US 7,601,868 B2
Amine derivative
Yuji Ishihara, Osaka (Japan); Makoto Kamata, Osaka (Japan); and Shiro Takekawa, Osaka (Japan)
Assigned to Takeda Pharmaceutical Company Limited, Osaka (Japan)
Appl. No. 10/545,120
PCT Filed Feb. 12, 2004, PCT No. PCT/JP2004/001467
§ 371(c)(1), (2), (4) Date Aug. 10, 2005,
PCT Pub. No. WO2004/072018, PCT Pub. Date Aug. 26, 2004.
Claims priority of application No. 2003-034010 (JP), filed on Feb. 12, 2003.
Prior Publication US 2006/0128690 A1, Jun. 15, 2006
Int. Cl. C07C 233/65 (2006.01); C07D 207/06 (2006.01); A61K 31/165 (2006.01); A61K 31/40 (2006.01)
U.S. Cl. 564—184  [548/567; 514/408; 514/617] 21 Claims
 
1. A compound represented by the formula:

OG Complex Work Unit Drawing
wherein
Ar1 is
a phenyl having a C3-6 cycloalkyl-C1-6 alkoxy, wherein the phenyl is optionally having a halogen atom
R is
(i) a hydrogen atom;
(ii) an optionally halogenated C1-6 alkyl;
(iii) a phenyl; or
(iv) a pyridyl,
each of (iii) and (iv) optionally having 1 to 5 substituents selected from the following Group C:
(a) a halogen atom,
(b) a C1-3 alkylenedioxy,
(c) a nitro,
(d) a cyano,
(e) an optionally halogenated C1-10 alkyl,
(f) an optionally halogenated C3-6 cycloalkyl,
(g) an optionally halogenated C1-10 alkoxy,
(h) an optionally halogenated C1-10 alkylthio,
(i) a hydroxy,
(j) an amino,
(k) a mono- or di-C1-10 alkylamino,
(l) a formyl,
(m) a carboxy,
(n) a carbamoyl,
(o) a thiocarbamoyl,
(p) an optionally halogenated C1-6 alkyl-carbonyl,
(q) a C1-6 alkoxy-carbonyl,
(r) a mono- or di-C1-6 alkyl-carbamoyl,
(s) an optionally halogenated C1-6 alkylsulfonyl,
(t) a formylamino,
(u) an optionally halogenated C1-6 alkyl-carboxamido,
(v) a C1-6 alkoxy-carboxamido,
(w) a C1-6 alkylsulfonylamino,
(x) a C1-6 alkyl-carbonyloxy,
(y) a C1-6 alkoxy-carbonyloxy,
(z) a mono- or di-C1-6 alkyl-carbamoyloxy,
(aa-1) phenyl,
(aa-2) a 5- or 6-membered aromatic heterocyclic group,
(aa-3) a 9- to 14-membered fused bi- or tri-cyclic aromatic hydrocarbon group, and
(aa-4) a 9- to 14-membered fused bi- or tri-cyclic aromatic heterocyclic group,
each of (aa-1 )-(aa-4) optionally having 1 to 5 substituents selected from the following Group B:
a halogen atom
a C1-3 alkylenedioxy,
a nitro,
a cyano,
an optionally halogenated C1-10 alkyl,
a hydroxy-C1-10 alkyl,
an optionally halogenated C3-6 cycloalkyl,
an optionally halogenated C1-10 alkoxy,
an optionally halogenated C1-10 alkylthio,
a hydroxy,
an amino,
a mono- or di-C1-10 alkylamino,
an amino-C1-10 alkyl,
a mono- or di-C1-10 alkylamino-C1-6 alkyl,
a formyl,
a carboxy,
a carbamoyl,
a thiocarbamoyl,
an optionally halogenated C1-6 alkyl-carbonyl,
a C1-6 alkoxy-carbonyl,
a 5- or 6-membered heterocyclylcarbonyl,
a mono- or di-C1-6 alkyl-carbamoyl,
a 5- or 6-membered heterocyclylcarbamoyl,
a carbamoyl-C1-6 alkyl,
a mono- or di-C1-6 alkyl-carbamoyl-C1-6 alkyl,
a 5- or 6-membered heterocyclylcarbonyl-C1-6 alkyl,
a 5- or 6-membered heterocyclylcarbamoyl-C1-6 alkyl,
an optionally halogenated C1-6 alkylsulfonyl,
a formylamino,
an optionally halogenated C1-6 alkyl-carboxamido,
a C1-6 alkoxy-carboxamido,
a C1-6 alkylsulfonylamino,
a C1-6 alkyl-carbonyloxy,
a C1-6 alkoxy-carbonyloxy,
a mono- or di-C1-6 alkyl-carbamoyloxy,
a mono- or di-C1-6 alkyl-carbamoyl-C1-6 alkoxy and
a 5- or 6-membered non-aromatic heterocyclic group;
Ra1, Ra2, Ra3 and Ra4 are the same or different and each is
(i) a hydrogen atom,
(ii) an optionally halogenated C1-6 alkyl,
(iii) a phenyl,
(vi) a halogen atom,
(v) a pyridyl,
(vi) a cyano,
(vii) an optionally halogenated C1-6 alkoxy,
(viii) an optionally halogenated C1-6 alkylthio,
(ix) an amino,
(x) a mono- or di-C1-6 alkylamino,
(xi) a formyl,
(xii) an optionally halogenated C1-6 alkyl-carbonyl, or
(xiii) an optionally halogenated C1-6 alkylsulfonyl,
each of (iii) and (v) optionally having 1 to 5 substituents selected from the above-mentioned Group C;
Ar is
(i) benzene, or
(ii) a 5- or 6-membered aromatic heterocycle, each of (i) and (ii) optionally having 1 to 4 substituents selected from the above-mentioned Group B;
Y is an optionally halogenated alkylene group; and
R1 and R2 are
(1) the same or different and each is a hydrogen atom or a C1-6 alkyl,
(2) R1 and R2 form a nitrogen-containing heterocycle together with the adjacent nitrogen atom, optionally having 1 to 5 substituent(s) selected from the following Group D:
(a) the above-mentioned Group B,
(b) a C7-19 aralkyl,
(c-1) phenyl,
(c-2) a 5- or 6-membered aromatic heterocyclic group,
(c-3) a 9- to 14-membered fused bi- or tri-cyclic aromatic hydrocarbon group, and
(c-4) a 9- to 14-membered fused bi- or tri-cyclic aromatic heterocyclic group, each of (b) and (c-1)-(c-4) optionally having 1 to 5 substituents selected from the above-mentioned Group B, or
(3) R1 and Y form a nitrogen-containing heterocycle together with the adjacent nitrogen atom, optionally having 1 to 5 substituent(s) selected from the above-mentioned Group D, and R2 is a hydrogen atom or a C1-6 alkyl;
or a salt thereof.