HIV protease inhibitors

Patent metadata

Field	Value
Publication number	US-10774053-B2
Application number	US-201816158446-A
Country	US
Kind code	B2
Filing date	Oct 12, 2018
Priority date	Oct 13, 2017
Publication date	Sep 15, 2020
Grant date	Sep 15, 2020

Abstract

The invention provides a compound of Formula I:

or a pharmaceutically acceptable salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of Formula I, processes for preparing compounds of Formula I, therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS symptoms in a mammal using compounds of Formula I.

First claim

What is claimed is:

1. A compound of Formula (I b ):

wherein,
n is 0-2;
m is 0-1;
R 1 is selected from the group consisting of hydrogen, halogen, cyano, C 2-6 alkynyl, —OR a , 5-10 membered heteroaryl, 3-12 membered heterocyclyl, 5-10 membered aryl and 3-10 membered cycloalkyl, wherein each 5-10 membered heteroaryl, 3-12 membered heterocyclyl, 5-10 membered aryl and 3-10 membered cycloalkyl is optionally substituted with 1-5 R 20 groups;
each R 2 is independently selected from the group consisting of hydrogen, cyano, C 1-6 alkyl, —NR a R b , halogen or —OR a , wherein the C 1-6 alkyl, is optionally substituted with 1-5 R 20 groups; or wherein R 1 and R 2 together with the atoms to which they are attached form a heteroaryl optionally substituted with 1-5 R 20 groups;
R 3 is C 1-6 alkyl, C 1-6 alkynyl, or 3-10 membered cycloalkyl, each optionally substituted with 1-5 R 20 groups;
R 5 is selected from the group consisting of cyano, halo, and 5-10 membered heteroaryl, where the 5-10 membered heteroaryl is optionally substituted with 1-5 R 20 groups;
R 6 is hydrogen, halogen, —CN, C 1-3 haloalkoxy, —C(O)NR a R b , or 5-10 membered heteroaryl optionally substituted with 1-5 R 20 groups;
each R 7 is independently selected from the group consisting of cyano, C 1-6 alkyl, C 1-6 alkoxy, —NR a R b , halogen, 5-10 membered aryl, 3-6 membered cycloalkyl, 5-10 membered heteroaryl and 3-12 membered heterocyclyl, wherein each C 1-6 alkyl, C 1-6 alkoxy, 5-10 membered aryl, 3-6 membered cycloalkyl, 5-10 membered heteroaryl and 3-12 membered heterocyclyl is optionally substituted with 1-5 R 20 groups;
each R a and R b is independently selected from the group consisting hydrogen, C 1-6 alkyl, 3-10 membered cycloalkyl, 3-12 membered heterocyclyl, 5-10 membered aryl, 5-10 membered heteroaryl, each of which is optionally substituted with from one to five R 21 groups; or R a and R b together with the atoms to which they are attached form a 3-12 membered heterocyclyl optionally substituted with one to five R 21 groups;
each R 20 is independently selected from the group consisting C 1-6 alkyl, 3-10 membered cycloalkyl, C 1-6 alkoxy, 3-12 membered heterocyclyl, 5-10 membered aryl, 5-10 membered heteroaryl, halogen, oxo, —OR a , —C(O)R a , —C(O)OR a , —C(O)NR a R b , —OC(O)NR a R b , —NR a R b , —NR a C(O)R b , —NR a C(O)OR b , —S(O) 0-2 R a , —S(O) 2 NR a R b , —NR a S(O) 2 R b , —N 3 , —CN, or —NO 2 , or two R 20 groups appended to the same group can join together to form a fused, spiro or bridged C 3-10 cylcloalkyl or 3-12 membered heterocyclyl ring, wherein each C 1-6 alkyl, 3-10 membered cycloalkyl, C 1-6 alkoxy, 3-12 membered heterocyclyl, 5-10 membered aryl, 5-10 membered heteroaryl is optionally substituted with from one to five halogen, oxo, —OR a , —C(O)R a , —C(O)OR a , —C(O)NR a R b , —OC(O)NR a R b , —NR a R b , —NR a C(O)R b , —NR a C(O)OR b , —S(O) 0-2 R a , —S(O) 2 NR a R b , —NR a S(O) 2 R b , —N3, —CN, 3-12 membered heterocyclyl, or —NO 2 ;
R a1 and R b1 each independently selected from the group consisting of hydrogen, C 1-6 alkyl, 3-10 membered cycloalkyl, —S(O) 2 R 21 each of which is optionally substituted with one to five R 21 groups; or wherein
R a1 and R b1 are appended to the same group to form a 3-12 membered heterocyclyl optionally substituted with from one to five R 21 groups; and
each R 21 is independently selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, 3-10 membered cycloalkyl, C 1-6 alkoxy, 3-12 membered heterocyclyl, 5-10 membered aryl, 5-10 membered heteroaryl, hydroxyl, amino, —S(O) 2 —CH 3 , C 1-6 alkylamino, —CN or halogen;
or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein R a1 and R b1 are each independently selected from hydrogen or cyclopropyl, wherein the cyclopropyl is optionally substituted with C 1-6 haloalkyl.

3. The compound of claim 2 , wherein the C 1-6 haloalkyl is CF 3 or CHF 2 .

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from the group consisting of:

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 taken together with the carbons and/or heteroatom to which they are attached, form groups consisting of:

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is selected from the group consisting of:

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is selected from the group consisting of:

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is selected from the group consisting of:

9. A compound selected from a group consisting of:

Assignees

• Gilead Sciences Inc

Inventors

• Cai Zhenhong R
• Cho Aesop
• Gonzalez Buenrostro Ana Zurisadai
• Han Xiaochun
• Jabri Salman Y
• Mcfadden Ryan
• Qi Yingmei
• Voigt Johannes
• Yang Hong
• Xu Jie
• Xu Lianhong

Classifications

• A61P31/18 Primary

  for HIV · CPC title

• C07D233/88

  Nitrogen atoms, e.g. allantoin · CPC title

• C07D401/10 Primary

  linked by a carbon chain containing aromatic rings · CPC title

• C07D417/10

  linked by a carbon chain containing aromatic rings · CPC title

• C07D491/107

  with only one oxygen atom as ring hetero atom in the oxygen-containing ring · CPC title