Granted Patent B2

US 11,046,698 · App. 16/046,481 · Granted Jun 29, 2021

Inventors: Craig E. Masse (Cambridge, MA); Jeremy Robert Greenwood (Brooklyn, NY); Sayan Mondal (New York, NY); Scott D. Cowen (Cambridge, MA); Thomas H. McLean (Cambridge, MA)

Assignee: Nimbus Lakshmi, Inc.

C07D487/04A61P11/06A61P17/06A61P29/00A61P35/00A61P37/02C07D519/00

Abstract

Claims (1109)

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:

R 3 is —C(O)NH 2 ; —C(O)NHR 3A ; or —C(O)N(R 3A ) 2 ;

R 5 is -L 1 -R 5A ;

R 6 is hydrogen, R A , or R B ;

or R 5 and R 6 are taken together with their intervening atoms to form a 4-7 membered partially unsaturated, or heteroaryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein said ring is substituted by R 5A and n instances of R C ;

R 7 is halogen, —NH 2 , —NHR 7A , or —NHC(O)R 7A ;

or R 6 and R 7 are taken together with their intervening atoms to form a 4-7 membered partially unsaturated, or heteroaryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein said ring is substituted by p instances of R C ;

L 1 is —N(R);

R 3A is R B , substituted by q instances of R C ;

R 5A is R A or R B , substituted by r instances of R C ;

R 7A is selected from the group consisting of hydrogen, methyl,

and

each instance of R A is independently halogen, —CN, —NO 2 , —OR, —SR, —NR 2 , —S(O) 2 R, —S(O) 2 NR 2 , —S(O)R, —S(O)NR 2 , —C(O)R, —C(O)OR, —C(O)NR 2 , —C(O)N(R)OR, —OC(O)R, —OC(O)NR 2 , —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR 2 , —N(R)C(NR)NR 2 , —N(R)S(O) 2 NR 2 , or —N(R)S(O) 2 R;

each instance of R B is independently C 1-6 aliphatic; phenyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3-7 membered saturated or partially unsaturated carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

each instance of R C is independently oxo, halogen, —CN, —NO 2 , —OR, —SR, —NR 2 , —S(O) 2 R, —S(O) 2 NR 2 , —S(O)R, —S(O)NR 2 , —C(O)R, —C(O)OR, —C(O)NR 2 , —C(O)N(R)OR, —OC(O)R, —OC(O)NR 2 , —N(R)C(O)OR, —N(R) C(O)R, —N(R)C(O)NR 2 , —N(R)C(NR)NR 2 , —N(R)S(O) 2 NR 2 , or —N(R)S(O) 2 R or an optionally substituted group selected from C 1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

each R is independently hydrogen, or an optionally substituted group selected from C 1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:

two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur;

wherein each hydrogen bound to carbon can be optionally and independently replaced by deuterium; and

each instance of n, p, q, and r is independently 0, 1, 2, 3, or 4.

2. The compound of claim 1 of formula V or VI:

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 2 of formula V-a or VI-a:

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 3 wherein R 7 is —NH 2 or —NHR 7A , or a pharmaceutically acceptable salt thereof.

5. The compound of claim 3 of one of formulas V-c or VI-c:

or a pharmaceutically acceptable salt thereof.

6. The compound of claim 5 wherein R 3A is R B , and is substituted by q instances of R C , provided that R 3A is not phenyl.

7. The compound of claim 6 wherein R 7A is methyl,

8. The compound of claim 7 wherein R 7A is methyl.

9. A compound selected from those depicted below, or a pharmaceutically acceptable salt thereof:

Compound

Structure

I-9

I-10

I-11

I-12

I-13

I-15

I-18

I-19

I-20

I-21

I-22

I-23

I-24

I-25

I-26

I-27

I-28

I-29

I-30

I-31

I-32

I-33

I-34

I-35

I-37

I-38

I-39

I-40

I-41

I-42

I-43

I-44

I-45

I-46

I-48

I-49

I-50

I-51

I-52

I-53

I-54

I-55

I-56

I-57

I-59

I-60

I-61

I-62

I-63

I-64

I-66

I-67

I-68

I-69

I-70

I-71

I-72

I-73

I-74

I-75

I-76

I-77

I-78

I-79

I-80

I-81

I-82

I-83

I-84

I-85

I-86

I-87

I-88

I-89

I-90

I-91

I-92

I-93

I-96

I-97

I-98

I-99

I-100

I-102

I-103

I-104

I-108

I-109

I-111

I-112

I-113

I-114

I-116

I-118

I-119

I-120

I-121

I-122

I-125

I-128

I-129

I-130

I-134

I-136

I-140

I-142

I-146

I-148

I-149

I-150

I-152

I-155

I-156

I-157

I-159

I-160

I-163

I-166

I-167

I-168

I-169

I-171

I-172

I-173

I-174

I-178

I-179

I-180

I-181

I-182

I-183

I-184

I-185

I-186

I-187

I-188

I-189

I-191

I-192

I-193

I-195

I-196

I-197

I-199

I-200

I-201

I-202

I-203

I-204

I-205

I-206

I-207

I-208

I-209

I-210

I-212

I-213

I-214

I-218

I-221

I-226

I-227

I-228

I-229

I-230

I-231

I-232

I-234

I-237

I-239

I-240

I-241

I-242

I-245

I-246

I-247

I-248

I-249

I-251

I-252

I-253

I-254

I-256

I-257

I-260

I-263

I-264

I-266

I-267

I-268

I-270

I-271

I-273

I-278

I-279

I-280

I-281

I-282

I-286

I-287

I-289

I-291

I-293

I-297

I-298

I-299

I-300

I-301

I-302

I-304

I-306

I-307

I-308

I-313

I-316

I-320

I-322

I-325

I-326

I-327

I-328

I-335

I-336

I-337

I-338

I-339

I-340

I-341

I-342

I-348

I-349

I-353

I-354

I-355

I-356

I-358

I-359

I-361

I-364

I-367

I-368

I-371

I-376

I-378

I-380

I-384

I-385

I-387

I-388

I-389

I-393

I-394

I-398

I-400

I-402

I-403

I-404

I-405

I-406

I-407

I-408

I-412

I-414

I-416

I-418

I-419

I-420

I-421

I-422

I-424

I-427

I-430

I-431

I-433

I-434

I-436

I-437

I-439

I-440

I-441

I-442

I-443

I-444

I-445

I-446

I-447

I-449

I-450

I-451

I-452

I-453

I-454

I-455

I-456

I-457

I-458

I-459

I-460

I-461

I-462

I-463

I-464

I-465

I-466

I-467

I-468

I-469

I-470

I-471

I-472

I-473

I-475

I-476

I-477

I-478

I-479

I-480

I-484

I-485

I-486

I-487

I-488

I-489

I-490

I-491

I-492

I-493

I-494

I-495

I-496

I-497

I-498

I-501

I-502

I-503

I-504

I-505

I-506

I-507

I-508

I-509

I-511

I-512

I-513

I-514

I-515

I-516

I-517

I-518

I-519

I-520

I-521

I-523

I-524

I-525

I-526

I-527

I-528

I-529

I-531

I-532

I-533

I-534

I-535

I-536

I-537

I-538

I-542

I-543

I-544

I-545

I-546

I-548

I-549

I-550

I-551

I-552

I-553

I-554

I-555

I-556

I-557

I-558

I-560

I-561

I-564

I-565

I-566

I-567

I-568

I-569

I-571

I-572

I-573

I-574

I-575

I-576

I-577

I-581

I-582

I-583

I-584

I-587

I-588

I-589

I-593

I-594

I-595

I-596

I-597

I-598

I-599

I-600

I-601

I-604

I-605

I-606

I-608

I-609

I-613

I-614

I-615

I-616

I-617

I-618

I-619

I-620

I-622

I-623

I-624

I-625

I-626

I-627

I-628

I-629

I-631

I-632

I-633

I-634

I-636

I-638

I-641

I-642

I-643

I-644

I-645

I-646

I-647

I-648

I-649

I-650

I-651

I-652

I-653

I-654

I-655

I-656

I-657

I-659

I-660

I-662

I-663

I-664

I-666

I-668

I-669

I-671

I-672

I-674

I-675

I-676

I-677

I-678

I-679

I-680

I-681

I-682

I-683

I-684

I-685

I-686

I-687

I-688

I-689

I-690

I-695

I-696

I-697

I-698

I-699

I-700

I-701

I-702

I-703

I-704

I-705

I-707

I-708

I-712

I-713

I-714

I-715

I-716

I-717

I-718

I-719

I-720

I-722

I-723

I-724

I-725

I-726

I-727

I-728

I-729

I-730

I-731

I-732

I-733

I-734

I-735

I-736

I-737

I-738

I-739

I-740

I-741

I-742

I-743

I-744

I-745

I-746

I-747

I-748

I-749

I-752

I-753

I-754

I-755

I-760

I-761

I-762

I-763

I-764

I-765

I-766

I-767

I-768

I-769

I-771

I-772

I-773

I-774

I-776

I-777

I-778

I-779

I-780

I-781

I-784

I-785

I-786

I-787

I-788

I-789

I-790

I-791

I-792

I-793

I-794

I-795

I-796

I-797

I-799

I-800

I-801

I-802

I-803

I-804

I-805

I-806

I-807

I-808

I-809

I-810

I-812

I-813

I-815

I-816

I-817

I-818

I-820

I-821

I-822

I-823

I-824

I-826

I-828

I-830

I-831

I-832

I-833

I-835

I-836

I-838

I-839

I-841

I-843

I-844

I-845

I-846

I-848

I-850

I-851

I-852

I-853

I-855

I-856

I-858

I-861

I-862

I-865

I-866

I-867

I-868

I-869

I-870

I-871

I-873

I-874

I-875

I-876

I-879

I-880

I-881

I-882

I-883

I-885

I-889

I-890

I-893

I-894

I-896

I-897

I-898

I-899

I-900

I-901

I-903

I-905

I-906

I-907

I-909

I-910

I-911

I-912

I-913

I-915

I-919

I-920

I-921

I-923

I-924

I-925

I-927

I-928

I-929

I-931

I-932

I-933

I-934

I-935

I-936

I-937

I-938

I-939

I-940

I-941

I-942

I-944

I-945

I-947

I-949

I-950

I-952

I-953

I-954

I-955

I-956

I-964

I-966

I-967

I-968

I-970

I-972

I-974

I-976

I-977

I-978

I-979

I-981

I-982

I-983

I-985

I-986

I-987

I-989

I-990

I-991

I-994

I-997

I-998

I-1001

I-1003

I-1004

I-1005

I-1006

I-1007

I-1008

I-1009

I-1011

I-1012

I-1013

I-1015

I-1016

I-1017

I-1018

I-1019

I-1020

I-1021

I-1022

I-1024

I-1026

I-1028

I-1029

I-1030

I-1031

I-1032

I-1033

I-1034

I-1035

I-1036

I-1037

I-1039

I-1040

I-1041

I-1042

I-1043

I-1044

I-1045

I-1046

I-1047

I-1048

I-1053

I-1054

I-1055

I-1056

I-1058

I-1060

I-1061

I-1064

I-1065

I-1067

I-1068

I-1069

I-1070

I-1071

I-1072

I-1075

I-1076

I-1077

I-1078

I-1079

I-1081

I-1083

I-1084

I-1085

I-1087

I-1089

I-1090

I-1091

I-1092

I-1100

I-1102

I-1103

I-1104

I-1106

I-1107

I-1108

I-1109

I-1110

I-1111

I-1112

I-1113

I-1114

I-1115

I-1116

I-1118

I-1119

I-1120

I-1121

I-1122

I-1123

I-1124

I-1125

I-1126

I-1127

I-1128

I-1129

I-1130

I-1131

I-1132

I-1134

I-1135

I-1136

I-1137

I-1138

I-1139

I-1140

I-1141

I-1142

I-1143

I-1144

I-1145

I-1146

I-1147

I-1148

I-1149

I-1150

I-1151

I-1152

I-1153

I-1154

I-1155

I-1156

I-1157

I-1158

I-1159

I-1160

I-1161

I-1162

I-1163

I-1164

I-1165

I-1166

I-1167

I-1168

I-1169

I-1170

I-1171

I-1172

I-1173

I-1174

I-1175

I-1176

I-1177

I-1178

I-1179

I-1180

I-1181

I-1182

I-1183

I-1184

I-1185

I-1186

I-1187

I-1188

I-1189

I-1190

I-1191

I-1192

I-1193

I-1194

I-1195

I-1196

I-1197

I-1198

I-1199

I-1200

I-1201

I-1202

I-1203

I-1204

I-1205

I-1206

I-1207

I-1208

I-1209

I-1210

I-1211

I-1212

I-1213

I-1214

I-1215

I-1216

I-1217

I-1218

I-1219

I-1220

I-1221

I-1222

I-1223

I-1224

I-1225

I-1226

I-1227

I-1228

I-1229

I-1230

I-1231

I-1232

I-1233

I-1234

I-1235

I-1236

I-1237

I-1238

I-1239

I-1240

I-1241

I-1242

I-1243

I-1244

I-1245

I-1246

I-1247

I-1248

I-1249

I-1250

I-1251

I-1252

I-1253

I-1254

I-1255

I-1256

I-1257

I-1258

I-1259

I-1260

I-1261

I-1262

I-1263

I-1264

I-1265

I-1266

I-1267

I-1268

I-1269

I-1270

I-1271

I-1272

I-1273

I-1274

I-1275

I-1276

I-1277

I-1278

I-1279

I-1280

I-1281

I-1282

I-1284

I-1285

I-1287

I-1288

I-1289

I-1290

I-1291

I-1292

I-1294

I-1295

I-1296

I-1297

I-1298

I-1300

I-1301

I-1302

I-1303

I-1304

I-1305

I-1306

I-1307

I-1308

I-1310

I-1311

I-1313

I-1315

I-1316

I-1317

I-1318

I-1319

I-1320

I-1321

I-1322

I-1324

I-1326

I-1327

I-1329

I-1330

I-1331

I-1332

I-1333

I-1334

I-1335

I-1336

I-1337

I-1338

I-1339

I-1340

I-1341

I-1342

I-1344

I-1345

I-1346

I-1347

I-1348

I-1349

I-1350

I-1351

I-1352

I-1355

I-1356

I-1357

I-1358

I-1359

I-1360

I-1361

I-1363

I-1367

I-1368

I-1369

I-1370

I-1371

I-1372

I-1373

I-1374

I-1375

I-1376

I-1377

I-1379

I-1380

I-1381

I-1382

I-1383

I-1384

I-1385

I-1386

I-1389

I-1390

I-1391

I-1392

I-1393

I-1394

I-1395

I-1396

I-1397

I-1399

I-1400

I-1401

I-1402

I-1403

I-1404

I-1405

I-1406

I-1407

I-1408

I-1409

I-1410

I-1411

I-1412

I-1413

I-1414

I-1415

10. The compound of claim 1 wherein R 5 is

11. The compound of claim 1 wherein R 3 is

12. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

Assignments (10)

Cited By (1)

US 12,221,453