wherein:

R₁ is —H;

X₁ is a bond, C₁ to C₅ alkyl, —C(O)—, —C(═CR₈R₉)—, —O—, —S(O)_t—, —NR₈—, —CR₈R₉—, —CHR₂₃, —CR₈(CR₉)—, —C(CR₈)₂—, —CR₈(OC(O)R₉)—, —C═NOR₉—, —C(O)NR₈—, —CH₂O—, —CH₂S—, —CH₂NR₈—, —OCH₂—, —SCH₂—, —NR₈CH₂—, or

R₂ is H, C₁ to C₆ alkyl, C₂ to C₆ alkenyl, C₂ to C₆ alkynyl, C₃ to C₆ cycloalkyl, —CH₂OH, C₇ to C₁₁ arylalkyl, phenyl, naphthyl, C₁ to C₃ perfluoroalkyl, CN, C(O)NH₂, CO₂R₁₂ or phenyl substituted independently by one or more of the groups independently selected from C₁ to C₃ alkyl, C₂ to C₄ alkenyl, C₂ to C₄ alkynyl, C₁ to C₃ alkoxy, C₁ to C₃ perfluoroalkyl, halogen, —NO₂, —NR₈R₉, —CN, —OH, and C₁ to C₃ alkyl substituted with 1 to 5 fluorines, or

R₂ is a heterocycle selected from the group consisting of pyridine, thiophene, benzisoxazole, benzothiophene, oxadiazole, pyrrole, pyrazole, imidazole and furan, each of which may be optionally substituted with one to three groups independently selected from C₁ to C₃ alkyl, C₁ to C₃ alkoxy, C₁ to C₃ perfluoroalkyl, halogen, —NO₂, —NR₈R₉, —CN, and C₁ to C₃ alkyl substituted with 1 to 5 fluorines;

X₂ is a bond or —CH₂—;

R₃ is phenyl, naphthyl, or phenyl or naphthyl substituted independently by one to four groups independently selected from C₁ to C₃ alkyl, hydroxy, phenyl, acyl, halogen, —NH₂, —CN, —NO₂, C₁ to C₃ alkoxy, C₁ to C₃ perfluoroalkyl, C₁ to C₃ alkyl substituted with 1 to 5 fluorines, NR₁₄R₁₅, —C(O)R₁₀, —C(O)NR₁₀R₁₁, —C(O)NR₁₁A, —C≡CR₈, —CH═CHR₈, —WA, —C≡CA, —CH═CHA, —WYA, —WYNR₁₁-A, —WYR₁₀, —WY(CH₂)_jA, —WCHR₁₁(CH₂)_jA, —W(CH₂)_jA, —W(CH₂)_jR₁₀, —CHR₁₁W(CH₂)_jR₁₀, —CHR₁₁W(CH₂)_jA, —CHR₁₁NR₁₂YA, —CHR₁₁NR₁₂YR₁₀, pyrrole, —W(CH₂)_jA(CH₂)_kD(CH₂)_pZ, —W(CR₁₈R₁₉)A(CH₂)_kD(CH₂)_pZ, —(CH₂)_jWA(CH₂)_kD(CH₂)_pZ, —CH═CHA(CH₂)_kD(CH₂)_pZ, —C≡CA(CH₂)_kD(CH₂)_pZ, —W(CH₂)_jC≡CA(CH₂)_kD(CH₂)_pZ, and —W(CH₂)_jZ, or

R₃ is a heterocycle selected from pyrimidine, thiophene, furan, benzothiophene, indole, benzofuran, benzimidazole, benzothiazole, benzoxazole, and quinoline, each of which may be optionally substituted with one to three groups independently selected from C₁ to C₃ alkyl, C₁ to C₃ alkoxy, hydroxy, phenyl, acyl, halogen, —NH₂, —CN, —NO₂, C₁ to C₃ perfluoroalkyl, C₁ to C₃ alkyl substituted with 1 to 5 fluorines, —C(O)R₁₀, —C(O)NR₁₀R₁₁, —C(O)NR₁₁A, —C≡CR₈, —CH═CHR₈, —WA, —C≡CA, —CH═CHA, —WYA, —WYR₁₀, —WY(CH₂)_jA, —W(CH₂)_jA, —W(CH₂)_jR₁₀, —CHR₁₁W(CH₂)_jR₁₀, —CHR₁₁W(CH₂)_jA, —CHR₁₁NR₁₂YA, —CHR₁₁NR₁₂YR₁₀, —WCHR₁₁(CH₂)_jA, —W(CH₂)_jA(CH₂)_kD(CH₂)_pZ, —W(CR₁₈R₁₉)A(CH₂)_kD(CH₂)_pZ, —(CH₂)_jWA(CH₂)_kD(CH₂)_pZ, —CH═CHA(CH₂)_kD(CH₂)_pZ, —C≡CA(CH₂)_kD(CH₂)_pZ, —W(CH₂)_jC≡CA(CH₂)_kD(CH₂)_pZ, and —W(CH₂)_jZ;

W is a bond, —O—, —S—, —S(O)—, —S(O)₂—, —NR₁₁—, or —N(COR₁₂)—;

Y is —CO—, —S(O)₂—, —CONR₁₃, —CONR₁₃CO—, —CONR₁₃SO₂—, —C(NCN)—, —CSNR₁₃, —C(NH)NR₁₃, or —C(O)O—;

j is 0 to 3;

k is 0 to 3;

t is 0 to 2;

D is a bond, —CH═CH—, —C≡C—, —C═, —C(O)—, phenyl, —O—, —NH—, —S—, —CHR₁₄—, —CR₁₄R₁₅—, —OCHR₁₄, —OCR₁₄R₁₅—, or —CH(OH)CH(OH)—;

p is 0 to 3;

Z is —CO₂R₁₁, —CONR₁₀R₁₁, —C(NR₁₀)NR₁₁R₁₂, —CONH₂NH₂, —CN, —CH₂OH, —NR₁₆R₁₇, phenyl, CONHCH(R₂₀)COR₁₂, phthalimide, pyrrolidine-2,5-dione, thiazolidine-2,4-dione, tetrazolyl, pyrrole, indole, oxazole, 2-thioxo-1,3-thiazolinin-4-one, C₁ to C₇ amines, C₃ to C₇ cyclic amines, or C₁ to C₃ alkyl substituted with one to two OH groups; wherein said pyrrole is optionally substituted with one or two substituents independently selected from the group consisting of —CO₂CH₃, —CO₂H, —COCH₃, —CONH₂ and —CN; wherein said C₁ to C₇ amines are optionally substituted with one to two substituents independently selected from the group consisting of —OH, halogen, —OCH₃, and —C≡CH; wherein said phenyl is optionally substituted with CO₂R₁₁, and wherein said C₃ to C₇ cyclic amines are optionally substituted with one or two substituents independently selected from the group consisting of —OH —CH₂OH, C₁ to C₃ alkyl, —CH₂OCH₃, —CO₂CH₃, and —CONH₂, and wherein said oxazole is optionally substituted with CH₂CO₂R₁₁;

A is phenyl, naphthyl, tetrahydronaphthyl, indan or biphenyl, each of which may be optionally substituted by one to four groups independently selected from halogen, C₁ to C₃ alkyl, C₂ to C₄ alkenyl, C₂ to C₄ alkynyl, acyl, hydroxy, halogen, —CN, —NO₂, —CO₂R₁₁, —CH₂CO₂R₁₁, phenyl, C₁ to C₃ perfluoroalkoxy, C₁ to C₃ perfluoroalkyl, —NR₁₀R₁₁, —CH₂NR₁₀R₁₁, —SR₁₁, C₁ to C₆ alkyl substituted with 1 to 5 fluorines, C₁ to C₃ alkyl substituted with 1 to 2 —OH groups, C₁ to C₆ alkoxy optionally substituted with 1 to 5 fluorines, or phenoxy optionally substituted with 1 to 2 CF₃ groups; or

A is a heterocycle selected from pyrrole, pyridine, pyridine-N-oxide, pyrimidine, pyrazole, thiophene, furan, quinoline, oxazole, thiazole, imidazole, isoxazole, indole, benzo[1,3]-dioxole, benzo[1,2,5]-oxadiazole, isochromen-1-one, benzothiophene, benzofuran, 2,3-dihydrobenzo[1,4]-dioxine, bitheinyl, quinazolin-2,4-91,3H]dione, and 3-H—isobenzofuran-1-one, each of which may be optionally substituted by one to three groups independently selected from halogen, C₁ to C₃ alkyl, acyl, hydroxy, —CN, —NO₂, C₁ to C₃ perfluoroalkyl, —NR₁₀R₁₁, —CH₂NR₁₀R₁₁, —SR₁₁, C₁ to C₃ alkyl substituted with 1 to 5 fluorines, and C₁ to C₃ alkoxy optionally substituted with 1 to 5 fluorines;

R₄, R₅, and R₆ are each, independently, —H or —F;

R₇ is C₁ to C₄ alkyl, C₁ to C₄ perfluoroalkyl, halogen, —NO₂, —CN, phenyl or phenyl substituted with one or two groups independently selected from halogen, C₁ to C₂ alkyl and OH;

provided that if X₁R₂ forms hydrogen, then R₃ is selected from:

(a) phenyl substituted by —W(CH₂)_jA(CH₂)_kD(CH₂)_pZ, —W(CR₁₈R₁₉)A(CH₂)_kD(CH₂)_pZ, —(CH₂)_jWA(CH₂)_kD(CH₂)_pZ, —CH═CHA(CH₂)_kD(CH₂)_pZ, —C≡CA(CH₂)_kD(CH₂)_pZ, or —W(CH₂)_jC≡CA(CH₂)_kD(CH₂)_pZ, wherein the phenyl moiety is further optionally substituted with one or two groups independently selected from C₁ to C₂ alkyl, C₁ to C₂ perfluoroalkyl, halogen, and CN; and

(b) a heterocycle selected from pyrimidine, thiophene, and furan, each of which is substituted by one of —W(CH₂)_jA(CH₂)_kD(CH₂)_pZ, —W(CR₁₈R₁₉)A(CH₂)_kD(CH₂)_pZ, —(CH₂)_jWA(CH₂)_kD(CH₂)_pZ, —CH═CHA(CH₂)_kD(CH₂)_pZ, —C≡CA(CH₂)_kD(CH₂)_pZ, or —W(CH₂)_jC≡CA(CH₂)_kD(CH₂)_pZ;

each R₈ is independently —H, or C₁ to C₃ alkyl;

each R₉ is independently —H, or C₁ to C₃ alkyl;

each R₁₀ is independently —H, —CH, C₁ to C₃ alkoxy, C₁ to C₇ alkyl, C₃ to C₇ alkenyl, C₃ to C₇ alkynyl, C₃ to C₇ cycloalkyl, —CH₂CH₂OCH₃, 2-methyl-tetrahydro-furan, 2-methyl-tetrahydro-pyran, 4-methyl-piperidine, morpholine, pyrrolidine, or phenyl optionally substituted with one or two C₁ to C₃ alkoxy groups, wherein said C₁ to C₇ alkyl is optionally substituted with 1, 2 or 3 groups independently selected from C₁ to C₃ alkoxy, C₁ to C₃ thioalkoxy and CN;

each R₁₁ is independently —H, C₁ to C₃ alkyl or R₂₂;

or R₁₀ and R₁₁, when attached to the same atom, together with said atom form:

a 5 to 7 membered saturated ring, optionally substituted by 1 to 2 groups independently selected from C₁ to C₃ alkyl, OH and C₁—C₃ alkoxy; or

a 5 to 7 membered ring containing 1 or 2 heteroatoms, optionally substituted by 1 to 2 groups independently selected from C₁ to C₃ alkyl, OH and C₁—C₃ alkoxy;

each R₁₂ is independently —H, or C₁ to C₃ alkyl;

each R₁₃ is independently —H, or C₁ to C₃ alkyl;

each R₁₄ and R₁₅ is, independently, C₁ to C₇ alkyl, C₃ to C₈ cycloalkyl, C₂ to C₇ alkenyl, C₂ to C₇ alkynyl, —CH, —F, C₇ to C₁₄ arylalkyl, where said arylalkyl is optionally substituted with 1 to 3 groups independently selected from NO₂, C₁ to C₆ alkyl, C₁ to C₃ perhaloalkyl, halogen, CH₂CO₂R₁₁, phenyl and C₁ to C₃ alkoxy, or R₁₄ and R₁₅ together with the atom to which they are attached can form a 3 to 7 membered saturated ring;

each R₁₆ and R₁₇ is, independently, hydrogen, C₁ to C₃ alkyl, C₁ to C₃ alkenyl, C₁ to C₃ alkynyl, phenyl, benzyl or C₃ to C₈ cycloalkyl, wherein said C₁ to C₃ alkyl is optionally substituted with one OH group, and wherein said benzyl is optionally substituted with 1 to 3 groups selected from C₁ to C₃ alkyl and C₁ to C₃ alkoxy; or

R₁₆ and R₁₇, together with the atom to which they are attached, can form a 3 to 8 membered heterocycle which is optionally substituted with one or two substituents independently selected from the group consisting of C₁ to C₃ alkyl, —OH, CH₂OH, —CH₂OCH₃, —CO₂CH₃, and —CONH₂;

each R₁₈ and R₁₉ is, independently, C₁ to C₃ alkyl;

each R20 is independently H, phenyl, or the side chain of a naturally occurring alpha amino acid;

each R₂₂ is independently arylalkyl optionally substituted with CH₂COOH; and

each R₂₃ is phenyl;

or a pharmaceutically acceptable salt thereof.