IP Library › Granted Patent US 11,578,087
Granted Patent B2
US 11,578,087 · App. 17/108,066 · Granted Feb 14, 2023

Oxaborole esters and uses thereof

Inventors: Tsutomu Akama (Sunnyvale, CA); David Scott Carter (Sunnyvale, CA); Jason S. Halladay (Los Gatos, CA); Robert T. Jacobs (Wake Forest, NC); Yang Liu (Foster City, CA); Jacob J. Plattner (Berkeley, CA); Yong-Kang Zhang (Cary, NC); Michael John Witty (Dover, GB)
Assignee: Anacor Pharmaceuticals, Inc.
C07F5/027A61K31/166A61K31/443A61K31/4525A61K31/69C07F5/025A61K31/4178A61K31/431A61K31/47A61K31/5377Y02A50/30
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Quick Facts
Patent No.
US 11,578,087
App. No.
17/108,066
Granted
Feb 14, 2023
Kind
B2
Abstract

The present invention provides oxaborole ester compounds and compositions thereof which are useful to treat diseases associated with parasites, such as Chagas Disease and African Animal Trypanosomosis.

Claims (41)

1. A compound of formula II:

or a pharmaceutically acceptable salt thereof, wherein:

R 2 is methyl, ethyl, propyl, isopropyl, cyclopropyl, or C 1-6 aliphatic substituted with halogen;

R 4 is isopropyl, —C(CH 3 ) 2 OH, phenyl, cyclopropyl, cyclobutyl,

R 5 is hydrogen; or

R 4 and R 5 are taken together with the carbon atom to which they are attached to form a ring selected from a 3- to 6-membered spiro heterocyclic ring having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur, and a 3- to 6-membered saturated or partially unsaturated monocyclic spiro carbocyclic ring;

L is a covalent bond, —CH 2 —, —CH 2 — substituted with one or two —CH 3 , —CH 2 CH 2 —,

R 6 is C 1-6 aliphatic optionally substituted with halogen or —(CH 2 ) 0-4 OC 1-4 aliphatic, or a member selected from the group consisting of:

wherein R 6 is substituted with one or more groups selected from the group consisting of R, -halogen, —OR, —NO 2 , —CN, —SR, —N(R) 2 , —C(O)R, —C(O)OR, —S(O)R, —S(O) 2 R, —C(O)N(R) 2 , —S(O) 2 N(R) 2 , —OC(O)R, —N(R)C(O)R, —N(R)C(O)OR, —N(R)S(O) 2 R, and —OC(O)N(R) 2 ;

wherein each R is independently hydrogen or C 1-6 aliphatic or C 1-6 aliphatic substituted with halogen;

wherein when L is a covalent bond, then R 6 is other than —OR, -halogen, —NO 2 , —CN, —SR, —N(R) 2 , —S(O)R, —S(O) 2 R, —SO 2 N(R) 2 , —OC(O)R, —N(R)C(O)R, —N(R)C(O)OR, —N(R)SO 2 R, or —OC(O)N(R) 2 ; and

wherein when L is other than a covalent bond it includes a carbon atom bonded to the carboxyl oxygen in Formula II.

2. The compound of claim 1 , wherein the compound is of formula III:

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 2 , wherein the compound is of formula III-a:

or a pharmaceutically acceptable salt thereof.

4. A compound of formula V:

or a pharmaceutically acceptable salt thereof, wherein

each R a is independently R, -halogen, —OR, —CN, —SR, —N(R) 2 , —C(O)R, —C(O)OR, —S(O)R, —S(O) 2 R, —C(O)N(R) 2 , —SO 2 N(R) 2 , —OC(O)R, —N(R)C(O)R, —N(R)C(O)OR, —N(R)SO 2 R, or —OC(O)N(R) 2 ;

each R is independently hydrogen or C 1-6 aliphatic or C 1-6 aliphatic substituted with halogen;

R 6 is C 1-6 aliphatic optionally substituted with halogen or —(CH 2 ) 0-4 OC 1-4 aliphatic, or a member selected from the group consisting of:

wherein R 6 is substituted with one or more groups selected from the group consisting of R, -halogen, —OR, —NO 2 , —CN, —SR, —N(R) 2 , —C(O)R, —C(O)OR, —S(O)R, —S(O) 2 R, —C(O)N(R) 2 , —S(O) 2 N(R) 2 , —OC(O)R, —N(R)C(O)R, —N(R)C(O)OR, —N(R)S(O) 2 R, and —OC(O)N(R) 2 ;

R b is hydrogen; and R b1 is hydrogen or methyl.

5. The compound of claim 4 , wherein the compound is of formula V-a or V-b:

or a pharmaceutically acceptable salt thereof, wherein

each R a is independently R, -halogen, —OR, —CN, —SR, —N(R) 2 , —C(O)R, —C(O)OR, —S(O)R, —S(O) 2 R, —C(O)N(R) 2 , —SO 2 N(R) 2 , —OC(O)R, —N(R)C(O)R, —N(R)C(O)OR, —N(R)SO 2 R, or —OC(O)N(R) 2 .

6. A compound of formula VI-a, VI-b, VI-c, VI-d, VI-e, or VI-f:

or a pharmaceutically acceptable salt thereof, wherein:

R 6 is C 1-6 aliphatic optionally substituted with halogen or —(CH 2 ) 0-4 OC 1-4 aliphatic, or a member selected from the group consisting of:

wherein R 6 is substituted with one or more groups selected from the group consisting of R, -halogen, —OR, —CN, —SR, —N(R) 2 , —C(O)R, —C(O)OR, —S(O)R, —S(O) 2 R, —C(O)N(R) 2 , —S(O) 2 N(R) 2 , —OC(O)R, —N(R)C(O)R, —N(R)C(O)OR, —N(R)S(O) 2 R, and —OC(O)N(R) 2 ,

each R a is independently R, -halogen, —OR, —CN, —SR, —N(R) 2 , —C(O)R, —C(O)OR, —S(O)R, —S(O) 2 R, —C(O)N(R) 2 , —SO 2 N(R) 2 , —OC(O)R, —N(R)C(O)R, —N(R)C(O)OR, —N(R)SO 2 R, or —OC(O)N(R) 2 ; each R is independently hydrogen or C 1-6 aliphatic or C 1-6 aliphatic substituted with halogen; and n is 0, 1 or 2.

7. A compound of formula VII-a, VII-b or VII-c:

or a pharmaceutically acceptable salt thereof, wherein:

R 6 is C 1-6 aliphatic optionally substituted with halogen or —(CH 2 ) 0-4 OC 1-4 aliphatic, or a member selected from the group consisting of:

wherein R 6 is substituted with one or more groups selected from the group consisting of R, -halogen, —OR, —CN, —SR, —N(R) 2 , —C(O)R, —C(O)OR, —S(O)R, —S(O) 2 R, —C(O)N(R) 2 , —S(O) 2 N(R) 2 , —OC(O)R, —N(R)C(O)R, —N(R)C(O)OR, —N(R)S(O) 2 R, and —OC(O)N(R) 2 ,

each R a is independently R, -halogen, —OR, —CN, —SR, —N(R) 2 , —C(O)R, —C(O)OR, —S(O)R, —S(O) 2 R, —C(O)N(R) 2 , —SO 2 N(R) 2 , —OC(O)R, —N(R)C(O)R, —N(R)C(O)OR, —N(R)SO 2 R, or —OC(O)N(R) 2 ; each R is independently hydrogen or C 1-6 aliphatic or C 1-6 aliphatic substituted with halogen; and n is 0, 1 or 2.

8. The compound of claim 1 , wherein the compound is of formula IX-a or IX-b:

or a pharmaceutically acceptable salt thereof, wherein R is hydrogen or methyl.

9. The compound of claim 8 , where L is selected from:

10. The compound of claim 1 , wherein the compound is selected from the group consisting of benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 2,4-difluorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-chlorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-trifluoromethylbenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo [c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-fluorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo [c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-chlorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-cyanobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo [c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorobenzyl (S)-2-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)-2-phenyl acetate, 3-trifluoromethylbenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo [c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-cyanobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3,5-difluorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluoro-3-(trifluoromethyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorobenzyl (S)-2-cyclopropyl-2-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)acetate, 3-chloro-4-fluorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorobenzyl (7-ethyl-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, benzyl (7-ethyl-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-trifluoromethoxybenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-trifluoromethoxybenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-(methyl sulfonyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorobenzyl (7-cyclopropyl-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, benzyl (7-cyclopropyl-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorobenzyl (S)-2-cyclobutyl-2-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)acetate, 4-fluorobenzyl (1-hydroxy-7-isopropyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorobenzyl 1-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)cyclobutane-1-carboxylate, (5-fluoropyridin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-(4-methylpiperazin-1-yl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorobenzyl (7-(difluoromethyl)-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-threoninate, 4-(methyl sulfonyl)benzyl (7-ethyl-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorobenzyl O-benzyl-N-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-threoninate, 3-(methyl sulfonyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo [c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-((dimethylamino)methyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-((4-methylpiperazin-1-yl)methyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-(morpholinomethyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-((4-methylpiperazin-1-yl)sulfonyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-(morpholinosulfonyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-(isopropylsulfinyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorobenzyl 3-fluoro-2-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)-3-methylbutanoate, 4-(isopropyl sulfonyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-(ethyl sulfonyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-(ethylsulfinyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3,4-difluorobenzyl (S)-3-hydroxy-2-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)-3-methylbutanoate, 3,5-difluorobenzyl (S)-3-hydroxy-2-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)-3-methylbutanoate, 3,4,5-trifluorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3,4,5-trifluorobenzyl (S)-3-hydroxy-2-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)-3-methylbutanoate, 2-methoxyethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-((4-methylpiperazin-1-yl)methyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, isopropyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-(pyrrolidin-1-ylmethyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, cyclopentylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, isobutyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, cyclohexylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, thiazol-5-ylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorophenethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, quinoxalin-2-ylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, thiazol-2-ylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, quinolin-2-ylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, quinolin-6-ylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, thiazol-4-ylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorobenzyl (1-hydroxy-5-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-(morpholinomethyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-(pyrrolidin-1-ylmethyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, cyclopentyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, cyclohexyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, oxetan-3-yl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, cyclobutyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, quinazolin-2-ylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (R)-tetrahydrofuran-3-yl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 1-methylpiperidin-4-yl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, ((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, ((S)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 2,2,2-trifluoroethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (4-(methoxymethyl)tetrahydro-2H-pyran-4-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 2,2,3,3,3-pentafluoropropyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (4,4-difluorocyclohexyl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (1,4-dioxepan-6-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo [c][1,2]oxaborole-6-carbonyl)-L-valinate, (2-(trifluoromethyl)pyrimidin-5-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo [c][1,2]oxaborole-6-carbonyl)-L-valinate, (2-(trifluoromethyl)pyrimidin-4-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (6-(trifluoromethyl)pyrimidin-4-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-(2-(pyrrolidin-1-yl)ethoxy)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-chloro-3-(2-morpholinoethoxy)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (5-(trifluoromethyl)pyridin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 2-(pyridin-2-yl)ethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, pyrazin-2-ylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, pyridin-3-ylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (6-cyanopyridin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, pyridin-4-ylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, pyridin-2-ylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (6-morpholinopyrazin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (6-morpholinopyridin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (R)-1-phenylethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (5-cyanopyridin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (6-(4-methylpiperazin-1-yl)pyridin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (5-fluoropyrimidin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (4-(trifluoromethyl)pyrimidin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (6-(4-methylpiperazin-1-yl)pyrazin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 2-(2,6-dimethylmorpholino)ethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (tetrahydrofuran-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 2-(1,4-oxazepan-4-yl)ethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, ((R)-tetrahydrofuran-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 2-(3-methylmorpholino)ethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (1-hydroxycyclopentyl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, cyclopentylmethyl 3-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)oxetane-3-carboxylate, (4-fluorotetrahydro-2H-pyran-4-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (1,4-dioxan-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, cyclopentylmethyl (S)-3-hydroxy-2-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)-3-methylbutanoate, (1-hydroxycyclohexyl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (6-(dimethylamino)pyrazin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (3-methyltetrahydrofuran-3-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, ((R)-tetrahydrofuran-3-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-fluoro-4-(2-(pyrrolidin-1-yl)ethoxy)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-fluoro-4-(3-(pyrrolidin-1-yl)propoxy)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-(2-morpholinoethoxy)benzyl(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, or a pharmaceutically acceptable salt thereof.

11. The compound of claim 1 , wherein the compound is selected from the group consisting of benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-chlorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-trifluoromethylbenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-chlorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-cyanobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorobenzyl (S)-2-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)-2-phenylacetate, 3-trifluoromethylbenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-cyanobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3,5-difluorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluoro-3-(trifluoromethyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorobenzyl (S)-2-cyclopropyl-2-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)acetate, 3-chloro-4-fluorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorobenzyl (7-ethyl-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, benzyl (7-ethyl-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-trifluoromethoxybenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-trifluoromethoxybenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorobenzyl 1-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)cyclobutane-1-carboxylate, (5-fluoropyridin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-(4-methylpiperazin-1-yl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorobenzyl (7-(difluoromethyl)-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-((dimethylamino)methyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-(morpholinomethyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-(morpholinosulfonyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorobenzyl 3-fluoro-2-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)-3-methylbutanoate, 4-(isopropylsulfonyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3,4-difluorobenzyl (S)-3-hydroxy-2-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)-3-methylbutanoate, 3,5-difluorobenzyl (S)-3-hydroxy-2-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)-3-methylbutanoate, 3,4,5-trifluorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3,4,5-trifluorobenzyl (S)-3-hydroxy-2-(1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)-3-methylbutanoate, 2-methoxyethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-((4-methylpiperazin-1-yl)methyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 3-(pyrrolidin-1-ylmethyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, cyclopentylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, isobutyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, cyclohexylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-fluorophenethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo [c][1,2]oxaborole-6-carbonyl)-L-valinate, quinoxalin-2-ylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, thiazol-2-ylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, quinolin-2-ylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-(morpholinomethyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-(pyrrolidin-1-ylmethyl)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, cyclopentyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, cyclohexyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, cyclobutyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, quinazolin-2-ylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, ((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, ((S)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 2,2,2-trifluoroethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (4-(methoxymethyl)tetrahydro-2H-pyran-4-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 2,2,3,3,3-pentafluoropropyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (4,4-difluorocyclohexyl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (2-(trifluoromethyl)pyrimidin-5-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (6-(trifluoromethyl)pyrimidin-4-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 4-chloro-3-(2-morpholinoethoxy)benzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (5-(trifluoromethyl)pyridin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 2-(pyridin-2-yl)ethyl (1-hydroxy-7-methyl-1, 3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, pyridin-3-ylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (6-cyanopyridin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, pyridin-2-ylmethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (6-morpholinopyrazin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (6-morpholinopyridin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (R)-1-phenylethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (5-cyanopyridin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (6-(4-methylpiperazin-1-yl)pyridin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (5-fluoropyrimidin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (4-(trifluoromethyl)pyrimidin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (6-(4-methylpiperazin-1-yl)pyrazin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 2-(2,6-dimethylmorpholino)ethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo [c][1,2]oxaborole-6-carbonyl)-L-valinate, (tetrahydrofuran-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo [c][1,2]oxaborole-6-carbonyl)-L-valinate, ((R)-tetrahydrofuran-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, 2-(3-methylmorpholino)ethyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (4-fluorotetrahydro-2H-pyran-4-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (1,4-di oxan-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (1-hydroxycyclohexyl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (6-(dimethylamino)pyrazin-2-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, (3-methyltetrahydrofuran-3-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, ((R)-tetrahydrofuran-3-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate, or a pharmaceutically acceptable salt thereof.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 21, 2023
From: AKAMA, TSUTOMU; CARTER, DAVID SCOTT; HALLADAY, JASON S.; JACOBS, ROBERT T.; LIU, YANG; ZHANG, YONG-KANG; PLATTNER, JACOB J.; WITTY, MICHAEL JOHN
To: ANACOR PHARMACEUTICALS, INC.
Reel/Frame 065659/0312 →
Continuity (4)
Continuation 16580676 · Sep 24, 2019
Continuation 15590159 · May 9, 2017
Provisional Application 62335565 · May 12, 2016
Related Publication 20210101916A1 · Apr 8, 2021