Modulators of ATP-binding cassette transporters

1. A compound of formula V-B-5:

wherein:

ring A 2 is a phenyl or a 5-6 membered heteroaryl ring, wherein ring A 2 and the phenyl ring fused thereto together have up 4 substituents independently selected from WR W ; and

W is a bond or is an optionally substituted C 1 -C 6 alkylidene chain wherein up to two methylene units of W are optionally and independently replaced by —CO—, —CS—, —COCO—, —CONR′—, —CONR′NR′—, —CO 2 —, —OCO—, —NR′CO 2 —, —O—, —NR′CONR′—, —OCONR′—, —NR′NR′, —NR′NR′CO—, —NR′CO—, —S—, —SO, —SO 2 —, —NR′—, —SO 2 NR′—, NR′SO 2 —, —NR′SO 2 NR′—;

R W is independently R′, halo, NO 2 , CN, CF 3 , or OCF 3 ;

X is a bond or is an optionally substituted C 1 -C 6 alkylidene chain wherein up to two methylene units of X are optionally and independently replaced by —CO—, —CS—, —COCO—,—CONR′—, —CONR′NR′—, —CO 2 —, —OCO—, —NR′CO 2 —, —O—, —NR′CONR′—, —OCONR′—, —NR′NR′, —NR′NR′CO—, —NR′CO—, —S—, —SO, —SO 2 —,—NR′—, —SO 2 NR′—, NR′SO 2 —, or —NR′SO 2 NR′—;

R X is independently R′, halo, NO 2 , CN, CF 3 , or OCF 3 ;

R′ is independently selected from hydrogen or an optionally substituted group selected from a C 1 -C 8 aliphatic group a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or two occurrences of R′ are taken together with the atom(s) to which they are bound to form an optionally substituted 3-12 membered saturated, partially unsaturated, or fully unsaturated monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and

m is 0-4.

2. The compound according to claim 1 , wherein ring A 2 is selected from:

wherein said ring is optionally substituted.

3. The compound according to claim 1 , wherein said compound has formula V-B-5-a:

wherein:

G 4 is hydrogen, halo, CN, CF 3 , CHF 2 , CH 2 F, optionally substituted C1-C6 aliphatic, aryl-C1-C6 alkyl, or a phenyl, wherein G 4 is optionally substituted with up to 4 WR W substituents; wherein up to two methylene units of said C1-C6 aliphatic or C1-C6 alkyl is optionally replaced with —CO—, —CONR′—, —CO 2 —, —OCO—, —NR′CO 2 —, —O—, —NR′CONR′—, —OCONR′—, —NR′CO—, —S—, —NR′—, —SO 2 NR′—, NR′SO 2 —, or —NR′SO 2 NR′—;

G 5 is hydrogen or an optionally substituted C1-C6 aliphatic;

wherein said indole ring system is further optionally substituted with up to 3 substituents independently selected from WR W .

4. The compound according to claim 3 , wherein G 4 is hydrogen, and G 5 is C1-C6 aliphatic, wherein said aliphatic is optionally substituted with C1-C6 alkyl, halo, cyano, or CF 3 , and wherein up to two methylene units of said C1-C6 aliphatic or C1-C6 alkyl is optionally replaced with —CO—, —CONR′—, —CO 2 —, —OCO—, —NR′CO 2 —, —O—, —NR′CONR′—, —OCONR′—, —NR′CO—, —S—, —NR′—, —SO 2 NR′—, NR′SO 2 —, or —NR′SO 2 NR′—.

5. The compound according to claim 3 , wherein G 4 is hydrogen, and G 5 is cyano, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, t-butyl, cyanomethyl, methoxyethyl, CH 2 C(O)OMe, (CH 2 ) 2 —NHC(O)O-tert-But, or cyclopentyl.

6. The compound according to claim 3 , wherein G 5 is hydrogen, and G 4 is halo, C1-C6 aliphatic or phenyl, wherein said aliphatic or phenyl is optionally substituted with C1-C6 alkyl, halo, cyano, or CF 3 , wherein up to two methylene units of said C1-C6 aliphatic or C1-C6 alkyl is optionally replaced with —CO—, —CONR′—, —CO 2 —, —OCO—, —NR′CO 2 —, —O—, —NR′CONR′—, —OCONR′—, —NR′CO—, —S—, —NR′—, —SO 2 NR′—, NR′SO 2 —, or —NR′SO 2 NR′—.

7. The compound according to claim 3 , wherein G 5 is hydrogen, and G 4 is halo, ethoxycarbonyl, t-butyl, 2-methoxyphenyl, 2-ethoxyphenyl, (4-C(O)NH(CH 2 ) 2 —NMe 2 )-phenyl, 2-methoxy-4-chloro-phenyl, pyridine-3-yl, 4-isopropylphenyl, 2,6-dimethoxyphenyl, sec-butylaminocarbonyl, ethyl, t-butyl, or piperidin-1-ylcarbonyl.

8. A compound selected from:

Cmpd

No.

Name

1

N-[5-(5-chloro-2-methoxy-phenyl)-1H-indol-6-yl]-4-oxo-1H-quinoline-3-carboxamide

22

4-Oxo-1,4-dihydro-quinoline-3-carboxylic acid N-(1′,2′-dihydrospiro[cyclopropane-1,3′-

[3H]indol]-6′-yl)-amide

27

N-[1-[2-[methyl-(2-methylaminoacetyl)-amino]acetyl]-1H-indol-6-yl]-4-oxo-1H-

quinoline-3-carboxamide

32

N-(5-chloro-1H-indol-6-yl)-4-oxo-1H-quinoline-3-carboxamide

33

N-(1H-indol-6-yl)-4-oxo-1H-quinoline-3-carboxamide

37

N-(1H-indol-7-yl)-4-oxo-1H-quinoline-3-carboxamide

44

N-(2-methylbenzothiazol-5-yl)-4-oxo-1H-quinoline-3-carboxamide

51

6-[(4-methyl-1-piperidyl)sulfonyl]-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-

3-carboxamide

54

4-oxo-N-(8-thia-7,9-diazabicyclo[4.3.0]nona-2,4,6,9-tetraen-5-yl)-1H-quinoline-3-

carboxamide

64

4-oxo-N-(2-oxo-1,3-dihydrobenzoimidazol-5-yl)-1H-quinoline-3-carboxamide

65

4-oxo-N-[5-(3-pyridyl)-1H-indol-6-yl]-1H-quinoline-3-carboxamide

66

N-(2,2-difluorobenzo[1,3]dioxol-5-yl)-4-oxo-1H-quinoline-3-carboxamide

67

6-ethyl-4-hydroxy-N-(1H-indol-6-yl)quinoline-3-carboxamide

73

4-oxo-N-(2-phenyl-3H-benzoimidazol-5-yl)-1H-quinoline-3-carboxamide

77

N-(5-fluoro-1H-indol-6-yl)-4-oxo-1H-quinoline-3-carboxamide

96

N-[3-(cyanomethyl)-1H-indol-6-yl]-4-oxo-1H-quinoline-3-carboxamide

100

N-(1H-indol-4-yl)-4-oxo-1H-quinoline-3-carboxamide

104

N-(2-methyl-1H-indol-6-yl)-4-oxo-1H-quinoline-3-carboxamide

105

1,4-dihydro-N-(3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-4-oxoquinoline-3-

carboxamide

107

7-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-1,2,3,4-tetrahydroisoquinoline-2-carboxylic

acid tert-butyl ester

108

4,4-dimethyl-7-[(4-oxo-1H-quinoline-3-yl)carbonylamino]-1,2,3,4-tetrahydroquinoline-

1-carboxylic acid tert-butyl ester

112

6-ethoxy-4-hydroxy-N-(1H-indol-6-yl)quinoline-3-carboxamide

113

N-(3-methyl-1H-indol-6-yl)-4-oxo-1H-quinoline-3-carboxamide

116

5-hydroxy-N-(1H-indol-6-yl)-4-oxo-1H-quinoline-3-carboxamide

124

6-fluoro-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carboxamide

130

4-hydroxy-N-(1H-indol-6-yl)-5,7-bis(trifluoromethyl)quinoline-3-carboxamide

145

6-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-1H-indole-4-carboxylic acid ethyl ester

146

4-oxo-N-(1,7,9-triazabicyclo[4.3.0]nona-2,4,6,8-tetraen-5-yl)-1H-quinoline-3-

carboxamide

148

4-oxo-N-[5-(1-piperidylcarbonyl)-1H-indol-6-yl]-1H-quinoline-3-carboxamide

152

4-oxo-N-(2-oxo-3H-benzooxazol-6-yl)-1H-quinoline-3-carboxamide

158

4-oxo-N-(5-phenyl-1H-indol-6-yl)-1H-quinoline-3-carboxamide

169

N-(1-methyl-1H-indol-6-yl)-4-oxo-1H-quinoline-3-carboxamide

175

4-Oxo-1,4-dihydro-quinoline-3-carboxylic acid N-(1′-Acetyl-1′,2′-

dihydrospiro[cyclopropane-1,3′-3H-indol]-6′-yl)-amide

183

7-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-1,2,3,4-tetrahydroquinoline-1-carboxylic

acid tert-butyl ester

184

N-(1H-indol-6-yl)-4-oxo-2-(trifluoromethyl)-1H-quinoline-3-carboxamide

186

N-(3-cyclopentyl-1H-indol-6-yl)-4-oxo-1H-quinoline-3-carboxamide

187

N-(1-acetyl-1H-indol-6-yl)-4-oxo-1H-quinoline-3-carboxamide

188

6-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-1H-indole-5-carboxylic acid ethyl ester

191

4-oxo-N-(5-quinolyl)-1H-quinoline-3-carboxamide

203

N-(1-benzyl-1H-indol-6-yl)-4-oxo-1H-quinoline-3-carboxamide

204

N-(4,4-dimethylchroman-7-yl)-4-oxo-1H-quinoline-3-carboxamide

207

2-[6-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-1H-indol-3-yl]acetic acid ethyl ester

216

N-(3H-benzoimidazol-2-yl)-4-oxo-1H-quinoline-3-carboxamide

217

N-(1H-indazol-5-yl)-4-oxo-1H-quinoline-3-carboxamide

230

N-(2-methyl-1H-indol-5-yl)-4-oxo-1H-quinoline-3-carboxamide

233

N-(1-acetylindolin-6-yl)-4-oxo-1H-quinoline-3-carboxamide

234

4-oxo-N-[5-(trifluoromethyl)-1H-indol-6-yl]-1H-quinoline-3-carboxamide

237

N-[5-(2-methoxyphenyl)-1H-indol-6-yl]-4-oxo-1H-quinoline-3-carboxamide

238

7′-[(4-oxo-1H-quinolin-3-ylcarbonyl)amino]-spiro[piperidine-4,4′(1′H)-quinoline], 2′,3′-

dihydro-carboxylic acid tert-butyl ester

241

4-oxo-N-(8-quinolyl)-1H-quinoline-3-carboxamide

244

4-oxo-N-(6,7,8,9-tetrahydro-5H-carbazol-2-yl)-1H-quinoline-3-carboxamide

254

6-fluoro-N-(5-fluoro-1H-indol-6-yl)-4-oxo-1H-quinoline-3-carboxamide

256

N-(1H-benzotriazol-5-yl)-4-oxo-1H-quinoline-3-carboxamide

258

N-indolin-6-yl-4-oxo-1H-quinoline-3-carboxamide

259

4-oxo-N-(3-sec-butyl-1H-indol-6-yl)-1H-quinoline-3-carboxamide

262

1,4-dihydro-N-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]thiazin-6-yl)-4-oxoquinoline-3-

carboxamide

270

N-(2-cyano-1H-indol-6-yl)-4-oxo-1H-quinoline-3-carboxamide

274

4-oxo-6-pyrrolidin-1-ylsulfonyl-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-

carboxamide

280

4-oxo-N-(6-quinolyl)-1H-quinoline-3-carboxamide

284

N-(1H-indazol-6-yl)-4-oxo-1H-quinoline-3-carboxamide

294

N-(1H-indol-5-yl)-4-oxo-1H-quinoline-3-carboxamide

299

4-oxo-N-(1,2,3,4-tetrahydroquinolin-7-yl)-1H-quinoline-3-carboxamide

300

N-(4,4-dimethyl-1,2,3,4-tetrahydroquinolin-7-yl)-4-oxo-1H-quinoline-3-carboxamide

303

N-(2-acetyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-oxo-1H-quinoline-3-carboxamide

320

4-oxo-N-(2-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carboxamide

327

N-[5-(2-ethoxyphenyl)-1H-indol-6-yl]-4-oxo-1H-quinoline-3-carboxamide

329

N-[2-(o-tolyl)benzooxazol-5-yl]-4-oxo-1H-quinoline-3-carboxamide

334

7′-[(4-oxo-1H-quinolin-3-ylcarbonyl)amino]-spiro[piperidine-4,4′(1′H)-1-acetyl-

quinoline], 2′,3′-dihydro-carboxylic acid tert-butyl ester

338

N-(3-methyl-1H-indol-4-yl)-4-oxo-1H-quinoline-3-carboxamide

339

N-(3-cyano-1H-indol-6-yl)-4-oxo-1H-quinoline-3-carboxamide

342

N-[5-(4-isopropylphenyl)-1H-indol-6-yl]-4-oxo-1H-quinoline-3-carboxamide

343

N-[5-(isobutylcarbamoyl)-1H-indol-6-yl]-4-oxo-1H-quinoline-3-carboxamide

345

6-fluoro-4-hydroxy-N-(1H-indol-6-yl)quinoline-3-carboxamide

347

N-[5-[4-(2-dimethylaminoethylcarbamoyl)phenyl]-1H-indol-6-yl]-4-oxo-1H-quinoline-

3-carboxamide

351

N-(5-ethyl-1H-indol-6-yl)-4-oxo-1H-quinoline-3-carboxamide

352

2-[6-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-1H-indol-3-yl]ethylaminoformic acid

tert-butyl ester

357

N-(3-isopropyl-1H-indol-6-yl)-4-oxo-1H-quinoline-3-carboxamide

358

6-chloro-4-hydroxy-N-(1H-indol-6-yl)quinoline-3-carboxamide

364

N-(2-methyl-8-quinolyl)-4-oxo-1H-quinoline-3-carboxamide

374

4-hydroxy-N-(1H-indol-6-yl)-2-methylsulfanyl-quinoline-3-carboxamide

376

4-oxo-N-(2-phenylbenzooxazol-5-yl)-1H-quinoline-3-carboxamide

377

6,8-difluoro-4-hydroxy-N-(1H-indol-6-yl)quinoline-3-carboxamide

381

4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carboxamide

383

N-(3-ethyl-1H-indol-6-yl)-4-oxo-1H-quinoline-3-carboxamide

386

N-(3,3-dimethylindolin-6-yl)-4-oxo-1H-quinoline-3-carboxamide

404

N-[5-(2,6-dimethoxyphenyl)-1H-indol-6-yl]-4-oxo-1H-quinoline-3-carboxamide

406

6-[(4-fluorophenyl)-methyl-sulfamoyl]-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-

quinoline-3-carboxamide

412

6-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-1H-indole-7-carboxylic acid ethyl ester

414

N-(3H-benzoimidazol-5-yl)-4-oxo-1H-quinoline-3-carboxamide

423

N-[3-(2-ethoxyethyl)-1H-indol-6-yl]-4-oxo-1H-quinoline-3-carboxamide

427

5-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-1,2,3,4-tetrahydroisoquinoline-2-carboxylic

acid tert-butyl ester

437

N-benzo[1,3]dioxol-5-yl-4-oxo-1H-quinoline-3-carboxamide

443

4-oxo-N-quinoxalin-6-yl-1H-quinoline-3-carboxamide

446

N-(1,1-dioxobenzothiophen-6-yl)-4-oxo-1H-quinoline-3-carboxamide

467

N-(2,3-dihydrobenzofuran-5-yl)-4-oxo-1H-quinoline-3-carboxamide

474

N-(3-methyl-2-oxo-3H-benzooxazol-5-yl)-4-oxo-1H-quinoline-3-carboxamide

478

4-oxo-N-(3-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carboxamide

479

N-(1H-indol-6-yl)-5-methoxy-4-oxo-1H-quinoline-3-carboxamide.