# US 10,307,407 B2 · 9H-pyrimido [4,5-B] indoles as BET bromodomain inhibitors

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- Number: US 10,307,407 B2
- Document ID: US10307407B2
- Status: Granted
- Kind: B2
- Application number: 15/553,593
- Filed: 2016-02-26
- Published: 2018-02-08
- Granted: 2019-06-04
- Earliest claimed: 2015-02-27
- Assignees: The Regents of the University of Michigan
- Applicants: The Regents of the University of Michigan
- Inventors: Shaomeng Wang; Yujun Zhao; Bing Zhou; Angelo Aguilar
- Web page: https://patentgrep.com/patent/US10307407B2

## CPC

- A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61P 35/00: Antineoplastic agents
- C07D 231/38: Nitrogen atoms (nitro radicals C07D231/16)
- C07D 261/06: having two or more double bonds between ring members or between ring members and non-ring members
- C07D 471/04: Ortho-condensed systems
- C07D 487/04: Ortho-condensed systems
- C07D 487/14: Ortho-condensed systems
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present disclosure provides substituted 9H-pyrimido [4,5-b] indoles and 5H-pyrido [4,3-b] indoles and related analogs represented by Formula I and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R1a, W, B1, B2, G, X1, Y1, Y2, and Y3 are as defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a condition or disorder responsive to inhibition of BET bromodomains such as cancer. The present disclosure is also directed to the use of compound of Formula I as synthetic intermediates.

## Claims

### Claim 1

A compound of Formula IV:
or a pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein G is optionally substituted heteroaryl;
Y1 is selected from the group consisting of —C(R2a)═ and —N═;
R1a is selected from the group consisting of hydrogen, hydroxy, alkyl, haloalkyl, alkoxy, alkylthio, amino, and fluoro;
R2b is selected from the group consisting of hydrogen, halo, alkyl and carboxamido;
W is L; and
L is a leaving group.

### Claim 2 (depends on 1)

The compound of claim 1, wherein G is optionally substituted 6-membered heteroaryl, or a pharmaceutically acceptable salt, hydrate, or solvate thereof.

### Claim 3 (depends on 1)

The compound of claim 1, wherein R1a is —OCH3, or a pharmaceutically acceptable salt, hydrate, or solvate thereof.

### Claim 4 (depends on 1)

The compound of claim 1, wherein Y1 is —N═, or a pharmaceutically acceptable salt, hydrate, or solvate thereof.

### Claim 5 (depends on 1)

The compound of claim 1, wherein Y1 is —CH═, or a pharmaceutically acceptable salt, hydrate, or solvate thereof.

### Claim 6 (depends on 1)

The compound of claim 1, wherein L is selected from the group consisting of —Cl, —I, —Br, and —OSO2R6, wherein R6 is selected from the group consisting of alkyl, haloalkyl, and optionally substituted aryl, or a pharmaceutically acceptable salt, hydrate, or solvate thereof.