# US 7,745,459 B2 · Quinolizinone compound and use thereof as HIV integrase inhibitor

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- Number: US 7,745,459 B2
- Document ID: US7745459B2
- Status: Granted
- Kind: B2
- Application number: 11/230,330
- Filed: 2005-09-20
- Published: 2006-04-20
- Granted: 2010-06-29
- Earliest claimed: 2004-09-21
- Assignees: Japan Tobacco Inc.
- Inventors: Motohide Satoh; Hisateru Aramaki; Hiroshi Nakamura; Masafumi Inoue; Hiroshi Kawakami; Hisashi Shinkai; Yuji Matsuzaki; Kazunobu Yamataka
- Web page: https://patentgrep.com/patent/US7745459B2

## CPC

- C07D 471/04: Ortho-condensed systems
- A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48)
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- C07D 455/02: containing not further condensed quinolizine ring 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)

## Abstract

A pharmaceutical agent having an anti-HIV action, particularly, a pharmaceutical agent having an integrase inhibitory action, is provided. The present invention relates to a quinolizinone compound represented by the following formula [I] wherein each symbol is as defined in the specification, a pharmaceutically acceptable salt thereof, and an anti-HIV agent containing same as an active ingredient. The compound of the present invention has an HIV integrase inhibitory action and is useful as an anti-HIV agent for the prophylaxis or therapy of AIDS. Moreover, by a combined use with other anti-HIV agents such as protease inhibitors, reverse transcriptase inhibitors and the like, the compounds can become a more effective anti-HIV agent. Since the compound has a high inhibitory activity specific for integrases, the compound can provide a safe pharmaceutical agent for human with a fewer side effects.

## Claims

### Claim 1

A pharmaceutical composition comprising a quinolizinone compound represented by the following formula [I], or a pharmaceutically acceptable salt thereof, as an active ingredient:
wherein
ring Cy is a phenyl or naphthyl group optionally substituted by 1 to 5 substituents selected from group A below,
wherein the group A is a group consisting of a cyano group, a nitro group, a halogen atom, a C1-4 alkyl group, a halo C1-4 alkyl group, a halo C1-4 alkyloxy group,
—ORa1, —SRa1, NRa1Ra2, —CONRa1Ra2, —SO2NRa1Ra2, —CORa3, —NRa1CORa3, SO2Ra3, —NRa1SO2Ra3, —COORa1, and —NRa2COORa3,
wherein Ra1 and Ra2 are the same or different and each is a hydrogen atom, or a C1-4 alkyl group, and Ra3 is a C1-4 alkyl group;
R1 is a hydrogen atom, a group selected from group B below, or a C1-10 alkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and group B below,
wherein the group B is a group consisting of a C3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from group A above,
a heterocyclic group (the heterocyclic group is as defined above) optionally substituted by 1 to 5 substituents selected from group A above, a cyano group, —ORa4, —SRa4, —NRa4Ra5, —CONRa4Ra5, —SO2NRa4Ra5, —CORa6, —NRa4CORa6, —SO2Ra6, —NRa4SO2Ra6, —COORa4, —NRa5COORa6, —NRa4CO—NRa5Ra12, —NRa4CO—COORa5, —O—W—ORa5, —NRa4—W—ORa5, —NRa4—W—SO2NRa5Ra12, —NRa4CO—W—Ra5, —NRa4CO—W—ORa5, —NRa4CO—W—COORa5, and —NRa4CO—W—NRa5CORa6,
wherein Ra4, Ra5 and Ra12 are the same or different and each is a hydrogen atom, a C1-4 alkyl group, a C3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from group A above, or a heterocyclic group (the heterocyclic group is as defined above) optionally substituted by 1 to 5 substituents selected from group A above, Ra6 is a C1-4 alkyl group, a C3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from group A above, or a heterocyclic group (the heterocyclic group is as defined above) optionally substituted by 1 to 5 substituents selected from group A above, and W is a C1-10 alkylene group;
R2 is a hydrogen atom or a C1-4 alkyl group;
Z is C—R31 or a nitrogen atom,
wherein R31 is a hydrogen atom, a cyano group, a hydroxy group, an amino group, a nitro group, a halogen atom, a C1-4 alkyl group, a C1-4 alkoxy group, a C1-4 alkylsulfanyl group, a halo C1-4 alkyl group, or a halo C1-4 alkyloxy group;
X is C—R32 or a nitrogen atom; and
Y is C—R33 or a nitrogen atom,
wherein R32 and R33 are the same or different and each is a hydrogen atom, a cyano group, a nitro group, a halogen atom,
a C3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from group A above,
a heterocyclic group (the heterocyclic group is as defined above) optionally substituted by 1 to 5 substituents selected from group A above, a C1-10 alkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and group B above, —ORa7, —SRa7, —NRa7Ra8, —NRa7CORa9, —COORa10, or —N═CH—NRa10Ra11,
wherein Ra7 and Ra8 are the same or different and each is a hydrogen atom, a group selected from group B above, or a C1-10 alkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and group B above, Ra9 is a C1-4 alkyl group, and Ra10 and Ra11 are the same or different and each is a hydrogen atom or a C1-4 alkyl group and a pharmaceutically acceptable carrier.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein X is C—R32 and Z is C—R31.

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, wherein ring Cy is a group represented by the formula:
wherein
R6 is a group selected from the group A (the group A is as defined in claim 1);
R4 and R5 are the same or different and each is a group selected from a hydrogen atom and the group A (the group A is as defined in claim 1), or
R4 and R5 may form a fused ring together with a benzene ring they substitute; and
m is 0 or an integer of 1 to 3, and when m is 2 or 3, then R6 of each may be the same or different.

### Claim 4

A quinolizinone compound represented by the following formula [II] or a pharmaceutically acceptable salt thereof:
wherein
R6 is a group selected from group A below,
wherein the group A is a group consisting of a cyano group, a nitro group, a halogen atom, a C1-4 alkyl group, a halo C1-4 alkyl group, a halo C1-4 alkyloxy group, —ORa1, —SRa1, —NRa1Ra2, —CONRa1Ra2, —SO2NRa1Ra2, —CORa3, —NRa2CORa3, —SO2Ra3, —NRa1SO2Ra3, —COORa1, and —NRa2COORa3,
wherein Ra1 and Ra2 are the same or different and each is a hydrogen atom, or a C1-4 alkyl group, and Ra3 is a C1-4 alkyl group;
R4 and R5 are the same or different and each is a group selected from a hydrogen atom and group A above, or
R4 and R5 may form a fused ring together with a benzene ring they substitute;
m is 0 or an integer of 1 to 3, and when m is 2 or 3, then R6 of each may be the same or different;
R1 is a hydrogen atom, a group selected from group B below or a C1-10 alkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and group B below,
wherein the group B is a group consisting of a C3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from group A above,
a heterocyclic group optionally substituted by 1 to 5 substituents selected from group A above,
wherein the heterocyclic group is a saturated or unsaturated ring group containing, besides carbon atom(s), at least one hetero atom selected from a nitrogen atom, an oxygen atom, and a sulfur atom,
a cyano group, —ORa4, —SRa4, —NRa4Ra5, —CONRa4Ra5, —SO2NRa4Ra5, —CORa6, —NRa4CORa6, —SO2Ra6, —NRa4SO2Ra6, —COORa4, —NRa5COORa6, —NRa4CO—NRa5Ra12, —NRa4CO—COORa5, —O_W—ORa5, —NRa4—W—ORa5, —NRa4—W—SO2NRa5Ra12, —NRa4CO—W—Ra5, —NRa4CO—W—NRa5, —NRa4CO—W—COORa5, and —NRa4CO—W—NRa5CORa6,
wherein Ra4, Ra5 and Ra12 are the same or different and each is a hydrogen atom, a C1-4 alkyl group, a C3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from group A above, or a heterocyclic group (the heterocyclic group is as defined above) optionally substituted by 1 to 5 substituents selected from group A above, Ra6 is a C1-4 alkyl group, a C3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from group A above or a heterocyclic group (the heterocyclic group is as defined above) optionally substituted by 1 to 5 substituents selected from group A above, and W is a C1-10 alkylene group;
R2 is a hydrogen atom or a C1-4 alkyl group;
Z is C—R31 or a nitrogen atom,
wherein R31 is a hydrogen atom, a cyano group, a hydroxy group, an amino group, a nitro group, a halogen atom, a C1-4 alkyl group, a C1-4 alkoxy group, a C1-4 alkylsulfanyl group, a halo C1-4 alkyl group, or a halo C1-4 alkyloxy group;
X is C—R32 or a nitrogen atom; and
Y is C—R33 or a nitrogen atom,
wherein R32 and R33 are the same or different and each is a hydrogen atom, a cyano group, a nitro group, a halogen atom,
a C3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from group A above,
a heterocyclic group (the heterocyclic group is as defined above) optionally substituted by 1 to 5 substituents selected from group A above,
a C1-10 alkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and group B above,
—ORa7, —SRa7, —NRa7Ra8, —NRa7CORa9, —COORa10 or —N═CH—NRa10Ra11,
wherein Ra7 and Ra8 are the same or different and each is a hydrogen atom, a group selected from group B above, or a C1-10 alkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and group B above, Ra9 is a C1-4 alkyl group, and Ra10 and Ra11 are the same or different and each is a hydrogen atom or a C1-4 alkyl group.

### Claim 5 (depends on 4)

The quinolizinone compound of claim 4, wherein X is C—R32 and Z is C—R31, or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 4)

The quinolizinone compound of claim 4, wherein R31 is a hydrogen atom, a cyano group, a hydroxy group or a C1-4 alkoxy group, or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 4)

The quinolizinone compound of claim 4, wherein R31 is a hydrogen atom, or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 4)

The quinolizinone compound of claim 4, wherein
R32 is a hydrogen atom, a cyano group, a halogen atom, a heterocyclic group (the heterocyclic group is as defined in claim 4) optionally substituted by 1 to 5 substituents selected from the group A (the group A is as defined in claim 4),
a C1-10 alkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and the group B (the group B is as defined in claim 4), —ORa7, —SRa7, —NRa7Ra5, —NRa7CORa9, —COORa10, or —N═CH—NRa10Ra11
wherein Ra7, Ra8, Ra9, Ra10 and Ra11 are as defined in claim 4,
or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 4)

The quinolizinone compound of claim 4, wherein
R32 is a hydrogen atom, a cyano group, a halogen atom, a C1-10 alkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and the group B (the group B is as defined in claim 4),
—ORa7, —SRa7, —NRa7Ra8, —NRa7CORa9 or —COOa10,
wherein Ra7, Ra8, Ra9 and Ra10 are as defined in claim 4,
or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 4)

The quinolizinone compound of claim 4, wherein
R32 is a hydrogen atom, —ORa7, —SRa7 or —NRa7Ra8,
wherein Ra7 and Ra8 are as defined in claim 4,
or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 4)

The quinolizinone compound of claim 4, wherein Y is C—R33,
or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 4)

The quinolizinone compound of claim 4, wherein
R33 is a hydrogen atom, a cyano group, a halogen atom, a heterocyclic group (the heterocyclic group is as defined in claim 4) optionally substituted by 1 to 5 substituents selected from the group A (the group A is as defined in claim 4),
a C1-10 alkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and the group B (the group B is as defined in claim 4), —ORa7, —SRa7, —NRa7Ra8, —NRa7CORa9, —COORa10, or —N═CH—NRa10Ra11,
wherein Ra7, Ra8, Ra9, Ra10 and Ra11 are as defined in claim 4,
or a pharmaceutically acceptable salt thereof.

### Claim 13 (depends on 4)

The quinolizinone compound of claim 4, wherein
R33 is a hydrogen atom, a C1-10 alkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and the group B (the group B is as defined in claim 4), —ORa7 or —NRa7Ra8,
wherein Ra7 and Ra8 are as defined in claim 4,
or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 4)

The quinolizinone compound of claim 4, wherein R33 is a hydrogen atom, —ORa7 or —NRa7Ra8,
wherein Ra7 and Ra8 are as defined in claim 4,
or a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 4, 8)

The quinolizinone compound of claim 8, wherein Ra7 and Ra8 are the same or different and each is a C1-10 alkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and the group B (the group B is as defined in claim 4), or a pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 4)

The quinolizinone compound of claim 4, wherein
R4 and R5 are the same or different and each is a hydrogen atom, a cyano group, a nitro group, a halogen atom, a C1-4 alkyl group, a halo C1-4 alkyl group, a halo C1-4 alkyloxy group, —ORa1, —SRa1, —NRa1Ra2, —CONRa1Ra2, —SO2NRa1Ra2, —NRa1CORa3, —SO2Ra3, —NRa1SO2Ra3, —COORa1 or —NRa2COORa3,
wherein Ra1, Ra2 and Ra3 are as defined in claim 4,
or a pharmaceutically acceptable salt thereof.

### Claim 17 (depends on 4)

The quinolizinone compound of claim 4, wherein
R4 is a hydrogen atom, a halogen atom, a C1-4 alkyl group, a halo C1-4 alkyloxy group, —ORa1, —NRa1Ra2, —CONRa1Ra2, —SO2NRa1Ra2, —NRa1CORa3, —SO2Ra3, —NRa1SO2Ra3 or —COORa1,
wherein Ra1, Ra2 and Ra3 are as defined in claim 4,
or a pharmaceutically acceptable salt thereof.

### Claim 18 (depends on 4)

The quinolizinone compound of claim 4, wherein R4 is a hydrogen atom or a halogen atom, or a pharmaceutically acceptable salt thereof.

### Claim 19 (depends on 4)

The quinolizinone compound of claim 4, wherein
R5 is a hydrogen atom, a cyano group, a nitro group, a halogen atom, a C1-4 alkyl group, a halo C1-4 alkyl, —ORa1, —SRa1, —NRa1Ra2, —CONRa1Ra2, —SO2NRa1Ra2 or —NRa1CORa3,
wherein Ra1, Ra2 and Ra3 are as defined in claim 4,
or a pharmaceutically acceptable salt thereof.

### Claim 20 (depends on 4)

The quinolizinone compound of claim 4, wherein R6 is a halogen atom, or a pharmaceutically acceptable salt thereof.

### Claim 21 (depends on 4)

The quinolizinone compound of claim 4, wherein m is 0 or 1, or a pharmaceutically acceptable salt thereof.

### Claim 22 (depends on 4)

The quinolizinone compound of claim 4, wherein
R1 is a hydrogen atom, a C3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the group A (the group A is as defined in claim 4), a cyano group, —NRa4Ra5, —NRa4CORa6, —NRa4SO2Ra6, —COORa4, —NRa5COO Ra6, —O—W—ORa5, —NRa4—W—ORa5, —NRa4—W—SO2NRa5Ra12,
wherein Ra4, Ra5, Ra6 and Ra12 are as defined in claim 4, or
a C1-10 alkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and the group B (the group B is as defined in claim 4),
or a pharmaceutically acceptable salt thereof.

### Claim 23 (depends on 4)

The quinolizinone compound of claim 4, wherein
R1 is a hydrogen atom, a cyano group, —NRa4CORa6, —NRa4SO2Ra6, —COORa4, —NRa5COORa6, —O—W—ORa5, —NRa4—W—ORa5, —NRa4—W—SO2NRa5Ra12,
wherein Ra4, Ra5, Ra6 and Ra12 are as defined in claim 4, or a C1-10 alkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and the group B (the group B is as defined in claim 4),
or a pharmaceutically acceptable salt thereof.

### Claim 24 (depends on 4)

The quinolizinone compound of claim 4, wherein R2 is a hydrogen atom, or a pharmaceutically acceptable salt thereof.

### Claim 25 (depends on 4)

The quinolizinone compound of claim 4, which is represented by the following formula [II-1] or [II-2],
wherein R32 and R33 are the same or different and each is a hydrogen atom or —ORa7 (Ra7 is as defined in claim 4), and the other symbols are as defined in claim 4, or a pharmaceutically acceptable salt thereof.

### Claim 26 (depends on 4)

The quinolizinone compound of claim 4, which is selected from the group consisting of
7-(3-chloro-2-fluorobenzyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-ethyl-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-(2-hydroxyethyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-((R)-1-hydroxymethyl-2-methylpropyl)-8-methoxy-4-oxo-4H-quinolizine-3-carboxylic acid,
7-benzyl-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-4-oxo-1-propyl-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-l-isopropyl-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-((R)-2-hydroxy-1-methylethyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-(1-hydroxymethyl-2-methylpropyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-((R)-1-hydroxymethyl-2,2-dimethylpropyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-((R)-1-hydroxymethyl-2,2-dimethylpropyl)-8-methoxy-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-hydroxymethyl-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-methoxymethyl-4-oxo-4H-quinolizine-3-carboxylic acid,
1-aminomethyl-7-(3-chloro-2-fluorobenzyl)-4-oxo-4H-quinolizine-3-carboxylic acid hydrochloric acid,
7-(3-chloro-2-fluorobenzyl)-l-methylaminomethyl-4-oxo-4}4H-quinolizine-3-carboxylic acid,
1-(acetylaminomethyl)-7-(3-chloro-2-fluorobenzyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-(methylsulfonylaminomethyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-(methoxycarbonylaminomethyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
1-(aminocarbonyl)methyl-7-(3-chloro-2-fluorobenzyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-(2-hydroxyethylamino)-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-methylsulfonylamino-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-cyano-4-oxo-4H-quinolizine-3-carboxylic acid,
3-(3-chloro-2-fluorobenzyl)-9-(2-hydroxyethyl)-6-oxo-6H-pyrido[1,2-a]pyrimidine-7-carboxylic acid,
1-(tert-butoxycarbonylaminomethyl)-7-(3-chloro-2-fluorobenzyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
l-carboxymethyl-7-(3-chloro-2-fluorobenzyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-[(2,2-dimethylpropionylamino)methyl]-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-dimethylaminomethyl-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-[(2-hydroxyacetylamino)methyl]-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-[(2-methoxyacetylamino)methyl]-4-oxo-4H-quinolizine-3-carboxylic acid,
1-1(N-(tert-butoxycarbonyl)-N-methylamino)methyl]-7-(3-chloro-2-fluorobenzyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-4-oxo-1-(propionylaminomethyl)-4H-quinolizine-3-carboxylic acid,
1-(butyrylaminomethyl)-7-(3-chloro-2-fluorobenzyl)-4-oxo-4H quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-(isobutyrylaminomethyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
1-(benzoylaminomethyl)-7-(3-chloro-2-fluorobenzyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-(ethoxycarbonylaminomethyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-[(morpholinocarbonyl)amino]methyl}-4H-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-[(3-ethylureido)methyl]-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-4-oxo-1-(phenylacetylaminomethyl)-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-[(oxalylamino)methyl]-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-4-oxo-1-[(2-phenoxyacetylamino)methyl]-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-[((S)-2-methoxypropionylamino)methyl]-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-[C(R)-2-methoxypropionylainino)methyl]-4-oxo-4H-quinolizine-3-carboxylic acid,
1-[(3-carboxyproplonylamino)methyl]7-(3-chloro-2-fluorobenzyl)-4-oxo-4H quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-[(2-ethoxyacetylamino)methyl]-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-[(2-methoxy-2-methylpropionylamino)methyl]-4-oxo-4H-quinolizine-3-carboxylic acid,
1-1(2-acetylaminoacetylamino)methyl]-7-(3-chloro-2 fluorobenzyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-chloro-2-fluorobenzyl)-1-methoxymethoxy-4-oxo-4H-quinolizine-3-carboxylic acid,
1-(tert-butozycarbonylamino)-7-(3-chloro-2-fluorobenzyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
1-acetylamino-7-(3-chloro-2-fluorobenzyl)-4-oxo-4H-quinolizine-3-carboxylic acid,
7-(3-fluorobenzyl)-4-oxo-4H-quinolizine-1,3-dicarboxylic acid 1-tert-butylester,
7-(2,3-dichlorobenzyl)-1-((R)-1-hydroxymethyl-2-methylpropyl)-4H-oxo-4H-quinolizine-3-carboxylic acid,
7-(2,3-dichlorobenzyl)-1-((R)-1-hydroxymethyl-2,2-dimethylpropyl)-4-oxo-4H-quinolizine-3-carboxylic acid, and
7-(3-chloro-2-fluorobenzyl)-1-((R)-1-hydroxymethyl-2,2-dimethylpropyl)-9-methoxy-4-oxo-4H-quinolizine-3-carboxylic acid,
or a pharmaceutically acceptable salt thereof.

### Claim 27 (depends on 4)

A pharmaceutical composition comprising a quinolizinone compound of claim 4, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

### Claim 28 (depends on 4)

A method for the treatment of an HIV infectious disease in a mammal, which comprises administering an effective amount of a quinolizinone compound of claim 4, or a pharmaceutically acceptable salt thereof to said mammal.

### Claim 29 (depends on 28)

The method for the treatment of an HIV infectious disease according to claim 28, which further comprises administering an effective amount of one or more other kinds of anti-HIV active substances to said mammal.

### Claim 30 (depends on 1)

A method for inhibiting HIV integrase in a mammal, which comprises administering an effective amount of the pharmaceutical composition agent of claim 1 or a pharmaceutically acceptable salt thereof to said mammal.

### Claim 31 (depends on 1)

A method for the treatment of an HIV infectious disease in a mammal, which comprises administering an effective amount of the pharmaceutical composition of claim 1, or a pharmaceutically acceptable salt thereof to said mammal.

### Claim 32 (depends on 27)

A commercial package comprising the composition of claim 27 and a written matter associated therewith, the written matter stating that the composition can or should be used for the treatment of an HIV infectious disease.

### Claim 33 (depends on 27)

A commercial package comprising the composition of claim 27 and a written matter associated therewith, the written matter stating that the composition can or should be used for inhibiting integrase.