HIV integrase inhibitors

• US 6,380,249 B1
• Filed: 06/01/1999
• Issued: 04/30/2002
• Est. Priority Date: 06/03/1998
• Status: Expired due to Fees

• Current Assignee: Tularik, Inc. (Amgen Inc.), Merck & Co., Inc.
• Original Assignee: Tularik, Inc. (Amgen Inc.), Merck & Co., Inc.
• Inventors: Jaen, Juan C., Payne, Linda S., Zhuang, Linghang, Vacca, Joseph P., Medina, Julio C., Melamed, Jeffrey, Wai, John S., Embrey, Mark W., Langford, H. Marie, Clark, David L., Fisher, Thorsten E., Egbertson, Melissa, Tran, Lekhanh, Guare, James P. Jr., Young, Steven D.
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): RAO, DEEPAK R
• Application Number:
  US09/323,417
• Time in Patent Office: 1,064 Days
• Field of Search: 514/238.8, 514/237.2, 514/255, 514/256, 514/247, 514/317, 514/366, 514/374, 514/381, 514/383, 514/406, 514/415, 514/438, 514/450, 514/452, 514/467, 514/530, 514/531, 514/538, 514/539, 514/541, 544/105, 544/1.H, 544/224, 544/318, 544/336, 544/397, 546/221, 546/301, 546/335, 546/342, 548/233, 548/253, 548/255, 548/268.6, 548/376.1, 548/510, 549/79, 549/10, 549/15, 549/436, 549/438, 560/19, 560/48, 560/51, 560/53, 562/433, 562/426, 562/441, 562/451, 562/452, 562/457, 562/459, 562/463, 562/462
• US Class Current: 514/530
• CPC Class Codes: C07C 217/60 linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
• CPC Class Codes: C07C 229/34 the carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 229/42 with carboxyl groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by saturated carbon chains
• CPC Class Codes: C07C 233/63 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
• CPC Class Codes: C07C 235/60 having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: C07C 255/41 the carbon skeleton being further substituted by carboxyl groups, other than cyano groups
• CPC Class Codes: C07C 2601/02 with a three-membered ring
• CPC Class Codes: C07C 2601/04 with a four-membered ring
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07C 2602/08 the other ring being five-membered, e.g. indane
• CPC Class Codes: C07C 2602/10 the other ring being six-membered, e.g. tetraline
• CPC Class Codes: C07C 271/16 to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
• CPC Class Codes: C07C 271/28 to a carbon atom of a non-condensed six-membered aromatic ring
• CPC Class Codes: C07C 323/62 having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
• CPC Class Codes: C07C 59/84 containing six membered aromatic rings
• CPC Class Codes: C07C 59/86 containing six-membered aromatic rings and other rings
• CPC Class Codes: C07C 59/88 containing halogen
• CPC Class Codes: C07C 59/90 containing singly bound oxygen-containing groups
• CPC Class Codes: C07C 69/738 Esters of keto-carboxylic acids or aldehydo-carboxylic acids
• CPC Class Codes: C07D 209/12 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 213/64 : attached in position 2 or 6
• CPC Class Codes: C07D 241/12 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 253/08 : condensed with carbocyclic rings or ring systems
• CPC Class Codes: C07D 263/58 : with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
• CPC Class Codes: C07D 295/088 : to an acyclic saturated chain
• CPC Class Codes: C07D 295/155 : with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 295/192 : from aromatic carboxylic acids
• CPC Class Codes: C07D 333/22 : Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom

Abstract

Certain six-membered aromatic and heteroaromatic-dioxobutyric acid derivatives are described as inhibitors of HIV integrase and inhibitors of HIV replication. These compounds are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

Claims

1. A compound of structural formula (I):

and tautomers and pharmaceutically acceptable salts thereof, wherein;

A is a six-membered aromatic ring substituted on carbon by R¹, R², R⁸, and R⁹, optionally fused with another ring system, and is selected from;

(1) phenyl,

(2) naphthyl,

R¹ is selected from;

(1) —

H,

(2) —

C_1-5 alkyl,

(3) —

C_1-6 alkyl-OR⁷;

(4) —

O—

C_1-6 alkyl-OR⁷,

(5) —

O—

C_1-6 alkyl-SR⁷,

(6) —

CF₃ or —

CH₂CF₃,

(7) —

F, Cl, or Br,

(8) —

NO₂,

(9) —

C_0-3 alkyl —

N(R⁴)(R⁵),

(10) -phenyl,

(11) substituted phenyl substituted with 1 or 2 substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) phenyl,

(e) —

CF₃,

(f) —

OCF₃,

(g) —

CN,

(h) hydroxy,

(i) phenyloxy, and

(j) substituted phenyloxy with 1, 2, or 3 substituents selected from;

(i) halogen,

(ii) C_1-6 alkyl,

(iii) —

CF₃, and

(iv) hydroxy;

(12) phenyl C_1-3 alkyl-, wherein the phenyl group may be unsubstituted or substituted with 1 to four substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) phenyl,

(e) —

CF₃,

(f) —

SCH₃,

(g) —

CN,

(h) hydroxy,

(i) phenyloxy,

(j) —

C_0-6 alkyl-N(R⁷)₂,

(l) substituted phenyloxy with 1, 2, or 3 substituents selected from;

(i) halogen,

(ii) C_1-6 alkyl,

(iii) —

CF₃, and

(iv) hydroxy;

(13) —

O—

R⁶,

(14) —

O—

C_1-6 alkyl, unsubstituted or substituted with one to three fluorine atoms,

(15) —

O—

C_1-6 alkyl-NH—

C(O)—

OR⁷;

(16) —

O—

C_2-6 alkyl-N(R⁴)(R⁵);

(17) —

S—

C_1-3 alkyl;

(18) —

C(O)CH₂C(O)C(O)OR⁷;

(19) —

CH₂—

CH(OH)—

CH₂—

O—

R⁷; and

(20) —

C(OH)(CH₃)—

CH₂N(R⁴)(R⁵);

R² is selected from;

(1) —

R³,

(2) —

C_1-6 alkyl substituted with R³, wherein one or more of the hydrogen atoms on C_1-6 alkyl may be replaced with a fluorine atom,

(3) —

O—

C_1-6 alkyl-SR⁶;

(4) —

C_1-6 alkyl (OR⁶)(R⁴),

(5) —

C_0-6 alkyl-N(R⁴)(R⁶),

(6) —

C_1-6 alkyl S—

R⁶,

(7) —

C_0-6 alkyl C(O)—

R⁶,

(8) —

C_0-6 alkyl C(O)CH₂—

C(O)—

OH,

(9) —

C_1-6 alkyl NR⁴C(O)—

R⁶,

(10) —

C_1-6 alkyl-C(O)N(R⁴)(R⁵), and

(11) —

CH₂(OR⁷)—

R⁶;

each R³ is independently selected from;

(1) phenyl;

(2) substituted phenyl with 1, 2, 3 or 4 substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) phenyl,

(e) —

CN,

(f) hydroxy,

(g) phenyloxy,

(h) —

C_0-6 alkyl-N(R⁷)₂,

(j) oxo, and

(k) substituted phenyloxy with 1, 2, or 3 substituents selected from;

(i) halogen,

(ii) C_1-6 alkyl,

(iii) —

CF₃, and

(iv) hydroxy;

(3) thienyl,

(4) substituted thienyl substituted on carbon with one or two substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) phenyl,

(e) —

S—

C_1-6 alkyl,

(f) —

CN,

(g) hydroxy,

(h) phenyloxy,

(i) —

C_0-6 alkyl-N(R⁷)₂,

(k) oxo, and

(l) substituted phenyloxy with 1, 2, or 3 substituents selected from;

(i) halogen,

(ii) C_1-6 alkyl,

(iii) —

CF₃, and

(iv) hydroxy;

(5) pyridyl,

(6) substituted pyridyl substituted on carbon with one or two substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) phenyl,

(e) —

S—

C_1-6 alkyl,

(f) —

CN,

(g) hydroxy,

(h) phenyloxy,

(i) —

C_0-6 alkyl-N(R⁷)₂,

(k) oxo, and

(l) substituted phenyloxy with 1, 2, or 3 substituents selected from;

(i) halogen,

(ii) C_1-6 alkyl,

(iii) —

CF₃, and

(iv) hydroxy;

(7) substituted imidazolyl substituted on carbon with one or two substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) phenyl,

(e) —

S—

C_1-6 alkyl,

(f) —

CN,

(g) hydroxy,

(h) phenyloxy,

(i) —

C_0-6 alkyl-N(R⁷)₂,

(k) oxo, and

(l) substituted phenyloxy with 1, 2, or 3 substituents selected from;

(i) halogen,

(ii) C_1-6 alkyl,

(iii) —

CF₃, and

(iv) hydroxy;

(8) pyrrolyl,

(9) substituted pyrrolyl substituted on carbon with one or two substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) phenyl,

(e) —

S—

C_1-6 alkyl,

(f) —

CN,

(g) hydroxy,

(h) phenyloxy,

(i) —

C_0-6 alkyl-N(R⁷)₂,

(k) oxo, and

(l) substituted phenyloxy with 1, 2, or 3 substituents selected from;

(i) halogen,

(ii) C_1-6 alkyl,

(iii) —

CF₃, and

(iv) hydroxy;

(10) pyrazolyl,

(11) substituted pyrazolyl substituted on carbon with one or two substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) phenyl,

(e) —

S—

C_1-6 alkyl,

(f) —

CN,

(g) hydroxy,

(h) phenyloxy,

(i) —

C_0-6 alkyl-N(R⁷)₂,

(k) oxo, and

(l) substituted phenyloxy with 1, 2, or 3 substituents selected from;

(i) halogen,

(ii) C_1-6 alkyl,

(iii) —

CF₃, and

(iv) hydroxy;

(12) piperidinyl,

(13) substituted piperidinyl substituted on carbon with one or two substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O,

(h) benzyl, and

(i) hydroxy;

(14) substituted morpholinyl substituted at a carbon or nitrogen atom with 1 or 2 substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O,

(h) benzyl, and

(i) hydroxy;

(15) hexahydrothieno[3,4-d]imidazolyl,

(16) substituted hexahydrothieno[3,4-d]substituted hexahydrothieno[3,4-d]imidazolyl with one or two substituents independently selected from;

(a) oxo,

(b) halogen,

(c) C_1-6 alkyl,

(d) C_1-6 alkyloxy-,

(e) —

CF₃,

(f) —

OCF₃,

(g) —

CN, and

(h) hydroxy,

(17) naphthyl,

(18) substituted naphthyl with 1, 2, or 3 substituents independently selected from;

(a) -halogen,

(b) —

C_1-6 alkyl,

(c) —

C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN, and

(g) -hydroxy,

(19) indolyl,

(20) substituted indolyl substituted on a carbon atom with one or two substituents independently selected from;

(a) -halogen,

(b) —

C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN, and

(g) -hydroxy;

(21) C_3-5 cycloalkyl fused with a phenyl ring,

(22) substituted C_3-6 cycloalkyl fused with a phenyl ring substituted on carbon with one or two substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy;

(23) pyrazinyl;

(24) substituted pyrazinyl substituted on nitrogen or carbon with one or two substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) phenyl,

(e) —

S—

C_1-6 alkyl,

(f) —

CN,

(g) hydroxy,

(h) phenyloxy,

(i) —

C_0-6 alkyl-N(R⁷)₂,

(k) oxo, and

(l) substituted phenyloxy with 1, 2, or 3 substituents selected from;

(i) halogen,

(ii) C_1-6 alkyl,

(iii) —

CF₃, and

(iv) hydroxy;

(25) pyrimidinyl;

(26) substituted pyrimidinyl substituted on nitrogen or carbon with one or two substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) phenyl,

(e) —

S—

C_1-6 alkyl,

(f) —

CN,

(g) hydroxy,

(h) phenyloxy,

(i) —

C_0-6 alkyl-N(R⁷)₂,

(k) oxo, and

(l) substituted phenyloxy with 1, 2, or 3 substituents selected from;

(i) halogen,

(ii) C_1-6 alkyl,

(iii) —

CF₃, and

(iv) hydroxy;

(27) triazolyl;

(28) substituted triazolyl with one or two substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) phenyl,

(e) —

S—

C_1-6 alkyl,

(f) —

CN,

(g) hydroxy,

(h) phenyloxy,

(i) —

C_0-6 alkyl-N(R⁷)₂,

(k) oxo, and

(l) substituted phenyloxy with 1, 2, or 3 substituents selected from;

(i) halogen,

(ii) C_1-6 alkyl,

(iii) —

CF₃, and

(iv) hydroxy;

(29) tetrazolyl;

(30) substituted tetrazolyl with a substituent selected from;

(a) halogen,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) phenyl,

(e) —

S—

C_1-6 alkyl,

(f) —

CN,

(g) hydroxy,

(h) phenyloxy,

(i) —

C_0-6 alkyl-N(R⁷)₂,

(k) oxo, and

(l) substituted phenyloxy with 1, 2, or 3 substituents selected from;

(i) halogen,

(ii) C_1-6 alkyl,

(iii) —

CF₃, and

(iv) hydroxy;

(31) C_3-6 cycloalkyl;

(32) substituted C_3-6 cycloalkyl substituted with one or two substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O,

(h) benzyl, and

(i) hydroxy;

(33) tetrahydrofuran;

(34) substituted tetrahydrofuran substituted with one or two substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O,

(h) benzyl, and

(i) hydroxy;

(35) piperazinyl;

(36) substituted piperazinyl substituted with one or two substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O,

(h) benzyl, and

(i) hydroxy;

(37) benzotriazolyl,

(38) substituted benzotriazolyl substituted on a carbon atom with one or two substituents independently selected from;

(a) -halogen,

(b) —

C_1-6 alkyl,

(c) —

C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN, and

(g) -hydroxy;

(39) benzoimidazolyl,

(40) substituted benzoimidazolyl substituted on a carbon atom with one or two substituents independently selected from;

(a) -halogen,

(b) —

C_1-6 alkyl,

(c) —

C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN, and

(g) -hydroxy;

each R⁴ is independently selected from;

(1) —

H,

(2) —

C_1-4 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_2-3 alkenyl,

(6) —

C_1-3 alkyl-R³,

(7) —

C_2-3 alkenyl-R³, and

(8) —

C(O)—

R³;

each R⁵ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_2-3 alkenyl,

(6) —

C_1-3 alkyl-R³,

(7) —

S(O)_n—

R³,

(8) —

C(O)—

R³,

(9) —

C(O)OR4, and

(10) —

C(O)C(O)OH;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

each R⁷ is independently selected from;

(1) —

H, and

(2) —

C_1-6 alkyl;

R⁸ is selected from hydrogen, methyl and —

O—

C_1-6 alkyl;

R⁹ is selected from;

(1) —

H,

(2) —

O—

C_1-3 alkyl,

(3) —

OH, and

(4) oxo;

and each n is independently selected from 0, 1 and 2; and

PROVIDED THAT when A is phenyl;

(1) R¹ is not;

(a) phenyl para to the dioxobutyric acid moiety,

(b) substituted phenyl para to the dioxobutyric acid moiety,

(c) —

C_1-3 alkyl phenyl para to the dioxobutyric acid moiety, or

(d) substituted —

C_1-3 alkyl phenyl para to the dioxobutyric acid moiety; and

(2) R² is not selected from;

(a) phenyl para to the dioxobutyric acid moiety,

(b) substituted phenyl para to the dioxobutyric acid moiety,

(c) —

C_1-6 alkyl phenyl para to the dioxobutyric acid moiety, and

(d) substituted —

C_1-6 alkyl phenyl para to the dioxobutyric acid moiety; and

(3) at least one of R¹, R², and R⁸ is not;

(a) —

H,

(b) C_1-6 alkyl, or

(c) R³ wherein R³ is cycloalkyl.

2. The compound according to claim 1, and tautomers and pharmaceutically acceptable salts thereof, wherein:

A is phenyl;

R¹ is selected from;

(1) —

H,

(2) —

CH₃,

(3) —

C_1-6 alkyl-OR⁷;

(4) —

O—

C_1-6 alkyl-OR⁷,

(5) —

O—

C_1-6 alkyl-SR⁷,

(6) —

CF₃ or —

CH₂CF₃,

(7) —

Cl,

(8) —

F,

(9) —

C_0-3 alkyl —

N(R⁴)(R⁵),

(10) -phenyl,

(11) phenyl C_1-3 alkyl-, wherein the phenyl group may be unsubstituted or substituted with 1 to four substituents independently selected from;

(a) —

F, —

Cl, or —

Br,

(b) CH₃,

(c) —

OCH₃, OCH₂CH₃, OCF₃, or OCH₂CF₃,

(d) —

CF₃,

(e) —

SCH₃,

(f) —

CN,

(g) hydroxy, and

(h) —

C_0-6 alkyl-N(R⁷)₂,

(12) —

O—

CH₂-phenyl, wherein the phenyl group may be unsubstituted or substituted with 1 to four substituents independently selected from;

(a) —

F, —

Cl, or —

Br,

(b) CH₃,

(c) —

OCH₃, OCH₂CH₃, OCF₃, or OCH₂CF₃,

(d) —

CF₃,

(e) —

SCH₃,

(f) —

CN,

(g) hydroxy, and

(h) —

C_0-6 alkyl-N(R⁷)₂,

(13) —

O—

C_1-6 alkyl, unsubstituted or substituted with one to three fluorine atoms,

(14) —

C(O)CH₂C(O)C(O)OH;

(15) —

O—

C_1-6 alkyl-NH—

C(O)—

OR⁷;

(16) —

O—

CH₂CH₂N(CH₃)₂,

(17) —

O—

CH(CH₃)CH₂N(CH₃)₂,

(18) —

O—

CH₂CH₂NH₂,

(19) —

O—

CH(CH₃)CH₂NH₂,

(20) —

S—

CH₃,

(21) —

CH₂—

CH(OH)—

CH₂—

O—

R⁷, and

(22) —

C(OH)(CH₃)—

CH₂N(R⁴)(R⁵);

R² is selected from;

(1) —

R³,

(2) —

C_1-6 alkyl substituted with R³, wherein one or more of the hydrogen atoms on C_1-6 alkyl may be replaced with a fluorine atom,

(3) —

O—

C_1-6 alkyl-SR⁶;

(4) —

C_1-6 alkyl (OR⁶)(R⁴),

(5) —

C_0-6 alkyl-N(R⁴)(R⁶),

(6) —

C_0-6 alkyl C(O)—

R⁶,

(7) —

C_0-6 alkyl C(O)CH₂—

C(O)—

OH,

(8) —

C_1-6 alkyl NR⁴C(O)—

R⁶,

(9) —

C_1-6 alkyl-C(O)N(R⁴)(R⁵), and

(10) —

CH₂(OR⁷)—

R⁶;

each R³ is independently selected from;

(1) phenyl;

(2) substituted phenyl with 1, 2, 3 or 4 substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) —

CN,

(e) hydroxy, and

(f) oxo;

(3) thienyl,

(4) substituted thienyl substituted on carbon with one or two substituents independently selected from;

(a) halogen, selected from F, Cl, and Br,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, and

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom;

(5) pyridyl,

(6) substituted pyridyl substituted on carbon with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br;

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) hydroxy, and

(e) oxo;

(7) pyrrolyl,

(8) pyrazolyl

(9) substituted pyrazolyl substituted on carbon with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br;

(b) —

CH₃,

(c) —

CF₃,

(d) —

OCH₃,

(e) —

OCF₃, and

(f) hydroxy;

(10) C_3-5 cycloalkyl fused with a phenyl ring,

(11) substituted C_3-5 cycloalkyl fused with a phenyl ring substituted on carbon with 1 or 2 substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) CH₃,

(c) methyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy;

(12) piperidinyl,

(13) substituted piperidinyl substituted on carbon with one or two substituents independently selected from;

(a) halogen selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) ═

O, and

(g) hydroxy;

(14) substituted morpholinyl substituted on carbon or nitrogen with 1 or 2 substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃, and

(f) hydroxy;

(15) hexahydrothieno[3,4-d]imidazolyl,

(16) naphthyl,

(17) substituted naphthyl with 1, 2, or 3 substituents independently selected from;

(a) -halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN, and

(g) -hydroxy,

(18) indolyl, and

(19) substituted 1,2,3,4-tetrahydronaphthalenyl substituted on carbon with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy;

(20) pyrazinyl;

(21) substituted pyrazinyl substituted on nitrogen or carbon with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) hydroxy,

(e) phenyloxy,

(f) —

C_0-6 alkyl-N(R⁷)₂, and

(22) pyrimidinyl;

(23) substituted pyrimidinyl substituted on nitrogen or carbon with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-, and

(d) phenyl,

(24) triazolyl;

(25) substituted triazolyl with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-, and

(d) hydroxy,

(26) tetrazolyl;

(27) substituted tetrazolyl with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-, and

(d) hydroxy,

(28) C_3-6 cycloalkyl;

(29) substituted C_3-6 cycloalkyl substituted with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃,

(30) tetrahydrofuran;

(31) substituted tetrahydrofuran substituted with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃,

(32) piperazinyl;

(33) substituted piperazinyl substituted with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) benzyl, and

(g) hydroxy;

(34) benzotriazolyl,

(35) substituted benzotriazolyl substituted on carbon with one or two substituents independently selected from;

(a) -halogen, selected from —

F, —

Cl, and —

Br,

(b) -methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃,

(36) benzoimidazolyl, and

(37) substituted benzoimidazolyl substituted on carbon with one or two substituents independently selected from;

(a) -halogen, selected from —

F, —

Cl, and —

Br,

(b) -methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃;

each R⁴ is independently selected from;

(1) —

H,

(2) —

C_1-4 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³, and

(6) —

C(O)—

R³;

each R⁵ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³,

(6) —

C(O)—

R³,

(7) —

C(O)OR⁴, and

(8) —

C(O)C(O)OH;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

each R⁷ is independently selected from;

(1) —

H, and

(2) —

C_1-6 alkyl;

R⁸ is selected from hydrogen, methyl and —

O—

C_1-6 alkyl; and

R⁹ is selected from;

(1) —

H,

(2) —

O—

C_1-3 alkyl,

(3) —

OH, and

(4) oxo; and

PROVIDED THAT;

(1) R¹ is not;

(a) phenyl para to the dioxobutyric acid/ester moiety,

(b) substituted phenyl para to the dioxobutyric acid moiety,

(c) C_1-3 alkyl phenyl para to the dioxobutyric acid moiety, or

(d) substituted —

C_1-3 alkyl phenyl para to the dioxobutyric acid moiety; and

(2) R² is not selected from;

(a) phenyl para to the dioxobutyric acid moiety,

(b) substituted phenyl para to the dioxobutyric acid moiety,

(c) —

C_1-6 alkyl phenyl para to the dioxobutyric acid moiety, and

(d) substituted —

C_1-6 alkyl phenyl para to the dioxobutyric acid moiety; and

(3) at least one of R¹, R², and R⁸ is not;

(a) —

H,

(b) C_1-6 alkyl, or

(c) R³ wherein R³ is cycloalkyl.

3. The compound according to claim 2, and tautomers and pharmaceutically acceptable salts thereof, wherein:

R¹ is selected from;

(1) —

H,

(2) —

CH₃,

(3) —

CH₂OCH₃,

(4) —

OCH₂CH₂OH,

(5) —

OCH₂CH₂OCH₃,

(6) —

(CH₂)₆—

OH,

(7) —

CF₃,

(8) —

F,

(9) —

Cl,

(10) —

C_0-3 alkyl-N(R⁴)(R⁵),

(11) -phenyl,

(12) phenyl C_1-3 alkyl-, wherein the phenyl group may be unsubstituted or substituted with 1 to four substituents independently selected from;

(a) —

F, —

Cl, or —

Br,

(b) CH₃,

(c) —

OCH₃, OCH₂CH₃, OCF₃, or OCH₂CF₃,

(d) —

CF₃,

(e) —

CN,

(f) hydroxy,

(g) —

C_0-6 alkyl-N(R⁷)₂,

(13) —

O—

CH₂-phenyl, wherein the phenyl group may be unsubstituted or substituted with 1 to four substituents independently selected from;

(a) —

F, —

Cl, or —

Br,

(b) CH₃,

(c) —

OCH₃, OCH₂CH₃, OCF₃, or OCH₂CF₃,

(d) —

CF₃,

(e) —

CN,

(f) hydroxy,

(g) —

C_0-6 alkyl-N(R⁷)₂,

(14) —

O—

CH₃,

(15) —

OCH₂CH₃,

(16) —

OCH₂CF₃,

(17) —

OCF₃,

(18) —

OCH(CH₃)₂,

(19) —

C(O)CH₂C(O)C(O)OH,

(20) —

O—

C_1-6 alkyl-NH—

C(O)—

OR⁷,

(21) —

O—

CH₂CH₂N(CH₃)₂,

(22) —

O—

CH(CH₃)CH₂N(CH₃)₂,

(23) —

O—

CH₂CH₂NH₂,

(24) —

O—

CH(CH₃)CH₂NH₂,

(25) —

S—

CH₃,

(26) —

CH₂—

CH(OH)—

CH₂—

O—

R⁷, and

(27) —

C(OH)(CH₃)—

CH₂N(R⁴)(R⁵);

R² is selected from;

(1) —

R³,

(2) —

CH₂—

R³,

(3) —

CH₂CH₂—

R³,

(4) —

CF₂—

R³,

(5) —

CH(CH₃)—

R³,

(6) —

C_1-6 alkyl (OR⁶)(R⁴),

(7) —

C_0-6 alkyl-N(R⁴)(R⁶),

(8) —

C(O)—

R³,

(9) —

C_0-6 alkyl C(O)CH₂—

C(O)—

OH,

(10) —

C_1-6 alkyl NR⁴C(O)—

R⁶,

(11) —

CH(OCH₃)R³, and

(12) —

CH(OH)R³;

each R³ is independently selected from;

(1) phenyl;

(2) substituted phenyl with 1, 2, or 3 substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) —

CH₃,

(c) methyloxy-,

(d) ethyloxy-,

(e) —

OCH₂CF₃,

(f) —

OCF₂CH₃,

(g) —

CF₃,

(h) —

CH₂CF₃,

(i) —

CF₂CH₃,

(j) —

OCF₃,

(k) —

CN, and

(l) hydroxy;

(3) thienyl,

(4) substituted thienyl substituted on a carbon atom with a substituent selected from;

(a) F,

(b) Cl, and

(c) methyl;

(5) pyridyl,

(6) substituted pyridyl substituted on a carbon with a substituent selected from;

(a) —

F,

(b) —

Cl,

(c) —

CH₃,

(d) —

CF₃,

(e) —

OCH₃,

(f) —

OCF₃,

(g) hydroxy, and

(h) oxo;

(7) pyrazolyl

(8) substituted pyrazolyl substituted on carbon with one or two substituents independently selected from;

(a) —

F,

(b) —

Cl,

(c) —

CH₃, and

(d) —

CF₃;

(9) C_3-5 cycloalkyl fused with a phenyl ring,

(10) piperidinyl,

(11) substituted piperidinyl substituted on carbon with a substituent selected from;

(a) methoxy-,

(b) —

OCF₃,

(c) ═

O, and

(d) hydroxy;

(12) naphthyl,

(13) pyrazinyl;

(14) substituted pyrazinyl substituted on nitrogen or carbon with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) —

CF₃,

(d) methoxy-,

(e) —

N(CH₃)₂, and

(15) pyrimidinyl,

(16) [1,2,3]-triazolyl,

(17) [1,2,4]-triazolyl,

(18) tetrazolyl;

(19) cyclopropyl,

(20) cyclobutyl,

(21) cyclopentyl,

(22) cyclohexyl,

(23) tetrahydrofuran,

(24) piperazinyl,

(25) substituted piperazinyl substituted with a substituent selected from;

(a) —

F,

(b) —

Cl,

(c) methyl,

(d) —

CF₃, and

(e) benzyl,

(26) benzotriazolyl, and

(27) benzoimidazolyl;

each R⁴ is independently selected from;

(1) —

H,

(2) —

C_1-4 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³, and

(6) —

C(O)—

R³;

each R⁵ is independently selected from;

(1) —

H,

(2) —

CH₃,

(3) —

CF₃,

(4) phenyl,

(5) -benzyl,

(6) —

C(O)OR⁴, and

(7) —

C(O)C(O)OH;

each R⁶ is independently selected from;

(1) —

C₁₃ alkyl-R³, and

(2) —

R³;

each R⁷ is independently selected from;

(1) —

H, and

(2) —

C_1-6 alkyl;

R⁸ is selected from;

(1) —

H,

(2) methoxy, and

(3) —

C_1-6 alkyl; and

R⁹ is selected from;

(1) —

H,

(2) —

O—

C_1-3 alkyl,

(3) —

OH, and

(4) oxo; and

PROVIDED THAT;

(1) R¹ is not;

(a) phenyl para to the dioxobutyric acid moiety,

(b) substituted phenyl para to the dioxobutyric acid moiety,

(c) C_1-3 alkyl phenyl para to the dioxobutyric acid moiety, or

(d) substituted —

C_1-3 alkyl phenyl para to the dioxobutyric acid moiety; and

(2) R² is not selected from;

(a) phenyl para to the dioxobutyric acid moiety,

(b) substituted phenyl para to the dioxobutyric acid moiety,

(c) —

C_1-6 alkyl phenyl para to the dioxobutyric acid moiety, and

(d) substituted —

C_1-6 alkyl phenyl para to the dioxobutyric acid moiety; and

(3) at least one of R¹, R², R⁸ and R⁹ is not;

(a) —

H,

(b) C1-6 alkyl, or

(c) R³ wherein R³ is cycloalkyl.

4. The compound according to claim 1 of structural formula:

and tautomers and pharmaceutically acceptable salts thereof, wherein;

R¹ is selected from;

(1) —

H,

(2) —

CH₃,

(3) —

C_1-6 alkyl-OR⁷;

(4) —

O—

C_1-6 alkyl-OR⁷,

(5) —

O—

C_1-6 alkyl-SR⁷,

(6) —

CF₃ or —

CH₂CF₃,

(7) —

Cl,

(8) —

F,

(9) —

C_0-3 alkyl —

N(R⁴)(R⁵),

(10) -phenyl,

(11) phenyl C_1-3 alkyl-, wherein the phenyl group may be unsubstituted or substituted with 1 to four substituents independently selected from;

(a) —

F, —

Cl, or —

Br,

(b) —

CH₃,

(c) —

OCH₃, OCH₂CH₃, OCF₃, or OCH₂CF₃,

(e) —

CF₃,

(f) —

SCH₃,

(g) —

CN,

(h) hydroxy,

(i) —

C_0-6 alkyl-N(R⁷)₂,

(12) —

O—

CH₂-phenyl, wherein the phenyl group may be unsubstituted or substituted with 1 to four substituents independently selected from;

(a) —

F, —

Cl, or —

Br,

(b) CH₃,

(c) —

OCH₃, —

OCH₂CH₃, —

OCF₃, or —

OCH₂CF₃,

(e) —

CF₃,

(f) —

SCH₃,

(g) —

CN,

(h) hydroxy,

(i) —

C_0-6 alkyl-N(R⁷)₂,

(13) —

O—

C_1-6 alkyl, unsubstituted or substituted with one to three fluorine atoms,

(14) —

C(O)CH₂C(O)C(O)OH,

(15) —

O—

C_1-6 alkyl-NH—

C(O)—

OR⁷,

(16) —

O—

CH₂CH₂N(CH₃)₂,

(17) —

O—

CH(CH₃)CH₂N(CH₃)₂,

(18) —

O—

CH₂CH₂NH₂,

(19) —

O—

CH(CH₃)CH₂NH₂,

(20) —

S—

CH₃,

(21) —

CH₂—

CH(OH)—

CH₂—

O—

R⁷, and

(22) —

C(OH)(CH₃)—

CH₂N(R⁴)(R⁵);

R² is selected from;

(1) —

R³;

(2) —

C_1-6 alkyl substituted with R³, wherein one or more of the hydrogen atoms on C_1-6 alkyl may be replaced with a fluorine atom,

(3) —

O—

C_1-6 alkyl-SR⁶,

(4) —

C_1-6 alkyl (OR⁶)(R⁴),

(5) —

C_0-6 alkyl-N(R⁴)(R⁶),

(6) —

C_0-6 alkyl C(O)—

R⁶,

(7) —

C_0-6 alkyl C(O)CH₂—

C(O)—

OH,

(8) —

C_1-6 alkyl NR⁴C(O)—

R⁶,

(9) —

C_1-6 alkyl-C(O)N(R⁴)(R⁵), and

(10) —

CH₂(OR⁷)—

R⁶;

each R³ is independently selected from;

(1) phenyl;

(2) substituted phenyl with 1, 2, 3 or 4 substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) —

CN,

(e) hydroxy, and

(f) oxo;

(3) thienyl,

(4) substituted thienyl substituted on carbon with one or two substituents independently selected from;

(a) halogen, selected from F, Cl, and Br,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, and

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom;

(5) pyridyl,

(6) substituted pyridyl substituted on carbon with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br;

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) hydroxy, and

(e) oxo;

(7) pyrrolyl,

(8) pyrazolyl

(9) substituted pyrazolyl substituted on carbon with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br;

(b) —

CH₃,

(c) —

CF₃,

(d) —

OCH₃,

(e) —

OCF₃, and

(f) hydroxy;

(10) C_3-5 cycloalkyl fused with a phenyl ring,

(11) substituted C_3-5 cycloalkyl fused with a phenyl ring substituted on carbon with 1 or 2 substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) CH₃,

(c) methyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy;

(12) piperidinyl,

(13) substituted piperidinyl substituted on carbon with one or two substituents independently selected from;

(a) halogen selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) ═

O, and

(g) hydroxy;

(14) substituted morpholinyl substituted on carbon or nitrogen with 1 or 2 substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃, and

(f) hydroxy;

(15) hexahydrothieno[3,4-d]imidazolyl,

(16) naphthyl,

(17) substituted naphthyl with 1, 2, or 3 substituents independently selected from;

(a) -halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN, and

(g) -hydroxy,

(18) indolyl,

(19) substituted 1,2,3,4-tetrahydronaphthalenyl substituted on carbon with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy;

(20) pyrazinyl;

(21) substituted pyrazinyl substituted on nitrogen or carbon with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) hydroxy,

(e) phenyloxy,

(f) —

C_0-6 alkyl-N(R⁷)₂, and

(22) pyrimidinyl;

(23) substituted pyrimidinyl substituted on nitrogen or carbon with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-, and

(d) phenyl,

(24) triazolyl;

(25) substituted triazolyl with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-, and

(d) hydroxy,

(26) tetrazolyl;

(27) substituted tetrazolyl with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-, and

(d) hydroxy,

(28) C_3-6 cycloalkyl;

(29) substituted C_3-6 cycloalkyl substituted with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃,

(30) tetrahydrofuran;

(31) substituted tetrahydrofuran substituted with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃,

(32) piperazinyl;

(33) substituted piperazinyl substituted with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) benzyl, and

(g) hydroxy;

(34) benzotriazolyl,

(35) substituted benzotriazolyl substituted on carbon with one or two substituents independently selected from;

(a) -halogen, selected from —

F, —

Cl, and —

Br,

(b) -methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃,

(36) benzoimidazolyl, and

(37) substituted benzoimidazolyl substituted on carbon with one or two substituents independently selected from;

(a) -halogen, selected from —

F, —

Cl, and —

Br,

(b) -methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃;

each R⁴ is independently selected from;

(1) —

H,

(2) —

C_1-4 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³, and

(6) —

C(O)—

R³;

each R⁵ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³,

(6) —

C(O)—

R³,

(7) —

C(O)OR⁴, and

(8) —

C(O)C(O)OH;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³; and

each R⁷ is independently selected from;

(1) —

H, and

(2) —

C_1-6 alkyl; and

PROVIDED THAT;

(1) at least one of R¹ and R² is not;

(a) H,

(b) C_1-6 alkyl, or

(c) R³ wherein R³ is cycloalkyl.

5. The compound according to claim 1 of structural formula:

and tautomers and pharmaceutically acceptable salts thereof, wherein;

R¹ is selected from;

(1) —

H,

(2) —

CH₃,

(3) —

C_1-6 alkyl-OR⁷;

(4) —

O—

C_1-6 alkyl-OR⁷,

(5) —

O—

C_1-6 alkyl-SR⁷,

(6) —

CF₃ or —

CH₂CF₃,

(7) —

Cl,

(8) —

F,

(9) —

C_0-3 alkyl —

N(R⁴)(R⁵),

(10) -phenyl,

(11) phenyl C_1-3 alkyl-, wherein the phenyl group may be unsubstituted or substituted with 1 to four substituents independently selected from;

(a) —

F, —

Cl, or —

Br,

(b) CH₃,

(c) —

OCH₃, OCH₂CH₃, OCF₃, or OCH₂CF₃,

(d) —

CF₃,

(e) —

SCH₃,

(f) —

CN,

(g) hydroxy, and

(h) —

C_0-6 alkyl-N(R⁷)₂,

(12) —

O—

CH₂-phenyl, wherein the phenyl group may be unsubstituted or substituted with 1 to four substituents independently selected from;

(a) —

F, —

Cl, or —

Br,

(b) —

CH₃,

(c) —

OCH₃, OCH₂CH₃, OCF₃, or OCH₂CF₃,

(d) —

CF₃,

(e) —

SCH₃,

(f) —

CN,

(g) hydroxy, and

(h) —

C_0-6 alkyl-N(R⁷)₂,

(13) —

O—

C_1-6 alkyl, unsubstituted or substituted with one to three fluorine atoms,

(14) —

C(O)CH₂C(O)C(O)OH,

(15) —

O—

C_1-6 alkyl-NH—

C(O)—

OR⁷,

(16) —

O—

CH₂CH₂N(CH₃)₂,

(17) —

O—

CH(CH₃)CH₂N(CH₃)₂,

(18) —

O—

CH₂CH₂NH₂,

(19) —

O—

CH(CH₃)CH₂NH₂,

(20) —

S—

CH₃,

(21) —

CH₂—

CH(OH)—

CH₂—

O—

R⁷, and

(22) —

C(OH)(CH₃)—

CH₂N(R⁴)(R⁵);

R² is selected from;

(1) —

R³,

(2) —

C_1-6 alkyl substituted with R³, wherein one or more of the hydrogen atoms on C_1-6 alkyl may be replaced with a fluorine atom,

(3) —

O—

C_1-6 alkyl-SR⁶;

(4) —

C_1-6 alkyl (OR⁶)(R⁴),

(5) —

C_0-6 alkyl-N(R⁴)(R⁶),

(6) —

C_0-6 alkyl C(O)—

R⁶,

(7) —

C_0-6 alkyl C(O)CH₂—

C(O)—

OH,

(8) —

C_1-6 alkyl NR⁴C(O)—

R⁶,

(9) —

C_1-6 alkyl-C(O)N(R⁴)(R⁵), and

(10) —

CH₂(OR⁷)—

R⁶;

each R³ is independently selected from;

(1) phenyl,

(2) substituted phenyl with 1, 2, 3 or 4 substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) —

CN,

(e) hydroxy, and

(f) oxo;

(3) thienyl,

(4) substituted thienyl substituted on carbon with one or two substituents independently selected from;

(a) halogen, selected from F, Cl, and Br,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, and

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom;

(5) pyridyl,

(6) substituted pyridyl substituted on carbon with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br;

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) hydroxy, and

(e) oxo;

(7) pyrrolyl,

(8) pyrazolyl

(9) substituted pyrazolyl substituted on carbon with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br;

(b) —

CH₃,

(c) —

CF₃,

(d) —

OCH₃,

(e) —

OCF₃, and

(f) hydroxy;

(10) C_3-5 cycloalkyl fused with a phenyl ring,

(11) substituted C_3-5 cycloalkyl fused with a phenyl ring substituted on carbon with 1 or 2 substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) CH₃,

(c) methyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy;

(12) piperidinyl,

(13) substituted piperidinyl substituted on carbon with one or two substituents independently selected from;

(a) halogen selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) ═

O, and

(g) hydroxy;

(14) substituted morpholinyl substituted on carbon or nitrogen with 1 or 2 substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃, and

(f) hydroxy;

(15) hexahydrothieno[3,4-d]imidazolyl,

(16) naphthyl,

(17) substituted naphthyl with 1, 2, or 3 substituents independently selected from;

(a) -halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN, and

(g) -hydroxy,

(18) indolyl,

(19) substituted 1,2,3,4-tetrahydronaphthalenyl substituted on carbon with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy;

(20) pyrazinyl;

(21) substituted pyrazinyl substituted on nitrogen or carbon with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) hydroxy,

(e) phenyloxy,

(f) —

C_0-6 alkyl-N(R⁷)₂, and

(22) pyrimidinyl;

(23) substituted pyrimidinyl substituted on nitrogen or carbon with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-, and

(d) phenyl,

(24) triazolyl;

(25) substituted triazolyl with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-, and

(d) hydroxy,

(26) tetrazolyl;

(27) substituted tetrazolyl with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-, and

(d) hydroxy,

(28) C_3-6 cycloalkyl;

(29) substituted C_3-6 cycloalkyl substituted with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃,

(30) tetrahydrofuran;

(31) substituted tetrahydrofuran substituted with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃,

(32) piperazinyl;

(33) substituted piperazinyl substituted with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) benzyl, and

(g) hydroxy;

(34) benzotriazolyl,

(35) substituted benzotriazolyl substituted on carbon with one or two substituents independently selected from;

(a) -halogen, selected from —

F, —

Cl, and —

Br,

(b) -methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃,

(36) benzoimidazolyl, and

(37) substituted benzoimidazolyl substituted on carbon with one or two substituents independently selected from;

(a) -halogen, selected from —

F, —

Cl, and —

Br,

(b) -methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃;

each R⁴ is independently selected from;

(1) —

H

(2) —

C_1-4 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³, and

(6) —

C(O)—

R³;

each R⁵ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³,

(6) —

C(O)—

R³,

(7) —

C(O)OR⁴, and

(8) —

C(O)C(O)OH;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

each R⁷ is independently selected from;

(1) —

H, and

(2) —

C_1-6 alkyl;

R⁸ is selected from methyl and —

O—

C_1-6 alkyl; and

PROVIDED THAT;

(1) at least one of R¹, R², and R⁸ is not;

(a) C_1-6 alkyl, or

(b) R³ wherein R³ is cycloalkyl.

6. The compound according to claim 1 of structural formula:

and tautomers and pharmaceutically acceptable salts thereof, wherein;

R¹ is selected from;

(1) —

H,

(2) —

CH₃,

(3) —

C_1-6 alkyl-OR⁷;

(4) —

O—

C_1-6 alkyl-OR⁷,

(5) —

O—

C_1-6 alkyl-SR⁷,

(6) —

CF₃ or —

CH₂CF₃,

(7) —

Cl,

(8) —

F,

(9) —

C_0-3 alkyl-N(R⁴)(R⁵),

(10) -phenyl,

(11) phenyl C_1-3 alkyl-, wherein the phenyl group may be unsubstituted or substituted with 1 to four substituents independently selected from;

(a) —

F, —

Cl, or —

Br,

(b) CH₃,

(c) —

OCH₃, OCH₂CH₃, OCF₃, or OCH₂CF₃,

(d) —

CF₃,

(e) —

SCH₃,

(f) —

CN,

(g) hydroxy,

(h) —

C_0-6 alkyl-N(R⁷)₂,

(12) —

O—

CH₂-phenyl, wherein the phenyl group may be unsubstituted or substituted with 1 to four substituents independently selected from;

(a) —

F, —

Cl, or —

Br,

(b) CH₃,

(c) —

OCH₃, OCH₂CH₃, OCF₃, or OCH₂CF₃,

(d) —

CF₃,

(e) —

SCH₃,

(f) —

CN,

(g) hydroxy,

(h) —

C_0-6 alkyl-N(R⁷)₂,

(13) —

O—

C_1-6 alkyl, unsubstituted or substituted with one to three fluorine atoms,

(14) —

C(O)CH₂C(O)C(O)OH,

(15) —

O—

C_1-6 alkyl-NH—

C(O)—

OR⁷,

(16) —

O—

CH₂CH₂N(CH₃)₂,

(17) —

O—

CH(CH₃)CH₂N(CH₃)₂,

(18) —

O—

CH₂CH₂NH₂,

(19) —

O—

CH(CH₃)CH₂NH₂,

(20) —

S—

CH₃,

(21) —

CH₂—

CH(OH)—

CH₂—

O—

R⁷, and

(22) —

C(OH)(CH₃)—

CH₂N(R⁴)(R⁵);

R² is selected from;

(1) —

R³,

(2) —

C_1-6 alkyl substituted with R³, wherein one or more of the hydrogen atoms on C_1-6 alkyl may be replaced with a fluorine atom,

(3) —

O—

C_1-6 alkyl-SR⁶,

(4) —

C_1-6 alkyl-(OR⁶)(R⁴),

(5) —

C_0-6 alkyl-N(R⁴)(R⁶),

(6) —

C_0-6 alkyl-C(O)—

R⁶,

(7) —

C_0-6 alkyl-C(O)CH₂—

C(O)—

OH,

(8) —

C_1-6 alkyl-NR⁴C(O)—

R⁶,

(9) —

C_1-6 alkyl-C(O)N(R⁴)(R⁵), and

(10) —

CH₂(OR⁷)—

R⁶;

each R³ is independently selected from;

(1) phenyl,

(2) substituted phenyl with 1, 2, 3 or 4 substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) —

CN,

(e) hydroxy, and

(f) oxo;

(3) thienyl,

(4) substituted thienyl substituted on carbon with one or two substituents independently selected from;

(a) halogen, selected from F, Cl, and Br,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, and

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom;

(5) pyridyl,

(6) substituted pyridyl substituted on carbon with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br;

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) hydroxy, and

(e) oxo;

(7) pyrrolyl,

(8) pyrazolyl

(9) substituted pyrazolyl substituted on carbon with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br;

(b) —

CH₃,

(c) —

CF₃,

(d) —

OCH₃,

(e) —

OCF₃, and

(f) hydroxy;

(10) C_3-5 cycloalkyl fused with a phenyl ring,

(11) substituted C_3-5 cycloalkyl fused with a phenyl ring substituted on carbon with 1 or 2 substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) CH₃,

(c) methyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy;

(12) piperidinyl,

(13) substituted piperidinyl substituted on carbon with one or two substituents independently selected from;

(a) halogen selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) ═

O, and

(g) hydroxy;

(14) substituted morpholinyl substituted at carbon or nitrogen with 1 or 2 substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃, and

(f) hydroxy;

(15) hexahydrothieno[3,4-d]imidazolyl,

(16) naphthyl,

(17) substituted naphthyl with 1, 2, or 3 substituents independently selected from;

(a) -halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN, and

(g) -hydroxy,

(18) indolyl, and

(19) substituted 1,2,3,4-tetrahydronaphthalenyl substituted on carbon with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy;

(20) pyrazinyl;

(21) substituted pyrazinyl substituted on nitrogen or carbon with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) hydroxy,

(e) phenyloxy,

(f) —

C_0-6 alkyl-N(R⁷)₂, and

(22) pyrimidinyl;

(23) substituted pyrimidinyl substituted on nitrogen or carbon with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-, and

(d) phenyl,

(24) triazolyl;

(25) substituted triazolyl with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-, and

(d) hydroxy,

(26) tetrazolyl;

(27) substituted tetrazolyl with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-, and

(d) hydroxy,

(28) C_3-6 cycloalkyl;

(29) substituted C_3-6 cycloalkyl substituted with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃,

(30) tetrahydrofuran;

(31) substituted tetrahydrofuran substituted with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃,

(32) piperazinyl;

(33) substituted piperazinyl substituted with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) benzyl, and

(g) hydroxy;

(34) benzotriazolyl,

(35) substituted benzotriazolyl substituted on carbon with one or two substituents independently selected from;

(a) -halogen, selected from —

F, —

Cl, and —

Br,

(b) -methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃,

(36) benzoimidazolyl, and

(37) substituted benzoimidazolyl substituted on carbon with one or two substituents independently selected from;

(a) -halogen, selected from —

F, —

Cl, and —

Br,

(b) -methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃;

each R⁴ is independently selected from;

(1) —

H,

(2) —

C_1-4 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³, and

(6) —

C(O)—

R³;

each R⁵ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³,

(6) —

C(O)—

R³,

(7) —

C(O)OR⁴, and

(8) —

C(O)C(O)OH;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

each R⁷ is independently selected from;

(1) —

H, and

(2) —

C_1-6 alkyl; and

R⁸ is selected from methyl and —

O—

C_1-6 alkyl; and

PROVIDED THAT;

(1) at least one of R¹, R², and R⁸ is not;

(a) C_1-6 alkyl, or

(b) R³ wherein R³ is cycloalkyl.

7. The compound according to claim 1 of structural formula:

and tautomers and pharmaceutically acceptable salts thereof, wherein;

R¹ is selected from;

(1) —

H,

(2) —

CH₃,

(3) —

C_1-6 alkyl-OR⁷,

(4) —

O—

C_1-6 alkyl-OR⁷,

(5) —

O—

C_1-6 alkyl-SR⁷,

(6) —

CF₃ or —

CH₂CF₃,

(7) —

Cl,

(8) —

F,

(9) —

C_0-3 alkyl —

N(R⁴)(R⁵),

(10) -phenyl,

(11) phenyl C_1-3 alkyl-, wherein the phenyl group may be unsubstituted or substituted with 1 to four substituents independently selected from;

(a) —

F, —

Cl, or —

Br,

(b) CH₃,

(c) —

OCH₃, OCH₂CH₃, OCF₃, or OCH₂CF₃,

(d) —

CF₃,

(e) —

SCH₃,

(f) —

CN,

(g) hydroxy,

(h) —

C_0-6 alkyl-N(R⁷)₂,

(12) —

O—

CH₂-phenyl, wherein the phenyl group may be unsubstituted or substituted with 1 to four substituents independently selected from;

(a) —

F, —

Cl, or —

Br,

(b) CH₃,

(c) —

OCH₃, OCH₂CH₃, OCF₃, or OCH₂CF₃,

(d) —

CF₃,

(e) —

SCH₃,

(f) —

CN,

(g) hydroxy,

(h) —

C_0-6 alkyl-NR⁷)₂,

(13) —

O—

C_1-6 alkyl, unsubstituted or substituted with one to three fluorine atoms, and

(14) —

C(O)CH₂C(O)C(O)OH,

(15) —

O—

C_1-6 alkyl-NH—

C(O)—

OR⁷,

(16) —

O—

CH₂CH₂N(CH₃)₂,

(17) —

O—

CH(CH₃)CH₂N(CH₃)₂,

(18) —

O—

CH₂CH₂NH₂,

(19) —

O—

CH(CH₃)CH₂NH₂,

(20) —

S—

CH₃,

(21) —

CH₂—

CH(OH)—

CH₂—

O—

R⁷, and

(22) —

C(OH)(CH₃)—

CH₂N(R⁴)(R⁵);

R² is selected from;

(1) —

R³,

(2) —

C_1-6 alkyl substituted with R³, wherein one or more of the hydrogen atoms on C_1-6 alkyl may be replaced with a fluorine atom,

(3) —

O—

C_1-6 alkyl-SR⁶,

(4) —

C_1-6 alkyl (OR⁶)(R⁴),

(5) —

C_0-6 alkyl-N(R⁴)(R⁶),

(6) —

C_0-6 alkyl C(O)—

R⁶,

(7) —

C_0-6 alkyl C(O)CH₂—

C(O)—

OH,

(8) —

C_1-6 alkyl NR⁴C(O)—

R⁶,

(9) —

C_1-6 alkyl-C(O)N(R⁴)(R⁵), and

(10) —

CH₂(OR⁷)—

R⁶;

each R³ is independently selected from;

(1) phenyl;

(2) substituted phenyl with 1, 2, 3 or 4 substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) —

CN,

(e) hydroxy, and

(f) oxo;

(3) thienyl,

(4) substituted thienyl substituted on carbon with one or two substituents independently selected from;

(a) halogen, selected from F, Cl, and Br,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, and

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom;

(5) pyridyl,

(6) substituted pyridyl substituted on carbon with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br;

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) hydroxy, and

(e) oxo;

(7) pyrrolyl,

(8) pyrazolyl

(9) substituted pyrazolyl substituted on carbon with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br;

(b) —

CH₃,

(c) —

CF₃,

(d) —

OCH₃,

(e) —

OCF₃, and

(f) hydroxy;

(10) C_3-5 cycloalkyl fused with a phenyl ring,

(11) substituted C_3-5 cycloalkyl fused with a phenyl ring substituted on carbon with 1 or 2 substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) CH₃,

(c) methyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy;

(12) piperidinyl,

(13) substituted piperidinyl substituted on carbon with one or two substituents independently selected from;

(a) halogen selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) ═

O, and

(g) hydroxy;

(14) substituted morpholinyl substituted on carbon or nitrogen with 1 or 2 substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃, and

(f) hydroxy;

(15) hexahydrothieno[3,4-d]imidazolyl,

(16) naphthyl,

(17) substituted naphthyl with 1, 2, or 3 substituents independently selected from;

(a) -halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN, and

(g) -hydroxy,

(18) indolyl, and

(19) substituted 1,2,3,4-tetrahydronaphthalenyl substituted on carbon with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy;

(20) pyrazinyl;

(21) substituted pyrazinyl substituted on nitrogen or carbon with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) hydroxy,

(e) phenyloxy,

(f) —

C_0-6 alkyl-N(R⁷)₂, and

(22) pyrimidinyl;

(23) substituted pyrimidinyl substituted on nitrogen or carbon with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-, and

(d) phenyl,

(24) triazolyl;

(25) substituted triazolyl with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-, and

(d) hydroxy,

(26) tetrazolyl;

(27) substituted tetrazolyl with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-, and

(d) hydroxy,

(28) C_3-6 cycloalkyl;

(29) substituted C_3-6 cycloalkyl substituted with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃,

(30) tetrahydrofuran;

(31) substituted tetrahydrofuran substituted with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃,

(32) piperazinyl;

(33) substituted piperazinyl substituted with one or two substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) benzyl, and

(g) hydroxy;

(34) benzotriazolyl,

(35) substituted benzotriazolyl substituted on carbon with one or two substituents independently selected from;

(a) -halogen, selected from —

F, —

Cl, and —

Br,

(b) -methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃,

(36) benzoimidazolyl, and

(37) substituted benzoimidazolyl substituted on carbon with one or two substituents independently selected from;

(a) -halogen, selected from —

F, —

Cl, and —

Br,

(b) -methyl,

(c) methoxy-,

(d) —

CF₃, and

(e) —

OCF₃;

each R⁴ is independently selected from;

(1) —

H,

(2) —

C_1-4 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C₁₃ alkyl-R³, and

(6) —

C(O)—

R³;

each R⁵ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³,

(6) —

C(O)—

R³,

(7) —

C(O)OR⁴, and

(8) —

C(O)C(O)OH;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

each R⁷ is independently selected from;

(1) —

H, and

(2) —

C_1-6 alkyl; and

R⁸ is selected from methyl and —

O—

C_1-6 alkyl; and

PROVIDED THAT;

(1) at least one of R¹, R², and R⁸ is not;

(b) C_1-6 alkyl, or

(c) R³ wherein R³ is cycloalkyl.

8. The compound according to claim 1 of structural formula:

and tautomers and pharmaceutically acceptable salts thereof, wherein;

R¹ is selected from;

(1) —

H,

(2) —

CH₃,

(3) —

CH₂OCH₃,

(4) —

OCH₂CH₂OH,

(5) —

OCH₂CH₂OCH₃,

(6) —

(CH₂)₆—

OH,

(7) —

CF₃,

(8) —

F,

(9) —

Cl,

(10) —

C_0-3 alkyl-N(R⁴)(R⁵),

(11) -phenyl,

(12) phenyl C_1-3 alkyl-, wherein the phenyl group may be unsubstituted or substituted with 1 to four substituents independently selected from;

(a) —

F, —

Cl, or —

Br,

(b) CH₃,

(c) —

OCH₃, OCH₂CH₃, OCF₃, or OCH₂CF₃,

(d) —

CF₃,

(e) —

CN,

(f) hydroxy,

(g) —

C_0-6 alkyl-NR⁷)₂,

(13) —

O—

CH₂-phenyl, wherein the phenyl group may be unsubstituted or substituted with 1 to four substituents independently selected from;

(a) —

F, —

Cl, or —

Br,

(b) —

CH₃,

(c) —

OCH₃, OCH₂CH₃, OCF₃, or OCH₂CF₃,

(d) —

CF₃,

(e) —

CN,

(f) hydroxy,

(g) —

C_0-6 alkyl-N(R⁷)₂,

(14) —

O—

CH₃,

(15) —

OCH₂CH₃,

(16) —

OCH₂CF₃,

(17) —

OCF₃,

(18) —

OCH(CH₃)₂,

(19) —

C(O)CH₂C(O)C(O)OH,

(20) —

O—

C_1-6 alkyl-NH—

C(O)—

OR⁷,

(21) —

O—

CH₂CH₂ N(CH₃)₂,

(22) —

O—

CH(CH₃)CH₂N(CH₃)₂,

(23) —

O—

CH₂CH₂NH₂,

(24) —

O—

CH(CH₃)CH₂NH₂,

(25) —

S—

CH₃,

(26) —

CH₂—

CH(OH)—

CH₂—

O—

R⁷, and

(27) —

C(OH)(CH₃)—

CH₂N(R⁴)(R⁵);

R² is selected from;

(1) —

R³,

(2) —

CH₂—

R³,

(3) —

CH₂CH₂—

R³,

(4) —

CF₂—

R³,

(5) —

CH(CH₃)—

R³,

(6) —

C_1-6 alkyl (OR⁶)(R⁴),

(7) —

C_0-6 alkyl-N(R⁴)(R⁶),

(8) —

C(O)—

R³,

(9) —

C_0-6 alkyl C(O)CH₂—

C(O)—

OH,

(10) —

C_1-6 alkyl NR⁴C(O)—

R⁶,

(11) —

CH(OCH₃)R³, and

(12) —

CH(OH)R³;

each R³ is independently selected from;

(1) phenyl;

(2) substituted phenyl with 1, 2, or 3 substituents independently selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) —

CH₃,

(c) methyloxy-,

(d) ethyloxy-,

(e) —

OCH₂CF₃,

(f) —

OCF₂CH₃,

(g) —

CF₃,

(h) —

CH₂CF₃,

(i) —

CF₂CH₃,

(j) —

OCF₃,

(k) —

CN, and

(l) hydroxy;

(3) thienyl,

(4) substituted thienyl substituted on a carbon atom with a substituent selected from;

(a) F,

(b) Cl, and

(c) methyl;

(5) pyridyl,

(6) substituted pyridyl substituted on a carbon with a substituent selected from;

(a) —

F,

(b) —

Cl,

(c) —

CH₃,

(d) —

CF₃,

(e) —

OCH₃,

(f) —

OCF₃,

(g) hydroxy, and

(h) oxo;

(7) pyrazolyl

(8) substituted pyrazolyl substituted on carbon with one or two substituents independently selected from;

(a) —

F,

(b) —

Cl,

(c) —

CH₃, and

(d) —

CF₃;

(9) C_3-5 cycloalkyl fused with a phenyl ring,

(10) piperidinyl,

(11) substituted piperidinyl substituted on carbon with a substituent selected from;

(a) methoxy-,

(b) —

OCF₃,

(c) ═

O, and

(d) hydroxy;

(12) naphthyl,

(13) pyrazinyl;

(14) substituted pyrazinyl substituted on nitrogen or carbon with a substituent selected from;

(a) halogen, selected from —

F, —

Cl, and —

Br,

(b) methyl,

(c) —

CF₃,

(d) methoxy-,

(e) —

N(CH₃)₂, and

(15) pyrimidinyl,

(16) [1,2,3]-triazolyl,

(17) [1,2,4]-triazolyl,

(18) tetrazolyl;

(19) cyclopropyl,

(20) cyclobutyl,

(21) cyclopentyl,

(22) cyclohexyl,

(23) tetrahydrofuran,

(24) piperazinyl;

(25) substituted piperazinyl substituted with a substituent selected from;

(a) —

F,

(b) —

Cl,

(c) methyl,

(d) —

CF₃, and

(e) benzyl,

(26) benzotriazolyl, and

(27) benzoimidazolyl;

each R⁴ is independently selected from;

(1) —

H,

(2) —

C_1-4 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³, and

(6) —

C(O)—

R³;

each R⁵ is independently selected from;

(1) —

H,

(2) —

CH₃,

(3) —

CF₃,

(4) phenyl,

(5) -benzyl,

(6) —

C(O)OR⁴, and

(7) —

C(O)C(O)OH;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³; and

each R⁷ is independently selected from;

(1) —

H, and

(2) —

C_1-6 alkyl.

9. A compound according to claim 1, selected from:

(1) 3-biphenyl-4-yl-2,4-dioxobutanoic acid,

(17) 4-(3-dibenzylaminophenyl)-2-hydroxy4-oxobut-2-enoic acid,

(19) 4-(3-benzyl-phenyl)-2,4-dioxo-butanoic acid,

(20) 4-(4-dibenzylaminophenyl)-2-hydroxy-4-oxobut-2-enoic acid,

(21) 4-(4-benzylaminophenyl)-2-hydroxy-4-oxobut-2-enoic acid,

and tautomers and pharmaceutically acceptable salts thereof.

12. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and an effective amount of a compound according to claim 2.

13. The pharmaceutical composition according to claim 12 additionally comprising a therapeutically effective amount of an AIDS treatment agent selected from

(1) an AIDS antiviral agent,

(2) an anti-infective agent, and

(3) an immunomodulator.

14. The composition of claim 13 wherein the antiviral agent is an HIV protease inhibitor.

15. The composition of claim 14 wherein the HIV protease inhibitor is N-(2(R)-hydroxy-1-(S)-indanyl)-2(R)-phenylmethyl-4(S)-hydroxy-5-(1-(4-(3-pyridylmethyl)-2(S)-N′

-(t-butylcarboxamido)-piperazinyl))-pentaneamide or a pharmaceutically acceptable salt thereof.

20. A method of inhibiting HIV integrase which comprises administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 1, or a tautomer or pharmaceutically acceptable salt thereof.

21. A method of treating infection by HIV or of treating AIDS or ARC which comprises administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 1, a tautomer or pharmaceutically acceptable salt thereof.

10. A compound selected from the group consisting of:

(3) 4-[3-Benzyloxy-5-(6-tert-butoxycarbonylamino-hexyloxy)-phenyl]-2,4-dioxobutanoic acid,

(4) 4-(3-Benzylphenyl)-2,4-dioxobutanoic acid,

(5) 4-[3-(2-chlorobenzyl)phenyl]-2,4-dioxobutanoic acid,

(6) 4-(4-Dibenzylaminophenyl)-2,4-dioxobutanoic acid,

(7) 4-(3-Dibenzylaminophenyl)-2,4-dioxobutanoic acid,

(9) 1-(3-Benzyloxyphenyl)-2,4-dioxobutanoic acid,

(10) 1-(2-Benzyloxyphenyl)-2,4-dioxobutanoic acid,

(11) 1-[3-(4-Fluorobenzyloxy)phenyl]-2,4-dioxobutanoic acid,

(12) 1-[3-(3,4-Difluorobenzyloxy)phenyl]-2,4-dioxobutanoic acid,

(13) 4-[3-(5-methyl-thiophen-2-ylmethyl)-phenyl]-2,4-dioxo-butyric acid,

(14) 4-{3-[(methyl-phenyl-amino)-methyl]-phenyl}-2,4-dioxo-butyric acid,

(15) 4-(3-benzyl-5-pyrazin-2-yl-phenyl)-2,4-dioxo-butyric acid,

(16) 2,4-dioxo-4-[3-(1,2,3,4-tetrahydronaphthalen-1-yl)-phenyl]butyric acid,

(17) 2,4-Dioxo-4-(3-phenylsulfanyl-phenyl)-butyric acid,

(18) 4-[3-(2,4-Difluoro-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(19) 4-[5-(4-Fluoro-benzyl)-2,3-dimethoxy-phenyl]-2,4-dioxo-butyric acid,

(20) 4-(5-Benzyl-2-isopropoxyphenyl)-2,4-dioxobutyric acid,

(21) 4-[5-Benzyl-2-(2-N,N-dimethylaminoethoxy)phenyl]-2,4-dioxobutyric acid,

(22) 4-[5-Benzyl-2-(pyridin-2-yloxy)phenyl]-2,4-dioxo-butyric acid,

(23) 4-(5-Benzyl-2-isopropoxy-3-methoxyphenyl)-2,4-dioxo-butyric acid,

(24) 4-(5-Benzyl-2,3-dimethoxyphenyl)-2,4-dioxobutyric acid,

(25) 4-(5-Benzyl-3-dimethylamino-2-methoxyphenyl)-2,4-dioxobutyric acid,

(27) 4-(3-Benzyl-5-pyrazin-2-ylmethylphenyl)-2,4-dioxobutyric acid,

(28) 4-(3-Benzyl-5-[1,2,3]triazol-2-ylmethylphenyl)-2,4-dioxobutyric acid,

(29) 4-[3-(3-Chloropyridin-2-ylmethyl)phenyl]-2,4-dioxobutyric acid,

(30) 4-[5-Benzyl-2-methoxy-3-(N,N-dimethylamninomethyl) phenyl]-2,4-dioxo-butyric acid,

(31) 4-(5-benzyl-3-methoxy-2-methoxyethoxyphenyl)-2,4-dioxobutyric acid,

(32) 4-(3-Benzyl-4-methoxyphenyl)-2,4-dioxobutyric acid,

(33) 4-(5-Benzyl-2-methoxyphenyl)-2,4-dioxobutyric acid,

(34) 4-(3-Benzyl-4-fluorophenyl)-2,4-dioxobutyric acid,

(35) 4-(3-Benzyl-4-N,N-dimethylaminophenyl)-2,4-dioxobutyric acid,

(36) 4-[5-(2-Methylbenzyl)-2,3-dimethoxyphenyl]-2,4-dioxobutyric acid,

(37) 2,4-Dioxo-4-(3-pyridin-2-ylmethylphenyl)butyric acid,

(38) 4-(5-Benzyl-3-N,N-dimethylaminophenyl)-2,4-dioxobutyric acid,

(39) 4-(5-Benzyl-3-methoxyphenyl)-2,4-dioxobutyric acid,

(40) 4-(5-Benzyl-2-benzyloxy-3-methoxyphenyl)-2,4-dioxobutyric acid,

(41) 4-[5-(3-Methylbenzyl)-2,3-dimethoxyphenyl]-2,4-dioxobutyric acid,

(42) 4-(5-Benzyl-3-benzyloxyphenyl)-2,4-dioxobutyric acid,

(43) 4-[5-Benzyl-2-(2-hydroxy)ethoxyphenyl]-2,4- dioxo-2-butanoic acid,

(44) 2,4-Dioxo-4-(3-pyridin-3-ylmethylphenyl)butyric acid,

(45) 4-[3-(3-Methyl-pyridin-2-ylmethyl)phenyl]-2,4-dioxo-butyric acid,

(46) 4-(5-Benzyl-2-methylsulfanylphenyl)-2,4-dioxobutyric acid,

(47) 4-(5-Benzyl-3-N-morpholinophenyl)-2,4-dioxobutyric acid,

(48) 4-(8-Benzyl-4-methyl-3,4-dihydro-2h-benzo[1,4]oxazin-6-yl)-2,4-dioxobutyric acid,

(49) 4-[5-(2-Chlorobenzyl)-3-N,N-dimethylaminophenyl]-2,4-dioxobutyric acid,

(50) 4-[5-(3-Chlorobenzyl)-3-N,N-dimethylaminophenyl]-2,4-dioxobutyric acid,

(51) 4-(5-Benzyl-2,3,4-trimethoxyphenyl)-2,4-dioxobutyric acid,

(52) 4-(6-Benzylbenzo[1,3]dioxol-4-yl)-2,4-dioxobutyric acid,

(53) 4-[3-Benzyl-5-(morpholine-4-carbonyl)phenyl]-2,4-dioxobutyric acid,

(54) 4-(3-Benzyl-5-pyridine-2-ylmethylphenyl)-2,4-dioxobutyric acid,

(55) 4-[3-Benzyl-5-(morpholinomethyl)phenyl]-2,4-dioxobutyric acid,

(56) 4-(3-Benzyl-5-pyridine-3-ylmethylphenyl)-2,4-dioxobutyric acid,

(57) 4-[3-Benzyl-5-(2-dimethylamino-1-hydroxy-1-methylethyl)phenyl]-2,4-dioxobutyric acid,

(58) 4-(5-Benzyl-2-N,N-dimethylaminophenyl)-2,4-dioxobutyric acid,

(59) 4-(5-Benzyl-2-fluorophenyl)-2,4-dioxobutyric acid,

(60) 4-(5-Benzyl-3-hydroxymethyl-2-methoxyphenyl)-2,4-dioxobutyric acid,

(61) 4-[5-Benzyl-2-(pyrazin-2-yloxy)phenyl]-2,4-dioxobutyric acid,

(62) 4-[3-Benzyl-5-(2-oxopiperidin-1-ylmethyl)phenyl]-2,4-dioxobutyric acid,

(63) 4-[5-Benzyl-2-methoxy-3-(morpholinomethyl)phenyl]-2,4-dioxobutyric acid,

(64) 4-[3-(2-Chlorobenzyl)-5-pyridin-2-ylmethylphenyl]-2,4-dioxobutyric acid,

(65) 4-[5-Benzyl-2-methoxy-3-(4-methylpiperazin-1-ylmethyl)phenyl]-2,4-dioxobutyric acid,

(66) 4-(5-Benzyl-2-methoxymethylphenyl)-2,4-dioxobutyric acid,

(67) 4-[3-(2-Fluorobenzyl)-5-morpholinomethylphenyl]-2,4-dioxobutyric acid,

(68) 4-[3-(4-Fluorobenzyl)-5-morpholinomethylphenyl]-2,4-dioxobutyric acid,

(69) 4-[3-(3-Fluorobenzyl)-5-morpholinomethylphenyl]-2,4-dioxobutyric acid,

(70) 4-[5-Benzyl-2-methoxy-3-(tert-butylcarbamoyl)phenyl]-2,4-dioxobutyric acid,

(71) 4-(3-Benzyl-5-[1,2,3]triazol-1-ylmethylphenyl)-2,4-dioxobutyric acid,

(72) 4-[5-Benzyl-3-(N′

-methyl-N-piperazinyl)phenyl]-2,4-dioxobutyric acid,

(73) 4-(3-Benzyl-5-[1,2,4]triazol-1-ylmethylphenyl)-2,4-dioxobutyric acid,

(75) 4-[5-Benzyl-2-(pyrimidin-2-yloxy)phenyl]-2,4-dioxobutyric acid,

(76) 4-(5-Benzyl-3-amino-2-methoxyphenyl)-2,4-dioxobutyric acid,

(77) 4-(5-Benzyl-2-ethoxyphenyl)-2,4-dioxobutyric acid,

(78) 4-[5-Benzyl-2-(2-morpholin-4-yl-ethoxy)phenyl]-2,4-dioxobutyric acid,

(79) 4-(5-Benzyl-2-trifluoroethoxyphenyl)-2,4-dioxobutyric acid,

(80) 4-(5-Benzyl-2-cyclobutyloxyphenyl)-2,4-dioxobutyric acid,

(81) 4-(5-Benzyl-2-cyclopentyloxyphenyl)-2,4-dioxobutyric acid,

(82) 4-(3-Benzyl-5-tetrazol-2-ylmethylphenyl)-2,4-dioxobutyric acid,

(83) 4-(5-Benzyl-2,3-diisopropoxyphenyl)-2,4-dioxobutyric acid,

(84) 4-(5-Benzyl-2-isopropoxy-3-N-methylaminophenyl)-2,4-dioxobutyric acid,

(85) 4-(5-Benzyl-2-isopropoxy-3-N,N-dimethylaminophenyl)-2,4-dioxo-butyric acid,

(86) 4-[5-Benzyl-2-isopropoxy-3-(2-N,N-dimethylaminoethoxy)phenyl]-2,4-dioxobutyric acid,

(87) 4-[5-Benzyl-2-isopropoxy-3-(morpholinomethyl)phenyl]-2,4-dioxo-butyric acid,

(88) 4-(5-Benzyl-2-isopropoxy-3-N,N-dimethylaminomethylphenyl)-2,4-dioxo-butyric acid,

(90) 2-Hydroxy-4-oxo-4-(3-phenylindan-5-yl)but-2-enoic acid,

(91) 4-(Dibenzylaminophenyl)-2-hydroxy-4-oxobut-2-enoic acid,

(92) 3-(3-Benzyl-5-carboxyacetylphenyl)-3-oxopropionic acid,

(93) 4-(4-Dibenzylaminophenyl)-2-hydroxy-4-oxobut-2-enoic acid,

(94) 4-(5-Benzyl-3-methoxy-2-methylthioethoxyphenyl)-2,4-dioxobutyric acid,

(97) 4-(2,3-Dimethoxy-5-pent4-enylphenyl)-2,4-dioxobutyric acid,

(98) 4-(5-Cyclopropylmethyl-2,3-dimethoxyphenyl)-2,4-dioxobutyric acid,

(99) (6-Benzyloxy-1-oxo-indan-2-ylidene)-hydroxyacetic acid,

(100) 4-(5-Benzyl-2-isopropoxy-3-[1,2,3]triazol-1-ylmethylphenyl)-2,4-dioxobutyric acid,

(101) 4-(5-Benzyl-2-isopropoxy-3-[1,2,4]triazol-1-ylmethylphenyl)-2,4-dioxobutyric acid,

(102) 4-[5-Benzyl-2-(3-N,N-dimethylaminopropoxy)-3-methoxyphenyl]-2,4-dioxobutyric acid,

(103) 4-[3-(Phenyldifluoromethyl)phenyl]-2,4-dioxobutyric acid,

(104) 4-(5-Benzyl-2-cyclopropyloxyphenyl)-2,4-dioxobutyric acid,

(105) 4-[5-Benzyl-2-isopropoxy-3-(1-piperidinylmethyl)phenyl]-2,4-dioxo-butyric acid,

(106) 4-[5-Benzyl-2-(2-dimethylamino-1-methylethoxy)phenyl]-2,4-dioxo-butyric acid,

(107) 4-[5-Benzyl-2-(1-methylpiperidin-4-yloxy)phenyl]-2,4-dioxo-butyric acid,

(108) 4-[3-Benzyl-5-(4-benzylpiperazin-1-yl)phenyl]-2,4-dioxo-butyric acid,

(109) 4-[5-Benzyl-2-isopropoxy-3-(pyridin-2-ylaminomethyl)phenyl]-2,4-dioxo-butyric acid,

(114) 4-[3-(2,4-difluoro-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(115) 2,4-dioxo-4-[3-(2,6-difluoro-benzyl)-phenyl]-butyric acid,

(116) 2,4-dioxo-4-[3-(2-4-6-trifluoro-benzyl)-phenyl]-butyric acid,

(117) 2,4-dioxo-4-[3-(2-fluoro-3-chloro-benzyl)-phenyl]-butyric acid,

(118) 2,4-dioxo4-[3-(2-methyl-4-fluoro-benzyl)-phenyl]-butyric acid,

(119) 4-[3-(2,3-dichloro-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(120) 4-[3-(2-chloro-3-methylbenzyl)phenyl]-2,4-dioxobutyric acid,

(121) 2,4-dioxo4-[3-(2,6-dichloro-benzyl)-phenyl]-butyric acid,

(122) 2,4-dioxo-4-[3-(2,3,4,5,6-penta-fluoro-benzyl)-phenyl]-butyric acid,

(123) 4-[3-(2-fluorobenzyl)phenyl]-2,4-dioxobutyric acid,

(124) 2,4-dioxo4-[3-(2-chloro-4-fluoro-benzyl)-phenyl]-butyric acid,

(125) 4-[3-(2-methylbenzyl)phenyl]-2,4-dioxobutyric acid,

(126) 2,4-dioxo-4-[3-(2-methoxybenzyl)phenyl]butyric acid,

(127) 4-[3-(2-chlorobenzyl)phenyl]-2,4-dioxobutyric acid,

(128) 4-[3-(2-bromobenzyl)phenyl]-2,4-dioxobutyric acid,

(129) 4-[5-(4-fluoro-benzyl)-2,3-dimethoxy-phenyl]-2,4-dioxo-butyric acid,

(130) 4-[3-(3-chloro-2-methyl-benzyl)phenyl]-2,4-dioxobutyric acid,

(131) 4-[3-(2,3-difluoro-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(132) 4-(3,5-dibenzylphenyl)-2,4-dioxo-butyric acid,

(133) 2,4-dioxo4-[3-(2-trifluoromethylbenzyl)phenyl]butyric acid,

(134) 4-[3-(4-fluorobenzyl)phenyl]-2,4-dioxobutyric acid,

(135) 4-[3-(3-chlorobenzyl)phenyl]-2,4-dioxobutyric acid,

(136) 2,4-dioxo-4-[3-(2-bromo-3-chloro-benzyl)-phenyl]-butyric acid,

(137) 4-(3-benzylphenyl)-2,4-dioxo-butyric acid,

(138) 4-[3-(2-fluoro-3-methyl-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(139) 4-[3-(3-chloro-4-fluoro-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(140) 2,4-dioxo-4-[3-(2-bromo4-fluoro-benzyl)-phenyl]-butyric acid,

(141) 4-[3-(3-bromobenzyl)phenyl]-2,4-dioxobutyric acid,

(142) 4-[3-(2,5-difluoro-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(143) 4-[3-(5-chloro-2-fluoro-benzyl)phenyl]-2,4-dioxobutyric acid,

(144) 4-[3-(3-methylbenzyl)phenyl]-2,4-dioxobutyric acid,

(145) 4-(3-benzyl-4-methyl-phenyl)-2,4-dioxo-butyric acid,

(146) 4-[3-(3,4-difluoro-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(147) 4-[3-(2,5-dichloro-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(148) 4-[3-(2-chloro-6-methyl-benzyl)phenyl]-2,4-dioxobutyric acid,

(149) 2,4-dioxo-4-[3-(2-trifluoromethyl-4-chloro-benzyl)-phenyl]-butyric acid,

(150) 4-[3-(2-bromo-5-chloro-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(151) 4-(3-naphthalen-1-ylmethyl-phenyl)-2,4-dioxo-butyric acid,

(152) 2,4-dioxo-4-[3-(3-fluorobenzyl)phenyl]butyric acid,

(153) 2,4-dioxo-4-(3-phenylsulfanyl-phenyl)-butyric acid,

(154) 2,4-dioxo4-[3-(1-phenylethyl)phenyl]butyric acid,

(155) 4-(3-benzyl-4,5-dimethylphenyl)-2,4-dioxo-butyric acid,

(156) 2,4-dioxo-4-[3-(3-methoxybenzyl)phenyl]butyric acid,

(157) 4-[3-(5-methyl-thiophen-2-ylmethyl)phenyl]-2,4-dioxo-butyric acid,

(158) 4-[3-(5-chloro-thiophen-2-ylmethyl)phenyl]-2,4-dioxo-butylic acid,

(159) 4-(3-benzyl-5-methylphenyl)-2,4-dioxo-butyric acid,

(160) 4-[3-(2-cyanobenzyl)phenyl]-2,4-dioxo-butyric acid,

(161) 4-[3-benzylphenyl]-2,4-dioxobutyric acid,

(162) 4-[3-(3,5-dichloro-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(163) 4-(5-benzyl-2,4-dimethylphenyl)-2,4-dioxo-butyric acid,

(164) 4-(5-benzyl-2-methylphenyl)-2,4-dioxo-butyric acid,

(165) 4-(3-cyclohexylmethyl-phenyl)-2,4-dioxo-butyric acid,

(166) 4-{3-[(methyl-phenyl-amino)-methyl]-phenyl}-2,4-dioxo-butyric acid,

(167) 4-[3-benzyl-5-(5-hydroxy-pentyl)-phenyl]-2,4-dioxo-butyric acid,

(168) 4-(3-benzyl-5-pyrazin-2-yl-phenyl)-2,4-dioxo-butyric acid,

(169) 4-[3-(3-tert-butoxy-2-hydroxy-propyl)-5-(2-methyl-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(170) 2,4-dioxo-4-[3-(2,3-dimethoxy-benzyl)-phenyl]-butyric acid,

(171) 4-[3-(methoxyphenylmethyl)phenyl]-2,4-dioxobutyric acid,

(172) 4-[3-[hydroxy-(tetrahydro-furan-3-yl)-methyl]-5-(2-methyl-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(173) 2,4-dioxo-4-(3-phenoxymethyl-phenyl)-butyric acid,

(175) 4-[3-benzyl-5-(cyclopropylcarboxamido)-phenyl]-2,4-dioxobutyric acid,

(176) 4-[3-benzyl-5-(t-butoxycarbamoyl)phenyl]-2,4-dioxobutyric acid,

(177) 4-[3-(hydroxy-phenyl-methyl)-phenyl]-2,4-dioxo-butyric acid,

(178) 4-(5-benzyl-2,3-dimethylphenyl)-2,4-dioxo-butyric acid,

(179) 4-[3-(3,5-dibromobenzyl)phenyl]-2,4-dioxo-butyric acid,

(180) 4-[3-(2-methyl-benzyl)-5-pyrimidin-2-yl-phenyl]-2,4-dioxo-butyric acid,

(181) 4-[3-benzyl-2-(pyrimidin-2-ylamino)-phenyl]-2,4-dioxo-butyric acid

(182) 4-[3-benzoimidazol-1-ylmethyl-5-(2-methyl-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(183) 2,4-dioxo-4-[3-(3-trifluoromethylbenzyl)phenyl]butyric acid,

(185) 2,4-dioxo-4-(3-[1,2,3]triazol-2-ylmethyl-phenyl)-butyric acid,

(186) 4-[3-benzyl-5-(6-methoxy-pyridin-2-yl)-phenyl]-2,4-dioxo-butyric acid,

(187) 4-(3-benzotriazol-2-ylmethyl-phenyl)-2,4-dioxo-butyric acid,

(188) 4-[3-benzyl-5-(2-(4-methylpiperazin-1-yl)-pyrazin-6-yl)phenyl]-2,4-dioxobutyric acid,

(189) 4-[4-(3-phenethyl)phenyl]-2,4-dioxobutyric acid,

(190) 4-[4-(3-chlorobenzyl)phenyl]-2,4-dioxobutyric acid,

(191) 4-(3-benzoimidazol-1-ylmethyl-phenyl)-2,4-dioxo-butyric acid,

(192) 4-[3-benzyloxy-5-(6-tert-butoxycarbonylamino-hexyloxy)phenyl]-2-hydroxy-4-oxo-but-2-enoic acid,

(193) 4-(3-benzotriazol-1-ylmethyl-phenyl)-2,4-dioxo-butyric acid,

(194) 4-[3-(3,5-dimethyl-pyrazol-1-ylmethyl)-phenyl]-2,4-dioxo-butylic acid,

(196) 4-(4-methyl-3-phenoxy-phenyl)-2,4-dioxo-butyric acid,

197) 4-[3-(2-hydroxy-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(198) 4-[3-benzyl-5-(6-dimethylamino-pyrazin-2-yl)-phenyl]-2,4-dioxo-butyric acid,

and tautomers and pharmaceutically acceptable salts thereof.

11. The compound according to claim 10 selected from:

(1) 4-(3-Benzylphenyl)-2,4-dioxobutanoic acid,

(2) 4-[3-(5-methyl-thiophen-2-ylmethyl)-phenyl]-2,4-dioxo-butyric acid,

(3) 4-{3-[(methyl-phenyl-amino)-methyl]-phenyl}-2,4-dioxo-butyric acid,

(4) 4-(3-benzyl-5-pyrazin-2-yl-phenyl)-2,4-dioxo-butyric acid,

(5) 2,4-dioxo-4-[3-(1,2,3,4-tetrahydronaphthalen-1-yl)-phenyl]butyric acid,

(6) 2,4-Dioxo-4-(3-phenylsulfanyl-phenyl)-butyric acid,

(7) 4-[3-(2,4-Difluoro-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(8) 4-[5-(4-Fluoro-benzyl)-2,3-dimethoxy-phenyl]-2,4-dioxo-butyric acid,

(9) 4-(5-Benzyl-2-isopropoxyphenyl)-2,4-dioxobutyric acid,

(10) 4-[5-Benzyl-2-(2-N,N-dimethylaminoethoxy)phenyl]-2,4-dioxobutyric acid,

(11) 4-[5-Benzyl-2-(pyridin-2-yloxy)phenyl]-2,4-dioxo-butylic acid,

(12) 4-(5-Benzyl-2-isopropoxy-3-methoxyphenyl)-2,4-dioxo-butyric acid,

(13) 4-(5-Benzyl-2,3-dimethoxyphenyl)-2,4-dioxobutyric acid,

(14) 4-(5-Benzyl-3-dimethylamino-2-methoxyphenyl)-2,4-dioxobutyric acid,

(16) 4-(3-Benzyl-5-pyrazin-2-ylmethylphenyl)-2,4-dioxobutyric acid,

(17) 4-(3-Benzyl-5-[1,2,3]triazol-2-ylmethylphenyl)-2,4-dioxobutyric acid,

(18) 4-[3-(3-Chloropyridin-2-ylmethyl)phenyl]-2,4-dioxobutyric acid,

(19) 4-[5-Benzyl-2-methoxy-3-(N,N-dimethylaminomethyl) phenyl]-2,4-dioxo-butyric acid,

(20) 4-(5-benzyl-3-methoxy-2-methoxyethoxyphenyl)-2,4-dioxobutyric acid,

(21) 4-(5-Benzyl-2-isopropoxy-3-[1,2,3]triazol-1-ylmethylphenyl)-2,4-dioxobutyric acid,

(22) 4-(5-Benzyl-2-isopropoxy-3-[1,2,4]triazol-1-ylmethylphenyl)-2,4-dioxobutyric acid,

(23) 4-[5-Benzyl-2-(3-N,N-dimethylaminopropoxy)-3-methoxyphenyl]-2,4-dioxobutyric acid,

(24) 4-[3-(Phenyldifluoromethyl)phenyl]-2,4-dioxobutyric acid,

(25) 4-(5-Benzyl-2-cyclopropyloxyphenyl)-2,4-dioxobutyric acid,

(26) 4-[5-Benzyl-2-isopropoxy-3-(1-piperidinylmethyl)phenyl]-2,4-dioxo-butyric acid,

(27) 4-[5-Benzyl-2-(2-dimethylamino-1-methylethoxy)phenyl]-2,4-dioxo-butyric acid,

(28) 4-[5-Benzyl-2-(1-methylpiperidin-4-yloxy)phenyl]-2,4-dioxo-butyric acid,

(29) 4-[3-Benzyl-5-(4-benzylpiperazin-1-yl)phenyl]-2,4-dioxo-butyric acid, and

(30) 4-[5-Benzyl-2-isopropoxy-3-(pyridin-2-ylaminomethyl)phenyl]-2,4-dioxo-butyric acid;

and tautomers and pharmaceutically acceptable salts thereof.

16. A method of inhibiting HIV integrase, comprising the administration to a mammal in need of such treatment a therapeutically effective amount of a compound of structural formula (I):

and tautomers and pharmaceutically acceptable salts thereof, wherein;

A is a six-membered aromatic ring substituted on carbon by R¹, R², R⁸, and R⁹;

optionally the aromatic ring may be fused with another ring system to form;

R¹ is selected from;

(1) —

H,

(2) —

C_1-5 alkyl,

(3) —

C_1-6 alkyl-OR⁷,

(4) —

O—

C_1-6 alkyl-OR⁷,

(5) —

O—

C_1-6 alkyl-SR⁷,

(6) —

CF₃ or —

CH₂CF₃,

(7) -halo,

(8) —

NO₂,

(9) —

C_0-3 alkyl —

N(R⁴)(R⁵),

(10) —

R⁶,

(11) —

C_2-5 alkenyl-R³,

(12) —

C_2-5 alkynyl-R³,

(13) —

O—

R⁶,

(14) —

O—

C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with fluorine atoms,

(15) —

O—

C_1-6 alkyl-NH—

C(O)—

OR⁷;

(16) —

O—

C_2-6 alkyl-N(R⁴)(R⁵);

(17) —

S—

C_1-3 alkyl;

(18) —

C(O)CH₂C(O)C(O)OR⁷;

(19) —

CH₂—

CH(OH)—

CH₂—

O—

R⁷; and

(20) —

C(OH)(CH₃)—

CH₂N(R⁴)(R⁵);

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³, wherein one or more of the hydrogen atoms on C_1-6 alkyl may be replaced with a fluorine atom,

(5) —

C_2-6 alkenyl,

(6) —

O—

R⁶,

(7) —

O—

C_1-6 alkyl-OR⁶,

(8) —

O—

C_1-6 alkyl-SR⁶,

(9) —

S(O)_n—

R⁶,

(10) —

C_1-6 alkyl (OR⁶)(R⁴),

(11) —

C_0-6 alkyl-N(R⁴)(R⁶),

(12) —

C_1-6 alkyl S(O)n—

R⁶,

(13) —

C_0-6 alkyl C(O)—

R⁶,

(14) —

C_0-6 alkyl C(O)CH₂—

C(O)—

OH,

(15) —

C_1-6 alkyl C(S)—

R⁶,

(16) —

C_1-6 alkyl NR⁴C(O)—

R⁶,

(17) —

C_1-6 alkyl-C(O)N(R⁴)(R⁵), and

(18) —

CH₂(OR⁷)—

R⁶;

each R³ is independently selected from;

(1) a 5 or 6 membered aromatic or heteroaromatic ring, containing 0, 1, 2, 3, or 4 heteroatoms selected from oxygen, nitrogen and sulfur, unsubstituted or substituted on nitrogen or carbon by 1 to 5 substituents selected from;

(a) halogen,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) phenyl,

(e) —

S—

C_1-6 alkyl,

(f) —

CN,

(g) hydroxy,

(h) phenyloxy,

(i) —

C_0-6 alkyl-N(R⁷)₂,

(k) oxo, and

(l) substituted phenyloxy with 1, 2, or 3 substituents selected from;

(i) halogen,

(ii) C_1-6 alkyl,

(iii) —

CF₃, and

(iv) hydroxy;

(2) a 3 to 6 membered saturated ring containing 0, 1 or 2 heteroatoms selected from oxygen, nitrogen or sulfur, unsubstituted or substituted with 1 to 5 substituents selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O,

(h) benzyl, and

(i) hydroxy;

(3) unsubstituted or substituted hexahydrothieno[3,4-d]imidazolyl with one or two substituents selected from;

(a) oxo,

(b) halogen,

(c) C_1-6 alkyl,

(d) C_1-6 alkyloxy-,

(e) —

CF₃,

(f) —

OCF₃,

(g) —

CN, and

(h) hydroxy;

(4) a 5 or 6 membered aromatic or heteroaromatic ring, containing 0, 1, 2 or 3 heteroatoms selected from oxygen, nitrogen and sulfur, fused with a phenyl ring;

wherein the ring system is unsubstituted or substituted on a nitrogen or carbon atom by 1 to 3 substituents selected from;

(a) -halogen,

(b) —

C_1-6 alkyl,

(c) —

C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN, and

(g) -hydroxy;

(5) a 3 to 6 membered saturated ring containing 0, 1 or 2 heteroatoms selected from oxygen, nitrogen or sulfur, fused with a phenyl ring, unsubstituted or substituted with 1 or 2 substituents selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy;

(6) a 5 to 6 membered ring containing 0, 1 or 2 heteroatoms selected from oxygen, nitrogen or sulfur, containing 2 or 3 double bonds, unsubstituted or substituted with 1 or 2 substituents selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy; and

(7) a 5 to 6 membered ring containing 0, 1 or 2 heteroatoms selected from oxygen, nitrogen or sulfur, containing 2 or 3 double bonds, fused with a phenyl ring, unsubstituted or substituted with 1 or 2 substituents selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy; and

each R⁴ is independently selected from;

(1) —

H,

(2) —

C_1-4 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_2-3 alkenyl,

(6) —

C_1-3 alkyl-R³,

(7) —

C_2-3 alkenyl-R³,

(8) —

S(O)_n—

R³, and

(9) —

C(O)—

R³;

each R⁵ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_2-3 alkenyl,

(6) —

C_1-3 alkyl-R³,

(7) —

C_2-3 alkenyl-R³,

(8) —

S(O)_n—

R³,

(9) —

C(O)—

R³,

(10) —

C(O)OR4, and

(11) —

C(O)C(O)OH;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

each R⁷ is independently selected from;

(1) —

H, and

(2) —

C_1-6 alkyl;

R⁸ is selected from;

(1) —

H,

(2) —

O—

C_1-6 alkyl and

(3) C_1-6 alkyl;

R⁹ is selected from;

(1) —

H,

(2) —

O—

C_1-3 alkyl,

(3) —

OH, and

(4) oxo; and

each n is independently selected from 0, 1 and 2.

17. The method according to claim 16, wherein the compound of structural formula (I) is selected from:

(1) 4-(3-Benzylphenyl)-2,4-dioxobutanoic acid,

(2) 4-[3-(5-methyl-thiophen-2-ylmethyl)-phenyl]-2,4-dioxo-butyric acid,

(3) 4-(3-[(methyl-phenyl-amino)-methyl]-phenyl)-2,4-dioxo-butyric acid,

(4) 4-(3-benzyl-5-pyrazin-2-yl-phenyl)-2,4-dioxo-butyric acid,

(5) 2,4-dioxo-4-[3-(1,2,3,4-tetrahydronaphthalen-1-yl)-phenyl]butyric acid,

(6) 2,4-Dioxo-4-(3-phenylsulfanyl-phenyl)-butyric acid,

(7) 4-[3-(2,4-Difluoro-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(8) 4-[5-(4-Fluoro-benzyl)-2,3-dimethoxy-phenyl]-2,4-dioxo-butyric acid,

(9) 4-(5-Benzyl-2-isopropoxyphenyl)-2,4-dioxobutyric acid,

(10) 4-[5-Benzyl-2-(2-N,N-dimethylaminoethoxy)phenyl]-2,4-dioxobutyric acid,

(11) 4-[5-Benzyl-2-(pyridin-2-yloxy)phenyl]-2,4-dioxo-butyric acid,

(12) 4-(5-Benzyl-2-isopropoxy-3-methoxyphenyl)-2,4-dioxo-butyric acid,

(13) 4-(5-Benzyl-2,3-dimethoxyphenyl)-2,4-dioxobutyric acid,

(14) 4-(5-Benzyl-3-dimethylamino-2-methoxyphenyl)-2,4-dioxobutyric acid,

(16) 4-(3-Benzyl-5-pyrazin-2-ylmethylphenyl)-2,4-dioxobutyric acid,

(17) 4-(3-Benzyl-5-[1,2,3]triazol-2-ylmethylphenyl)-2,4-dioxobutyric acid,

(18) 4-[3-(3-Chloropyridin-2-ylmethyl)phenyl]-2,4-dioxobutyric acid,

(19) 4-[5-Benzyl-2-methoxy-3-(N,N-dimethylaminomethyl) phenyl]-2,4-dioxo-butyric acid,

(20) 4-(5-benzyl-3-methoxy-2-methoxyethoxyphenyl)-2,4-dioxobutyric acid,

(21) 4-(5-Benzyl-2-isopropoxy-3-[1,2,3]triazol-1-ylmethylphenyl)-2,4-dioxobutyric acid,

(22) 4-(5-Benzyl-2-isopropoxy-3-[1,2,4]triazol-1-ylmethylphenyl)-2,4-dioxobutyric acid,

(23) 4-[5-Benzyl-2-(3-N,N-dimethylaminopropoxy)-3-methoxyphenyl]-2,4-dioxobutyric acid,

(24) 4-[3-(Phenyldifluoromethyl)phenyl]-2,4-dioxobutyric acid,

(25) 4-(5-Benzyl-2-cyclopropyloxyphenyl)-2,4-dioxobutyric acid,

(26) ⁴-[5-Benzyl-2-isopropoxy-3-(1-piperidinylmethyl)phenyl]-2,4-dioxo-butyric acid,

(27) 4-[5-Benzyl-2-(2-dimethylamino-1-methylethoxy)phenyl]-2,4-dioxo-butyric acid,

(28) 4-[5-Benzyl-2-(1-methylpiperidin-4-yloxy)phenyl]-2,4-dioxo-butyric acid,

(29) 4-[3-Benzyl-5-(4-benzylpiperazin-1-yl)phenyl]-2,4-dioxo-butyric acid, and

(30) 4-[5-Benzyl-2-isopropoxy-3-(pyridin-2-ylaminomethyl)phenyl]-2,4-dioxo-butyric acid;

and tautomers and pharmaceutically acceptable salts thereof.

18. A method of treating infection by HIV, or of treating AIDS or ARC, comprising the administration to a human in need of such treatment a therapeutically effective amount of a compound of structural formula (I):

and tautomers and pharmaceutically acceptable salts thereof, wherein;

A is a six-membered aromatic ring substituted on carbon by R¹, R², R⁸, and R⁹;

optionally the aromatic ring may be fused with another ring system to form;

R¹ is selected from;

(1) —

H,

(2) —

C_1-5 alkyl,

(3) —

C_1-6 alkyl-OR⁷,

(4) —

O—

C_1-6 alkyl-OR⁷,

(5) —

O—

C_1-6 alkyl-SR⁷,

(6) —

CF₃ or —

CH₂CF₃,

(7) -halo,

(8) —

NO₂,

(9) —

C_0-3 alkyl —

N(R⁴)(R⁵),

(10) —

R⁶,

(11) —

C_2-5 alkenyl-R³,

(12) —

C_2-5 alkynyl-R³,

(13) —

O—

R⁶,

(14) —

O—

C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with fluorine atoms,

(15) —

O—

C_1-6 alkyl-NH—

C(O)—

OR⁷,

(16) —

O—

C_2-6 alkyl-N(R⁴)(R⁵),

(17) —

S—

C_1-3 alkyl,

(18) —

C(O)CH₂C(O)C(O)OR⁷,

(19) —

CH₂—

CH(OH)—

CH₂—

O—

R⁷, and

(20) —

C(OH)(CH₃)—

CH₂N(R⁴)(R⁵);

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³, wherein one or more of the hydrogen atoms on C_1-6 alkyl may be replaced with a fluorine atom,

(5) —

C_2-6 alkenyl,

(6) —

O—

R⁶,

(7) —

O—

C_1-6 alkyl-OR⁶,

(8) —

O—

C_1-6 alkyl-SR⁶,

(9) —

S(O)_n—

R⁶,

(10) —

C_1-6 alkyl (OR⁶)(R⁴),

(11) —

C_0-6 alkyl-N(R⁴)(R⁶),

(12) —

C_1-6 alkyl S(O)_n—

R⁶,

(13) —

C_0-6 alkyl C(O)—

R⁶,

(14) —

C_0-6 alkyl C(O)CH₂—

C(O)—

OH,

(15) —

C_1-6 alkyl C(S)—

R⁶,

(16) —

C_1-6 alkyl NR⁴C(O)—

R⁶,

(17) —

C_1-6 alkyl-C(O)N(R⁴)(R⁵), and

(18) —

CH₂(OR⁷)—

R⁶;

each R³ is independently selected from;

(1) a 5 or 6 membered aromatic or heteroaromatic ring, containing 0, 1, 2, 3, or 4 heteroatoms selected from oxygen, nitrogen and sulfur, unsubstituted or substituted on nitrogen or carbon by 1 to 5 substituents selected from;

(a) halogen,

(b) C_1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(c) C_1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom,

(d) phenyl,

(e) —

S—

C_1-6 alkyl,

(f) —

CN,

(g) hydroxy,

(h) phenyloxy,

(i) —

C_0-6 alkyl-N(R⁷)₂,

(k) oxo, and

(l) substituted phenyloxy with 1, 2, or 3 substituents selected from;

(i) halogen,

(ii) C_1-6 alkyl,

(iii) —

CF₃, and

(iv) hydroxy;

(2) a 3 to 6 membered saturated ring containing 0, 1 or 2 heteroatoms selected from oxygen, nitrogen or sulfur, unsubstituted or substituted with 1 to 5 substituents selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O,

(h) benzyl, and

(i) hydroxy;

(3) unsubstituted or substituted hexahydrothieno[3,4-d]imidazolyl with one or two substituents selected from;

(a) oxo,

(b) halogen,

(c) C_1-6 alkyl,

(d) C_1-6 alkyloxy-,

(e) —

CF₃,

(f) —

OCF₃,

(g) —

CN, and

(h) hydroxy;

(4) a 5 or 6 membered aromatic or heteroaromatic ring, containing 0, 1, 2 or 3 heteroatoms selected from oxygen, nitrogen and sulfur, fused with a phenyl ring;

wherein the ring system is unsubstituted or substituted on a nitrogen or carbon atom by 1 to 3 substituents selected from;

(a) -halogen,

(b) —

C_1-6 alkyl,

(c) —

C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN, and

(g) -hydroxy;

(5) a 3 to 6 membered saturated ring containing 0, 1 or 2 heteroatoms selected from oxygen, nitrogen or sulfur, fused with a phenyl ring, unsubstituted or substituted with 1 or 2 substituents selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy;

(6) a 5 to 6 membered ring containing 0, 1 or 2 heteroatoms selected from oxygen, nitrogen or sulfur, containing 2 or 3 double bonds, unsubstituted or substituted with 1 or 2 substituents selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy; and

(7) a 5 to 6 membered ring containing 0, 1 or 2 heteroatoms selected from oxygen, nitrogen or sulfur, containing 2 or 3 double bonds, fused with a phenyl ring, unsubstituted or substituted with 1 or 2 substituents selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy; and

each R⁴ is independently selected from;

(1) —

H,

(2) —

C_1-4 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_2-3 alkenyl,

(6) —

C_1-3 alkyl-R³,

(7) —

C_2-3 alkenyl-R³,

(8) —

S(O)_n—

R³, and

(9) —

C(O)—

R³;

each R⁵ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_2-3 alkenyl,

(6) —

C_1-3 alkyl-R³,

(7) —

C_2-3 alkenyl-R³,

(8) —

S(O)_n—

R³,

(9) —

C(O)—

R³,

(10) —

C(O)OR4, and

(11) —

C(O)C(O)OH;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

each R⁷ is independently selected from;

(1) —

H, and

(2) —

C_1-6 alkyl;

R⁸ is selected from;

(1) —

H,

(2) —

O—

C_1-6 alkyl and

(3) C_1-6 alkyl;

R⁹ is selected from;

(1) —

H,

(2) —

O—

C_1-3 alkyl,

(3) —

OH, and

(4) oxo; and

each n is independently selected from 0, 1 and 2.

19. The method according to claim 18 wherein the compound of structural formula (I) is selected from:

(1) 4-(3-Benzylphenyl)-2,4-dioxobutanoic acid,

(2) 4-[3-(5-methyl-thiophen-2-ylmethyl)-phenyl]-2,4-dioxo-butyric acid,

(3) 4-{3-[(methyl-phenyl-amino)-methyl]-phenyl}-2,4-dioxo-butyric acid,

(4) 4-(3-benzyl-5-pyrazin-2-yl-phenyl)-2,4-dioxo-butyric acid,

(5) 2,4-dioxo-4-[3-(1,2,3,4-tetrahydronaphthalen-1-yl)-phenyl]butyric acid,

(6) 2,4-Dioxo-4-(3-phenylsulfanyl-phenyl)-butyric acid,

(7) 4-[3-(2,4-Difluoro-benzyl)-phenyl]-2,4-dioxo-butyric acid,

(8) 4-[5-(4-Fluoro-benzyl)-2,3-dimethoxy-phenyl]-2,4-dioxo-butyric acid,

(9) 4-(5-Benzyl-2-isopropoxyphenyl)-2,4-dioxobutyric acid,

(10) 4-[5-Benzyl-2-(2-N,N-dimethylaminoethoxy)phenyl]-2,4-dioxobutyric acid,

(11) 4-[5-Benzyl-2-(pyzidin-2-yloxy)phenyl]-2,4-dioxo-butyric acid,

(12) 4-(5-Benzyl-2-isopropoxy-3-methoxyphenyl)-2,4-dioxo-butyric acid,

(13) 4-(5-Benzyl-2,3-dimethoxyphenyl)-2,4-dioxobutyric acid,

(14) 4-(5-Benzyl-3-dimethylamino-2-methoxyphenyl)-2,4-dioxobutyric acid,

(15)

(16) 4-(3-Benzyl-5-pyrazin-2-ylmethylphenyl)-2,4-dioxobutyric acid,

(17) 4-(3-Benzyl-5-[1,2,3]triazol-2-ylmethylphenyl)-2,4-dioxobutyric acid,

(18) 4-[3-(3-Chloropyridin-2-ylmethyl)phenyl]-2,4-dioxobutyric acid,

(19) 4-[5-Benzyl-2-methoxy-3-(N,N-dimethylaminomethyl) phenyl]-2,4-dioxo-butyric acid,

(20) 4-(5-benzyl-3-methoxy-2-methoxyethoxyphenyl)-2,4-dioxobutyric acid,

(21) 4-(5-Benzyl-2-isopropoxy-3-[1,2,3]triazol-1-ylmethylphenyl)-2,4-dioxobutyric acid,

(22) 4-(5-Benzyl-2-isopropoxy-3-[1,2,4]triazol-1-ylmethylphenyl)-2,4-dioxobutyric acid,

(23) 4-[5-Benzyl-2-(3-N,N-dimethylaminopropoxy)-3-methoxyphenyl]-2,4-dioxobutyric acid,

(24) 4-[3-(Phenyldifluoromethyl)phenyl]-2,4-dioxobutyric acid,

(25) 4-(5-Benzyl-2-cyclopropyloxyphenyl)-2,4-dioxobutyric acid,

(26) 4-[5-Benzyl-2-isopropoxy-3-(1-piperidinylmethyl)phenyl]-2,4-dioxo-butyric acid,

(27) 4-[5-Benzyl-2-(2-dimethylamino-1-methylethoxy)phenyl]-2,4-dioxo-butyric acid,

(28) 4-[5-Benzyl-2-(1-methylpiperidin-4-yloxy)phenyl]-2,4-dioxo-butyric acid,

(29) 4-[3-Benzyl-5-(4-benzylpiperazin-1-yl)phenyl]-2,4-dioxo-butyric acid, and

(30) 4-[5-Benzyl-2-isopropoxy-3-(pyridin-2-ylaminomethyl)phenyl]-2,4-dioxo-butyric acid;

and tautomers and pharmaceutically acceptable salts thereof.