IP Library › Granted Patent US 11,267,777

Granted Patent B2

US 11,267,777 · App. 15/777,565 · Granted Mar 8, 2022

Deuterated EPI-743

Inventors: Julie F. Liu (Lexington, MA); Darren H. Wong (Charleston, MA)

Assignee: Concert Pharmaceuticals, Inc.

C07C50/06 C07B59/001 C07B2200/05 C07C2601/16

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Quick Facts

Patent No.: US 11,267,777
App. No.: 15/777,565
Granted: Mar 8, 2022
Kind: B2

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Abstract

This invention relates to novel α-tocotrienol quinones of Formula I: (I), and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering Vitamin E.

Claims (1203)

1. A compound of Formula Ia:

or a pharmaceutically acceptable salt thereof, wherein:

each of R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 is independently selected from —CH 3 and —CD 3 ;

each of R 7 and R 8 is —CD 3 ;

Y 1a and Y 1b are the same and are each hydrogen or each deuterium;

Y 2a and Y 2b are the same and are each hydrogen or each deuterium;

Y 3a and Y 3b are the same and are each hydrogen or each deuterium;

Y 4a and Y 4b are the same and are each hydrogen or each deuterium;

Y 6a and Y 6b are the same and are each hydrogen or each deuterium;

Y 7a and Y 7b are the same and are each hydrogen or each deuterium;

Y 9a and Y 9b are the same and are each hydrogen or each deuterium;

Y 10a and Y 10b are the same and are each deuterium;

each of Y 5 and Y 8 is independently selected from hydrogen and deuterium; and

Y 11 is deuterium.

2. The compound of claim 1 , wherein R 1 , R 2 and R 3 are the same.

3. The compound of claim 1 , wherein at least one of R 5 and R 6 is —CD 3 .

4. The compound of claim 1 , wherein each of Y 9a , Y 9b Y 10a , Y 10b , and Y 11 is the same.

5. The compound of claim 1 , wherein each of Y 6a , Y 6b Y 7a , Y 7b , and Y 8 is the same.

6. The compound of claim 1 , wherein each of Y 3a , Y 3b Y 4a , Y 4b , and Y 5 is the same.

7. The compound of claim 1 , wherein each of Y 1a , Y 1b Y 2a , and Y 2b is the same.

8. The compound of claim 1 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.

9. The compound of claim 1 , wherein the compound is selected from any one of:

or a pharmaceutically acceptable salt thereof, and wherein any atom not designated as deuterium is present at its natural isotopic abundance.

10. The compound of claim 1 , wherein the isotopic enrichment for each designated deuterium atom is at least 90%.

11. The compound of claim 10 wherein the isotopic enrichment for each designated deuterium atom is at least 95%.

12. The compound of claim 11 wherein the isotopic enrichment for each designated deuterium atom is at least 97%.

13. A pharmaceutical composition comprising a compound of claim 1 ; and a pharmaceutically acceptable carrier.

14. A method of treating a disease or condition selected from Leigh syndrome, Friedreich's ataxia, Parkinson's disease, Pearson syndrome, cobalamin C deficiency syndrome, hearing loss, Rett's syndrome, autism spectrum disorders, inherited mitochondrial respiratory chain diseases, multisystem genetic disorders, Tourette's disease, metabolic disorders, mitochondrial disorders, Leber's hereditary optic neuropathy, and Huntington's disease in a subject comprising the step of administering to the subject in need thereof a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

15. The method of claim 14 , wherein the disease or condition is selected from Leigh syndrome, Friedreich's ataxia, Parkinson's disease, Pearson syndrome, cobalamin C deficiency syndrome, hearing loss, Rett's syndrome, autism spectrum disorders, inherited mitochondrial respiratory chain diseases, multisystem genetic disorders, Tourette's disease, and Leber's hereditary optic neuropathy.

16. The method of claim 15 , wherein the disease or condition is Leigh syndrome.

17. A method of treating a disease or condition selected from Leigh syndrome, Friedreich's ataxia, Parkinson's disease, Pearson syndrome, cobalamin C deficiency syndrome, hearing loss, Rett's syndrome, autism spectrum disorders, inherited mitochondrial respiratory chain diseases, multisystem genetic disorders, Tourette's disease, metabolic disorders, mitochondrial disorders, Leber's hereditary optic neuropathy, and Huntington's disease in a subject comprising the step of administering to the subject in need thereof a pharmaceutical composition of claim 13 .

18. The compound of claim 1 , wherein R 1 , R 2 and R 3 are the same; each of Y 1a , Y 1b Y 2a , and Y 2b is the same; each of Y 3a , Y 3b Y 4a , Y 4b and Y 5 is the same; each of Y 6a , Y 6b Y 7a , Y 7b , and Y 8 is the same; each of Y 9a , Y 9b Y 10a , Y 10b , and Y 11 is the same; and any atom not designated as deuterium is present at its natural isotopic abundance, wherein the compound is selected from any one of the compounds set forth in the following table:

Compound

Y 1a /Y 1b /

Y 3a /Y 3b /

Y 6a /Y 6b

Y 9a /Y 9b /

R 1 /R 3 /R 3

R 4

R 5

R 6

Y 2a /Y 2b

4a/Y 4b /Y 5

Y 7a /Y 7b /Y 8

Y 10a /Y 10b /Y 11

163

CD 3

CH 3

164

CH 3

CD 3

CH 3

165

CH 3

CD 3

CH 3

166

CH 3

CD 3

167

CD 3

CH 3

168

CD 3

CH 3

CD 3

CH 3

169

CD 3

CH 3

CD 3

170

CH 3

CD 3

CH 3

171

CH 3

CD 3

CH 3

CD 3

172

CH 3

CD 3

173

CD 3

CH 3

174

CD 3

CH 3

CD 3

175

CD 3

CH 3

CD 3

176

CH 3

CD 3

177

CD 3

178

CH 3

211

CD 3

CH 3

212

CH 3

CD 3

CH 3

213

CH 3

CD 3

CH 3

214

CH 3

CD 3

215

CD 3

CH 3

216

CD 3

CH 3

CD 3

CH 3

217

CD 3

CH 3

CD 3

218

CH 3

CD 3

CH 3

219

CH 3

CD 3

CH 3

CD 3

220

CH 3

CD 3

221

CD 3

CH 3

222

CD 3

CH 3

CD 3

223

CD 3

CH 3

CD 3

224

CH 3

CD 3

225

CD 3

226

CH 3

243

CD 3

CH 3

244

CH 3

CD 3

CH 3

245

CH 3

CD 3

CH 3

246

CH 3

CD 3

247

CD 3

CH 3

248

CD 3

CH 3

CD 3

CH 3

249

CD 3

CH 3

CD 3

250

CH 3

CD 3

CH 3

251

CH 3

CD 3

CH 3

CD 3

252

CH 3

CD 3

253

CD 3

CH 3

254

CD 3

CH 3

CD 3

255

CD 3

CH 3

CD 3

256

CH 3

CD 3

257

CD 3

258

CH 3

259

CD 3

CH 3

260

CH 3

CD 3

CH 3

261

CH 3

CD 3

CH 3

262

CH 3

CD 3

263

CD 3

CH 3

264

CD 3

CH 3

CD 3

CH 3

265

CD 3

CH 3

CD 3

266

CH 3

CD 3

CH 3

267

CH 3

CD 3

CH 3

CD 3

268

CH 3

CD 3

269

CD 3

CH 3

270

CD 3

CH 3

CD 3

271

CD 3

CH 3

CD 3

272

CH 3

CD 3

273

CD 3

274

CH 3

291

CD 3

CH 3

292

CH 3

CD 3

CH 3

293

CH 3

CD 3

CH 3

294

CH 3

CD 3

295

CD 3

CH 3

296

CD 3

CH 3

CD 3

CH 3

297

CD 3

CH 3

CD 3

298

CH 3

CD 3

CH 3

299

CH 3

CD 3

CH 3

CD 3

300

CH 3

CD 3

301

CD 3

CH 3

302

CD 3

CH 3

CD 3

303

CD 3

CH 3

CD 3

304

CH 3

CD 3

305

CD 3

306

CH 3

307

CD 3

CH 3

308

CH 3

CD 3

CH 3

309

CH 3

CD 3

CH 3

310

CH 3

CD 3

311

CD 3

CH 3

312

CD 3

CH 3

CD 3

CH 3

313

CD 3

CH 3

CD 3

314

CH 3

CD 3

CH 3

315

CH 3

CD 3

CH 3

CD 3

316

CH 3

CD 3

317

CD 3

CH 3

318

CD 3

CH 3

CD 3

319

CD 3

CH 3

CD 3

320

CH 3

CD 3

321

CD 3

322

CH 3

323

CD 3

CH 3

324

CH 3

CD 3

CH 3

325

CH 3

CD 3

CH 3

326

CH 3

CD 3

327

CD 3

CH 3

328

CD 3

CH 3

CD 3

CH 3

329

CD 3

CH 3

CD 3

330

CH 3

CD 3

CH 3

331

CH 3

CD 3

CH 3

CD 3

332

CH 3

CD 3

333

CD 3

CH 3

334

CD 3

CH 3

CD 3

335

CD 3

CH 3

CD 3

336

CH 3

CD 3

337

CD 3

338

CH 3

339

CD 3

CH 3

340

CH 3

CD 3

CH 3

341

CH 3

CD 3

CH 3

342

CH 3

CD 3

343

CD 3

CH 3

344

CD 3

CH 3

CD 3

CH 3

345

CD 3

CH 3

CD 3

346

CH 3

CD 3

CH 3

347

CH 3

CD 3

CH 3

CD 3

348

CH 3

CD 3

349

CD 3

CH 3

350

CD 3

CH 3

CD 3

351

CD 3

CH 3

CD 3

352

CH 3

CD 3

353

CD 3

354

CH 3

or a pharmaceutically acceptable salt thereof, wherein the isotopic enrichment for each designated deuterium atom is at least 90%.

19. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof, wherein any atom not designated as deuterium is present at its natural isotopic abundance.

20. The compound of claim 18 , wherein the isotopic enrichment for each designated deuterium atom is at least 90%.

21. The compound of claim 19 , wherein the isotopic enrichment for each designated deuterium atom is at least 95%.

Assignments (2)

MERGER Recorded Sep 14, 2023

From: CONCERT PHARMACEUTICALS, INC.

To: SUN PHARMACEUTICAL INDUSTRIES, INC.

Reel/Frame 064907/0514 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 26, 2019

From: LIU, JULIE F.; WONG, DARREN H.

To: CONCERT PHARMACEUTICALS, INC.

Reel/Frame 050161/0687 →

Continuity (2)

Provisional Application 62257567 · Nov 19, 2015

Related Publication 20210269382A1 · Sep 2, 2021