Cyclic amine phenyl beta-3 adrenergic receptor agonists

A compound of formula I having the structure

• wherein
• A is Ar;
• X is —OCH2—, —SCH2—, or a bond;
• T1 is (CH2)m;
• T2 is (CH2)n;
• T is a bond;
• R1, R2, and R3 are each, independently, hydrogen, alkyl of 1–6 carbon atoms, cycloalkyl of 3–8 carbon atoms, hydroxy, halogen, trifluoromethyl, alkoxy of 1–6 carbon atoms, benzyloxy, allyloxy, propargyloxy, acyloxy of 2–7 carbon atoms, cyano, nitro, amino, aminocarbonyl, alkylamino of 1–6 carbon atoms, dialkylamino of 1–6 carbon atoms per alkyl group, formamido, ureido, acylamino of 2–7 carbon atoms, alkylsulfonylamino of 1–6 carbon atoms, arylsulfonylamino, dialkyloxyphosphorylamino of 1–6 carbon atoms per alkyl group, dihydroxyphosphorylamino, —CO2-alkyl of 1–6 carbon atoms, or Ar optionally substituted with R11;
• R4 is hydrogen, alkyl of 1–6 carbon atoms, halogen, hydroxy, alkyoxy of 1–6 carbon atoms, alkylthio of 1–6 carbon atoms, amino, alkylamino of 1–6 carbon atoms, carboxy, acyl of 2–7 carbon atoms, ArCO—, alkoxycarbonyl of 2–7 carbon atoms, aminocarbonyl, alkylaminocarbonyl of 2–7 carbon atoms, alkylsulfonyl of 1–6 carbon atoms, or alkylsulfonylamino of 1–6 carbon atoms,
• R5 is
• X1 is CO or SO2;
• R6 is hydrogen;
• alkyl of 1–6 carbon atoms optionally substituted by a —COOH, —CO2-alkyl of 1–6 carbon atoms, —CO2Ar, or —CO2-alkyl-Ar group wherein the alkyl moiety has 1–6 carbon atoms;
• or cycloalkyl of 3–8 carbon atoms;
• R7 and R8 are each, independently, hydrogen;
• alkyl of 1–6 carbon atoms optionally substituted by R11, R12, and R13;
• alkenyl of 2–7 carbon atoms optionally substituted by R11, R12, and R13;
• alkynyl of 2–7 carbon atoms optionally substituted with R11;
• cycloalkyl of 3–8 carbon atoms optionally substituted by R11, R12, and R13;
• bicycloalkyl of 7–11 carbon atoms optionally substituted by R11, R12, and R13;
• —CO2-alkyl of 1–6 carbon atoms;
• Het optionally substituted by R11, R12, or R13;
• or Ar optionally substituted by R11, R12, and R13;
• R9 is alkyl optionally substituted by R11, R12, and R13;
• Ar optionally mono-, di-, or tri-substituted by R15;
• Ar fused to a cycloalkyl ring of 3–8 carbon atoms, and optionally mono-, di-, or tri-substituted by R15;
• Het optionally mono-, di-, or tri-substituted by R15;
• R11, R12, or R13 are each, independently, alkyl of 1–6 carbon atoms, halogen, alkenyl of 2–7 carbon atoms, alkynyl of 2–7 carbon atoms, cycloalkyl of 3–8 carbon atoms, Ar-alkyl having 1–6 carbon atoms in the alkyl moiety, Ar optionally substituted with R14, Het optionally substituted with R14, hydroxy, alkoxy of 1–6 carbon atoms, Ar-oxy, oxo, —CN, —CHO, —CO2H, —OCO2-alkyl of 1–6 carbon atoms, —CO2-alkyl of 1–6 carbon atoms, —CO2-Ar, —CO2-alkyl-Ar wherein the alkyl moiety has 1–6 carbon atoms, —OCO2-Ar, —CONH2, —CONHOH, amino, alkylamino of 1–6 carbon atoms, dialkylamino of 1–6 carbon atoms per alkyl moiety, —NHCONH-alkyl of 1–6 carbon atoms, —NHSO2-alkyl of 1–6 carbon atoms, —NHSO2-Ar, or —NHSO2-Het;
• or when R11 and R12 are contained on a common carbon atom of an alkyl moiety, they may be taken together to form a spiro cycloalkyl ring of 3–8 carbon atoms;
• R14 is halogen, alkoxy of 1–6 carbon atoms, alkyl of 1–6 carbon atoms, alkenyl of 2–7 carbon atoms, alkynyl of 2–7 carbon atoms, hydroxy, acyl of 2–7 carbon atoms, —SO2-alkyl of 1–6 carbon atoms, —CO2-alkyl of 1–6 carbon atoms, or alkoxycarbonylalkyl of 3–13 carbon atoms;
• R15 is
• (a) hydroxy, halogen, —CN, —NR16R16, —OR16, —SR16, triflouromethyl, alkyl of 1–6 carbon atoms, —SO2R17, —O-alkyl-CO2R17 wherein the alkyl moiety contains 1–6 carbon atoms, —CO2R17, —OCOR17, —NR16COR17, —COR17, —NR16SO2R17, or —NR16CO2R16;
• or
• (b) alkyl of 1–6 carbon atoms mono-, or di-substituted with hydroxy;
• halogen;
• —CN;
• —NR16NR16;
• —OR16;
• —SR16;
• triflouromethyl;
• alkyl of 1–6 carbon atoms;
• —SO2R17;
• —CO2R17;
• —OCOR17;
• —NR16COR17;
• —COR17;
• —NR16SO2R17;
• —NR16CO2R16;
• Ar which may be optionally mono- or di-substituted by R16, —OR16, —NR16R16, or halogen;
• or Het which may be optionally mono- or di-substituted by R16, —OR16, —NR16R16, or halogen;
• (c) Het optionally mono- or di-substituted by R16, —OR16, —NR16R16, or halogen;
• or
• (d) Ar optionally mono- or di-substituted by R16, —OR16, —NR16R16, or halogen;
• R16 is hydrogen, alkyl of 1–6 carbon atoms, cycloalkylalkyl of 4–14 carbon atoms, benzyl, Ar or Het, wherein the Ar or Het moieties may be optionally mono-, di-, or tri-substituted with halogen, nitro, alkylamino of 1–6 carbon atoms, dialkylamino of 1–6 carbon atoms per alkyl moiety, trifluoromethyl, alkyl of 1–6 carbon atoms, alkoxy of 1–6 carbon atoms, alkylthio of 1–6 carbon atoms, —CO2H, —CO2alkyl of 1–6 carbon atoms, or —SO2alkyl of 1–6 carbon atoms;
• R17 is R16 or —NR16R16;
• Het is a monocyclic or bicyclic heterocycle of 5–10 ring atoms, having 1–4 heteroatoms selected from oxygen, nitrogen, and sulfur;
• wherein the heterocycle may be saturated, unsaturated, or partially unsaturated;
• and may be optionally fused to a phenyl ring;
• Ar is an aromatic ring system containing 1–2 carbocyclic aromatic rings having 6–10 carbon atoms;
• m=2;
• n=2;
• or a pharmaceutically acceptable salt thereof.