	US 7,521,473 B2
	Inhibitors of protein tyrosine phosphatase 1B
Jinbo Lee, Acton, Mass. (US); Zhao-Kui Wan, Arlington, Mass. (US); Douglas P. Wilson, Ayer, Mass. (US); Bruce C. Follows, Littleton, Mass. (US); Steven J. Kirincich, Concord, Mass. (US); Michael J. Smith, Poland, Ohio (US); Jun-Jun Wu, Arlington, Mass. (US); Kenneth W. Foreman, Syosset, N.Y. (US); David V. Erbe, Boston, Mass. (US); Yan-Ling Zhang, Lexington, Mass. (US); Weixin Xu, Acton, Mass. (US); and Steve Y. Tam, Wellesley, Mass. (US)
Assigned to Wyeth, Madison, N.J. (US)
Filed on Feb. 23, 2005, as Appl. No. 11/63,475.
Claims priority of provisional application 60/547049, filed on Feb. 25, 2004.
Prior Publication US 2005/0203087 A1, Sep. 15, 2005
Int. Cl. A61K 31/381 (2006.01); C07D 333/38 (2006.01)

U.S. Cl. 514—445 [514/252.13; 514/326; 514/444; 514/448; 544/379; 549/60; 549/64; 549/68; 549/71; 549/72; 546/213; 546/280.4]

59 Claims

1. A compound of formula (I),

wherein R₁is C(O)OR₅, C(O)R₅, or C(O)NR₅R₆;

R₂is R₅;

X is —O—C_1-3alkylene, —NR₈—C_1-3alkylene, —S—C_1-3alkylene, —SO—C_1-3alkylene-, —SO₂—C_1-3alkylene, —C_1-4alkylene, —C_2-4alkenylene, —C_2-4alkynylene-; wherein any of the alkylene, alkenylene or alkynylene groups is optionally substituted with one or more halogen, oxo, imido, CN, OCF₃, OH, NH₂, NO₂, or Q;

Y is absent, —O—, or —NR₆—;

R₃is H, halogen, CN, CFR₃, OCF₃, C_1-3alkyl, C_3-4cycloalkyl, C_1-3alkoxy, or aryl;

R₄is A-B-E-D, where A is arylene or heteroarylene, each A being optionally substituted with one or more of C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, halogen, CN, OCF₃, OH, NH₂, CHO, NO₂, or Q; where any of the alkyl, alkenyl or alkynyl is optionally substituted with one or more halogen, oxo, CN, OCF₃, OH, NH₂, NO₂, N₃, or Q;

B is absent or —NR₅—, —NR₇—, —N(R₅)CH₂—, —N(R₉)—, —N(R₉)C(O)—, —N(R₉)C(O)C(R₁₁)(R₁₂)—, N(R₉)C(O)C(O)—, —N(R₉)C(O)N(R₁₀)—, —N(R₉)SO₂—, —N(R₉)SO₂C(R₁₀)(R₁₁)—, —N(R₉)(R₁₀)C(R₁₁)(R₁₂)—, —N(R₉)C(R₁₁)(R₁₂)C(R₁₃)(R₁₄)—, —O—, —O—C(R₁₁)(R₁₂), —O—C(R₁₁)(R₁₂)C(R₁₃)(R₁₄)—, —C(R₁₁)(R₁₂)—O—, —C(R₁₁)(R₁₂)—O—C(R₁₃)(R₁₄)—, —C(R₁₁)(R₁₂)N(R₉)—, —C(R₁₁)(R₁₂)N(R₉C(R₁₃)(R₁₄)—, —C(R₁₁)(R₁₂)S—, —C(R₁₁)(R₁₂)SC(R₁₃)(R₁₄)—, or —C(R₁₁)(R₁₂)SO₂C(R₁₃)(R₁₄)—;

E is absent or C_3-12cycloalkylene, 3- to 12-membered heterocycdiyl, arylene, C_1-12alkylene, C_2-12alkenylene, or C_2-12alkynylene, where each E is optionally substituted with one or more C_1-3alkyl, C_1-3alkoxy, halogen, CN, OH, NH₂, or NO₂;

D is one or more H, halogen, OH, NH₂, CHO, CN, NO₂, CF₃, or Q;

each Q, independently, is —R₅, —R₇, —OR₅, —OR₇, —NR₅R₆, —NR₅R₇, —N⁺R₅R₆R₈, S(O)_nR₅, or —S(O)_nR₇, where n is 0, 1, or 2;

each R₅, R₆, and R₈, independently, is H, C_1-12alkyl, C_2-12alkenyl, C_2-12alkynyl, C_3-12cycloalkyl, C_1-12alkoxyC_1-12alkyl, cycloalkylC_1-6alkyl, 3- to 8-membered heterocycyl, heterocycylC_1-6alkyl, aryl, arylC_1-6alkyl, arylC_2-6alkenyl, or arylC_2-6alkynyl, where each R₅, R₆, and R₈is optionally substituted with one or more R₉, —OR₉, —OC(O)OR₉, —C(O)R₉, —C(O)OR₉, —C(O)NR₉R₁₀, —SR₉, —S(O)R₉, —S(O)₂R₉, —NR₉R₁₀, —N⁺R₉R₁₀R₁₁, —NR₉C(O)R₁₀, —NC(O)NR₉R₁₀, —NR₉S(O)₂R₁₀, oxo, halogen, CN, OCF₃, CF₃, OH, or NO₂;

R₇is —C(O)R₅, —C(O)OR₅, —C(O)NR₅R₆, —S(O)₂R₅, —S(O)R₅, or —S(O)₂NR₅R₆; and

each R₉, R₁₀, R₁₁, R₁₂, R₁₃and R₁₄is, independently, H, C_1-12alkyl, C_2-12alkenyl, C_2-12alkynyl, C_3-12cycloalkyl, aryl, or arylC_1-12alkyl; where any of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or arylalkyl, groups is optionally substituted with one or more halogen, oxo, CN, OCF₃, OH, NH₂, or NO₂; or a salt thereof.