HIV integrase inhibitors

• US 6,306,891 B1
• Filed: 06/01/1999
• Issued: 10/23/2001
• 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: Hazuda, Daria Jean, Selnick, Harold G., Medina, Julio C., Wai, John S., Clark, David L., Young, Steven D., Egbertson, Melissa, Guare, James P. Jr.
• Primary Examiner(s): Lambkin, Deborah C.
• Application Number:
  US09/323,519
• Time in Patent Office: 875 Days
• Field of Search: 514/423, 514/406, 514/396, 514/326, 514/419, 548/540, 548/469, 548/374.1, 548/333.5, 546/208
• US Class Current: 514/423
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

Nitrogen-containing heteroaryl dioxo-butyric 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 five-membered heteroaromatic ring containing 1 or 2 nitrogen atoms and substituted on carbon or nitrogen by R¹, R² and R⁸;

the heteroaromatic ring may optionally be fused with a phenyl ring to form a fused ring system, provided that when A is a fused ring system, the nitrogen-containing heteroaromatic ring is substituted by the dioxobutyric acid/ester moiety;

R₁ is selected from;

(1) —

H,

(2) —

C_1-5 alkyl,

(3) —

CF₃,

(4) -halo,

(5) —

NO₂,

(6) —

N(R⁴)(R⁵),

(7) —

R⁶,

(8) —

C_2-5 alkenyl-R³,

(9) —

C_2-5 alkynyl-R³,

(10) —

O—

R⁶,

(11) —

O—

C_1-6 alkyl, and

(12) —

C(O)CH₂C(O)C(O)OR⁷;

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³,

(5) —

O—

R⁶,

(6) —

O—

C_1-6 alkyl-OR⁶,

(7) —

S(O)n-R⁶,

(8) —

C_1-6 alkyl (OR⁶)(R⁴),

(9) —

C_1-6 alkyl-N(R⁴)(R⁶),

(10) —

C_1-6 alkyl S(O)n-R⁶,

(11) —

C_1-6 alkyl C(O)—

R⁶,

(12) —

C_1-6 alkyl C(S)—

R⁶,

(13) —

C_1-6 alkyl NR⁴C(O)—

R⁶, and

(14) —

C_1-6 alkyl-C(O)N(R⁴)(R⁵);

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 a nitrogen or carbon atom by 1 to 5 substituents 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;

(2) a 3 to 6 membered saturated ring containing 0 or 1 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, and

(h) 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, or 2 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 or 1 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; and

(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;

each R⁴ 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, 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, and

(9) —

C(O)—

R³;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

R⁷ is selected from;

(1) —

H, and

(2) C_1-6 alkyl;

R⁸ is selected from;

(1) —

H,

(2) C_1-6 alkyl-oxy, and

(3) C_1-6 alkyl; and

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

further provided that when R⁷ is C_1-6 alkyl, then R² is not —

H or —

C_1-6 alkyl.

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

A is selected from;

(1) pyrrolyl,

(2) imidazolyl,

(3) pyrazolyl, and

(4) indolyl, provided that the nitrogen-containing heteroaromatic ring is substituted by the dioxobutyric moiety in structural formula (I);

R¹ is selected from;

(1) —

H,

(2) —

CH₃,

(3) —

CF₃,

(4) -halo,

(5) —

NO₂,

(6) —

N(R⁴)(R⁵),

(7) -phenyl,

(8) 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,

(9) phenyl C_1-3 alkyl-,

(10) substituted phenyl C_1-3 alkyl-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,

(11) —

C_2-5 alkenyl-R³,

(12) —

C_2-5 alkynyl-R³, and

(13) —

C(O)CH₂C(O)C(O)OR⁷;

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³,

(5) —

O—

R⁶,

(6) —

O—

C_1-6 alkyl-OR⁶,

(7) —

S(O)n-R⁶,

(8) —

C_1-6 alkyl (OR⁶)(R⁴),

(9) —

C_1-6 alkyl-N(R⁴)(R⁶),

(10) —

C_1-6 alkyl S(O)n-R⁶,

(11) —

C_1-6 alkyl C(O)—

R⁶,

(12) —

C_1-6 alkyl C(S)—

R⁶,

(13) —

C_1-6 alkyl NR⁴C(O)—

R⁶, and

(14) —

C_1-6 alkyl-C(O)N(R⁴)(R⁵);

each R³ is independently selected from;

(1) phenyl;

(2) substituted phenyl with 1, 2, or 3 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;

(3) thienyl;

(4) substituted thienyl 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) 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;

(5) pyridyl;

(6) substituted pyridyl 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) 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;

(7) imidazolyl;

(8) substituted imidazolyl 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) 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;

(9) pyrrolyl;

(10) substituted pyrrolyl 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) 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;

(11) pyrazolyl;

(12) substituted pyrazolyl 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) 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;

(13) C_3-6 cycloalkyl;

(14) substituted C_3-6 cycloalkyl 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, and

(h) hydroxy;

(15) piperidinyl;

(16) substituted piperidinyl 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,

(g) ═

O, and

(h) hydroxy;

(17) morpholinyl;

(18) substituted morpholinyl substituted at a carbon or nitrogen atom with 1 or 2 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;

(19) naphthyl;

(20) 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;

(21) indolyl;

(22) 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;

(23) C_3-6 cycloalkyl fused with a phenyl ring;

(24) substituted C_3-6 cycloalkyl fused with a phenyl ring 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,

(g) ═

O, and

(h) hydroxy;

each R⁴ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl, and

(3) —

CF₃;

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, and

(9) —

C(O)—

R³;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

R⁷ is H;

R⁸ is selected from;

(1) —

H,

(2) —

OCH₃, and

(3) —

CH₃; and

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

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

A is selected from;

(1) pyrrolyl,

(2) imidazolyl,

(3) pyrazolyl, and

(4) indolyl, provided that the nitrogen-containing heteroaromatic ring is substituted by the dioxobutyric moiety in structural formula (I);

R¹ is selected from;

(1) —

H,

(2) —

CH₃,

(3) —

CF₃,

(4) -halo,

(5) —

NO₂,

(6) —

N(R⁴)(R⁵),

(7) -phenyl,

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

(a) halo,

(b) methyl, and

(c) methoxy,

(9) phenyl C_1-3 alkyl-,

(10) substituted phenyl C_1-3 alkyl-substituted with 1 or 2 substituents independently selected from;

(a) halo,

(b) methyl, and

(c) methoxy,

(11) —

C_2-5 alkenyl-R³, and

(12) —

C(O)CH₂C(O)C(O)OR⁷;

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³,

(5) —

O—

R⁶,

(6) —

O—

C_1-6 alkyl-OR⁶,

(7) —

S(O)n-R⁶,

(8) —

C_1-6 alkyl (OR⁶)(R⁴),

(9) —

C_1-6 alkyl-N(R⁴)(R⁶),

(10) —

C_1-6 alkyl S(O)n-R⁶,

(11) —

C_1-6 alkyl NR⁴C(O)—

R⁶, and

(12) —

C_1-6 alkyl-C(O)N(R⁴)(R⁵);

each R³ is independently selected from;

(1) phenyl,

(2) substituted phenyl with 1, 2, or 3 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,

(3) thienyl,

(4) pyridyl,

(5) imidazolyl,

(6) pyrrolyl,

(7) pyrazolyl,

(8) C_3-6 cycloalkyl,

(9) substituted C_3-6 cycloalkyl 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, and

(h) hydroxy;

(10) piperidinyl,

(11) morpholinyl,

(12) naphthyl,

(13) indolyl, and

(14) C_3-6 cycloalkyl fused with a phenyl ring;

each R⁴ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl, and

(3) —

CF₃;

each R⁵ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃, and

(4) —

R³,

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

R⁷ is H; and

R⁸ is selected from;

(1) —

H, and

(2) CH₃; and

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

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) —

C_1-5 alkyl,

(3) —

CF₃,

(4) -halo,

(5) —

NO₂,

(6) —

N(R⁴)(R⁵),

(7) -phenyl,

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

(a) halo,

(b) methyl, and

(c) methoxy,

(9) phenyl C_1-3 alkyl-,

(10) substituted phenyl C_1-3 alkyl-substituted with 1 or 2 substituents independently selected from;

(a) halo,

(b) methyl, and

(c) methoxy,

(11) —

C_2-5 alkenyl-R³,

(12) —

C_2-5 alkynyl-R³, and

(13) —

C(O)CH₂C(O)C(O)OR⁷

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³,

(5) —

O—

R⁶,

(6) —

O—

C_1-6 alkyl-OR⁶,

(7) —

S(O)n-R⁶,

(8) —

C_1-6 alkyl (OR⁶)(R⁴),

(9) —

C_1-6 alkyl-N(R⁴)(R⁶),

(10) —

C_1-6 alkyl S(O)n-R⁶,

(11) —

C_1-6 alkyl C(O)—

R⁶,

(12) —

C_1-6 alkyl C(S)—

R⁶,

(13) —

C_1-6 alkyl NR⁴C(O)—

R⁶, and

(14) —

C_1-6 alkyl-C(O)N(R⁴)(R⁵);

each R³ is independently selected from;

(1) phenyl,

(2) substituted phenyl with 1, 2, or 3 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,

(3) thienyl,

(4) substituted thienyl 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) 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;

(5) pyridyl,

(6) substituted pyridyl 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) 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,

(7) imidazolyl,

(8) substituted imidazolyl 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) phenyl,

(e) —

CF₃,

(f) —

OCF₃,

(g) —

CN,

(h) hydroxy,

(i) phcnyloxy, and

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

(i) halogen,

(ii) C_1-6 alkyl,

(iii) —

CF₃, and

(iv) hydroxy;

(9) pyrrolyl,

(10) substituted pyrrolyl 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) 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,

(11) pyrazolyl,

(12) substituted pyrazolyl 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) 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,

(13) C_3-6 cycloalkyl,

(14) substituted C_3-6 cycloalkyl with 1 or 2 substituents independently selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O, and

(h) hydroxy,

(15) piperidinyl,

(16) substituted piperidinyl 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,

(g) ═

O, and

(h) hydroxy,

(17) morpholinyl,

(18) substituted morpholinyl substituted at a carbon or nitrogen atom with 1 or 2 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,

(19) naphthyl,

(20) 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,

(g) ═

O, and

(h) hydroxy,

(21) indolyl,

(22) 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,

(g) ═

O, and

(h) hydroxy,

(23) C_3-6 cycloalkyl fused with a phenyl ring,

(24) substituted C_3-6 cycloalkyl fused with a phenyl ring 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,

(g) ═

O, and

(h) hydroxy;

each R⁴ 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, 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, and

(9) —

C(O)—

R³;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

R⁷ is selected from;

(1) —

H, and

(2) C_1-6 alkyl;

R⁸ is selected from;

(1) —

H, and

(2) C_1-6 alkyl; and

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

and further provided that when R⁷ is C_1-6 alkyl, then R² is not —

H or —

C_1-6 alkyl.

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

and tautomers and pharmaceutically acceptable salts thereof, wherein;

R¹ is selected from;

(1) —

H,

(2) —

C_1-5 alkyl,

(3) —

CF₃,

(4) -halo,

(5) —

NO₂,

(6) —

N(R⁴)(R⁵),

(7) -phenyl,

(8) substituted phenyl substituted with 1 substituent independently selected from;

(a) halo,

(b) methyl, and

(c) methoxy,

(9) phenyl C_1-3 alkyl-,

(10) substituted phenyl C_1-3 alkyl-substituted with 1 or 2 substituents independently selected from;

(a) halo,

(b) methyl, and

(c) methoxy,

(11) —

C_2-5 alkenyl-R³, and

(12) —

C(O)CH₂C(O)C(O)OR⁷;

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³,

(5) —

O—

R⁶,

(6) —

O—

C_1-6 alkyl-OR⁶,

(7) —

C_1-6 alkyl (OR⁶)(R⁴),

(8) —

C_1-6 alkyl-N(R⁴)(R⁶),

(9) —

C_1-6 alkyl C(O)—

R⁶,

(10) —

C_1-6 alkyl NR⁴C(O)—

R⁶, and

(11) —

C_1-6 alkyl-C(O)N(R⁴)(R⁵);

each R³ is independently selected from;

(1) phenyl,

(2) substituted phenyl with 1, 2, or 3 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_1-2 alkyl,

(iii) —

CF₃, and

(iv) hydroxy;

(3) thienyl,

(4) pyridyl,

(5) imidazolyl,

(6) pyrrolyl,

(7) pyrazolyl,

(8) C_3-6 cycloalkyl,

(10) piperidinyl,

(11) morpholinyl,

(12) substituted morpholinyl substituted with a substituent selected from;

(a) halogen,

(b) C_1-6 alkyl,

(c) C_1-6 alkyloxy-,

(d) —

CF₃,

(e) —

OCF₃,

(f) —

CN,

(g) ═

O,

(h) hydroxy;

(12) naphthyl,

(13) indolyl, and

(14) C_3-6 cycloalkyl fused with a phenyl ring;

each R⁴ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³,

(6) —

S(O)_n—

R³, and

(7) —

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) —

S(O)_n—

R³, and

(7) —

C(O)—

R³;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

R⁷ is selected from;

(1) —

H, and

(2) C_1-4 alkyl;

R⁸ is selected from;

(1) —

H, and

(2) —

CH₃; and

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

and further provided that when R⁷ is C_1-4 alkyl, then R² is not —

H or —

C_1-6 alkyl.

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

and tautomers and pharmaceutically acceptable salts thereof, wherein;

R¹ is selected from;

(1) —

H,

(2) —

C_1-5 alkyl,

(3) —

CF₃,

(4) -halo, wherein halo is selected from;

—

F, Cl, —

Br, and —

I;

(5) —

NO₂,

(6) —

N(R⁴)(R⁵),

(7) -phenyl,

(8) phenyl C_1-3 alkyl-,

(9) substituted phenyl C_1-3 alkyl-substituted with 1 or 2 substituents independently selected from;

(a) halo, wherein halo is selected from;

—

F, —

Cl, and —

Br;

(10) —

C_2-5 alkynyl-R³, and

(11) —

C(O)CH₂C(O)C(O)OR⁷;

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³,

(5) —

O—

R⁶,

(6) —

O—

C_1-6 alkyl-OR⁶,

(7) —

C_1-6 alkyl (OR⁶)(R⁴),

(8) —

C_1-6 alkyl-N(R⁴)(R⁶),

(9) —

C_1-6 alkyl C(O)—

R⁶, and

(10) —

C_1-6 alkyl NR⁴C(O)—

R⁶;

each R³ is independently selected from;

(1) phenyl;

(2) substituted phenyl with 1, 2, or 3 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, wherein halogen is selected from —

F, —

Cl, and Br,

(ii) methyl,

(iii) —

CF₃, and

(iv) hydroxy;

(3) C_3-6 cycloalkyl,

(4) morpholinyl,

(5) substituted morpholinyl substituted with oxo; and

(6) naphthyl;

each R⁴ is independently selected from;

(1) —

H, and

(2) —

C_1-3 alkyl,

each R⁵ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³,

(6) —

S(O)_n—

R³, and

(7) —

C(O)—

R³;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R₃, and

(2) —

R³;

R⁷ is —

H;

R⁸ is selected from;

(1) —

H, and

(2) —

CH₃; and

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

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

and tautomers and pharmaceutically acceptable salts thereof, wherein;

R¹ is selected from;

(1) —

H,

(2) —

C_1-5 alkyl,

(3) —

CF₃,

(4) -halo;

wherein halo is selected from;

—

F, Cl, —

Br, and —

I;

(5) —

NO₂,

(6) —

N(R⁴)(R⁵),

(7) -phenyl,

(8) phenyl C_1-3 alkyl-,

(9) substituted phenyl C_1-3 alkyl-substituted with 1 or 2 substituents independently selected from;

(a) halo, wherein halo is selected from;

—

F, —

Cl, and —

Br, and

(10) —

C_2-5 alkynyl-R³;

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³,

(5) —

O—

R⁶,

(6) —

O—

C_1-6 alkyl-OR⁶,

(7) —

C_1-6 alkyl (OR⁶)(R⁴),

(8) —

C_1-6 alkyl-N(R⁴)(R⁶),

(9) —

C_1-6 alkyl C(O)—

R⁶, and

(10) —

C_1-6 alkyl NR⁴C(O)—

R⁶;

each R³ is independently selected from;

(1) phenyl,

(2) substituted phenyl with 1, 2, or 3 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, wherein halogen is selected from —

F, —

Cl, and Br,

(ii) methyl,

(iii) —

CF₃, and

(iv) hydroxy,

(3) C_3-6 cycloalkyl,

(4) morpholinyl,

(5) substituted morpholinyl substituted with oxo, and

(6) naphthyl;

each R⁴ is independently selected from;

(1) —

H, and

(2) —

C_1-3 alkyl;

each R⁵ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³,

(6) —

S(O)_n—

R³, and

(7) —

C(O)—

R³;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³; and

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

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

and tautomers and pharmaceutically acceptable salts thereof, wherein;

R¹ is selected from;

(1) —

H,

(2) —

C_1-5 alkyl,

(3) —

CF₃,

(4) -halo, wherein halo is selected from;

—

F, Cl, —

Br, and —

I;

(5) —

NO₂,

(6) —

N(R⁴)(R⁵),

(7) -phenyl,

(8) phenyl C_1-3 alkyl-,

(9) substituted phenyl C_1-3 alkyl-substituted with 1 or 2 substituents independently selected from;

(a) halo, wherein halo is selected from;

—

F, —

Cl, and —

Br, and

(10) —

C_2-5 alkynyl-R³;

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³,

(5) —

O—

R⁶,

(6) —

O—

C_1-6 alkyl-OR⁶,

(7) —

C_1-6 alkyl (OR⁶)(R⁴),

(8) —

C_1-6 alkyl-N(R⁴)(R⁶),

(9) —

C_1-6 alkyl C(O)—

R⁶, and

(10) —

C_1-6 alkyl NR⁴C(O)—

R⁶;

each R³ is independently selected from;

(1) phenyl,

(2) substituted phenyl with 1, 2, or 3 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, wherein halogen is selected from —

F, —

Cl, and Br,

(ii) methyl,

(iii) —

CF₃, and

(iv) hydroxy,

(3) C_3-6 cycloalkyl,

(4) morpholinyl,

(5) substituted morpholinyl substituted with oxo, and

(6) naphthyl;

each R⁴ is independently selected from;

(1) —

H, and

(2) —

C_1-3 alkyl;

each R⁵ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³,

(6) —

S(O)_n—

R³, and

(7) —

C(O)—

R³,

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

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

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

and tautomers and pharmaceutically acceptable salts thereof, wherein;

R¹ is selected from;

(1) —

H,

(2) —

C_1-5 alkyl,

(3) —

CF₃,

(4) -halo,

(5) —

NO₂,

(6) —

N(R⁴)(R⁵),

(7) -phenyl,

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

(a) halo,

(b) methyl, and

(c) methoxy,

(9) phenyl C_1-3 alkyl-,

(10) substituted phenyl C_1-3 alkyl-substituted with 1 or 2 substituents independently selected from;

(a) halo,

(b) methyl, and

(c) methoxy,

(11) —

C_2-5 alkenyl-R³,

(12) —

C_2-5 alkynyl-R³, and

(13) —

C(O)CH₂C(O)C(O)OR⁷;

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³,

(5) —

O—

R⁶,

(6) —

O—

C_1-6 alkyl-OR⁶,

(7) —

S(O)n-R⁶,

(8) —

C_1-6 alkyl (OR⁶)(R⁴),

(9) —

C_1-6 alkyl-N(R⁴)(R⁶),

(10) —

C_1-6 alkyl S(O)n-R⁶,

(11) —

C_1-6 alkyl C(O)—

R⁶,

(12) —

C_1-6 alkyl C(S)—

R⁶,

(13) —

C_1-6 alkyl NR⁴C(O)—

R⁶, and

(14) —

C_1-6 alkyl-C(O)N(R⁴)(R⁵);

each R³ is independently selected from;

(1) phenyl;

(2) substituted phenyl with 1, 2, or 3 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;

(3) thienyl;

(4) substituted thienyl 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) 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;

(9) pyrrolyl;

(10) substituted pyrrolyl 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) 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;

(11) pyrazolyl;

(12) substituted pyrazolyl 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) 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;

(13) C_3-6 cycloalkyl;

(14) substituted C_3-6 cycloalkyl 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, and

(h) hydroxy;

(15) piperidinyl;

(16) substituted piperidinyl 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,

(g) ═

O, and

(h) hydroxy;

(17) morpholinyl;

(18) substituted morpholinyl substituted at a carbon or nitrogen atom with 1 or 2 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;

(19) naphthyl;

(20) 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,

(g) ═

O, and

(h) hydroxy;

(21) indolyl;

(22) 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,

(g) ═

O, and

(h) hydroxy;

(23) C_3-6 cycloalkyl fused with a phenyl ring;

(24) substituted C_3-6 cycloalkyl fused with a phenyl ring 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,

(g) ═

O, and

(h) hydroxy;

each R⁴ 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, 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) —

C₂₃ alkenyl-R³,

(8) —

S(O)_n—

R³, and

(9) —

C(O)—

R³;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R², and

(2) —

R³;

R⁷ is selected from;

(1) —

H, and

(2) C_1-6 alkyl;

R⁸ is selected from;

(1) —

H, and

(2) C_1-6 alkyl; and

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

and further provided that when R⁷ is C_1-6 alkyl, then R² is not —

H or —

C_1-6 alkyl.

10. The compound according to claim 9 of structural formula:

and tautomers and pharmaceutically acceptable salts thereof, wherein;

R¹ is selected from;

(1) —

H,

(2) —

C_1-5 alkyl,

(3) —

CF₃,

(4) -halo, wherein halo is selected from;

—

F, Cl, —

Br, and —

I;

(5) —

NO₂,

(6) —

N(R⁴)(R⁵),

(7) -phenyl,

(8) phenyl C_1-3 alkyl-,

(9) substituted phenyl C_1-3 alkyl-substituted with 1 or 2 substituents independently selected from;

(a) halo, wherein halo is selected from;

—

F, —

Cl, and —

Br, and

(10) —

C_2-5 alkynyl-R³;

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³,

(5) —

O—

R⁶,

(6) —

O—

C_1-6 alkyl-OR⁶,

(7) —

C_1-6 alkyl (OR⁶)(R⁴),

(8) —

C_1-6 alkyl-N(R⁴)(R⁶),

(9) —

C_1-6 alkyl C(O)—

R⁶, and

(10) —

C_1-6 alkyl NR⁴C(O)—

R⁶;

each R³ is independently selected from;

(1) phenyl,

(2) substituted phenyl with 1, 2, or 3 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, wherein halogen is selected from —

F, —

Cl, and Br,

(ii) methyl,

(iii) —

CF₃, and

(iv) hydroxy,

(3) C_3-6 cycloalkyl,

(4) morpholinyl,

(5) substituted morpholinyl substituted with oxo; and

(6) naphthyl;

each R⁴ is independently selected from;

(1) —

H, and

(2) —

C_1-3 alkyl;

each R⁵ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³,

(6) —

S(O)_n—

R³, and

(7) —

C(O)—

R³;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

R⁸ is selected from;

(1) —

H, and

(2) CH₃; and

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

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

and tautomers and pharmaceutically acceptable salts thereof, wherein;

A is pyrazolyl;

R¹ is selected from;

(1) —

H,

(2) —

C_1-5 alkyl,

(3) —

CF₃,

(4) -halo,

(5) —

NO₂,

(6) —

N(R⁴)(R⁵),

(7) -phenyl,

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

(a) halo,

(b) methyl, and

(c) methoxy,

(9) phenyl C_1-3 alkyl-,

(10) substituted phenyl C_1-3 alkyl-substituted with 1 or 2 substituents independently selected from;

(a) halo,

(b) methyl, and

(c) methoxy,

(11) —

C_2-5 alkenyl-R³,

(12) —

C_2-5 alkynyl-R³, and

(13) —

C(O)CH₂C(O)C(O)OR⁷;

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³,

(5) —

O—

R⁶,

(6) —

O—

C_1-6 alkyl-OR⁶,

(7) —

S(O)n-R⁶,

(8) —

C_1-6 alkyl (OR⁶)(R⁴),

(9) —

C_1-6 alkyl-N(R⁴)(R⁶),

(10) —

C_1-6 alkyl S(O)n-R⁶,

(11) —

C_1-6 alkyl C(O)—

R⁶,

(12) —

C_1-6 alkyl C(S)—

R⁶,

(13) —

C_1-6 alkyl NR⁴C(O)—

R⁶, and

(14) —

C_1-6 alkyl-C(O)N(R⁴)(R⁵);

each R³ is independently selected from;

(1) phenyl;

(2) substituted phenyl with 1, 2, or 3 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;

(3) thienyl;

(4) substituted thienyl 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) 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;

(5) pyridyl;

(6) substituted pyridyl 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) 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;

(7) imidazolyl;

(8) substituted imidazolyl 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) 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;

(9) pyrrolyl;

(10) substituted pyrrolyl 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) 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;

(11) pyrazolyl;

(12) substituted pyrazolyl 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) 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;

(13) C_3-6 cycloalkyl;

(14) substituted C_3-6 cycloalkyl 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, and

(h) hydroxy;

(15) piperidinyl;

(16) substituted piperidinyl 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,

(g) ═

O, and

(h) hydroxy;

(17) morpholinyl;

(18) substituted morpholinyl substituted at a carbon or nitrogen atom with 1 or 2 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;

(19) naphthyl;

(20) 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,

(g) ═

O, and

(h) hydroxy;

(21) indolyl;

(22) 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,

(g) ═

O, and

(h) hydroxy;

(23) C_3-6 cycloalkyl fused with a phenyl ring;

(24) substituted C_3-6 cycloalkyl fused with a phenyl ring 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,

(g) ═

O, and

(h) hydroxy;

each R⁴ 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, 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, and

(9) —

C(O)—

R³;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

R⁷ is selected from;

(1) —

H, and

(2) C_1-6 alkyl;

R⁸ is selected from;

(1) —

H, and

(2) C_1-6 alkyl; and

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

and further provided that when R⁷ is C_1-6 alkyl, then R² is not —

H or —

C_1-6 alkyl.

12. The compound according to claim 11 wherein:

R¹ is selected from;

(1) —

H,

(2) —

C_1-5 alkyl,

(3) —

CF₃,

(4) -halo, wherein halo is selected from;

—

F, Cl, —

Br, and —

I;

(5) —

NO₂,

(6) —

N(R⁴)(R⁵),

(7) -phenyl,

(8) phenyl C_1-3 alkyl-,

(9) substituted phenyl C_1-3 alkyl-substituted with 1 or 2 substituents independently selected from;

(a) halo, wherein halo is selected from;

—

F, —

Cl, and —

Br, and

(10) —

C_2-5 alkynyl-R³;

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³,

(5) —

O—

R⁶,

(6) —

O—

C_1-6 alkyl-OR⁶,

(7) —

C_1-6 alkyl (OR⁶)(R⁴),

(8) —

C_1-6 alkyl-N(R⁴)(R⁶),

(9) —

C_1-6 alkyl C(O)—

R⁶, and

(10) —

C_1-6 alkyl NR⁴C(O)—

R⁶;

each R³ is independently selected from;

(1) phenyl,

(2) substituted phenyl with 1, 2, or 3 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, wherein halogen is selected from —

F, -Cl, and Br,

(ii) methyl,

(iii) —

CF₃, and

(iv) hydroxy,

(3) C_3-6 cycloalkyl,

(4) morpholinyl,

(5) substituted morpholinyl substituted with oxo, and

(6) naphthyl;

each R⁴ is independently selected from;

(1) —

H, and

(2) —

C_1-3 alkyl;

each R⁵ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³,

(6) —

S(O)_n—

R³, and

(7) —

C(O)—

R³;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

each R⁷ is independently selected from;

(1) —

H,

(2) —

CH₂CH₃, and

(3) —

CH₃; and

R⁸ is selected from;

(1) —

H, and

(2) —

CH₃; and

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

and further provided that when R⁷ is —

CH₂CH₃ or —

CHCH₃, then R² is not —

H or —

C_1-6 alkyl;

and tautomers and pharmaceutically acceptable salts thereof.

13. The compound according to claim 12 of structural formula:

and tautomers and pharmaceutically acceptable salts thereof.

14. The compound according to claim 12 of structural formula:

and tautomers and pharmaceutically acceptable salts thereof.

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

and tautomers and pharmaceutically acceptable salts thereof, wherein;

A is imidazolyl;

R¹ is selected from;

(1) —

H,

(2) —

C_1-5 alkyl,

(3) —

CF₃,

(4) -halo,

(5) —

NO₂,

(6) —

N(R⁴)(R⁵),

(7) -phenyl,

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

(a) halo,

(b) methyl, and

(c) methoxy,

(9) phenyl C_1-3 alkyl-,

(10) substituted phenyl C_1-3 alkyl-substituted with 1 or 2 substituents independently selected from;

(a) halo,

(b) methyl, and

(c) methoxy,

(11) —

C_2-5 alkenyl-R³,

(12) —

C_2-5 alkynyl-R³, and

(13) —

C(O)CH₂C(O)C(O)OR⁷;

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³,

(5) —

O—

R⁶,

(6) —

O—

C_1-6 alkyl-OR⁶,

(7) —

S(O)n-R⁶,

(8) —

C_1-6 alkyl (OR⁶)(R⁴),

(9) —

C_1-6 alkyl-N(R⁴)(R⁶),

(10) —

C_1-6 alkyl S(O)n-R⁶,

(11) —

C_1-6 alkyl C(O)—

R⁶,

(12) —

C_1-6 alkyl C(S)—

R⁶,

(13) —

C_1-6 alkyl NR⁴C(O)—

R⁶, and

(14) —

C_1-6 alkyl-C(O)N(R⁴)(R⁵);

each R³ is independently selected from;

(1) phenyl;

(2) substituted phenyl with 1, 2, or 3 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;

(3) thienyl;

(4) substituted thienyl 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) 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;

(5) pyridyl;

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

(a) halogen,

(b) C_1-6alkyl,

(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;

(7) imidazolyl;

(8) substituted imidazolyl 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) 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;

(9) pyrrolyl;

(10) substituted pyrrolyl 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) 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;

(11) pyrazolyl

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

(a) halogen,

(b) C_1-6alkyl,

(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;

(13) C_3-6 cycloalkyl;

(14) substituted C_3-6 cycloalkyl 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, and

(h) hydroxy;

(15) piperidinyl;

(16) substituted piperidinyl 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,

(g) ═

O, and

(h) hydroxy;

(17) morpholinyl,

(18) substituted moipholinyl substituted at a carbon or nitrogen atom with 1 or 2 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;

(19) naphthyl;

(20) 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,

(g) ═

O, and

(h) hydroxy;

(21) indolyl;

(22) 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,

(g) ═

O, and

(h) hydroxy;

(23) C_3-6 cycloalkyl fused with a phenyl ring;

(24) substituted C_3-6 cycloalkyl fused with a phenyl ring 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,

(g) ═

O, and

(h) hydroxy;

each R⁴ 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, 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, and

(9) —

C(O)—

R³;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

R⁷ is selected from;

(1) —

H, and

(2) C_1-6 alkyl;

R⁸ is selected from;

(1) —

H, and

(2) C_1-6 alkyl; and

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

and further provided that when R⁷ is C_1-6 alkyl, then R² is not —

H or —

C_1-6 alkyl.

16. The compound according to claim 15 of structural formula:

and tautomers and pharmaceutically acceptable salts thereof, wherein;

R¹ is selected from;

(1) —

H,

(2) —

C_1-5 alkyl,

(3) —

CF₃,

(4) -halo, wherein halo is selected from;

—

F, Cl, —

Br, and —

I;

(5) —

NO₂,

(6) —

N(R⁴)(R⁵),

(7) -phenyl,

(8) phenyl C_1-3 alkyl-,

(9) substituted phenyl C_1-3 alkyl-substituted with 1 or 2 substituents independently selected from;

(a) halo, wherein halo is selected from;

—

F, —

Cl, and —

Br, and

(10) —

C_2-5 alkynyl-R³;

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³,

(5) —

O—

R⁶,

(6) —

O—

C_1-6 alkyl-OR⁶,

(7) —

C_1-6 alkyl (OR⁶)(R⁴),

(8) —

C_1-6 alkyl-N(R⁴)(R⁶),

(9) —

C_1-6 alkyl C(O)—

R⁶, and

(10) —

C_1-6 alkyl NR⁴C(O)—

R⁶;

each R³ is independently selected from;

(1) phenyl,

(2) substituted phenyl with 1, 2, or 3 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, wherein halogen is selected from —

F, —

Cl, and Br,

(ii) methyl,

(iii) —

CF₃, and

(iv) hydroxy,

(3) C_3-6 cycloalkyl,

(4) morpholinyl,

(5) substituted morpholinyl substituted with oxo, and

(6) naphthyl;

each R⁴ is independently selected from;

(1) —

H, and

(2) —

C_1-3 alkyl;

each R⁵ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³,

(6) —

S(O)_n—

R³, and

(7) —

C(O)—

R³;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³; and

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

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

and tautomers and pharmaceutically acceptable salts thereof, wherein;

A is indolyl and the dioxobutyric acid/ester moeity is attached to the nitrogen containing ring of the indole;

R¹ is selected from;

(1) —

H,

(2) —

C_1-5 alkyl,

(3) —

CF₃,

(4) -halo,

(5) —

NO₂,

(6) —

N(R⁴)(R⁵),

(7) -phenyl,

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

(a) halo,

(b) methyl, and

(c) methoxy,

(9) phenyl C_1-3 alkyl-,

(10) substituted phenyl C_1-3 alkyl-substituted with 1 or 2 substituents independently selected from;

(a) halo,

(b) methyl, and

(c) methoxy,

(11) —

C_2-5 alkenyl-R³,

(12) —

C_2-5 alkynyl-R³, and

(13) —

C(O)CH₂C(O)C(O)OR⁷;

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³,

(5) —

O—

R⁶,

(6) —

O—

C_1-6 alkyl-OR⁶,

(7) —

S(O)n-R⁶,

(8) —

C_1-6 alkyl (OR⁶)(R⁴),

(9) —

C_1-6 alkyl-N(R⁴)(R⁶),

(10) —

C_1-6 alkyl S(O)n-R⁶,

(11) —

C_1-6 alkyl C(O)—

R⁶,

(12) —

C_1-6 alkyl C(S)—

R⁶,

(13) —

C_1-6 alkyl NR⁴C(O)—

R⁶, and

(14) —

C_1-6 alkyl-C(O)N(R⁴)(R⁵);

each R³ is independently selected from;

(1) phenyl;

(2) substituted phenyl with 1, 2, or 3 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;

(3) thienyl;

(4) substituted thienyl 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) 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;

(5) pyridyl;

(6) substituted pyridyl 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) 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;

(7) imidazolyl;

(8) substituted imidazolyl 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) 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;

(9) pyrrolyl;

(10) substituted pyrrolyl 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) 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;

(11) pyrazolyl;

(12) substituted pyrazolyl 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) 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;

(13) C_3-6 cycloalkyl,

(14) substituted C_3-6 cycloalkyl 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, and

(h) hydroxy;

(15) piperidinyl;

(16) substituted piperidinyl 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,

(g) ═

O, and

(h) hydroxy;

(17) morpholinyl,

(18) substituted morpholinyl substituted at a carbon or nitrogen atom with 1 or 2 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;

(19) naphthyl;

(20) 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,

(g) ═

O, and

(h) hydroxy;

(21) indolyl;

(22) 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,

(g) ═

O, and

(h) hydroxy;

(23) C_3-6 cycloalkyl fused with a phenyl ring;

(24) substituted C_3-6 cycloalkyl fused with a phenyl ring 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,

(g) ═

O, and

(h) hydroxy;

each R⁴ 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, 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, and

(9) —

C(O)—

R³;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³;

R⁷ is selected from;

(1) —

H, and

(2) C_1-6 alkyl;

R⁸ is selected from;

(1) —

H, and

(2) C_1-6 alkyl; and

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

and further provided that when R⁷ is C_1-6 alkyl, then R² is not —

H or —

C_1-6 alkyl.

18. The compound according to claim 17 of structural formula:

or a tautomer or a pharmaceutically acceptable salt thereof, wherein;

R¹ is selected from;

(1) —

H,

(2) —

C_1-5 alkyl,

(3) —

CF₃,

(4) -halo, wherein halo is selectcd from;

—

F, Cl, —

Br, and —

I;

(5) —

NO₂,

(6) —

N(R⁴)(R⁵),

(7) -phenyl,

(8) phenyl C_1-3 alkyl-,

(9) substituted phenyl C_1-3 alkyl-substituted with 1 or 2 substituents independently selected from;

(a) halo, wherein halo is selected from;

—

F, —

Cl, and —

Br, and

(10) —

C_2-5 alkynyl-R³;

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³,

(5) —

O—

R⁶,

(6) —

O—

C_1-6 alkyl-OR⁶,

(7) —

C_1-6 alkyl (OR⁶)(R⁴),

(8) —

C_1-6 alkyl-N(R⁴)(R⁶)

(9) —

C_1-6 alkyl C(O)—

R⁶, and

(10) —

C_1-6 alkyl NR⁴C(O)—

R⁶;

each R³ is independently selected from;

(1) phenyl,

(2) substituted phenyl with 1, 2, or 3 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, wherein halogen is selected from —

F, —

Cl, and Br,

(ii) methyl,

(iii) —

CF₃, and

(iv) hydroxy,

(3) C_3-6 cycloalkyl,

(4) morpholinyl,

(5) substituted morpholinyl substituted with oxo, and

(6) naphthyl;

each R⁴ is independently selected from;

(1) —

H, and

(2) —

C_1-3 alkyl;

each R⁵ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³,

(6) —

S(O)_n—

R³, and

(7) —

C(O)—

R³;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³; and

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

19. The compound according to claim 17 of structural formula:

or a tautomer or a pharmaceutically acceptable salt thereof, wherein;

R¹ is selected from;

(1) —

H,

(2) —

C_1-5 alkyl,

(3) —

CF₃,

(4) -halo, wherein halo is selected from;

—

F, Cl, —

Br, and —

I,

(5) —

NO₂,

(6) —

N(R⁴)(R⁵),

(7) -phenyl,

(8) phenyl C_1-3 alkyl-,

(9) substituted phenyl C_1-3 alkyl-substituted with 1 or 2 substituents independently selected from;

(a) halo, wherein halo is selected from;

—

F, —

Cl, and —

Br, and

(10) —

C_2-5 alkynyl-R³;

R² is selected from;

(1) —

H,

(2) —

R³,

(3) —

C_1-6 alkyl,

(4) —

C_1-6 alkyl substituted with R³,

(5) —

O—

R⁶,

(6) —

O—

C_1-6 alkyl-OR⁶,

(7) —

C_1-6 alkyl (OR⁶)(R⁴),

(8) —

C_1-6 alkyl-N(R⁴)(R⁶),

(9) —

C_1-6 alkyl C(O)—

R⁶, and

(10) —

C_1-6 alkyl NR⁴C(O)—

R⁶;

each R³ is independently selected from;

(1) phenyl,

(2) substituted phenyl with 1, 2, or 3 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, wherein halogen is selected from —

F, —

Cl, and Br,

(ii) methyl,

(iii) —

CF₃, and

(iv) hydroxy,

(3) C_3-6 cycloalkyl,

(4) morpholinyl,

(5) substituted morpholinyl substituted with oxo, and

(6) naphthyl;

each R⁴ is independently selected from;

(1) —

H, and

(2) —

C_1-3 alkyl;

each R⁵ is independently selected from;

(1) —

H,

(2) —

C_1-3 alkyl,

(3) —

CF₃,

(4) —

R³,

(5) —

C_1-3 alkyl-R³,

(6) —

S(O)_n—

R³, and

(7) —

C(O)—

R³;

each R⁶ is independently selected from;

(1) —

C_1-3 alkyl-R³, and

(2) —

R³; and

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

20. The compound according to claim 1 selected from:

(1) 4-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid methyl ester,

(2) 4-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(3) 4-[1-(4-methylbenzyl)-1-H-pyrrol-2-yl]-2,4-dioxobutyric acid ethyl ester,

(4) 4-[1-(4-methylbenzyl)-1-H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(5) 4-[1-(4-fluorobenzyl)-1-H-pyrrol-2-yl]-2,4-dioxobutyric acid ethyl ester,

(6) 4-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid isopropyl ester,

(7) 4-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid n-butyl ester,

(8) 4-(1-benzyl-1H-pyrrol-2-yl)-2,4-dioxobutyric acid, 2

(9) 4-(1-naphthalen-2-ylmethyl-1H-pyrrol-2-yl)-2,4-dioxobutyric acid,

(10) 4-(1-biphenyl-4-ylmethyl-1H-pyrrol-2-yl)-2,4-dioxobutyric acid,

(11) 4-(1-naphthalen-1-ylmethyl-1H-pyrrol-2-yl)-2,4-dioxobutyric acid,

(12) 2,4-dioxo-4-[1-(4-phenylbutyl)-1H-pyrrol-2-yl]-butyric acid,

(13) 4-[1-(4-chlorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(14) 2,4-dioxo-4-(1-phenethyl-1H-pyrrol-2-yl)-butyric acid,

(15) 4-[1-(2-methylbenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(16) 4-[1-(3,4-difluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(17) 4-[1-(4-bromobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(18) 4-[1-(2-bromobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(19) 4-[1-(3-bromobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(20) 4-[1-(3-chlorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(21) 4-[1-(3-methylbenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(22) 4-[1-(2-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(23) 2,4-dioxo-4-(1-hexyl-1H-pyrrol-2-yl)-butyric acid,

(24) 4-(1-biphenyl-2-ylmethyl-1H-pyrrol-2-yl)-2,4-dioxobutyric acid,

(25) 2,4-dioxo-4-[1-(4-phenoxybutyl)-1H-pyrrol-2-yl]-butyric acid,

(26) 4-[1-(3-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(27) 4-[1-(2-chlorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(28) 4-[1-(4-fluorobenzyl)-4-iodo-1H-pyrrol-2-yl]-2,4-dioxo-butyric acid,

(29) 4-[1-(4-methoxybenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(30) 4-[1-(2,4,5-trifluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(31) 4-[1-(2,3-difluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(32) 4-[1-(3,5-difluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(33) 4-[1-(2,5-difluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(34) 4-[1-(2,5,6-difluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(35) 4-[1-(2-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(36) 4-[1-(4-trifluoromethylbenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(37) 4-[1-(4-cyanobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(38) 4-[1-(3-methoxybenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(39) 2-hydroxy-4-[1-(4-hydroxybenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(40) 4-(1-cyclopentylmethyl-1H-pyrrol-2-yl)-2,4-dioxobutyric acid,

(41) 4-{1-[3-(4-fluorophenyl)propyl]-1H-pyrrol-2-yl}-2,4-dioxobutyric acid,

(42) 4-{1-[2-(4-fluorophenyl)ethyl]-1H-pyrrol-2-yl }-2,4-dioxobutyric acid,

(43) 4-[1-(3-phenylpropyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(44) 4-(1-ethyl-1H-pyrrol-2-yl)-2,4-dioxobutyric acid,

(45) 4-[1-(3-fluorobenzyl)-1-H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(46) 4-[1-(2-chlorobenzyl)-1-H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(47) 4-[1-(3-benzoylaminopropyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(48) 4-{1-[3-(4-fluorophenoxy)benzyl]-1H-pyrrol-2-yl}]-2,4-dioxobutyric acid,

(49) 4-(1-cyclohexylmethyl-1-H-pyrrol-2-yl)-2,4-dioxo-butyric acid methyl ester

(50) 4-(1-cyclohexylmethyl-1-H-pyrrol-2-yl)-2,4-dioxo-butyric acid,

(51) 4-[1-(4-fluorobenzyl)-4-phenylethynyl-1H-pyrrol-2-yl-2,4-dioxobutyric acid ethyl ester,

(52) 4-[1-(4-fluorobenzyl)-4-phenylethynyl-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(53) 4-[1-(4-fluorobenzyl)-4-phenethyl-1H-pyrrol-2-yl]-2,4-dioxobutyric acid ethyl ester,

(54) 4-[1-(4-fluorobenzyl)-4-phenethyl-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(55) 4-[5-(4-fluorobenzyl)-1-methyl-1H-pyrrol-2-yl]-2,4-dioxobutyric acid methyl ester,

(56) 4-[5-(4-fluorobenzyl)-1-methyl-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(57) 4-[5-(3-chlorobenzyl)-1-methyl-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(58) 4-[5-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(59) 4-[5-(3-chlorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(60) 4-[5-(benzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(61) 4-[5-(3-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(62) 4-[5-(4-fluorobenzyl)-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(63) 4-[5-(3-chlorobenzyl)-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(64) 4-[5-(benzyl)-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(65) 4-[5-(3-chlorobenzyl)-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(66) 4-[5-(4-fluorobenzyl)-1-methyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(67) 4-[5-(3-chlorobenzyl)-1-methyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(68) 4-[5-(benzyl)-1-methyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(69) 4-[5-(3-fluorobenzyl)-1-methyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(70) 4-(5-benzyl-1H-pyrrol-3-yl)-2,4-dioxobutyric acid,

(71) 4-[2,5-bis-(3-chlorobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(72) 4-[1-(4-Fluorobenzyl)-5-phenyl-1H-pyrrol-2-yl]-2,4-dioxobutyric acid ethyl ester,

(73) 4-[1-(4-Fluorobenzyl)-5-phenyl-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(74) 4-[4-Dimethylamino-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid ethyl ester,

(75) 4-[4-Dimethylamino-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(76) 4-[1-(4-Fluorobenzyl)-4-nitro-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(77) 4-[4-(Benzylamino)-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(78) 4-[5-Nitro-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric

(79) 4-[1-benzyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid methyl ester,

(80) 4-[1-benzyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(81) 4-[1-(4-fluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(82) 4-[1-(3-bromobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(83) 4-[1-(4-fluorobenzyl)-4-methyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(84) 4-[2,4-dimethyl-1-(4-fluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(85) 4-[1-(3,4-difluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(86) 4-[1-(3-chlorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(87) 4-[1-(4-chlorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(88) 4-[1-(4-bromobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(89) 4-[1-(3,4-dichlorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(90) 4-[1-(2-methylbenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(91) 4-[1-(3-chlorobenzyl)-4-methyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(92) 4-[1-(3-trifluoromcthylbenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(93) 4-[1-(4-methylbenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(94) 4-[1-(4-methoxybenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(95) 4-[1-(3-methylbenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(96) 4-{1-[3-(4-fluorophenyl)-propyl]-1H-pyrrol-3-yl}-2,4-dioxobutyric acid,

(97) 4-[1-(4-bromobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(98) 4-[1-(4-chlorobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(99) 4-[4-Benzylmethylamino-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric, ethyl ester

(100) 4-[4-Benzylmethylamino-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(101) 4-[4-Phenyl-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid ethyl ester,

(102) 4-[4-Phenyl-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(103) 4-[1-(4-fluorobenzyl)-4-methanesulfonylamino-1H-pyrrol-3-yl]-2,4-dioxo-butyric acid ethyl ester,

(104) 4-[1-(4-fluorobenzyl)-4-methanesulfonylamino-1H-pyrrol-3-yl]-2,4-dioxo-butyric acid,

(105) 4-[1-(4-Fluorobenzyl)-3-acetylamino-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(106) 4-[4-acetylamino-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(108) 4-[4-(4-fluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(109) 4-[1,4-bis-(4-fluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(110) 4-[5-(3-ethoxycarbonyl-3-oxopropionyl)-1-(4-fluorobenzyl)-1H-pyrazol-3-yl]-2,4-dioxobutyric acid ethyl ester,

(111) 4-[1-(4-fluorobenzyl)-1H-pyrazol-4-yl]-2,4-dioxobutyric acid ethyl ester,

(112) 4-[1-(4-fluorobenzyl)-1H-pyrazol-4-yl]-2,4-dioxobutyric acid,

(113) 4-[4-Dimethylamino-1-(4-fluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(114) 4-[1-(4-Fluorobenzyl)-5-methyl-1H-pyrazol-4-yl]-2-hydroxy-4-oxobut-2-enoic acid,

(115) 4-[2-(4-fluorobenzyl)-2H-pyrazol-3-yl]-2,4-dioxo-butyric acid ethyl ester,

(116) 4-[2-(4-fluorobenzyl)-2H-pyrazol-3-yl]-2,4-dioxo-butyric acid,

(117) 4-[2-(4-fluorobenzyl)-3-methyl-1H-pyrazol-4-yl]-2,4-dioxobutyric acid ethyl ester,

(118) 1-[1-(4-fluorobenzyl)-3-methyl-1H-pyrazol-4-yl]-2,4-dioxobutyric acid,

(119) 4-[3-methyl-1-(3-chlorobenzyl)-1H-pyrazol-4-yl]-2,4-dioxobutyric acid ethyl ester,

(120) 4-[3-methyl-1-(3-chlorobenzyl)-1H-pyrazol-4-yl]-2,4-dioxobutyric acid,

(121) 4-[5-methyl-1-(3-chlorobenzyl)-1H-pyrazol-4-yl]-2,4-dioxobutyric acid,

(122) 4-[5-methyl-1-(3-chlorobenzyl)-1H-pyrazol-4-yl]-2,4-dioxobutyric acid ethyl ester,

(123) 4-[5-methyl-1-(3-chlorobenzyl)-1H-pyrazol-4-yl]-2,4-dioxobutyric acid,

(124) 4-[1-(4-fluoro-benzyl)-1H-imidazol-2-yl]-2,4-dioxo-butyric acid,

(125) 4-[1-(4-fluorobenzyl)-1H-imidazol-2-yl]-2,4-dioxo-butyric acid ethyl ester,

(126) 4-[1-(4-fluorobenzyl)-1H-imidazol-2-yl]-2,4-dioxo-butylic acid,

(127) 4-(1-Benzyl-1H-imidazol-2-yl)-2,4-dioxobutyric acid,

(128) 4-[1-(4-fluorobenzyl)-1H-imidazol-4-yl]-2,4-dioxo-butyric acid ethyl ester,

(129) 4-[1-(4-fluorobenzyl)-1H-imidazol-4-yl]-2,4-dioxo-butyric acid,

(130) 4-[1-(4-fluorobenzyl)-1H-indol-2-yl]-2,4-dioxobutyric acid methyl ester,

(131) 4-[1-(4-fluorobenzyl)-1H-indol-2-yl]-2,4-dioxobutyric acid,

(132) 2-hydroxy-4-(1-methyl-1-H-indol-2-yl)-2,4-dioxobutyric acid,

(133) 4-[1-(4-fluorobenzyl)-1H-indol-3-yl]-2,4-dioxobutyric acid,

(134) 1-[1-(4-fluorobenzyl)-1H-indol-3-yl]-2,4-dioxobutyric acid ethyl ester,

(135) 1-[1-(4-fluorobenzyl)-1H-indol-3-yl]-2,4-dioxobutyric acid,

(136) 4-[1-fluorobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(137) 4-[4-(3-chlorobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxo-butylic acid,

(138) 4-[4-(4-fluorobenzyl)-1-methyl-1-H-pyrrol-3-yl]-2,4-dioxo-butyric acid,

(139) 4-[2,5-dimethyl-1-(4-fluorobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxo-butyric acid,

(140) 4-[1-(3,5-dichlorobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(141) 4-[1-(3-thiophenemethyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(142) 4-[1-2,4-dimethylbenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(143) 4-[1-(3-chloro-5-methyl-benzyl)-1-H-pyrrol-3-yl]-2,4-dioxo-butyric acid,

(144) 4-[1-(1-naphthalenemethyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(145) 4-[1-(2-thiophencmethyl)-1-H-pyrrole-3-yl]-2,4-dioxobutyric acid, and

(146) 4-[4-(3-chlorobenzyl)-1-methyl-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

or a tautomer or a pharmaceutically acceptable salt thereof.

21. The compound according to claim 1 selected from:

(1) 4-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(2) 4-[1-(4-methylbenzyl)-1-H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(3) 4-(1-benzyl-1H-pyrrol-2-yl)-2,4-dioxobutyric acid,

(4) 4-(1-naphthalen-2-ylmethyl-1H-pyrrol-2-yl)-2,4-dioxobutyric acid,

(5) 4-(1-biphenyl-4-ylmethyl-1H-pyrrol-2-yl)-2,4-dioxobutyric acid,

(6) 4-(1-naphthalen-1-ylmethyl-1H-pyrrol-2-yl)-2,4-dioxobutyric acid,

(7) 2,4-dioxo-4-[1-(4-phenylbutyl)-1H-pyrrol-2-yl]-butyric acid,

(8) 4-[1-(4-chlorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(9) 2,4-dioxo-4-(1-phenethyl-1H-pyrrol-2-yl)-butyric acid,

(10) 4-[1-(2-methylbenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(11) 4-[1-(3,4-difluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(12) 4-[1-(4-bromobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(13) 4-[1-(2-bromobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(14) 4-[1-(3-bromobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(15) 4-[1-(3-chlorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(16) 4-[1-(3-methylbenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(17) 4-[4-(2-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(18) 2,4-dioxo-4-(1-hexyl-1H-pyrrol-2-yl)-butyric acid,

(19) 4-(1-biphenyl-2-ylmethyl-1H-pyrrol-2-yl)-2,4-dioxobutyric acid,

(20) 2,4-dioxo-4-[1-(4-phenoxybutyl)-1H-pyrrol-2-yl]-butyric acid,

(21) 4-[1-(3-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(22) 4-[1-(2-chlorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(23) 4-[1-(4-fluorobenzyl)-4-iodo-1H-pyrrol-2-yl]-2,4-dioxo-butyric acid,

(24) 4-[1-(4-methoxybenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(25) 4-[1-(2,4,5-trifluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(26) 4-[1-(2,3-difluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(27) 4-[1-(3,5-difluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(28) 4-[1-(2,5-difluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(29) 4-[1-(2,5,6-difluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(30) 4-[1-(2-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(31) 4-[1-(4-trifluoromethylbenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(32) 4-[1-(4-cyanobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(33) 4-[1-(3-methoxybenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(34) 2-hydroxy-4-[1-(4-hydroxybenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(35) 4-(1-cyclopentylmethyl-1H-pyrrol-2-yl)-2,4-dioxobutyric acid,

(36) 4-{1-[3-(4-fluorophenyl)propyl]-1H-pyrrol-2-y}-2,4-dioxobutyric acid,

(37) 4-{1-[2-(4-fluorophenyl)ethyl]-1H-pyrrol-2-yl}-2,4-dioxobutyric acid,

(38) 4-[1-(3-phenylpropyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(39) 4-(1-ethyl-1H-pyrrol-2-yl)-2,4-dioxobutyric acid,

(40) 4-[1-(3-fluoro-benzyl)-1-H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(41) 4-[1-(2-chloro-benzyl)-1-H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(42) 4-[1-(3-benzoylaminopropyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(43) 4-{1-[3-(4-fluorophenoxy)benzyl]-1H-pyrrol-2-yl}]-2,4-dioxobutyric acid,

(44) 4-(1-cyclohexylmethyl-1-H-pyrrol-2-yl)-2,4-dioxo-butyric acid,

(45) 4-[1-(4-fluorobenzyl)-4-phenylethynyl-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(46) 4-[1-(4-fluorobenzyl)-4-phenethyl-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(47) 4-[5-(4-fluorobenzyl)-1-methyl-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(48) 4-[5-(3-chlorobenzyl)-1-methyl-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(49) 4-[5-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(50) 4-[5-(3-chlorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(51) 4-[5-(benzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(52) 4-[5-(3-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(53) 4-[5-(4-fluorobenzyl)-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(54) 4-[5-(3-chlorobenzyl)-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(55) 4-[5-(benzyl)-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(56) 4-[5-(3-chlorobenzyl)-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(57) 4-[5-(4-fluorobenzyl)-1-methyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(58) 4-[5-(3-chlorobenzyl)-1-methyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(59) 4-[5-(benzyl)-1-methyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(60) 4-[5-(3-fluorobenzyl)-1-methyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(61) 4-(5-benzyl-1H-pyrrol-3-yl)-2,4-dioxobutyric acid,

(62) 4-[2,5-bis-(3-chlorobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(63) 4-[1-(4-Fluorobenzyl)-5-phenyl-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(64) 4-[4-Dimethylamino-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(65) 4-[1-(4-Fluorobenzyl)-4-nitro-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(66) 4-[4-(Benzylamino)-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(67) 4-[5-Nitro-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric

(68) 4-[1-benzyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(69) 4-[1-(4-fluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(70) 4-[1-(3-bromobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(71) 4-[1-(4-fluorobenzyl)-4-methyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(72) 4-[2,4-dimethyl-1-(4-fluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(73) 4-[1-(3,4-difluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(74) 4-[1-(3-chlorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(75) 4-[1-(4-chlorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(76) 4-[1-(4-bromobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(77) 4-[1-(3,4-dichlorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(78) 4-[1-(2-methylbenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(79) 4-[1-(3-chlorobenzyl)-4-methyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(80) 4-[1-(3-trifluoromethylbenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(81) 4-[1-(4-methylbenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(82) 4-[1-(4-methoxybenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(83) 4-[1-(3-methylbenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(84) 4-{1-[3-(4-fluorophenyl)-propyl]-1H-pyrrol-3-yl}-2,4-dioxobutyric acid,

(85) 4-[1-(4-bromobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(86) 4-[1-(4-chlorobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(87) 4-[4-Benzylmethylamino-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(88) 4-[4-Phenyl-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(89) 4-[1-(4-fluorobenzyl)-4-methanesulfonylamino-1H-pyrrol-3-yl]-2,4-dioxo-butyric acid,

(90) 4-[1-(4-Fluorobenzyl)-3-acetylamino-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(91) 4-[4-acetylamino-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(93) 4-[4-(4-fluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(94) 4-[1,4-bis-(4-fluorobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(95) 4-[1-(4-fluorobenzyl)-1H-pyrazol-4-yl]-2,4-dioxobutyric acid,

(96) 4-[4-Dimethylamino-1-(4-fluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(97) 4-[1-(4-Fluorobenzyl)-5-methyl-1H-pyrazol-4-yl]-2-hydroxy-4-oxobut-2-enoic acid,

(98) 4-[2-(4-fluorobenzyl)-2H-pyrazol-3-yl]-2,4-dioxo-butyric acid,

(99) 1-[1-(4-fluorobenzyl)-3-methyl-1H-pyrazol-4-yl]-2,4-dioxobutyric acid,

(100) 4-[3-methyl-1-(3-chlorobenzyl)-1H-pyrazol-4-yl]-2,4-dioxobutyric acid,

(101) 4-[5-methyl-1-(3-chlorobenzyl)-1H-pyrazol-4-yl]-2,4-dioxobutyric acid,

(102) 4-[5-methyl-1-(3-chlorobenzyl)-1H-pyrazol-4-yl]-2,4-dioxobutyric acid,

(103) 4-[1-(4-fluoro-benzyl)-1H-imidazol-2-yl]-2,4-dioxo-butyric acid,

(104) 4-[1-(4-fluorobenzyl)-1H-imidazol-2-yl]-2,4-dioxo-butyric acid,

(105) 4-(1-Benzyl-1H-imidazol-2-yl)-2,4-dioxobutyric acid,

(106) 4-[1-(4-fluorobenzyl)-1H-imidazol-4-yl]-2,4-dioxo-butyric acid,

(107) 4-[1-(4-fluorobenzyl)-1H-indol-2-yl]-2,4-dioxobutyric acid,

(108) 2-hydroxy-4-(1-methyl-1-H-indol-2-yl)-2,4-dioxobutyric acid,

(109) 4-[1-(4-fluorobenzyl)-1H-indol-3-yl]-2,4-dioxobutyric acid,

(110) 1-[1-(4-fluorobenzyl)-1H-indol-3-yl]-2,4-dioxobutyric acid, ethyl ester,

(111) 1-[1-(4-fluorobenzyl)-1H-indol-3-yl]-2,4-dioxobutyric acid,

(112) 4-[1-(3-fluorobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(113) 4-[4-(3-chlorobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxo-butyric acid,

(114) 4-[4-(4-fluorobenzyl)-1-methyl-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(115) 4-[2,5-dimethyl-1-(4-fluorobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(116) 4-[1-(3,5-dichlorobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(117) 4-[1-(3-thiophenemethyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(118) 4-[1-2,4-dimethylbenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(119) 4-[1-(3-chloro-5-methyl-benzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(120) 4-[1-(1-naphthalenemethyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(121) 4-[1-(2-thiophenemethyl)-1-H-pyrrole-3-yl]-2,4-dioxobutyric acid, and

(122) 4-[4-(3-chlorobenzyl)-1-methyl-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

or a tautomer or a pharmaceutically acceptable salt thereof.

22. The compound according to claim 21 selected from:

(1) 4-[1-(2-thiophenemethyl)-1-H-pyrrole-3-yl]-2,4-dioxobutyric acid, and

(2) 4-[4-(3-chlorobenzyl)-1-methyl-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(3) 4-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(4) 4-[5-(3-chlorobenzyl)-1-methyl-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(5) 4-[5-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(6) 4-[5-(4-fluorobenzyl)-1-methyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(7) 4-[5-(3-chlorobenzyl)-1-methyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(8) 4-[5-(benzyl)-1-methyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(9) 4-[5-(3-fluorobenzyl)-1-methyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(10) 4-[4-Dimethylamino-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(11) 4-[1-benzyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(12) 4-[1-(3-bromobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(13) 4-[1-(4-fluorobenzyl)-4-methyl-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(14) 4-[1-(3,4-difluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(15) 4-[1-(3-chlorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(16) 4-[1-(2-methylbenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(17) 4-[1-(3-methylbenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(18) 4-[4-Benzylmethylamino-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid,

(19) 4-[4-(4-fluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(20) 4-[1,4-bis-(4-fluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(21) 4-[1-(3-fluorobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(22) 4-[4-(3-chlorobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxo-butyric acid,

(23) 4-[4-(4-fluorobenzyl)-1-methyl-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(24) 4-[2,5-dimethyl-1-(4-fluorobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(25) 4-[1-(3,5-dichlorobenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(26) 4-[1-(3-thiophenemethyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(27) 4-[1-2,4-dimethylbenzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid,

(28) 4-[1-(3-chloro-5-methyl-benzyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid, and

(29) 4-[1-(1-naphthalenemethyl)-1-H-pyrrol-3-yl]-2,4-dioxobutyric acid, or a tautomer or a pharmaceutically acceptable salt thereof.

23. A pharmaceutical composition useful for inhibiting HIV integrase, comprising an effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier.

24. The pharmaceutical composition of claim 23, useful for treating infection by HIV, or for treating AIDS or ARC.

25. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in combination with 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.

26. The composition of claim 25 wherein the antiviral agent is an HIV protease inhibitor.

27. The composition of claim 26 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.

28. A pharmaceutical composition made by combining the compound of claim 1 and a pharmaceutically acceptable carrier.

29. A process for making a pharmaceutical composition comprising combining a compound of claim 1 and a pharmaceutically acceptable carrier.

30. 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 claim 1.

31. A method of treating infection by HIV, or of treating AIDS or ARC, comprising the administration to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 1.