Patent EA-001217-B1 (EA)
Title: SELECTIVE b3 ADRENERGIC AGONISTS
Inventor: BELL MICHAEL G
IPC: C07C233/52
Filed: 1996-09-20
Abstract: 1. A compound of formula:   wherein: R1 is OH, halo, SO2NHR2, CO2R2, CONHR2, NHCOR2,  -NH(optionally substituted aryl), CF3, or CF2H; wherein a thermin "aryl" is optionally substituted phenyl or naphtyl R1' is H, halo, C1-C4 alkyl, OH, SO2NHR2, CO2R2, CONHR2, NHCOR2, CF3 or CF2H; R2 is H, C1-C4 alkyl, or aryl, where aryl as defined above; R3 is H or C1-C4 alkyl; R4 is a moiety selected from the group consisting of:   R5 and R6 are independently C1-C4 alkyl; R7 is an optionally substituted heterocycle or a group selected from the group consisting of:    wherein a thermin "heterocycle" is a stable optionally substituted, saturated or unsaturated 5- or 6-membered cycle, having from 1 to 4 heteroatoms, which are identical or different and which are selected from the group consisting of sulfur, oxygen and nitrogen; wherein if the heterocycle comprises two neighboring carbon atoms, said neighboring carbon atoms can cross-link forming a group of formula -CH=CH-; provided that (1) when the heterocycle ring is 5-membered, heteroatoms comprise not more than 2 sulfur atoms or 2 oxygen atoms, but both not simultaneously; and (2) when the heterocycle is 6-membered and aromatic, sulfur and oxygen are absent; R8 is independently H, halo or C1-C4 alkyl; R9 is halo, CN, OR10, C1-C4 alkyl, C1-C4 haloalkyl, CO2R2, CONR11R12, CONH(C1-C4 alkyl or C1-C4 alkoxy), SR2, CSNR2, CSNR11R12, SO2R2, SO2NR11R12, SOR2, NR11R12, aryl, heterocycle, optionally substituted aryl, optionally substituted heterocycle, or C1-C4 alkyl or C2-C4 alkenyl optionally substituted with CN, where aryl and heterocycle are as defined above; R10 is independently C1-C4-alkyl, C1-C4-haloalkyl, (CH2)n(C3-C8) cycloalkyl, (CH2)n-aryl,  (CH2)n heterocycle, optionally substituted (CH2)n(C3-C8) cycloalkyl, (CH2)n optionally substituted aryl or (CH2)n-optionally substituted heterocycle, wherearyl and heterocycle are as define above; R11 and R12 are independently H, C1-C4 alkyl, or combine with the nitrogen to which each are bound to form morpholinyl, piperidinyl, pyrrolidinyl, or piperazinyl; X1 is O or S; X2 is absent or a straight or branched C1-C5 alkylene; m i 0 or 1; n is 0, 1, 2, or 3; o is 1, 2, 3, 4, 5, or 6; or a pharmaceutically acceptable salt or solvate thereof. 2. A compound of claim 1 wherein R1 is halo, CF3, CONHR2, or NH (optionally substituted aryl); and R4 is   3. A compound of claim 2 wherein R7 is a group of formula   wherein R9 is halo, CN, OR10, CO2R2, CONR11R12, SR2, SO R2, SO2NR11R12, SOR2, or NR11R12. 4. A compound of claim 3 wherein R7 is a groupof formula   and R9 is halo, CN, CO2R2 or OR10. 5. A compound of formula I for using as a pharmaceutical preparation. 6. A compound of formula I for treating Type II diabetes. 7. A compound of formula I for treating obesity. 8. A compound of formula I for using as a preparation bound to the β3 receptor (having an affinity to the β3 receptor). 9. A pharmaceutical formulation comprising as an active ingredient a compound of any claim 1 to 4, associated with one or more pharmaceutically acceptable carriers, excipients or diluents. 10. A process of preparing a compound of Formula I which comprises reacting an epoxide of the formula:   with an amine of formula   and further forming an acid addition salt.