# US 10,370,358 B2 · Compounds for the treatment of HIV

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- Number: US 10,370,358 B2
- Document ID: US10370358B2
- Status: Granted
- Kind: B2
- Application number: 15/902,883
- Filed: 2018-02-22
- Published: 2018-07-12
- Granted: 2019-08-06
- Earliest claimed: 2011-07-06
- Assignees: Gilead Sciences, Inc.
- Applicants: Gilead Sciences, Inc.
- Inventors: Steven S. Bondy; Carina E. Cannizzaro; Chien-Hung Chou; Randall L. Halcomb; Yunfeng Eric Hu; John O. Link; Qi Liu; Scott D. Schroeder; Winston C. Tse; Jennifer R. Zhang
- Web page: https://patentgrep.com/patent/US10370358B2

## CPC

- C07D 401/12: linked by a chain containing hetero atoms as chain links
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A61K 31/4545: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
- A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings
- A61K 31/4985: Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
- A61K 31/50: Pyridazines; Hydrogenated pyridazines
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/14: for RNA viruses
- A61P 31/18: for HIV
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07C 403/14: having side-chains substituted by doubly-bound oxygen atoms
- C07D 213/40: Acylated substituent nitrogen atom
- C07D 401/14: containing three or more hetero rings
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 403/14: containing three or more hetero rings
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 409/14: containing three or more hetero rings
- C07D 413/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07D 471/06: Peri-condensed systems
- C07D 487/04: Ortho-condensed systems
- C07D 491/04: Ortho-condensed systems
- C07D 491/052: the oxygen-containing ring being six-membered
- C07D 495/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

The invention provides compounds of formula (I): or a salt thereof as described herein. The invention also provides 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.

## Claims

### Claim 1

A method for treating an HIV infection in a human, comprising administering a compound of formula I:
or a pharmaceutically acceptable salt thereof, to the human, wherein:
A is pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, wherein any pyridinyl, pyrimidinyl, pyrazinyl, or pyridazinyl of A is substituted with one Z1 group and optionally substituted with 1, 2, or 3 Z2 groups;
B is absent; or B is —O− and the nitrogen to which the —O− group is attached is N+;
W is —CR3aR3b—;
R1 is a bicyclic-heteroaryl, tricyclic-heteroaryl, bicyclic-heterocycle or tricyclic-heterocycle, wherein any bicyclic-heteroaryl, tricyclic-heteroaryl, bicyclic-heterocycle or tricyclic-heterocycle of R1 is optionally substituted with 1, 2, 3, 4, or 5 Z3 groups;
R2 is a 6-membered aryl, 5-membered heteroaryl or 6-membered heteroaryl, wherein any 6-membered aryl, 5-membered heteroaryl or 6-membered heteroaryl of R2 is optionally substituted with 1, 2, or 3 Z4 groups;
each R3a and R3b is independently selected from H, (C1-C6)alkyl, (C1-C3)haloalkyl, (C1-C6)heteroalkyl, heterocyclyl(C1-C6)alkyl-;
each Z1 is independently selected from (C2-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl, heterocycle and —ORn1, wherein any (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl and heterocycle of Z1 is optionally substituted with 1, 2, 3, 4, or 5 Z1a or Z1b groups and wherein any (C2-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Z1 is optionally substituted with 1, 2, 3, 4, or 5 Z1a groups;
each Z1a is independently selected from (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl, heterocycle, halogen, —CN, —ORn2, —OC(O)Rp2, —OC(O)NRq2Rr2, —SRn2, —S(O)Rp2, —S(O)2OH, —S(O)2Rp2, —S(O)2NRq2Rr2, —NRq2Rr2, —NRn2CORp2, —NRn2CO2Rp2, —NRn2CONRq2Rr2, —NRn2S(O)2Rp2, —NRn2S(O)2ORp2, —NRp2 S(O)2NRq2Rr2, NO2, —C(O)Rn2, —C(O)ORn2, —C(O)NRq2Rr2 and —S(O)2NRn2CORp2, wherein any (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl and heterocycle of Z1a is optionally substituted with 1, 2, 3, 4, or 5 Z1c or Z1d groups;
each Z1b is independently selected from (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl, wherein any (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Z1b is optionally substituted with 1, 2, 3, 4, or 5 Z1c groups;
each Z1c is independently selected from (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl, heterocycle,
halogen, —CN, —ORn3, —OC(O)Rp3, C(O)NRq3Rr3, —SRn3, —S(O)Rp3, —S(O)2 OH, —S(O)2Rp3, —S(O)2NRq3Rr3, —NRq3Rr3, —NRn3CORp3, —NRn3 CO2Rp3, —NRn3 ONRq3Rr3, —NRn3 S(O)2Rp3, —NRn3 S(O)2 ORp3, —NRn3S(O2NRq3Rr3, NO2, —C(O)Rn3, —C(O)ORn3, —C(O)NRq3Rr3, (C6-C20)haloaryl, haloheteroaryl, haloheterocycle and (C1-C8)heteroalkyl;
each Z1d is independently selected from (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl and (C1-C8)haloalkyl;
each Rn1 is independently selected from (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl and (C6-C20)aryl, wherein any (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl and heterocycle of Rn1 is optionally substituted with 1, 2, 3, 4, or 5 Z1a or Z1b groups, and wherein any (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Rn1 is optionally substituted with 1, 2, 3, 4, or 5 Z1a groups;
each Rn2 is independently selected from H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl and (C6-C20)aryl, wherein any (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl and heterocycle of Rn2 is optionally substituted with 1, 2, 3, 4, or 5 Z1c or Z1a groups, and wherein any (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Rn2 is optionally substituted with 1, 2, 3, 4, or 5 Z1c groups;
each Rp2 is independently selected from (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl and (C6-C20)aryl, wherein any (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl and heterocycle of Rp2 is optionally substituted with 1, 2, 3, 4, or 5 Z1c or Z1a groups, and wherein any (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Rp2 is optionally substituted with 1, 2, 3, 4, or 5 Z1c groups;
Rq2 and Rr2 are each independently selected from H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl and (C6-C20)aryl, wherein any (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl and heterocycle of Rq2 or Rr2 is optionally substituted with 1, 2, 3, 4, or 5 Z1c or Z1d groups, and wherein any (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Rq2 or Rr2 is optionally substituted with 1, 2, 3, 4, or 5 Z1c groups, or Rq2 and Rr2 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 Z1c or Z1d groups;
each Rn3 is independently selected from H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl, (C6-C20)aryl, (C6-C20)haloaryl, haloheteroaryl, haloheterocycle, (C1-C8)haloalkyl and (C1-C8)heteroalkyl;
each Rp3 is independently selected from (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl, (C6-C20)aryl, (C6-C20)haloaryl, haloheteroaryl, haloheterocycle, (C1-C8)haloalkyl and (C1-C8)heteroalkyl;
Rq3 and Rr3 are each independently selected from H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl, (C6-C20)aryl, haloaryl, haloheteroaryl, haloheterocycle, (C1-C8)haloalkyl and (C1-C8)heteroalkyl, or Rq3 and Rr3 together with the nitrogen to which they are attached form a 5, 6 or 7-membered heterocycle;
each Z2 is independently selected from (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C7)carbocycle, halogen, CN, OH and —O(C1-C6)alkyl;
each Z3 is independently selected from (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, (C6-C20)aryl, halogen, —CN, —ORn4, —S(O)Rp4, —NRn4CO2Rp4, —NRn4S(O)2Rp4, —C(O)Rn4, —C(O)ORn4, —C(O)NRq4Rr4 and —B(ORq4)(ORr4) wherein any (C3-C7)carbocycle and (C6-C20)aryl of Z3 is optionally substituted with 1, 2, 3, 4, or 5 Z3a or Z3b groups, and wherein any (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Z3 is optionally substituted with 1, 2, 3, 4, or 5 Z3a groups;
each Z3a is independently selected from (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl, heterocycle, halogen, —CN, —ORn5, —OC(O)Rp5, —OC(O)NRq5Rr5, —SRn5, —S(O)Rp5, —S(O)2OH, —S(O)2Rp5, —S(O)2NRq5Rr5, —NRq5Rr5, —NRn5CORp5, —NRn5CO2Rp5, —NRn5CONRq5Rr5, —NRn5S(O)2Rp5, —NRn5S(O)2ORp5, —NRn5S(O)2NRq5Rr5, NO2, —C(O)Rn5, —C(O)ORn5, and —C(O)NRq5Rr5, wherein any (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl and heterocycle of Z1a is optionally substituted with 1, 2, 3, 4, or 5 Z3c or Z3d groups;
each Z3b is independently selected from (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl, wherein any (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Z3b is optionally substituted with 1, 2, 3, 4, or 5 Z3c groups;
each Z3c is independently selected from (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl, heterocycle, halogen, —CN, —ORn6, —OC(O)Rp6, —OC(O)NRq6Rr6, —SRn6, —S(O)Rp6, —S(O)2OH, —S(O)2Rp6, —S(O)2NRq6Rn5, —NRq6Rr6, —NRn6CORp6, —NRn6CO2Rp6, —NRn6CONRq6Rr6, —NRn6S(O)2Rp6, —NRn6S(O)2ORp6, —NRn6S(O)2 NRq6Rr6, NO2, —C(O)Rn6, —C(O)ORn6, —C(O)NRq6Rr6, (C6-C20)haloaryl, haloheteroaryl, haloheterocycle and (C1-C8)heteroalkyl;
each Z3d is independently selected from (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, and (C1-C8)haloalkyl;
each Rn4 is independently selected from H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl and (C6-C20)aryl, wherein any (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl and heterocycle of Rn4 is optionally substituted with 1, 2, 3, 4, or 5 Z3a or Z3b groups, and wherein any (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Rn4 is optionally substituted with 1, 2, 3, 4, or 5 Z3a groups;
each Rp4 is independently selected from (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl and (C6-C20)aryl, wherein any (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl, or heterocycle of Rp4 is optionally substituted with 1, 2, 3, 4, or 5 Z3a or Z3b groups, and wherein any (C1-C8)alkyl, (C2-C8)alkenyl or (C2-C8)alkynyl of Rp4 is optionally substituted with 1, 2, 3, 4, or 5 Z3a groups;
Rq4 and Rr4 are each independently selected from H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl and (C6-C20)aryl, wherein any (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl and heterocycle of Rq4 or Rr4 is optionally substituted with one or more Z3a or Z3b groups, and wherein any (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Rq4 or Rr4 is optionally substituted with 1, 2, 3, 4, or 5 Z1a groups, or Rq4 and Rr4 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 Z3a or Z3b groups;
each Rn5 is independently selected from H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl and (C6-C20)aryl, wherein any (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl and heterocycle of Rn5 is optionally substituted with 1, 2, 3, 4, or 5 Z3c or Z3d groups, and wherein any (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Rn5 is optionally substituted with 1, 2, 3, 4, or 5 Z3a groups;
each Rp5 is independently selected from (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl and (C6-C20)aryl, wherein any (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl and heterocycle of Rp5 is optionally substituted with 1, 2, 3, 4, or 5 Z3c or Z3d groups, and wherein any (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Rp5 is optionally substituted with 1, 2, 3, 4, or 5 Z3c groups;
Rq5 and Rr5 are each independently selected from H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl and (C6-C20)aryl, wherein any (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl and heterocycle of Rq5 or Rr5 is optionally substituted with 1, 2, 3, 4, or 5 Z3c or Z3d groups, and wherein any (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Rq5 or Rr5 is optionally substituted with 1, 2, 3, 4, or 5 Z3c groups, or Rq5 and Rr5 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 Z3c or Z3d groups;
each Rn6 is independently selected from H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl, (C6-C20)aryl, (C6-C20)haloaryl, haloheteroaryl, haloheterocycle, (C1-C8)haloalkyl and (C1-C8)heteroalkyl;
each Rp6 is independently selected from (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl, (C6-C20)aryl, (C6-C20)haloaryl, haloheteroaryl, haloheterocycle, (C1-C8)haloalkyl and (C1-C8)heteroalkyl;
Rq6 and Rr6 are each independently selected from H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl, (C6-C20)aryl, (C6-C20)haloaryl, haloheteroaryl, haloheterocycle, (C1-C8)haloalkyl and (C1-C8)heteroalkyl, or Rq6 and Rr6 together with the nitrogen to which they are attached form a 5, 6 or 7-membered heterocycle;
each Z4 is independently selected from (C3-C7)carbocycle, halogen, methyl and —CN;
each Z4c is independently selected from of (C3-C7)carbocycle, (C6-C20)aryl, heteroaryl, heterocycle, halogen, —CN, —ORn9, —OC(O)Rp9, —OC(O)NRq9Rr9, —SRn9, —S(O)Rp9, —S(O)2OH, —S(O)2Rp9, —S(O)2NRq9Rr9, —NRq9Rr9, —NRn9CORp9, —NRn9CO2Rp9, —NRn9CONRq9Rr9, —NRn9S(O)2Rp9, —NRn9S(O)2ORp9, —NRn9S(O)2 NRq9Rr9, NO2, —C(O)Rn9, —C(O)ORn9, —C(O)NRq9Rr9, (C6-C20)haloaryl, haloheteroaryl, haloheterocycle and (C1-C8)heteroalkyl;
each Z4d is independently selected from of (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl and (C1-C8)haloalkyl;
each Rn9 is independently selected from H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl, (C6-C20)aryl, (C6-C20)haloaryl, haloheteroaryl, haloheterocycle, (C1-C8)haloalkyl and (C1-C8)heteroalkyl;
each Rp9 is independently selected from (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl, (C6-C20)aryl, (C6-C20)haloaryl, haloheteroaryl, haloheterocycle, (C1-C8)haloalkyl and (C1-C8)heteroalkyl; and
Rq9 and Rr9 are each independently selected from H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, heterocycle, heteroaryl, (C6-C20)aryl, (C6-C20)haloaryl, haloheteroaryl, haloheterocycle, (C1-C8)haloalkyl and (C1-C8)heteroalkyl; or Rq9 and Rr9 together with the nitrogen to which they are attached form a 5, 6 or 7-membered heterocycle.

### Claim 2 (depends on 1)

The method of claim 1, wherein the compound of formula I is a compound of formula Icc:
or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein each R3a and R3b is H.

### Claim 4 (depends on 1)

The method of claim 1, wherein A is selected from:
wherein each Z2a is independently selected from H and Z2.

### Claim 5 (depends on 1)

The method of claim 1, wherein Z1 is selected from (C6-C20)aryl, heteroaryl and heterocycle, wherein any (C6-C20)aryl, heteroaryl, or heterocycle of Z1 is optionally substituted with 1, 2, 3, 4, or 5 Z1a or Z1b groups.

### Claim 6 (depends on 1)

The method of claim 1, wherein each Z1a is independently selected from (C6-C20)aryl, heteroaryl, heterocycle, (C3-C7)carbocycle, halogen, —CN, —ORn2, —S(O)2Rp2, —S(O)2NRq2Rr2, —NRq2Rr2, —NRn2CORp2, —NRn2CO2Rp2, —NRn2CONRq2Rr2, —NRn2S(O)2Rp2, —C(O)Rn2 and —C(O)NRq2Rr2, wherein any (C6-C20)aryl, heteroaryl, heterocycle and (C3-C7)carbocycle of Z1a is optionally substituted with 1, 2, 3, 4, or 5 Z1c or Z1d groups; and each Z1b is independently selected from (C1-C8)alkyl and (C2-C8)alkynyl, wherein any (C1-C8)alkyl and (C2-C8)alkynyl of Z1b is optionally substituted with 1, 2, 3, 4, or 5 Z1c groups.

### Claim 7 (depends on 1)

The method of claim 1, wherein R2 is a 6-membered aryl wherein the 6-membered aryl is optionally substituted with 1, 2, or 3 Z4 groups.

### Claim 8 (depends on 1)

The method of claim 1, wherein R2 is selected from:

### Claim 9 (depends on 1)

The method of claim 1, wherein R1 is bicyclic-heteroaryl, tricyclic-heteroaryl, bicyclic-heterocycle or tricyclic-heterocycle, wherein any bicyclic-heteroaryl, tricyclic-heteroaryl, bicyclic-heterocycle or tricyclic-heterocycle of R1 contains at least one partially unsaturated ring, and wherein any bicyclic-heteroaryl, tricyclic-heteroaryl, bicyclic-heterocycle or tricyclic-heterocycle of R1 is optionally substituted with 1, 2, 3, 4, or 5 Z3 groups.

### Claim 10 (depends on 1)

The method of claim 1, wherein each Z3 is independently selected from methyl, trifluoromethyl, hydroxy, methoxy, benzyloxy, fluoro, —NHSO2CH3, 2-hydroxyprop-2yl, difluromethyl and amino.

### Claim 11 (depends on 1)

The method of claim 1, wherein the compound of formula I is selected from:
or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 1)

The method of claim 1, comprising administering to the human in need thereof a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof, in combination with a therapeutically effective amount of one or more additional therapeutic agents selected from the group consisting HIV protease inhibiting compounds, HIV non-nucleoside inhibitors of reverse transcriptase, HIV nucleoside inhibitors of reverse transcriptase, HIV nucleotide inhibitors of reverse transcriptase, HIV integrase inhibitors, gp41 inhibitors, CXCR4 inhibitors, gp120 inhibitors, CCR5 inhibitors, capsid polymerization inhibitors, and other drugs for treating HIV, and combinations thereof.