Substituted macrocyclic indole derivatives

Patent metadata

Field	Value
Publication number	US-11891404-B2
Application number	US-202217940617-A
Country	US
Kind code	B2
Filing date	Sep 8, 2022
Priority date	Nov 17, 2017
Publication date	Feb 6, 2024
Grant date	Feb 6, 2024

Abstract

The present invention relates to substituted macrocyclic indole derivatives of general formula (I):

in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , A and L are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients.

First claim

The invention claimed is:

1. A compound selected from:

and
pharmaceutically acceptable sans hereof.

2. The compound of claim 1 , wherein the compound is selected from

3. The compound of claim 1 , wherein the compound is selected from

4. The compound of claim 1 , wherein the compound is selected from

5. The compound of claim 1 , wherein the compound is selected from

6. A method of inhibiting proliferation of a cell and/or inducing apoptosis in a cell, comprising contacting the cell with a compound according to claim 1 .

7. A method of treating a disease, comprising administering a compound according to claim 1 , wherein the disease is a hyperproliferative disease.

8. The method according to claim 7 , wherein the hyperproliferative disease is cancer.

9. The method according to claim 8 , wherein the cancer is selected from bladder cancer, bone cancer, brain cancer, breast cancer, colon/colorectal cancer, endometrial/uterine cancer, gastric cancer, head and neck cancer, kidney cancer, leukemia, liver cancer, lymphoma, lung cancer, melanoma, myeloma, neuroblastoma, ovarian cancer, pancreatic cancer, prostate cancer, rhabdoid tumor, sarcoma, skin cancer, esophageal cancer, and gallbladder cancer.

10. The method according to claim 8 , wherein the cancer is selected from medulloblastoma, glioma, glioblastoma, ductal breast cancer, colorectal cancer, uterine cancer, stomach cancer, adenocarcinoma, small cell gastric cancer, squamous cell carcinoma, renal medullary carcinoma, acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia, plasma cell leukemia (PCL), hepatocellular carcinoma, non-small cell lung cancer, adenocarcinoma, small cell lung cancer, B-cell lymphoma, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, Hodgkin's lymphoma, B-cell non-Hodgkins lymphoma (NHL), T-cell NHL, cutaneous NHL, mantle cell lymphoma, Sezary syndrome, anaplastic large cell NHL (ALCL), mesothelioma, multiple myeloma, neuroblastoma, ovarian carcinoma, adenocarcinoma high grade serous and serous papillary, serous, cystadenocarcinoma, pancreatic cancer, prostate cancer, rhabdoid tumor, rhabdomyosarcoma, melanoma, mesothelioma, and chronic lymphocytic leukemia (CLL).

Assignees

• Bayer Ag
• Bayer Pharma AG
• Broad Inst Inc

Inventors

• Thede Kai
• Mengel Anne
• Christ Clara
• Kuhnke Joachim
• Johannes Sarah Anna Liesa
• Buchgraber Philipp
• Klar Ulrich
• Rauh Ulrike
• Kaulfuss Stefan
• Fernandez-Montalvan Amaury Ernesto
• Werbeck Nicolas
• Moenning Ursula
• Nowak-Reppel Katrin
• Wittrock Sven
• Mckinney David
• Serrano-Wu Michael H
• Lemke Chris
• Fitzgerald Mark
• Nasveschuk Christopher
• Lazarski Kiel
• Ferrara Steven James
• Furst Laura
• Wei Guo
• Mccarren Patrick Ryan
• Harvey Rebecca Ann

Classifications

• C07D498/14 Primary

  Ortho-condensed systems · CPC title

• A61K31/4162

  condensed with heterocyclic ring systems · CPC title

• A61K31/437

  the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title