Therapeutic compounds

Patent metadata

Field	Value
Publication number	US-9951043-B2
Application number	US-201414771779-A
Country	US
Kind code	B2
Filing date	Feb 28, 2014
Priority date	Mar 1, 2013
Publication date	Apr 24, 2018
Grant date	Apr 24, 2018

Abstract

Compounds of formula (I) or salts thereof are disclosed. Also disclosed are pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods for treating a Retroviridae viral infection including an infection caused by the HIV virus.

First claim

What is claimed is:

1. A compound of formula Hie:

wherein
A 1 is OH, C—Z 3 , or nitrogen;
A 2 is CH or nitrogen;
R 1 is 6-12 membered aryl, 5-12 membered heteroaryl, or 3-12 membered heterocycle, wherein any 6-12 membered aryl, 5-12 membered heteroaryl, or 3-12 membered heterocycle of R 1 is optionally substituted with 1, 2, 3, 4 or 5 Z 4 groups, wherein the Z 4 groups are the same or different;
each R 3a and R 3b is independently H or (C 1 -C 3 )alkyl;
Z 1 is 6-12 membered aryl, 5-14 membered heteroaryl, or 3-14 membered heterocycle, wherein any 6-12 membered aryl, 5-14 membered heteroaryl, or 3-14 membered heterocycle of Z 1 is optionally substituted with 1, 2, 3, 4 or 5 Z 1a or Z 1b , wherein the Z 1a and Z 1b groups are the same or different;
each Z 1a is independently (C 3 -C 7 )carbocycle, 5-12 membered heteroaryl, 3-12 membered heterocycle, halogen, —CN, —OR n1 , —OC(O)R p1 , —OC(O)NR q1 R r1 , —SR n1 , —S(O)R p1 , —S(O) 2 OH, —S(O) 2 R p1 , —S(O) 2 NR q1 R r1 , —NR q1 R r1 , —NR n1 COR p1 , —NR n1 CO 2 R p1 , —NR n1 CONR q1 R r1 , —NR n1 S(O) 2 R p1 , —NR n1 S(O) 2 OR p1 , —NR n1 S(O) 2 NR q1 R r1 , —C(O)R n1 , —C(O)OR n1 , —C(O)Nr q1 R r1 and —S(O) 2 NR n1 COR p1 , wherein any (C 3 -C 7 )carbocycle, 5-12 membered heteroaryl and 3-12 membered heterocycle of Z 1a is optionally substituted with 1, 2, 3, 4 or 5 Z 1c or Z 1d groups, wherein the Z 1c and Z 1d groups are the same or different;
each Z 1b is independently (C 1 -C 8 )alkyl optionally substituted with 1, 2, 3, 4 or 5 halogen, which are the same or different;
each Z 1c is independently halogen, —CN, —OH, —NH 2 , —C(O)N q2 R r2 , or (C 1 -C 8 )heteroalkyl;
each Z 1d is independently (C 1 -C 8 )alkyl or (C 1 -C 8 )haloalkyl;
each R n1 is independently H, (C 1 -C 8 )alkyl, (C 3 -C 7 )carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl, wherein any (C 3 -C 7 )carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl of R n1 is optionally substituted with 1, 2, 3, 4 or 5 Z 1c or Z 1d groups, wherein the Z 1c and Z 1d groups are the same or different, and wherein any (C 1 -C 8 )alkyl of R n1 is optionally substituted with 1, 2, 3, 4 or 5 Z 1c groups, wherein the Z 1c groups are the same or different;
each R p1 is independently (C 1 -C 8 )alkyl, (C 3 -C 7 )carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl, wherein any (C 3 -C 7 )carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl of R p1 is optionally substituted with 1, 2, 3, 4 or 5 Z 1c or Z 1d groups, wherein the Z 1c and Z 1d groups are the same or different, and wherein any (C 1 -C 8 )alkyl of R p1 is optionally substituted with 1, 2, 3, 4 or 5 Z 1c groups, wherein the Z 1c groups are the same or different;
each R q1 and R r1 is independently H, (C 1 -C 8 )alkyl, (C 3 -C 7 )carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl, wherein any (C 3 -C 7 )carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl of R q1 or R r1 is optionally substituted with 1, 2, 3, 4 or 5 Z 1c or Z 1d groups, wherein the Z 1c and Z 1d groups are the same or different, and wherein any (C 1 -C 8 )alkyl of R q1 or R r1 is optionally substituted with 1, 2, 3, 4 or 5 Z 1c groups, wherein the Z 1c groups are the same or different, or R q1 and R r1 together with the nitrogen to which they are attached form a 5, 6 or 7-membered heterocycle, wherein the 5, 6 or 7-membered heterocycle is optionally substituted with 1, 2, 3, 4 or 5 Z 1c or Z 1d groups, wherein the Z 1c and Z 1d groups are the same or different;
each R q2 and R r2 is independently H, (C 1 -C 8 )alkyl, (C 3 -C 7 )carbocycle, or R q2 and R r2 together with the nitrogen to which they are attached form a 5, 6, or 7-membered heterocycle;
Z 2 is (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, 6-12 membered aryl, 5-12 membered C-linked-heteroaryl, 3-12 membered C-linked-heterocycle, —C(O)R n3 , or —C(O)NR q3 R r3 , wherein any 6-12 membered aryl, 5-12 membered C-linked-heteroaryl, or 3-12 membered C-linked-heterocycle of Z 2 is optionally substituted with 1, 2, 3, 4 or 5 Z 2b or Z 2c groups, wherein the Z 2b and Z 2c groups are the same or different, and wherein any (C 2 -C 8 )alkenyl or (C 2 -C 8 )alkynyl of Z 2 is optionally substituted with 1, 2, 3, 4, or 5 Z 2c groups, wherein the Z 2c groups are the same or different;
each R n3 is independently H or (C 1 -C 4 )alkyl;
each R q3 and R r3 is independently H or (C 1 -C 4 )alkyl;
each Z 2b is independently oxo, (C 1 -C 4 )alkyl, (C 1 -C 4 )heteroalkyl or (C 1 -C 4 )haloalkyl;
each Z 2c is independently oxo, halogen, —CN, —OR n4 , —OC(O)R p4 , —OC(O)NR q4 R r4 , —SR n4 , —S(O)R p4 , —S(O) 2 OH, —S(O) 2 R p4 , —S(O) 2 NR q4 R r4 , —NR q4 R r4 , —NR n4 COR p4 , —NR n4 CO 2 R p4 , —NR n4 CONR q4 R n4 , —NR n4 S(O) 2 R p4 , —NR n4 S(O) 2 OR p4 , —NR n4 S(O) 2 NR q4 R r4 , —NO 2 , —C(O)R n4 , —C(O)OR n4 , or —C(O)NR q4 R r4 ;
each R n4 is independently H, (C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, or (C 1 -C 4 )heteroalkyl,
each R p4 is independently (C 1 -C 8 )alkyl, (C 1 -C 4 )haloalkyl, or (C 1 -C 4 )heteroalkyl;
each R q4 and R r4 is independently H, (C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, or (C 1 -C 4 )heteroalkyl;
each Z 3 is independently a (C 1 -C 4 )heteroalkyl,
each Z 4 is independently oxo, (C 1 -C 8 )alkyl, (C 3 -C 7 )carbocycle, halogen, —CN, —OR n5 , —NR q5 R r5 , —NR n5 COR p5 , —NR n5 CO 2 R p5 , —C(O)R n5 , —C(O)OR n5 , or —C(O)NR q5 R r5 , wherein any (C 3 -C 7 )carbocycle or (C 1 -C 8 )alkyl of Z 4 is optionally substituted with 1, 2, 3, 4 or 5 Z 4a groups, wherein the Z 4a groups are the same or different;
each Z 4a is independently halogen, —CN, or —OR n6 ;
each R n5 , R p5 , R q5 , R r5 , and R n6 is independently H or (C 1 -C 4 )alkyl;
each Z 5 is independently halogen, which may be same or different; and
n 0, 1, 2, or 3;
or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is

wherein
C together with the two carbon atoms to which it is attached forms a 3-7 membered monocyclic-carbocycle or 5-9 membered bicyclic-carbocycle, wherein any 3-7 membered monocyclic-carbocycle or 5-9 membered bicyclic-carbocycle of C is optionally substituted with 1, 2, 3, or 4 Z 4 groups, wherein the Z 4 groups are the same or different.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z 1 is

wherein each Z 1w is independently Z 1a , Z 1b , or H.

5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof,
wherein:
each Z 1a is independently halogen, —CN, —OR n1 , —NR n1 S(O) 2 R p1 , —NR n1 S(O) 2 NR q1 R r1 , —NR q1 R r1 , —NR n1 COR p1 , —NR n1 CONR q1 R r1 , or —NR n1 CO 2 R p1 ;
each Z 1b is independently (C 1 -C 8 alkyl), wherein the (C 1 -C 8 alkyl) is optionally substituted with 1, 2, or 3 halogen, which are the same or different; and
at least one of Z 1w is Z 1a or Z 1b .

6. The co

Assignees

• Gilead Sciences Inc

Inventors

• Brizgys Gediminas
• Canales Eda
• Chou Chien-Hung
• Graupe Michael
• Halcomb Randall L
• Hu Yunfeng Eric
• Lazerwith Scott E
• Link John O
• Liu Qi
• Lu Yafan
• Saito Roland D
• Schroeder Scott D
• Somoza John R
• Tse Winston C
• Zhang Jennifer R

Classifications

• C07D491/052

  the oxygen-containing ring being six-membered · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D417/14

  containing three or more hetero rings · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title