IP Library › Granted Patent US 9,260,432

Granted Patent B2

US 9,260,432 · App. 13/394,025 · Granted Feb 16, 2016

Substituted derivatives of bicyclic [4.3.0] heteroaryl compounds

Inventors: Roger D. Tung (Lexington, MA); Craig E. Masse (Cambridge, MA)

Assignee: Concert Pharmaceuticals, Inc.

C07D487/04 C07D513/04 C07B2200/05

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Quick Facts

Patent No.: US 9,260,432
App. No.: 13/394,025
Granted: Feb 16, 2016
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

This invention relates to novel compounds of the Formula A, B, or C, and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising one or more compounds of this invention and a carrier.

Claims (1105)

1. A compound of Formula A:

or a pharmaceutically acceptable salt thereof, wherein

each Z 2 is hydrogen or deuterium;

each Z 3 is hydrogen or deuterium;

each Z 4 is hydrogen or deuterium;

each Z 5 is hydrogen or deuterium;

the bicyclic ring system bearing X and Q is:

a 1H-pyrrolo[2,3-d]pyrimidine-2,4(3H,7H)-dione ring where X is CR 1a and Q is NR 7 ;

either (a) Y 1 is OH, and Y 2 is hydrogen or deuterium, or (b) Y 1 and Y 2 are taken together with the carbon to which they are attached to form C═O;

R 1a is hydrogen, —CH 3 or —CD 3 ;

R 2 is —CH 3 or —CD 3 ;

R 5 is hydrogen or deuterium; and

R 7 is —CH 3 , —CD 3 , hydrogen or deuterium; and wherein

any atom not designated as deuterium is present at its natural isotopic abundance.

2. The compound of claim 1 , wherein the compound has the Formula A(i) wherein the bicyclic ring system bearing X and Q is a 1H-pyrrolo[2,3-d]pyrimidine-2,4(3H,7H)-dione ring:

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 2 , wherein R 1a is CH 3 .

4. The compound of claim 2 , wherein R 1a is CD 3 .

5. The compound of claim 2 , wherein R 1a is hydrogen.

6. The compound of claim 2 , wherein R 2 is CH 3 .

7. The compound of claim 2 , wherein R 2 is CD 3 .

8. The compound of claim 1 , wherein each Z 2 , Z 3 , Z 4 and Z 5 is hydrogen.

9. The compound of claim 1 , wherein each Z 2 , Z 3 , Z 4 and Z 5 is deuterium.

10. The compound of claim 1 , wherein Z 2 is deuterium and either each of Z 3 , Z 4 and Z 5 is hydrogen or each of Z 3 , Z 4 and Z 5 is deuterium.

11. The compound of claim 1 , wherein Y 1 and Y 2 are taken together with the carbon to which they are attached to form C═O.

12. The compound of claim 1 , wherein Y 1 is OH, and Y 2 is hydrogen or deuterium.

13. The compound of claim 2 , wherein the compound is of Formula A(i), wherein R 7 is hydrogen, Z 3 , Z 4 , and Z 5 are each hydrogen, and the compound is selected from the group consisting of the compounds in the table below:

Compound

R 1a

R 2

R 5

Z 2

Y 1

Y 2

100

CH 3

taken together as ═O

101

CD 3

CH 3

taken together as ═O

102

CH 3

CD 3

taken together as ═O

103

CD 3

taken together as ═O

104

CH 3

taken together as ═O

105

CD 3

CH 3

taken together as ═O

106

CH 3

CD 3

taken together as ═O

107

CD 3

taken together as ═O

108

CH 3

taken together as ═O

109

CD 3

CH 3

taken together as ═O

110

CH 3

CD 3

taken together as ═O

111

CD 3

taken together as ═O

112

CH 3

taken together as ═O

113

CD 3

CH 3

taken together as ═O

114

CH 3

CD 3

taken together as ═O

115

CD 3

taken together as ═O

116

CH 3

117

CD 3

CH 3

118

CH 3

CD 3

119

CD 3

120

CH 3

121

CD 3

CH 3

122

CH 3

CD 3

123

CD 3

124

CH 3

125

CD 3

CH 3

126

CH 3

CD 3

127

CD 3

128

CH 3

129

CD 3

CH 3

130

CH 3

CD 3

131

CD 3

132

CH 3

133

CD 3

CH 3

134

CH 3

CD 3

135

CD 3

136

CH 3

137

CD 3

CH 3

138

CH 3

CD 3

139

CD 3

140

CH 3

141

CD 3

CH 3

142

CH 3

CD 3

143

CD 3

144

CH 3

145

CD 3

CH 3

146

CH 3

CD 3

147

CD 3

or a pharmaceutically acceptable salt of the compound.

14. The compound of claim 2 , wherein the compound is of Formula A(i), wherein R 7 is CH 3 or CD 3 , Z 3 , Z 4 , and Z 5 are each hydrogen, and the compound is selected from the group consisting of the compounds in the table below:

Compound

R 7

R 1a

R 2

R 5

Z 2

Y 1

Y 2

200

CH 3

taken together as ═O

201

CD 3

CH 3

taken together as ═O

202

CH 3

CD 3

taken together as ═O

203

CD 3

taken together as ═O

204

CH 3

taken together as ═O

205

CD 3

CH 3

taken together as ═O

206

CH 3

CD 3

taken together as ═O

207

CD 3

taken together as ═O

208

CH 3

taken together as ═O

209

CD 3

CH 3

taken together as ═O

210

CH 3

CD 3

taken together as ═O

211

CD 3

taken together as ═O

212

CH 3

taken together as ═O

213

CD 3

CH 3

taken together as ═O

214

CH 3

CD 3

taken together as ═O

215

CD 3

taken together as ═O

216

CH 3

217

CD 3

CH 3

218

CH 3

CD 3

219

CD 3

220

CH 3

221

CD 3

CH 3

222

CH 3

CD 3

223

CD 3

224

CH 3

225

CD 3

CH 3

226

CH 3

CD 3

227

CD 3

228

CH 3

229

CD 3

CH 3

230

CH 3

CD 3

231

CD 3

232

CH 3

233

CD 3

CH 3

234

CH 3

CD 3

235

CD 3

236

CH 3

237

CD 3

CH 3

238

CH 3

CD 3

239

CD 3

240

CH 3

241

CD 3

CH 3

242

CH 3

CD 3

243

CD 3

244

CH 3

245

CD 3

CH 3

246

CH 3

CD 3

247

CD 3

248

CH 3

CD 3

CH 3

taken together as ═O

249

CD 3

CH 3

taken together as ═O

250

CH 3

CD 3

taken together as ═O

251

CD 3

taken together as ═O

252

CH 3

CD 3

CH 3

taken together as ═O

253

CD 3

CH 3

taken together as ═O

254

CH 3

CD 3

taken together as ═O

255

CD 3

taken together as ═O

256

CH 3

CD 3

CH 3

taken together as ═O

257

CD 3

CH 3

taken together as ═O

258

CH 3

CD 3

taken together as ═O

259

CD 3

taken together as ═O

260

CH 3

CD 3

CH 3

taken together as ═O

261

CD 3

CH 3

taken together as ═O

262

CH 3

CD 3

taken together as ═O

263

CD 3

taken together as ═O

264

CH 3

CD 3

CH 3

265

CD 3

CH 3

266

CH 3

CD 3

267

CD 3

268

CH 3

CD 3

CH 3

269

CD 3

CH 3

270

CH 3

CD 3

271

CD 3

272

CH 3

CD 3

CH 3

273

CD 3

CH 3

274

CH 3

CD 3

275

CD 3

276

CH 3

CD 3

CH 3

277

CD 3

CH 3

278

CH 3

CD 3

279

CD 3

280

CH 3

CD 3

CH 3

281

CD 3

CH 3

282

CH 3

CD 3

283

CD 3

284

CH 3

CD 3

CH 3

285

CD 3

CH 3

286

CH 3

CD 3

287

CD 3

288

CH 3

CD 3

CH 3

289

CD 3

CH 3

290

CH 3

CD 3

291

CD 3

292

CH 3

CD 3

CH 3

293

CD 3

CH 3

294

CH 3

CD 3

295

CD 3

or a pharmaceutically acceptable salt of the compound.

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

16. A method of treating a disease or condition in a patient in need thereof, comprising administering to the patient an effective amount of a composition of claim 15 , wherein the disease is diabetic nephropathy, hypertensive nephropathy or intermittent claudication on the basis of chronic occlusive arterial disease of the limbs.

17. The compound of claim 1 , wherein any atom designated as deuterium has an isotopic enrichment of at least 90%.

18. The compound of claim 17 , wherein any atom designated as deuterium has an isotopic enrichment of at least 95%.

Assignments (2)

MERGER Recorded Aug 2, 2023

From: CONCERT PHARMACEUTICALS, INC.

To: SUN PHARMACEUTICAL INDUSTRIES, INC.

Reel/Frame 064465/0383 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 14, 2012

From: TUNG, ROGER D.; MASSE, CRAIG E.

To: CONCERT PHARMACEUTICALS INC.

Reel/Frame 028783/0686 →

Continuity (2)

Provisional Application 61239371 · Sep 2, 2009

Related Publication 20120295925A1 · Nov 22, 2012