Substituted pyrrolo[2,3-d]pyrimidine as a protein kinase B inhibitor

• US 8,101,623 B2
• Filed: 10/10/2008
• Issued: 01/24/2012
• Est. Priority Date: 10/11/2007
• Status: Active Grant

• Current Assignee: Astrazeneca AB (Astrazeneca PLC)
• Original Assignee: Astrazeneca AB (Astrazeneca PLC)
• Inventors: Luke, Richard William Arthur, Matusiak, Zbigniew Stanley
• Primary Examiner(s): Moore, Susanna
• Application Number:
  US12/249,477
• Publication Number:
  US 20090163524A1
• Time in Patent Office: 1,201 Days
• Field of Search: 544/280, 514/265.1
• US Class Current: 514/265.1
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 473/34 attached in position 6, e.g. adenine
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

The invention relates to a novel group of compounds of Formula (I) or salts thereof:

wherein Y, Z¹, Z², R¹, R⁴, R⁵ and n are as described in the specification, which may be useful in the treatment or prevention of a disease or medical condition mediated through protein kinase B (PKB) such as cancer. The invention also relates to pharmaceutical compositions comprising compounds of Formula (I), methods of treatment of diseases mediated by PKB using said compounds and methods for preparing compounds of Formula (I).

Claims

1. The compound (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide:

2. A pharmaceutical composition comprising the compound according to claim 1, or a pharmaceutically-acceptable salt thereof, together with a pharmaceutically acceptable diluent or carrier.

3. A method of treating breast cancer in a mammal comprising administering an effective amount the compound of claim 1, or a pharmaceutically acceptable salt thereof, to the mammal.

7. A process for the preparation of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, which comprises

reaction of an acid of Formula (II) with (S)-3-amino-3-(4-chlorophenyl)propan-1-ol:

8. The process as claimed in claim 7, wherein P¹ represents a tert-butoxycarbonyl protecting group.

9. A process for the preparation of the compound claimed in claim 1, or a pharmaceutically acceptable salt thereof, which process comprises the reaction of (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)piperidine-4-carboxamide with a bicyclic heterocycle of Formula (V):

10. The process as claimed in claim 9, wherein L₁ is chlorine.

4. The compound (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7H-pyrrolo-[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide.

5. A pharmaceutical composition comprising the compound according to claim 4 together with a pharmaceutically acceptable diluent or carrier.

6. A method of treating breast cancer in a mammal comprising administering an effective amount of the compound of claim 4 to the mammal.