-7 carbocyclyl, optionally substituted 5-10 membered heterocyclyl, optionally substituted C 6-10 aryl, and optionally substituted 5-10 membered heteroaryl.
2 . The compound of claim 1 , having the structure of the formula Ill or IV:
or a pharmaceutically acceptable salt thereof, wherein:
Y 7 is selected from the group consisting of CH 2 , O, S and NH;
each R 1 , R 2 , R 3 and R 4 are independently selected from —H, optionally substituted C 1-4 alkyl, optionally substituted C 3-7 carbocyclyl, optionally substituted 4-10 membered heterocyclyl, optionally substituted C 6-10 aryl, and optionally substituted 5-10 membered heteroaryl;
R 5 is present 1 to 5 times and each R 5 is independently selected from the group consisting of H, OH, halogen, —CF 3 , optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 7 carbocyclyl, optionally substituted 5-10 membered heterocyclyl, optionally substituted C 6-10 aryl, optionally substituted 5-10 membered heteroaryl, cyano, C 1 -C 6 alkoxy(C 1 -C 6 )alkyl, aryloxy, sulfhydryl (mercapto), and —(CH 2 ) p —Y 3 —(CH 2 ) q M′;
p and q are each independently 0 or 1;
Y 3 is selected from the group consisting of —S—, —S(O)—, —S(O) 2 —, —O—, —CH 2 —, and —NR 1 —;
M′ is selected from the group consisting of —C(O)NR 1 R 2 ; —C(O)NR 1 OR 2 ; —NR 1 C(O)R 2 ; —NR 1 C(O)NR 2 R 3 ; —NR 1 C(O)OR 2 ; —NR 1 S(O) 2 R 2 ; —NR 1 S(O) 2 NR 2 R 3 ; —C(═NR)R 2 ; —C(═NR 1 )NR 2 R 3 ; —NR 1 CR 2 (═NR 3 ); —NR 1 C(═NR 2 )NR 3 R 4 ; C 1-4 alkyl optionally substituted with 0-2 substituents selected from the group consisting, —OR 1 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; C 6-10 aryl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 1 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; C 3-7 carbocyclyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 1 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; 5-10 membered heteroaryl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 1 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; and 3-10 membered heterocyclyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 1 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ;
R 6 is selected from the group consisting of H, halogen, substituted —C 1-6 alkyl, —OH, —C(O)OR, optionally substituted —O—C 1-6 alkyl, —NR 1 R 2 , —N(OR 1 )R 2 , optionally substituted —S—C 1-6 alkyl, —C(O)NR 1 R 2 , —S(O) 2 NR 1 R 2 , CN, optionally substituted —S(O)—C 1-6 alkyl, optionally substituted —S(O) 2 —C 1-6 alkyl, and a carboxylic acid isostere; and
R is selected from —H, alkali metal, NH 4 + , —C 1-9 alkyl, —CR 10 R 11 OC(O)C 1-9 alkyl, —CR 10 R 11 OC(O)OC 1-9 alkyl, —CR 10 R 11 OC(O)C 6-10 aryl, —CR 10 R 11 OC(O)OC 6-10 aryl and
3 . The compound of claim 1 or 2 , having the structure of Formula (IIIa)
or a pharmaceutically acceptable salt thereof.
4 . The compound of claim 1 or 2 , having the structure of Formula (IIIb)
or a pharmaceutically acceptable salt thereof.
5 . The compound of claim 1 or 2 , having the structure of Formula (IIIc)
or a pharmaceutically acceptable salt thereof, wherein:
m is 0, 1, or 2; and
J, L, and M are each independently selected from the group consisting of CR 5 and N.
6 . The compound of claim 1 , 2 , or 5 , having the structure of Formula (IIId)
or a pharmaceutically acceptable salt thereof.
7 . The compound of claim 1 or 2 , having the structure of Formula (IVa)
or a pharmaceutically acceptable salt thereof wherein:
m is 0, 1, or 2; and
J, L, and M are each independently selected from the group consisting of CR 5 and N.
8 . The compound of claim 1 , 2 , or 7 , having the structure of Formula (IVb)
or a pharmaceutically acceptable salt thereof.
9 . The compound of any one of claims 1 to 8 , wherein Y 7 is CH 2 , O, or S.
10 . The compound of claim 1 or 2 , having the structure of (III-1) or (IV-1):
or a pharmaceutically acceptable salt thereof, wherein:
J, L, and M are each independently selected from the group consisting of CR 5 and N.
11 . The compound of claim 10 , having the structure of (III-2) or (IV-2):
or a pharmaceutically acceptable salt thereof.
12 . The compound of claim 1 , wherein n 1 is 1 and Q 1 and Q 2 are deuterium.
13 . The compound of any one of claims 1 - 2 , 4 - 5 , 7 , and 12 , wherein Y 7 is O, n 1 is 1, and m is 1.
14 . The compound of any one of claims 10 to 13 , wherein M is CR 5 .
15 . The compound of any one of claims 10 to 13 , wherein M is N.
16 . The compound of any one of claims 10 to 15 , wherein J and L are each independently CR 5 .
17 . The compound of claim 16 , wherein J and L are CH.
18 . The compound of any one of claims 10 to 13 , wherein J is N.
19 . The compound of any one of claims 10 to 15 and 18 , wherein L and M are each independently CR 5 .
20 . The compound of claim 19 , wherein L and M are CH.
21 . The compound of any one of claims 10 to 13 , wherein L is N.
22 . The compound of any one of claims 10 to 13 and 21 , wherein J and M are each independently CR 5 .
23 . The compound of claim 22 , wherein J and M are CH.
24 . The compound of any one of claims 10 to 15 and 21 , wherein M is CH.
25 . The compound of any one of claims 1 to 24 , wherein each R 5 is independently selected from the group consisting of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 carbocyclyl, C 1 -C 6 heteroalkyl, 5-10 membered heterocyclyl, C 6 -C 10 aryl, 5-10 membered heteroaryl, cyano, hydroxy, —OR 3 , —SR 3 , —S(O) 2 M′, —P(O)R 1 M′, and halogen.
26 . The compound of claim 25 , wherein R 5 is halogen.
27 . The compound of claim 26 , wherein R 5 is F.
28 . The compound of claim 25 , wherein R 5 is alkoxy.
29 . The compound of claim 28 , wherein R 5 is —OCH 3 .
30 . The compound of claim 28 , wherein R 5 is —OCH 2 CH 3 .
31 . The compound of any one of claims 1 to 25 , wherein R 5 is —OH.
32 . The compound of any one of claims 1 to 25 , wherein R 5 is —SH.
33 . The compound of any one of claims 1 to 25 , wherein R 5 is —SCH 3 .
34 . The compound of any one of claims 1 to 25 , wherein R 5 is —S(O) 2 M′.
35 . The compound of claim 34 , wherein R 5 is —S(O) 2 CH 3 .
36 . The compound of any one of claims 1 to 25 , wherein R 5 is —SOM′.
37 . The compound of claim 36 , wherein R 5 is —SOCH 3 .
38 . The compound of any one of claims 1 to 25 , wherein R 5 is cyano.
39 . The compound of any one of claims 1 to 25 , wherein R 5 is —C≡CH.
40 . The compound of any one of claims 1 to 24 , wherein R 5 is —CHF 2 .
41 . The compound of any one of claims 1 to 24 , wherein R 5 is —CF 3 .
42 . The compound of any one of claims 1 to 24 , wherein R 5 is —C(O)NR 1 R 2 .
43 . The compound of claim 42 , wherein R 5 is —C(O)NH 2 .
44 . The compound of any one of claims 1 to 24 , wherein R 5 is —C(═NR)R 2 .
45 . The compound of claim 44 , wherein R 5 is —CH═N—OCH 3 .
46 . The compound of any one of claims 1 to 24 , wherein R 5 is —COOR 1 .
47 . The compound of claim 46 , wherein R 5 is —COOH.
48 . The compound of any one of claims 1 to 24 , wherein R 5 is a C 2-4 alkynyl, triazole, or diazole, optionally substituted with 0-2 substituents selected from —(CH 2 ) 0-4 OR 1 , —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 .
49 . The compound of claim 48 , wherein R 5 is
50 . The compound of any one of claims 1 to 24 , wherein R 5 is —(CH 2 ) p —Y 3 —(CH 2 ) q M′.
51 . The compound of claim 50 , wherein Y 3 is —S—, —O—, or —NH—.
52 . The compound of claim 50 or 51 , wherein M′ is a 5-10 membered heteroaryl or 3-10 membered heterocyclyl, each optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —(CH 2 ) 0-4 OR 1 , —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 .
53 . The compound of claim 52 , wherein M′ is azetine, thiadiazole, triazole, dioxolane, pyridine, morpholine, or cyclopropyl, each optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —(CH 2 ) 0-4 OR 1 , —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 .
54 . The compound of claim 53 , wherein M′ is
each optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —(CH 2 ) 0-4 OR 1 , —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 .
55 . The compound of claim 54 , wherein M′ is
56 . The compound of claim 50 or 51 , wherein M′ is cyano.
57 . The compound of claim 50 or 51 , wherein M′ is —OH.
58 . The compound of claim 50 or 51 , wherein M′ is —S(O) 2 R or —S(O) 2 NR 1 R 2 .
59 . The compound of claim 58 , wherein M′ is —S(O) 2 CH 3 or —S(O) 2 NH 2 .
60 . The compound of claim 50 or 51 , wherein M′ is —C(O)NR 1 R 2 .
61 . The compound of claim 60 , wherein M′ is —C(O)NH 2 .
62 . The compound of claim 50 , wherein Y 3 is —S(O)— or —S(O) 2 —.
63 . The compound of any one of claims 50 - 51 and 62 , wherein M′ is C 1-4 alkyl optionally substituted with 0-2 substituents selected from the group consisting of —OR 1 , —CN, —NR 1 R 2 , -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; C 2-4 alkenyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —(CH 2 ) 0-4 OR 1 , —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; or C 2-4 alkynyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —(CH 2 ) 0-4 OR 1 , —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 .
64 . The compound of claim 63 , wherein M′ is —C≡CH.
65 . The compound of claim 63 , wherein M′ is —C≡C—(CH 2 ) 0-4 OR 1 , —C≡C—(CH 2 ) 0-4 NR 1 R 2 , or —C≡C—(CH 2 ) 0-4 -heterocyclyl.
66 . The compound of claim 65 , wherein M′ is —C≡C—(CH 2 )—OCH 3 , —C≡C—(CH 2 )—OH, —C≡C—(CH 2 )—NH 2 , or
67 . The compound of claim 63 , wherein M′ is —(CH 2 ) 3 NH 2 , CH 2 F, CHF 2 , CF 3 , CH(CH 2 OH) 2 , or CH 2 N(CH 3 ) 2 .
68 . The compound of claim 63 , wherein M′ is C 1-4 alkyl.
69 . The compound of any one of claims 10 to 12 , wherein R 5 is present twice.
70 . The compound of any one of claims 10 to 12 , wherein:
L and M are each independently CR 5 ;
J is CH; and
each R 5 is independently selected from the group consisting of OH, halogen, CN, —C(O)OR 1 ; —C(O)NR 1 R 2 ; —C(O)NR 1 OR 2 ; —NR 1 C(O)R 2 ; —NR 1 C(O)NR 2 R 3 ; —NR 1 C(O)OR 2 ; —NR 1 S(O) 2 R 2 ; —NR 1 S(O) 2 NR 2 R 3 ; —C(═NR 1 )R 2 ; —C(═NR 1 )NR 2 R 3 ; —NR 1 CR 2 (═NR 3 ); —NR 1 C(═NR 2 )NR 3 R 4 ; —S(O)(CH 2 ) 1-3 R 4 , —S(O) 2 NR 1 R 2 , —S(O) 2 NR 1 OR 3 , —NR 1 S(O) 2 NR 1 OR 3 , optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 7 carbocyclyl, optionally substituted 5-10 membered heterocyclyl, optionally substituted C 6-10 aryl, optionally substituted 5-10 membered heteroaryl, cyano, C 1 -C 6 alkoxy(C 1 -C 6 )alkyl, aryloxy, sulfhydryl (mercapto), and —(CH 2 ) p —Y 3 —(CH 2 ) q M′.
71 . The compound of any one of claims 69 to 70 , wherein each R 5 is independently halogen or —OM′
72 . The compound of claim 71 , wherein each R 5 is independently F or —OCH 3 .
73 . The compound of claim 71 , wherein each R 5 is independently Cl or —OCH 3 .
74 . The compound of any one of claims 1 to 73 , wherein R 6 is —COOR or —P(O)(OR) 2 .
75 . The compound of claim 74 , wherein R 6 is —COOH or —P(O)(OH) 2 .
76 . The compound of claim 1 , having the structure selected from the group consisting of
and pharmaceutically acceptable salts thereof.
77 . The compound of claim 1 , having the structure selected from the group consisting
and pharmaceutically acceptable salts thereof.
78 . A compound having the structure selected from the group consisting of
and pharmaceutically acceptable salts thereof.
79 . A compound having the structure of the formula I′ or II′:
or a pharmaceutically acceptable salt thereof, wherein:
each G is independently selected from the group consisting of —C(O)R 4 , —C(O)(CH 2 ) 0-3 SR 3 , —C(O)(CH 2 ) 1-3 R 4 , —C(O)OR 3 , —C(O)NR 1 R 2 , —C(O)NR 1 OR 3 , —NR 1 C(O)R 4 , —NR 1 C(O)NR 1 R 2 , —NR 1 C(O)OR 3 , —NR 1 S(O) 2 R 3 , —NR 1 S(O) 2 NR 1 R 2 , —C(═NR 1 )R 4 , —C(═NR 1 )NR 1 R 2 , —NR 1 CR 4 (═NR 2 ), —NR 1 C(═NR 2 )NR 1 R 2 , —S(O) 2 R 3 , —S(O)(CH 2 ) 1-3 R 3 , —S(O) 2 NR 1 R 2 , —S(O) 2 NR 1 OR 3 , —NR 1 S(O) 2 NR 1 OR 3 , —CN, —OR 1 , —SR 1 , —NR 1 R 2 , optionally substituted C 1-10 alkyl, optionally substituted C 2-10 alkenyl, optionally substituted C 2-10 alkynyl, optionally substituted C 3-7 carbocyclyl, optionally substituted 5-10 membered heterocyclyl, optionally substituted C 6-10 aryl, optionally substituted 5-10 membered heteroaryl, optionally substituted C 3-7 carbocyclyl-C 1-6 alkyl, optionally substituted 5-10 membered heterocyclyl-C 1-6 alkyl, optionally substituted C 6-10 aryl-C 1-6 alkyl, and optionally substituted 5-10 membered heteroaryl-C 1-6 alkyl;
Y 1 is selected from the group consisting of CR 1 and N;
each Y 2 is independently selected from the group consisting of —S—, —S(O)—, —S(O) 2 —, —O—, —CR 1 R 2 —, and —NR 2 —, or Y 2 —(CH 2 ) n -G is CH 3 ;
Y 4 is selected from the group consisting of —O—, —S—, and —NR 1 —;
Y 5 is selected from the group consisting of —OH, —SH, and —NHR 1 ;
Y 6 is selected from the group consisting of —OH, optionally substituted —O—C 1-6 alkyl, —NR 1 R 2 , and —N(OR 3 )R 2 ,
Q 1 and Q 2 is each independently H or —Y 2 —(CH 2 ) n -G;
each n is independently an integer from 0 to 3;
m is 0 or 1;
A is selected from the group consisting of C 3-10 carbocyclyl, C 6-10 aryl, 5-10 membered heteroaryl, and 5-10 membered heterocyclyl;
each R 1 , R 2 , R 3 , and R 4 are independently selected from —H, halogen, optionally substituted C 1-4 alkyl, optionally substituted O—C 1-4 alkyl, optionally substituted C 3-7 carbocyclyl, optionally substituted 4-10 membered heterocyclyl, optionally substituted C 6-10 aryl, and optionally substituted 5-10 membered heteroaryl;
R 5 is present 1 to 5 times and each R 5 is independently selected from the group consisting of H, OH, halogen, CN, —C(O)OR 1 ; —C(O)NR 1 R 2 ; —C(O)NR 1 OR 2 ; —NR 1 C(O)R 2 ; —NR 1 C(O)NR 2 R 3 ; —NR 1 C(O)OR 2 ; —NR 1 S(O) 2 R 2 ; —NR 1 S(O) 2 NR 2 R 3 ; —C(═NR 1 )R 2 ; —C(═NR 1 )NR 2 R 3 ; —NR 1 CR 2 (═NR 1 ); —NR 1 C(═NR 2 )NR 3 R 4 ; —S(O)(CH 2 ) 1-3 R 4 , —S(O) 2 NR 1 R 2 , —S(O) 2 NR 1 OR 3 , —NR 1 S(O) 2 NR 1 OR 3 , optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 7 carbocyclyl, optionally substituted 5-10 membered heterocyclyl, optionally substituted C 6-10 aryl, optionally substituted 5-10 membered heteroaryl, cyano, C 1 -C 6 alkoxy(C 1 -C 6 )alkyl, aryloxy, sulfhydryl (mercapto), and —(CH 2 ) p —Y 3 —(CH 2 ) q M′;
p and q are each independently 0, 1, or 2;
Y 3 is selected from the group consisting of —S—, —S(O)—, —S(O) 2 —, —O—, —CR 1 R 2 —, and —NR 1 —;
M′ is selected from the group consisting of halogen, cycano, —OH, —C(O)NR 1 R 2 ; —C(O)NR 1 OR 2 ; —NR 1 C(O)R 2 ; —NR 1 C(O)NR 2 R 3 ; —NR 1 C(O)OR 2 ; —NR 1 S(O) 2 R 2 ; —NR 1 S(O) 2 NR 2 R 3 ; —C(═NR 1 )R 2 ; —C(═NR 1 )NR 2 R 3 ; —NR 1 CR 2 (═NR 3 ); —NR 1 C(═NR 2 )NR 3 R 4 ; —S(O) 2 R 1 , —S(O) 2 NR 1 R 2 , —S(O) 2 NR 1 OR 3 , C 1-4 alkyl optionally substituted with 0-2 substituents selected from the group consisting of —OR 1 , —CN, —NR 1 R 2 , -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; C 2-4 alkenyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —(CH 2 ) 0-4 OR 1 , —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; C 2-4 alkynyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —(CH 2 ) 0-4 OR 1 , —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; C 6-10 aryl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —(CH 2 ) 0-4 OR 1 , —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; C 3-7 carbocyclyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —(CH 2 ) 0-4 OR 1 , —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; 5-10 membered heteroaryl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —(CH 2 ) 0-4 OR 1 , —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; and 3-10 membered heterocyclyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —(CH 2 ) 0-4 OR, —(CH 2 ) 0-4 CN, —(CH 2 ) 0-4 NR 1 R 2 , —(CH 2 ) 0-4 -heterocyclyl, halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ;
R 6 is selected from the group consisting of is selected from the group consisting of —H, halogen, optionally substituted —C 1-6 alkyl, —OH, —C(O)OR, —P(O)(OR) 2 , P(O)(OR)R 1 , optionally substituted —O—C 1-6 alkyl, —NR 1 R 2 , —N(OR 3 )R 2 , optionally substituted —S—C 1-6 alkyl, —C(O)NR 1 R 2 , —S(O) 2 NR 1 R 2 , CN, optionally substituted —S(O)—C 1-6 alkyl, optionally substituted —S(O) 2 —C 1-6 alkyl, and a carboxylic acid isostere;
R is selected from —H, —C 1-9 alkyl, —CR 10 R 11 OC(O)C 1-9 alkyl, —CR 10 R 11 OC(O)OC 1-9 alkyl, —CR 10 R 11 OC(O)C 6-10 aryl, —CR 10 R 11 OC(O)OC 6-10 aryl, —CR 10 R 11 OC(O)NR 10 C 1-9 alkyl, —CR 10 R 11 OC(O)NR 10 C 6-10 aryl, and
R 7 is selected from the group consisting of OH, optionally substituted —O—C 1-6 alkyl, —NR 1 R 2 , and —N(OR 3 )R 2 ; and
R 10 and R 11 are independently selected from the group consisting of —H, optionally substituted C 1-4 alkyl, optionally substituted C 3-7 carbocyclyl, optionally substituted 5-10 membered heterocyclyl, optionally substituted C 6-10 aryl, and optionally substituted 5-10 membered heteroaryl.
80 . The compound of claim 79 having the structure of formula I or II:
each G is independently selected from the group consisting of —C(O)R 4 , —C(O)(CH 2 ) 0-3 SR 3 , —C(O)(CH 2 ) 1-3 R 4 , —C(O)OR 3 , —C(O)NR 1 R 2 , —C(O)NR 1 OR 3 , —NR 1 C(O)R 4 , —NR 1 C(O)NR 1 R 2 , —NR 1 C(O)OR 3 , —NR 1 S(O) 2 R 3 , —NR 1 S(O) 2 NR 1 R 2 , —C(═NR 1 )R 4 , —C(═NR 1 )NR 1 R 2 , —NR 1 CR 4 (═NR 2 ), —NR 1 C(═NR 2 )NR 1 R 2 , —S(O) 2 R 3 , optionally substituted C 1-10 alkyl, optionally substituted C 2-10 alkenyl, optionally substituted C 2-10 alkynyl, optionally substituted C 3-7 carbocyclyl, optionally substituted 5-10 membered heterocyclyl, optionally substituted C 6-10 aryl, optionally substituted 5-10 membered heteroaryl, optionally substituted C 3-7 carbocyclyl-C 1-6 alkyl, optionally substituted 5-10 membered heterocyclyl-C 1-6 alkyl, optionally substituted C 6-10 aryl-C 1-6 alkyl, and optionally substituted 5-10 membered heteroaryl-C 1-6 alkyl;
Q is H or —Y 2 —(CH 2 ) n -G;
each R 1 , R 2 , R 3 , and R 4 are independently selected from —H, optionally substituted C 1-4 alkyl, optionally substituted C 3-7 carbocyclyl, optionally substituted 4-10 membered heterocyclyl, optionally substituted C 6-10 aryl, and optionally substituted 5-10 membered heteroaryl;
R 5 is present 1 to 5 times and each R 5 is independently selected from the group consisting of H, OH, halogen, —CF 3 , optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 7 carbocyclyl, optionally substituted 5-10 membered heterocyclyl, optionally substituted C 6-10 aryl, optionally substituted 5-10 membered heteroaryl, cyano, C 1 -C 6 alkoxy(C 1 -C 6 )alkyl, aryloxy, sulfhydryl (mercapto), and —(CH 2 ) p —Y 3 —(CH 2 ) q M′;
p and q are each independently 0 or 1;
Y 3 is selected from the group consisting of —S—, —S(O)—, —S(O) 2 —, —O—, —CH 2 —, and —NR 1 —;
M′ is selected from the group consisting of —C(O)NR 1 R 2 ; —C(O)NR 1 OR 2 ; —NR 1 C(O)R 2 ; —NR 1 C(O)NR 2 R 3 ; —NR 1 C(O)OR 2 ; —NR 1 S(O) 2 R 2 ; —NR 1 S(O) 2 NR 2 R 3 ; —C(═NR 1 )R 2 ; —C(═NR 1 )NR 2 R 3 ; —NR 1 CR 2 (═NR 3 ); —NR 1 C(═NR 2 )NR 3 R 4 ; C 1-4 alkyl optionally substituted with 0-2 substituents selected from the group consisting, —OR 1 , —NR 1 R 2 , halogen, C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; C 6-10 aryl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 1 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; C 3-7 carbocyclyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 1 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; 5-10 membered heteroaryl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 1 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; and 3-10 membered heterocyclyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 1 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 2 ; and
R is selected from —H, —C 1-9 alkyl, —CR 10 R 11 OC(O)C 1-9 alkyl, —CR 10 R 11 OC(O)OC 1-9 alkyl, —CR 10 R 11 OC(O)C 6-10 aryl, —CR 10 R 11 OC(O)OC 6-10 aryl and
81 . The compound of claim 79 or 80 , wherein the compound has the structure of formula I
or a pharmaceutically acceptable salt thereof.
82 . The compound of any one of claims 79 to 81 , wherein Q is —Y 2 —(CH 2 ) n -G.
83 . The compound of any one of claims 79 to 81 , wherein the compound has the structure of formula I-1
or a pharmaceutically acceptable salt thereof, wherein:
G is selected from the group consisting of —C(O)R 4 , —C(O)(CH 2 ) 0-3 SR 3 , —C(O)OR 3 , —C(O)NR 1 R 2 , —C(O)NR 1 OR 3 , —NR 1 C(O)R 4 , —NR 1 C(O)NR 1 R 2 , —NR 1 C(O)OR 3 , —NR 1 S(O) 2 R 3 , —NR 1 S(O) 2 NR 1 R 2 , —C(═NR 1 )R 4 , —C(═NR 1 )NR 1 R 2 , —NR 1 CR 4 (═NR 2 ), —NR 1 C(═NR 2 )NR 1 R 2 , —S(O) 2 R 3 , optionally substituted C 1-10 alkyl, optionally substituted C 2-10 alkenyl, optionally substituted C 2-10 alkynyl, optionally substituted C 3-7 carbocyclyl, optionally substituted 5-10 membered heterocyclyl, optionally substituted C 6-10 aryl, optionally substituted 5-10 membered heteroaryl, optionally substituted C 3-7 carbocyclyl-C 1-6 alkyl, optionally substituted 5-10 membered heterocyclyl-C 1-6 alkyl, optionally substituted C 6-10 aryl-C 1-6 alkyl, and optionally substituted 5-10 membered heteroaryl-C 1-6 alkyl;
each R 1 , R 2 , R 3 , and R 4 are independently selected from —H, optionally substituted C 1-4 alkyl, optionally substituted C 3-7 carbocyclyl, optionally substituted 5-10 membered heterocyclyl, optionally substituted C 6-10 aryl, and optionally substituted 5-10 membered heteroaryl; and
R is selected from —H, —C 1-9 alkyl, —CR 10 R 11 OC(O)C 1-9 alkyl, —CR 10 R 11 OC(O)OC 1-9 alkyl, and
84 . The compound of any one of claims 79 - 81 and 83 , having the structure of formula Ia:
or a pharmaceutically acceptable salt thereof, wherein:
n is 0 or 1; and
J, L, and M are each independently selected from the group consisting of CR 3 and N.
85 . The compound of any one of claims 79 - 81 and 83 , having the structure of (Ib):
or pharmaceutically acceptable salt thereof.
86 . The compound of any one of claims 79 - 81 and 83 , having the structure of (Ic):
or pharmaceutically acceptable salt thereof.
87 . The compound of claim 79 or 80 having the structure of formula IIa:
or a pharmaceutically acceptable salt thereof, wherein:
n is 0 or 1; and
J, L, and M are each independently selected from the group consisting of CR 5 and N.
88 . The compound of claim 87 , having the structure of (IIb):
or pharmaceutically acceptable salt thereof.
89 . The compound of claim 87 , having the structure of (IIc):
or pharmaceutically acceptable salt thereof.
90 . The compound of any one of claims 79 - 89 , wherein Y 2 is selected from the group consisting of —S—, —SO 2 —, —O—, or —NH—.
91 . The compound of any one of claims 79 - 90 , wherein M is N.
92 . The compound of any one of claims 79 - 90 , wherein M is CR 5 .
93 . The compound of any one of claims 79 - 92 , wherein J and L are each independently CR 5 .
94 . The compound of any one of claims 79 - 83 , wherein Y 4 is —O—.
95 . The compound of any one of claims 79 - 83 wherein R 7 is —OH.
96 . The compound of any one of claims 79 - 81 and 83 , having the structure of Formula (Id):
or pharmaceutically acceptable salt thereof.
97 . The compound of any one of claims 79 - 90 , wherein:
Y 2 is —O— or —S—; G is selected from the group consisting of C 1-4 alkyl, phenyl, imidazole, pyrazole, triazole, tetrazole, thiazole, thiadiazole, oxazole, oxadiazole, isoxazole, isothiazole, pyridine, pyrazine, pyrimidine, pyridazine, and pyrazine, each optionally substituted by 0-2 substituents selected from the group consisting of hydroxy, C 1 -C 6 alkoxy, C 1 -C 6 alkoxy(C 1 -C 6 )alkyl, aryloxy, halo(C 1 -C 6 )alkoxy, amino, C-amido, and N-amido; and J, L and M are CR 5 .
98 . The compound of claim 97 , wherein G is C 1-4 alkyl.
99 . The compound of claim 98 , wherein G is —CH 3 .
100 . The compound of claim 97 , wherein G is thiadiazole optionally substituted with amino.
101 . The compound of claim 18 , wherein G is
102 . The compound of any one of claims 79 - 90 , wherein:
M is CR 5 ; and each R 5 is independently selected from the group consisting of —H, —C 1-4 alkyl, and halogen, —CF 3 , and —(CH 2 ) p —Y 3 —(CH 2 ) q M′.
103 . The compound of claim 102 , wherein R 5 is halogen.
104 . The compound of claim 103 , wherein R 5 is F.
105 . The compound of any one of claims 79 - 90 , wherein:
R 5 is —(CH 2 ) p —Y 3 —(CH 2 ) q M′; m is 0; p is 0; Y 3 is S or O; and M′ is hydrogen; hydroxyl; C 1 -C 4 alkyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 3-10 cycloalkyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 6 -C 10 aryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; 5 to 10 membered heteroaryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; and 4 to 10 membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen.
106 . The compound of claim 105 , wherein R 5 is —S—C 1 -C 6 alkyl, —S—C 1 -C 6 cycloalkyl, or —S-4 to 10 membered heterocyclyl.
107 . The compound of claim 106 , wherein R 5 is —S—CH 3 .
108 . The compound of claim 105 , wherein R 5 is —O—C 1 -C 6 alkyl, —O—C 1 -C 6 cycloalkyl, or —O-4 to 10 membered heterocyclyl.
109 . The compound of claim 108 , wherein R 5 is
110 . The compound of claim 108 , wherein R 5 is —OCH 3 .
111 . The compound of any one of claims 79 - 17 and 23 - 31 , wherein:
n is 0 or 1;
Y 2 is —NH—;
G is selected from the group consisting of —C(O)R 4 , —C(O)(CH 2 ) 0-3 SR 3 , —C(O)(CH 2 ) 1-3 R 4 , —C(O)OR 3 , —C(O)NR 1 R 2 , —S(O) 2 R 3 , —C(═NR 1 )R 4 , and —C(═NR)NR 1 R 2 .
112 . The compound of claim 111 , wherein G is selected from the group consisting of —C(O)R 4 , —C(O)(CH 2 ) 0-3 SR 3 , —C(O)OR 3 , —C(O)NR 1 R 2 , —S(O) 2 R 3 , —C(═NR 1 )R 4 , and —C(═NR 1 )NR 1 R 2 .
113 . The compound of claim 111 or 112 , wherein G is —C(O)R 4 .
114 . The compound of claim 111 or 112 , wherein G is —C(O)(CH 2 )R 4 .
115 . The compound of any one of claims 111 to 114 , wherein R 4 is optionally substituted C 1-4 alkyl.
116 . The compound of claim 115 , wherein R 4 is C 1-4 alkyl substituted with C 1 -C 4 alkylthio.
117 . The compound of claim 116 , wherein R 4 is —CH 2 SCH 3
118 . The compound of claim 115 , wherein R 4 is C 1-4 alkyl substituted with 5-10 membered heteroaryl optionally substituted with halo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, and C 1 -C 6 haloalkoxy.
119 . The compound of claim 118 , wherein R 4 is
120 . The compound of claim any one of claims 111 to 114 , wherein R is optionally substituted 5-10 membered heteroaryl.
121 . The compound of claim 120 , wherein R 4 is 5-10 membered heteroaryl substituted with amino.
122 . The compound of claim 120 , wherein R 4 is
123 . The compound of any one of claims 1 to 96 , wherein G is —C(O)CH 2 SR 3 .
124 . The compound of claim 123 , wherein R 3 is C 1-4 alkyl.
125 . The compound of claim 123 , wherein R 3 is 5-10 membered heterocyclyl.
126 . The compound of any one of claims 79 to 96 and 23 - 31 , wherein G is —C(O)(CH 2 )SCH 3 .
127 . The compound of any one of claims 79 to 96 and 23 - 31 , wherein G is
128 . The compound of any one of claims 79 to 96 and 23 - 31 , wherein G is
129 . The compound of any one of claims 79 - 96 and 102 - 110 , wherein Y 2 is —S(O) 2 —.
130 . The compound of claim 129 , wherein G is optionally substituted C 6-10 aryl.
131 . The compound of any one of claims 79 - 130 , wherein Y 1 is CH.
132 . The compound of any one of claims 79 - 130 , wherein Y 1 is N.
133 . The compound of claim 79 - 81 and 83 - 132 , wherein Q 1 and Q 2 are deuterium.
134 . The compound of claim 79 , having the structure selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
135 . The compound of any one of claims 1 - 134 , wherein the pharmaceutically acceptable salt is an alkaline metal salt or ammonium salt.
136 . The compound of claim 135 , wherein the pharmaceutically acceptable salt is a sodium salt.
137 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of any one of claims 1 - 136 and a pharmaceutically acceptable excipient.
138 . The pharmaceutical composition of claim 137 , further comprising an additional medicament.
139 . The composition of claim 138 , wherein the additional medicament is selected from an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, or an anti-allergic agent.
140 . The composition of claim 139 , wherein the additional medicament is a β-lactam antibacterial agent.
141 . The composition of claim 140 , wherein the β-lactam antibacterial agent is selected from Amoxicillin, Ampicillin (Pivampicillin, Hetacillin, Bacampicillin, Metampicillin, Talampicillin), Epicillin, Carbenicillin (Carindacillin), Ticarcillin, Temocillin, Azlocillin, Piperacillin, Mezlocillin, Mecillinam (Pivmecillinam), Sulbenicillin, Benzylpenicillin (G), Clometocillin, Benzathine benzylpenicillin, Procaine benzylpenicillin, Azidocillin, Penamecillin, Phenoxymethylpenicillin (V), Propicillin, Benzathine phenoxymethylpenicillin, Pheneticillin, Cloxacillin (Dicloxacillin, Flucloxacillin), Oxacillin, Meticillin, Nafcillin, Faropenem, Tomopenem, Razupenem, Cefazolin, Cefacetrile, Cefadroxil, Cefalexin, Cefaloglycin, Cefalonium, Cefaloridine, Cefalotin, Cefapirin, Cefatrizine, Cefazedone, Cefazaflur, Cefradine, Cefroxadine, Ceftezole, Cefaclor, Cefamandole, Cefininox, Cefonicid, Ceforanide, Cefotiam, Cefprozil, Cefbuperazone, Cefuroxime, Cefuzonam, Cefoxitin, Cefotetan, Cefmetazole, Loracarbef, Cefixime, Ceftriaxone, Cefcapene, Cefdaloxime, Cefdinir, Cefditoren, Cefetamet, Cefinenoxime, Cefodizime, Cefoperazone, Cefotaxime, Cefpimizole, Cefpiramide, Cefpodoxime, Cefsulodin, Cefteram, Ceftibuten, Ceftiolene, Ceftizoxime, Flomoxef, Latamoxef, Cefepime, Cefozopran, Cefpirome, Cefquinome, Ceftobiprole, Ceftaroline, CXA-101, RWJ-54428, MC-04,546, ME 1036, Ceftiofur, Cefquinome, Cefovecin, RWJ-442831, RWJ-333441, or RWJ-333442.
142 . The composition of claim 140 wherein the β-lactam antibacterial agent is selected from Ceftazidime, Biapenem, Doripenem, Ertapenem, Imipenem, Meropenem, Tebipenem, Tebipenem pivoxil, Apapenem, or Panipenem.
143 . The composition of claim 140 , wherein the β-lactam antibacterial agent is selected from Aztreonam, Tigemonam, BAL30072, SYN 2416, or Carumonam.
144 . A method of treating a bacterial infection, comprising administering to a subject in need thereof, a compound according any one of claims 1 - 136 .
145 . The method of claim 144 , further comprising administering to the subject an additional medicament.
146 . The method of claim 145 , wherein the additional medicament is selected from an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, or an antiallergic agent.
147 . The method of claim 146 , wherein the additional medicament is a β-lactam antibacterial agent.
148 . The method of claim 147 , wherein the β-lactam antibacterial agent is selected from Amoxicillin, Ampicillin (Pivampicillin, Hetacillin, Bacampicillin, Metampicillin, Talampicillin), Epicillin, Carbenicillin (Carindacillin), Ticarcillin, Temocillin, Azlocillin, Piperacillin, Mezlocillin, Mecillinam (Pivmecillinam), Sulbenicillin, Benzylpenicillin (G), Clometocillin, Benzathine benzylpenicillin, Procaine benzylpenicillin, Azidocillin, Penamecillin, Phenoxymethylpenicillin (V), Propicillin, Benzathine phenoxymethylpenicillin, Pheneticillin, Cloxacillin (Dicloxacillin, Flucloxacillin), Oxacillin, Meticillin, Nafcillin, Faropenem, Tomopenem, Razupenem, Cefazolin, Cefacetrile, Cefadroxil, Cefalexin, Cefaloglycin, Cefalonium, Cefaloridine, Cefalotin, Cefapirin, Cefatrizine, Cefazedone, Cefazaflur, Cefradine, Cefroxadine, Ceftezole, Cefaclor, Cefamandole, Cefininox, Cefonicid, Ceforanide, Cefotiam, Cefprozil, Cefbuperazone, Cefuroxime, Cefuzonam, Cefoxitin, Cefotetan, Cefmetazole, Loracarbef, Cefixime, Ceftriaxone, Cefcapene, Cefdaloxime, Cefdinir, Cefditoren, Cefetamet, Cefinenoxime, Cefodizime, Cefoperazone, Cefotaxime, Cefpimizole, Cefpiramide, Cefpodoxime, Cefsulodin, Cefteram, Ceftibuten, Ceftiolene, Ceftizoxime, Flomoxef, Latamoxef, Cefepime, Cefozopran, Cefpirome, Cefquinome, Ceftobiprole, Ceftaroline, CXA-101, RWJ-54428, MC-04,546, ME 1036, Ceftiofur, Cefquinome, Cefovecin, RWJ-442831, RWJ-333441, or RWJ-333442.
149 . The method of claim 147 , wherein the β-lactam antibacterial agent is selected from Ceftazidime, Biapenem, Doripenem, Ertapenem, Imipenem, Meropenem, Tebipenem, Tebipenem pivoxil, Apapenem, or Panipenem.
150 . The method of claim 147 , wherein the β-lactam antibacterial agent is selected from Aztreonam, Tigemonam, BAL30072, SYN 2416, or Carumonam.
151 . The method of any one of claims 144 - 150 , wherein the subject is a mammal.
152 . The method of claim 151 , wherein the mammal is a human.
153 . The method of any one of claims 144 - 152 , wherein the infection comprises a bacteria selected from Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Burkholderia cepacia, Aeromonas hydrophilia, Francisella tularensis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter baumannii, Bordetella pertussis, Bordetella para pertussis, Bordetella bronchiseptica, Haemophilus ducreyi, Pasteurella multocida, Pasteurella haemolytica, Branhamella catarrhalis, Borrelia burgdorferi, Kingella, Gardnerella vaginalis, Bacteroides distasonis, Bacteroides 3452A homology group, Clostridium difficile, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus pyogenes, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Staphylococcus intermedius, Staphylococcus hyicus subsp. hyicus, Staphylococcus haemolyticus, Staphylococcus hominis , or Staphylococcus saccharolyticus.
154 . The method of any one of claims 144 - 152 , wherein the infection comprises a bacteria selected from Pseudomonas aeruginosa, Pseudomonas fluorescens, Stenotrophomonas maltophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudotuberculosis, Yersinia intermedia, Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Helicobacter pylori, Campylobacter fetus, Campylobacter jejuni, Campylobacter coli, Vibrio cholerae, Vibrio parahaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella, Bacteroides fragilis, Bacteroides vulgatus, Bacteroides ovalus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides eggerthii , or Bacteroides splanchnicus.Cited by (0)
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