Novel dihydroquinolizinones for the treatment and prophylaxis of hepatitis B virus infection

• US 20160207914A9
• Filed: 01/30/2015
• Published: 07/21/2016
• Est. Priority Date: 01/30/2014
• Status: Active Grant

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Han, Xingchun, Javanbakht, Hassan, Jiang, Min, Liang, Chungen, Wang, Jianping, Wang, Yongguang, Wang, Zhanguo, Weikert, Robert James, Yang, Song, Zhou, Chengang
• Granted Patent: US 9,458,153 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: 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
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: C07D 455/06 containing benzo [a] quinolizine ring systems
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

The invention provides novel compounds having the general formula:

wherein R¹, R², R³, R⁴, R⁵ and R⁶ are as described herein, compositions including the compounds and methods of using the compounds.

Claims

1. A compound of formula I

2. A compound according to claim 1, wherein

R¹ is hydrogen, fluoro, chloro, bromo, methyl, methylamino, methoxy or ethoxy;

R² is hydrogen, fluoro, chloro, bromo, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, propoxy, trifluoromethoxy, cyano, cyclopropyl, hydroxy or phenylmethyl-O—

;

R³ is hydrogen, bromo, methyl, propyl, trifluoromethyl, cyano, phenylmethyl-N(methyl)-, tert-butoxycarbonylpiperazinyl, hydroxy, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, difluoromethylmethyl-O—

, difluoromethylethyl-O—

, trifluoromethoxy, trifluoromethylmethyl-O—

, trifluoromethylethyl-O—

, ethyldifluoromethyl-O—

, vinyldifluoromethyl-O—

, propargyl-O—

, hydroxymethylpropargyl-O—

, methoxyethyl-O—

, methoxypropyl-O—

, methoxybutyl-O—

, ethoxyethyl-O—

, methoxyethyl-O-ethyl-O—

, aminoethyl-O—

, aminopentyl-O—

, aminohexyl-O—

, aminooctyl-O—

, tert-butoxycarbonylaminopentyl-O—

, tert-butoxycarbonylaminohexyl-O—

, tert-butoxycarbonylaminooctyl-O—

, methylcarbonylaminoethyl-O—

, methylcarbonylaminopentyl-O—

, methylsulfonylaminoethyl-O—

, methylsulfonylaminopentyl-O—

, methylsulfonylethyl-O—

, methylsulfonylpropyl-O—

, methylsulfanylpropyl-O—

, cyanopropyl-O—

, cyanocyclopropylmethyl-O—

, cyclopropylmethyl-O—

, cyclohexylethyl-O—

, hydroxyethyl-O—

, hydroxypropyl-O—

, hydroxy-dimethylpropyl-O—

, hydroxy-difluoropropyl-O—

, hydroxybutyl-O—

, hydroxypentyl-O—

, hydroxyhexyl-O—

, aminoethyl-O-propyl-O—

, ethylamino-ethyl-O-propyl-O—

, imidazolylethyl-O—

, pyrazolylpropyl-O—

, triazolylpropyl-O—

, morpholinylethyl-O—

, morpholinylpropyl-O—

, (2-oxo-pyrrolidinyl)ethyl-O—

, (2-oxo-pyrrolidinyl)propyl-O—

, phenylmethyl-O—

, phenylethyl-O—

, pyrrolidinylethyl-O—

, pyrrolidinylpropyl-O—

, pyrrolidinylcarbonylmethyl-O—

, tetrahydropyranylmethyl-O—

or carboxypropyl-O—

;

R⁴ is hydrogen, fluoro, chloro, bromo, methyl or cyano;

provided that R¹, R², R³ and R⁴ are not hydrogen simultaneously;

R⁵ is hydrogen or methyl;

R⁶ is hydrogen, methyl, ethyl, propyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, trifluoromethylmethyl, cyclopropyl, cyclobutyl, methylcyclopropyl or phenylmethyl;

or pharmaceutically acceptable salts, or enantiomers thereof.

3. A compound according to claim 1, wherein

R¹ is hydrogen, halogen, C_1-6alkylamino or C_1-6alkoxy;

R² is hydrogen, halogen, C_1-6alkyl, C_1-6alkoxy, C_3-7cycloalkyl, hydroxy or phenyl-C_xH_2x—

O—

;

R³ is hydrogen;

halogen;

C_1-6alkyl;

cyano;

phenyl-C_xH_2x—

N(C_1-6alkyl)-;

C_1-6alkoxycarbonylpiperazinyl;

or R⁷—

O—

, wherein R⁷ is hydrogen;

C_1-6alkyl, which is unsubstituted or substituted with one to three substituents independently selected from fluoro, hydroxy and C_2-6alkenyl;

C_1-6alkoxyC_1-6alkyl;

C_1-6alkoxyC_1-6alkoxyC_1-6alkyl;

aminoC_1-8alkyl;

C_1-6alkylcarbonylaminoC_1-8alkyl;

C_1-6alkylsulfonylaminoC_1-8alkyl;

C_1-6alkylsulfanylC_1-6alkyl;

C_1-6alkylsulfonylC_1-6alkyl;

cyanoC_1-6alkyl;

C_3-7cycloalkylC_1-6alkyl;

cyanoC_3-7cycloalkylC_1-6alkyl;

phenylC_1-6alkyl;

pyrrolidinylcarbonylC_1-6alkyl;

C_2-6alkynyl;

hydroxyC_1-6alkylC_2-6alkynyl;

aminoC_1-6alkoxyC_1-6alkyl;

C_1-6alkylaminoC_1-6alkoxyC_1-6alkyl;

carboxyC_1-6alkyl;

C_1-6alkoxycarbonylaminoC_1-8alkyl;

heteroarylC_1-6alkyl, wherein heteroaryl is N-containing monocyclic heteroaryl;

or heterocycloalkylC_1-6alkyl, wherein heterocycloalkyl is monocyclic heterocycloalkyl;

R⁴ is hydrogen, halogen, C_1-6alkyl or cyano;

provided that R¹, R², R³ and R⁴ are not hydrogen simultaneously;

R⁵ is hydrogen or C_1-6alkyl;

R⁶ is hydrogen;

C_1-6alkyl, which is unsubstituted or once, twice or three times substituted by fluoro;

C_3-7cycloalkyl;

C_1-6alkylC_3-7cycloalkyl;

or phenyl-C_xH_2x—

;

x is 1-6;

or pharmaceutically acceptable salts, or enantiomers thereof.

4. A compound according to claim 3, wherein

R¹ is hydrogen, fluoro, chloro, bromo, methylamino, methoxy or ethoxy;

R² is hydrogen, fluoro, chloro, methyl, ethyl, methoxy, ethoxy, propoxy, cyclopropyl, hydroxy or phenylmethyl-O—

;

R³ is hydrogen, bromo, methyl, propyl, cyano, phenylmethyl-N(methyl)-, tert-butoxycarbonylpiperazinyl, hydroxy, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, difluoromethylmethyl-O—

, difluoromethylethyl-O—

, trifluoromethylmethyl-O—

, ethyldifluoromethyl-O—

, vinyldifluoromethyl-O—

, propargyl-O—

, hydroxymethylpropargyl-O—

, methoxyethyl-O—

, methoxypropyl-O—

, methoxybutyl-O—

, ethoxyethyl-O—

, methoxyethyl-O-ethyl-O—

, aminoethyl-O—

, aminopentyl-O—

, aminohexyl-O—

, aminooctyl-O—

, tert-butoxycarbonylaminopentyl-O—

, tert-butoxycarbonylaminohexyl-O—

, tert-butoxycarbonylaminooctyl-O—

, methylcarbonylaminoethyl-O—

, methylcarbonylaminopentyl-O—

, methylsulfonylaminoethyl-O—

, methylsulfonylaminopentyl-O—

, methylsulfonylethyl-O—

, methylsulfonylpropyl-O—

, methylsulfanylpropyl-O—

, cyanopropyl-O—

, cyanocyclopropylmethyl-O—

, cyclopropylmethyl-O—

, cyclohexylethyl-O—

, hydroxyethyl-O—

, hydroxypropyl-O—

, hydroxy-dimethylpropyl-O—

, hydroxy-difluoropropyl-O—

, hydroxybutyl-O—

, hydroxypentyl-O—

, hydroxyhexyl-O—

, aminoethyl-O-propyl-O—

, ethylamino-ethyl-O-propyl-O—

, imidazolylethyl-O—

, pyrazolylpropyl-O—

, triazolylpropyl-O—

, morpholinylethyl-O—

, morpholinylpropyl-O—

, (2-oxo-pyrrolidinyl)ethyl-O—

, (2-oxo-pyrrolidinyl)propyl-O—

, phenylmethyl-O—

, phenylethyl-O—

, pyrrolidinylethyl-O—

, pyrrolidinylpropyl-O—

, pyrrolidinylcarbonylmethyl-O—

, tetrahydropyranylmethyl-O—

or carboxypropyl-O—

;

R⁴ is hydrogen, chloro, bromo, methyl or cyano;

provided that R¹, R², R³ and R⁴ are not hydrogen simultaneously;

R⁵ is hydrogen or methyl;

R⁶ is hydrogen, methyl, ethyl, propyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, trifluoromethylmethyl, cyclopropyl, cyclobutyl, methylcyclopropyl or phenylmethyl;

or pharmaceutically acceptable salts, or enantiomers thereof.

5. A compound of formula IA according to claim 1,

6. A compound according to claim 1, wherein

R¹ is hydrogen, fluoro, chloro or methoxy;

R² is hydrogen, fluoro, chloro, methyl, ethyl, methoxy, ethoxy, propoxy, cyclopropyl, hydroxy or phenylmethyl-O—

;

R⁴ is hydrogen or chloro;

R⁵ is hydrogen or methyl;

R⁶ is hydrogen, methyl, ethyl, propyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, trifluoromethylmethyl, cyclopropyl, cyclobutyl, methylcyclopropyl or phenylmethyl;

R⁷ is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, difluoromethylmethyl, difluoromethylethyl, trifluoromethylmethyl, ethyldifluoromethyl, vinyldifluoromethyl, propargyl, hydroxymethylpropargyl, methoxyethyl, methoxypropyl, methoxybutyl, ethoxyethyl, methoxyethyl-O-ethyl, aminoethyl, aminopentyl, aminohexyl, aminooctyl, tert-butoxycarbonylaminopentyl, tert-butoxycarbonylaminohexyl, tert-butoxycarbonylaminooctyl, methylcarbonylaminoethyl, methylcarbonylaminopentyl, methylsulfonylaminoethyl, methylsulfonylaminopentyl, methylsulfonylethyl, methylsulfonylpropyl, methylsulfanylpropyl, cyanopropyl, cyanocyclopropylmethyl, cyclopropylmethyl, cyclohexylethyl, hydroxyethyl, hydroxypropyl, hydroxy-dimethylpropyl, hydroxy-difluoropropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, aminoethyl-O-propyl, ethylamino-ethyl-O-propyl-, imidazolylethyl, pyrazolylpropyl, triazolylpropyl, morpholinylethyl, morpholinylpropyl, (2-oxo-pyrrolidinyl)ethyl, (2-oxo-pyrrolidinyl)propyl, phenylmethyl, phenylethyl, pyrrolidinylethyl, pyrrolidinylpropyl, pyrrolidinylcarbonylmethyl, tetrahydropyranylmethyl or carboxypropyl;

or pharmaceutically acceptable salts, or enantiomers thereof.

7. A compound according to claim 1, wherein

R¹ is hydrogen or halogen;

R² is C_1-6alkyl, halogen or C_3-7cycloalkyl;

R⁴ is hydrogen;

R⁵ is hydrogen or C_1-6alkyl;

R⁶ is C_1-6alkyl or C_1-6alkylC_3-7cycloalkyl;

R⁷ is C_1-6alkyl, C_1-6alkoxyC_1-6alkyl;

or phenylC_1-6alkyl;

or pharmaceutically acceptable salts, or enantiomers thereof.

8. A compound according to claim 1, wherein

R¹ is hydrogen, fluoro or chloro;

R² is methyl, ethyl, fluoro, chloro or cyclopropyl;

R⁴ is hydrogen;

R⁵ is hydrogen or methyl;

R⁶ is methyl, ethyl, isopropyl, isobutyl, tert-butyl or methylcyclopropyl;

R⁷ is methyl, ethyl, methoxyethyl, methoxypropyl or phenylmethyl;

or pharmaceutically acceptable salts, or enantiomers thereof.

9. A compound according to claim 1, wherein

R¹ is hydrogen;

R² is C_1-6alkoxy;

R⁴ is hydrogen or halogen;

R⁵ is hydrogen or C_1-6alkyl;

R⁶ is hydrogen;

C_1-6alkyl, which is unsubstituted or once, twice or three times substituted by fluoro;

C_3-7cycloalkyl;

C_1-6alkylC_3-7cycloalkyl;

or phenyl-C_xH_2x—

;

R⁷ is hydrogen;

C_1-6alkyl, which is unsubstituted or substituted with one to three substituents independently selected from fluoro, hydroxy and C_2-6alkenyl;

C_1-6alkoxyC_1-6alkyl;

C_1-6alkoxyC_1-6alkoxyC_1-6alkyl;

aminoC_1-8alkyl;

C_1-6alkylcarbonylaminoC_1-8alkyl;

C_1-6alkylsulfonylaminoC_1-8alkyl;

C_1-6alkylsulfanylC_1-6alkyl;

C_1-6alkylsulfonylC_1-6alkyl;

cyanoC_1-6alkyl;

cyanoC_3-7cycloalkylC_1-6alkyl;

C_3-7cycloalkylC_1-6alkyl;

phenylC_1-6alkyl;

pyrrolidinylcarbonylC_1-6alkyl;

C_2-6alkynyl;

hydroxyC_1-6alkylC_2-6alkynyl;

aminoC_1-6alkoxyC_1-6alkyl;

C_1-6alkylaminoC_1-6alkoxyC_1-6alkyl;

carboxyC_1-6alkyl;

C_1-6alkoxycarbonylaminoC_1-8alkyl;

imidazolylC_1-6alkyl;

pyrazolylC_1-6alkyl;

triazolylC_1-6alkyl;

morpholinylC_1-6alkyl;

(2-oxo-pyrrolidinyl)C_1-6alkyl;

pyrrolidinylC_1-6alkyl;

or tetrahydropyranylC_1-6alkyl;

x is 1-6;

or pharmaceutically acceptable salts, or enantiomers thereof.

10. A compound according to claim 1, wherein

R¹ is hydrogen;

R² is methoxy, ethoxy or propoxy;

R⁴ is hydrogen or chloro;

R⁵ is hydrogen or methyl;

R⁶ is hydrogen, methyl, ethyl, propyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, trifluoromethylmethyl, cyclopropyl, cyclobutyl, methylcyclopropyl or phenylmethyl;

R⁷ is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, difluoromethylmethyl, difluoromethylethyl, trifluoromethylmethyl, ethyldifluoromethyl, vinyldifluoromethyl, propargyl, hydroxymethylpropargyl, methoxyethyl, methoxypropyl, methoxybutyl, ethoxyethyl, methoxyethyl-O-ethyl, aminoethyl, aminopentyl, aminohexyl, aminooctyl, tert-butoxycarbonylaminopentyl, tert-butoxycarbonylaminohexyl, tert-butoxycarbonylaminooctyl, methylcarbonylaminoethyl, methylcarbonylaminopentyl, methylsulfonylaminoethyl, methylsulfonylaminopentyl, methylsulfonylethyl, methylsulfonylpropyl, methylsulfanylpropyl, cyanopropyl, cyanocyclopropylmethyl, cyclopropylmethyl, cyclohexylethyl, hydroxyethyl, hydroxypropyl, hydroxy-dimethylpropyl, hydroxy-difluoropropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, aminoethyl-O-propyl, ethylamino-ethyl-O-propyl-, imidazolylethyl, pyrazolylpropyl, triazolylpropyl, morpholinylethyl, morpholinylpropyl, (2-oxo-pyrrolidinyl)ethyl, (2-oxo-pyrrolidinyl)propyl, phenylmethyl, phenylethyl, pyrrolidinylethyl, pyrrolidinylpropyl, pyrrolidinylcarbonylmethyl, tetrahydropyranylmethyl or carboxypropyl;

or pharmaceutically acceptable salts, or enantiomers thereof.

11. A compound according to claim 1, wherein

R¹ is hydrogen or halogen;

R² is halogen, C_1-6alkyl, C_1-6alkoxy or C_3-7cycloalkyl;

R⁴ is hydrogen;

R⁵ is hydrogen or C_1-6alkyl;

R⁶ is C_1-6alkyl, which is unsubstituted or once, twice or three times substituted by fluoro;

C_3-7cycloalkyl or C_1-6alkylC_3-7cycloalkyl;

R⁷ is C_1-6alkyl, which is unsubstituted or substituted with one to three substituents independently selected from fluoro and hydroxy;

C_1-6alkoxyC_1-6alkyl;

aminoC_1-8alkyl;

C_1-6alkylcarbonylaminoC_1-8alkyl;

C_1-6alkylsulfonylaminoC_1-8alkyl;

C_1-6alkylsulfanylC_1-6alkyl;

C_1-6alkylsulfonylC_1-6alkyl;

C_3-7cycloalkylC_1-6alkyl;

phenylC_1-6alkyl;

C_1-6 alkylaminoC_1-6alkoxyC_1-6alkyl;

C_1-6alkoxycarbonylaminoC_1-8alkyl;

morpholinylC_1-6alkyl or tetrahydropyranylC_1-6alkyl;

or pharmaceutically acceptable salts, or enantiomers thereof.

12. A compound according to claim 1, wherein

R¹ is hydrogen, fluoro, or chloro;

R² is fluoro, chloro, methyl, ethyl, methoxy, ethoxy or cyclopropyl;

R⁴ is hydrogen;

R⁵ is hydrogen or methyl;

R⁶ is methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethylmethyl, cyclobutyl or methylcyclopropyl;

R⁷ is methyl, ethyl, propyl, butyl, isobutyl, cyclopropylmethyl, difluoromethylmethyl, difluoroethylmethyl, difluoromethylethyl, trifluoromethylmethyl, ethyldifluoromethyl, methoxyethyl, methoxypropyl, ethoxyethyl, aminohexyl, aminooctyl, tert-butoxycarbonylaminopentyl, tert-butoxycarbonylaminooctyl, methylcarbonylaminopentyl, methylsulfonylaminopentyl, methylsulfonylpropyl, methylsulfanylpropyl, hydroxypropyl, hydroxy-dimethylpropyl, hydroxy-difluoropropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, ethylamino-ethyl-O-propyl-, morpholinylethyl, morpholinylpropyl, phenylmethyl or tetrahydropyranylmethyl;

or pharmaceutically acceptable salts, or enantiomers thereof.

13. A compound according to claim 1, or pharmaceutically acceptable salts, or enantiomers thereof, wherein R¹ is hydrogen.

14. A compound according to claim 1, or pharmaceutically acceptable salts, or enantiomers thereof, wherein R² is halogen or C_1-6alkoxy.

15. A compound according to claim 1, or pharmaceutically acceptable salts, or enantiomers thereof, wherein R² is chloro or methoxy.

16. A compound according to claim 1, or pharmaceutically acceptable salts, or enantiomers thereof, wherein R⁵ is hydrogen.

17. A compound according to claim 1, or pharmaceutically acceptable salts, or enantiomers thereof, wherein R⁶ is C_1-6alkyl or C_1-6alkylC_3-7cycloalkyl.

18. A compound according to claim 1, or pharmaceutically acceptable salts, or enantiomers thereof, wherein R⁶ is ethyl, isopropyl, tert-butyl or methylcyclopropyl.

19. A compound according to claim 1, or pharmaceutically acceptable salts, or enantiomers thereof, wherein R⁷ is C_1-6alkoxyC_1-6alkyl, hydroxyC_1-6alkyl or aminoC_1-6alkyl.

20. A compound according to claim 1, or pharmaceutically acceptable salts, or enantiomers thereof, wherein R⁷ is methoxyethyl, methoxypropyl, hydroxydimethylpropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, aminobutyl, aminopentyl or aminohexyl.

21. A compound according to claim 1, selected from

9-Benzyloxy-10-methoxy-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-Hydroxy-10-methoxy-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9,11-Dimethoxy-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-Ethoxy-10-methoxy-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9,10-Diethoxy-6-ethyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-9,10-Diethoxy-6-ethyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-9,10-Diethoxy-6-ethyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-Benzyloxy-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-9-Benzyloxy-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-9-Benzyloxy-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-Ethyl-10-methoxy-2-oxo-9-(2,2,2-trifluoroethoxy)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-Ethyl-10-methoxy-2-oxo-9-(2,2,2-trifluoroethoxy)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-9-isopropoxy-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-10-methoxy-2-oxo-9-(2-phenylethoxy)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-Butoxy-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-(2-Cyclohexylethoxy)-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-10-methoxy-2-oxo-9-prop-2-ynoxy-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-10-methoxy-2-oxo-9-(2-oxo-2-pyrrolidin-1-yl-ethoxy)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-10-methoxy-9-[2-(2-methoxyethoxyl)ethoxy]-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-10-methoxy-9-(2-morpholinoethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-9-(2-hydroxyethoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-9-(3-hydroxy-2,2-dimethyl-propoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-Ethyl-9-(3-hydroxy-2,2-dimethyl-propoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-Ethyl-9-(3-hydroxy-2,2-dimethyl-propoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-9-(3-hydroxypropoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-9-(2-imidazol-1-ylethoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-10-methoxy-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-Ethyl-10-methoxy-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-Ethyl-10-methoxy-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-(Cyclopropylmethoxy)-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-9-(Cyclopropylmethoxy)-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-9-(Cyclopropylmethoxy)-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-9-isobutoxy-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-Ethyl-9-isobutoxy-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-Ethyl-9-isobutoxy-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-Ethoxy-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-9-Ethoxy-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-9-Ethoxy-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-10-methoxy-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-Ethyl-10-methoxy-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-Ethyl-10-methoxy-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-(2-Ethoxyethoxy)-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-9-(2-Ethoxyethoxy)-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-9-(2-Ethoxyethoxy)-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-(2,2-Difluoroethoxy)-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-9-(2,2-Difluoroethoxy)-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-9-(2,2-Difluoroethoxy)-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-10-methoxy-2-oxo-9-(tetrahydropyran-4-ylmethoxy)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-Ethyl-10-methoxy-2-oxo-9-(tetrahydropyran-4-ylmethoxy)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-Ethyl-10-methoxy-2-oxo-9-(tetrahydropyran-4-ylmethoxy)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-10-methoxy-2-oxo-9-(2-pyrrolidin-1-ylethoxy)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-(3-Cyanopropoxy)-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-10-methoxy-9-(2-methylsulfonylethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-10-methoxy-2-oxo-9-[2-(2-oxopyrrolidin-1-yl)ethoxy]-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-Ethyl-10-methoxy-2-oxo-9-[2-(2-oxopyrrolidin-1-yl)ethoxy]-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-9-[2-(methanesulfonamido)ethoxy]-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-[(1-Cyanocyclopropyl)methoxy]-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-(2-Acetamidoethoxy)-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Chloro-9-methoxy-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9,10-Dimethoxy-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-9,10-Dimethoxy-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-9,10-Dimethoxy-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9,10-Dimethoxy-7-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-9,10-dimethoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(6R)-(+)-6-Ethyl-9,10-dimethoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(6S)-(−

)-6-Ethyl-9,10-dimethoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-Methoxy-6,10-dimethyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9,10-Diethoxy-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-Ethoxy-6-methyl-10-hydroxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9,10-Diethoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

2-Oxo-9,10-dipropoxy-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-10-methoxy-2-oxo-9-propoxy-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-Ethyl-10-methoxy-2-oxo-9-propoxyl-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-Ethyl-10-methoxy-2-oxo-9-propoxyl-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

8-Chloro-9-methoxy-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

8-Chloro-9,10-dimethoxy-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Benzyloxy-9-methoxy-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Ethoxy-9-methoxy-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-Methoxy-6-methyl-2-oxo-10-propoxy-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6,10-Diethyl-9-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Cyclopropyl-6-ethyl-9-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-10-Cyclopropyl-6-ethyl-9-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-10-Cyclopropyl-6-ethyl-9-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9,10-Dimethoxy-2-oxo-6-propyl-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Cyclopropyl-9,10-dimethoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Isopropyl-9,10-dimethoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-Isopropyl-9,10-dimethoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-Isopropyl-9,10-dimethoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Isobutyl-9,10-dimethoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-Isobutyl-9,10-dimethoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-Isobutyl-9,10-dimethoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Chloro-6-isobutyl-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-10-Chloro-6-isobutyl-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-10-Chloro-6-isobutyl-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Chloro-6-isopropyl-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-10-Chloro-6-isopropyl-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-10-Chloro-6-isopropyl-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Fluoro-6-isopropyl-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

11-Chloro-6-isopropyl-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9,10-Dimethoxy-2-oxo-6-(trifluoromethyl)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-Benzyloxy-6-ethyl-10-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-9-Benzyloxy-6-ethyl-10-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-9-Benzyloxy-6-ethyl-10-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-10-Chloro-9-ethoxy-6-ethyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-10-Chloro-9-ethoxy-6-ethyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Chloro-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-10-Chloro-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-10-Chloro-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Methoxy-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-10-Methoxy-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-10-Methoxy-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Isopropyl-10-methoxy-2-oxo-9-(2,2,2-trifluoroethoxy)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-Isopropyl-10-methoxy-2-oxo-9-(2,2,2-trifluoroethoxy)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-Isopropyl-10-methoxy-2-oxo-9-(2,2,2-trifluoroethoxy)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-Isopropyl-10-methoxy-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-Isopropyl-10-methoxy-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-10-methoxy-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-tert-Butyl-10-methoxy-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-tert-Butyl-10-methoxy-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Methoxy-9-(2-methoxyethoxy)-6-(1-methylcyclopropyl)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-10-Methoxy-9-(2-methoxyethoxy)-6-(1-methylcyclopropyl)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-10-Methoxy-9-(2-methoxyethoxy)-6-(1-methylcyclopropyl)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

11-Chloro-10-fluoro-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-11-Chloro-10-fluoro-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-11-Chloro-10-fluoro-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Fluoro-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-(2,2-difluoro-3-hydroxy-propoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-9-(2,2-Difluoroethoxy)-6-isopropyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-9-(2,2-Difluoroethoxy)-6-isopropyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-(3-Hydroxy-2,2-dimethyl-propoxy)-6-isopropyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-9-(3-Hydroxy-2,2-dimethyl-propoxy)-6-isopropyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-9-(3-Hydroxy-2,2-dimethyl-propoxy)-6-isopropyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-(3-Hydroxypropoxy)-6-isopropyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Isopropyl-10-methoxy-9-(4-methoxybutoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-(3-hydroxy-2,2-dimethyl-propoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-tert-Butyl-9-(3-hydroxy-2,2-dimethyl-propoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-tert-Butyl-9-(3-hydroxy-2,2-dimethyl-propoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-(5-hydroxypentoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-tert-Butyl-9-(5-hydroxypentoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-tert-Butyl-9-(5-hydroxypentoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-(6-hydroxyhexoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-tert-Butyl-9-(6-hydroxyhexoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-tert-Butyl-9-(6-hydroxyhexoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-(4-hydroxybutoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-(4-hydroxybut-2-ynoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-(6-Aminohexoxy)-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-[6-(tert-Butoxycarbonylamino)hexoxy]-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-9-[6-(tert-Butoxycarbonylamino)hexoxy]-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-9-[6-(tert-Butoxycarbonylamino)hexoxy]-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-9-(6-Aminohexoxy)-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid hydrochloride;

(−

)-9-(6-Aminohexoxy)-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid hydrochloride;

9-(8-Aminooctoxy)-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-[8-(tert-Butoxycarbonylamino)octoxy]-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-9-[8-(tert-Butoxycarbonylamino)octoxy]-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-9-[8-(tert-Butoxycarbonylamino)octoxy]-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-9-(8-Aminooctoxy)-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid hydrochloride;

(−

)-9-(8-Aminooctoxy)-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid hydrochloride;

9-[5-(tert-Butoxycarbonylamino)pentoxy]-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-9-(5-Aminopentoxy)-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid hydrochloride;

(−

)-9-(5-Aminopentoxy)-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid hydrochloride;

9-(5-Acetamidopentoxy)-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-[5-(methanesulfonamido)pentoxy]-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-(2-Aminoethoxy)-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-[3-(2-Aminoethoxyl)propoxy]-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-[3-[2-(ethylamino)ethoxy]propoxy]-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-(3,3-difluoropropoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-(1,1-difluoropropoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-(1,1-difluoroallyloxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-10-methoxy-9-(3-methylsulfanylpropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-tert-Butyl-10-methoxy-9-(3-methylsulfanylpropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-tert-Butyl-10-methoxy-9-(3-methylsulfanylpropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-10-methoxy-9-(3-methylsulfonylpropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-tert-Butyl-10-methoxy-9-(3-methylsulfonylpropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-tert-Butyl-10-methoxy-9-(3-methylsulfonylpropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-10-methoxy-9-(2-morpholinoethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid hydrochloride;

(+)-6-teBrt-utyl-10-methoxy-9-(2-morpholinoethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-tert-Butyl-10-methoxy-9-(2-morpholinoethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-10-methoxy-9-(3-morpholinopropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid hydrochloride;

(+)-6-tert-Butyl-10-methoxy-9-(3-morpholinopropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-tert-Butyl-10-methoxy-9-(3-morpholinopropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-10-methoxy-2-oxo-9-[3-(2-oxopyrrolidin-1-yl)propoxy]-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-10-methoxy-2-oxo-9-(3-pyrrolidin-1-ylpropoxy)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Cyclobutyl-10-methoxy-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9,10-Dimethoxy-2-oxo-6-(2,2,2-trifluoroethyl)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Methoxy-9-(3-methoxypropoxy)-2-oxo-6-(2,2,2-trifluoroethyl)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-10-Methoxy-9-(3-methoxypropoxy)-2-oxo-6-(2,2,2-trifluoroethyl)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-10-Methoxy-9-(3-methoxypropoxy)-2-oxo-6-(2,2,2-trifluoroethyl)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-10-chloro-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-tert-Butyl-10-chloro-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-6-tert-Butyl-10-chloro-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Chloro-9-(3-methoxypropoxy)-6-(1-methylcyclopropyl)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-10-Chloro-9-(3-methoxypropoxy)-6-(1-methylcyclopropyl)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-10-Chloro-9-(3-methoxypropoxy)-6-(1-methylcyclopropyl)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Methoxy-9-(3-methoxypropoxy)-6-(1-methylcyclopropyl)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-10-Methoxy-9-(3-methoxypropoxy)-6-(1-methylcyclopropyl)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-10-Methoxy-9-(3-methoxypropoxy)-6-(1-methylcyclopropyl)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Benzyl-9,10-dimethoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Chloro-6-ethyl-9-(2-methoxyethoxy)-7-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(6R*,7S*)-10-Chloro-6-ethyl-9-(2-methoxyethoxy)-7-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(6R*,7R*)-10-Chloro-6-ethyl-9-(2-methoxyethoxy)-7-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10,11-Difluoro-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-10,11-Difluoro-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(−

)-10,11-Difluoro-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-10-methoxy-2-oxo-9-(3-pyrazol-1-ylpropoxy)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-10-methoxy-2-oxo-9-[3-(1,2,4-triazol-1-yl)propoxy]-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-(3-carboxypropoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-Bromo-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

11-Bromo-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-9-Bromo-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-(4-tert-Butoxycarbonylpiperazin-1-yl)-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-[Benzyl(methyl)amino]-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Methyl-11-(methylamino)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-10-methoxy-2-oxo-9-propyl-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Methoxy-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-Bromo-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-Cyano-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

8-Bromo-11-ethoxy-6-ethyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

8-Cyano-11-ethoxy-6-ethyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-9,10-dimethyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-8,9-dimethyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

or pharmaceutically acceptable salt, enantiomer or diastereomer thereof.

22. A compound according to claim 1, selected from

9-Benzyloxy-10-methoxy-6-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9,10-Diethoxy-6-ethyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-Ethyl-10-methoxy-2-oxo-9-(2,2,2-trifluoroethoxy)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-Butoxy-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-9-(3-hydroxy-2,2-dimethyl-propoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-10-methoxy-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-(Cyclopropylmethoxy)-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-9-isobutoxy-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-Ethoxy-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-10-methoxy-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-(2-Ethoxyethoxy)-6-ethyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-10-methoxy-2-oxo-9-(tetrahydropyran-4-ylmethoxy)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-9,10-dimethoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(6R)-(+)-6-Ethyl-9,10-dimethoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Ethyl-10-methoxy-2-oxo-9-propoxy-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6,10-Diethyl-9-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Cyclopropyl-6-ethyl-9-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Isopropyl-9,10-dimethoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Isobutyl-9,10-dimethoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Chloro-6-isobutyl-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Chloro-6-isopropyl-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Fluoro-6-isopropyl-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-Benzyloxy-6-ethyl-10-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Chloro-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Methoxy-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-10-Methoxy-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Isopropyl-10-methoxy-2-oxo-9-(2,2,2-trifluoroethoxy)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-Isopropyl-10-methoxy-9-(2-methoxyethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-10-methoxy-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-6-tert-Butyl-10-methoxy-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Methoxy-9-(2-methoxyethoxy)-6-(1-methylcyclopropyl)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-10-Methoxy-9-(2-methoxyethoxy)-6-(1-methylcyclopropyl)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

11-Chloro-10-fluoro-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Fluoro-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-(2,2-difluoro-3-hydroxy-propoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(+)-9-(2,2-Difluoroethoxy)-6-isopropyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-(3-Hydroxy-2,2-dimethyl-propoxy)-6-isopropyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-(3-Hydroxypropoxy)-6-isopropyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-Isopropyl-10-methoxy-9-(4-methoxybutoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-(3-hydroxy-2,2-dimethyl-propoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-(5-hydroxypentoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-(6-hydroxyhexoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-(4-hydroxybutoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-(6-Aminohexoxy)-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-[8-(tert-Butoxycarbonylamino) octoxy]-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-[5-(tert-Butoxycarbonylamino)pentoxy]-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

9-(5-Acetamidopentoxy)-6-tert-butyl-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-[5-(methanesulfonamido)pentoxy]-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-[3-[2-(ethylamino)ethoxy]propoxy]-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-(3,3-difluoropropoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-9-(1,1-difluoropropoxy)-10-methoxy-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-10-methoxy-9-(3-methylsulfanylpropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-10-methoxy-9-(3-methylsulfonylpropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-10-methoxy-9-(2-morpholinoethoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid hydrochloride;

6-tert-Butyl-10-methoxy-9-(3-morpholinopropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid hydrochloride;

6-Cyclobutyl-10-methoxy-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Methoxy-9-(3-methoxypropoxy)-2-oxo-6-(2,2,2-trifluoroethyl)-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

6-tert-Butyl-10-chloro-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Chloro-9-(3-methoxypropoxy)-6-(1-methylcyclopropyl)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10-Methoxy-9-(3-methoxypropoxy)-6-(1-methylcyclopropyl)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

(6R*,7S*)-10-Chloro-6-ethyl-9-(2-methoxyethoxy)-7-methyl-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

10,11-Difluoro-6-isopropyl-9-(3-methoxypropoxy)-2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid;

or pharmaceutically acceptable salt, enantiomer or diastereomer thereof.

23. A process for the preparation of a compound according to claim 1, comprising

(a) hydrolysis of a compound of formula (A)

24. A pharmaceutical composition comprising a compound in accordance with claim 1 and a therapeutically inert carrier.

25. A method of inhibiting HBsAg production or secretion in a patient, comprising administering a compound of claim 1 to a patient in need thereof.

26. A method of inhibiting HBV DNA production in a patient, comprising administering a compound of claim 1 to a patient in need thereof.

27. A compound according to claim 1, manufactured according to a process of claim 23.

28. A method for the treatment or prophylaxis of HBV infection in a patient, which method comprises administering an effective amount of a compound as defined in claim 1 to a patient in need thereof.