1.-133. (canceled)
134. A method for inhibiting VR1 function in a cell, comprising contacting a cell capable of expressing VR1 with an effective amount of a compound or a pharmaceutically acceptable salt of the compound of formula I:
wherein:
R1 is -halo, \u2014CH3, \u2014NO2, \u2014CN, \u2014OH, \u2014OCH3, \u2014NH2, \u2014C(halo)3, \u2014CH(halo)2, or \u2014CH2(halo);
each R2 is independently:
(a) -halo, \u2014CN, \u2014OH, \u2014NO2, \u2014O(C1-C6)alkyl, or \u2014NH2;
(b) \u2014(C1-C10)alkyl, \u2014(C2-C10)alkenyl, \u2014(C2-C10)alkynyl, \u2014(C3-C10)cycloalkyl, \u2014(C8-C14)bicycloalkyl, \u2014(C8-C14)tricycloalkyl, \u2014(C5-C10)cycloalkenyl, \u2014(C8-C14)bicycloalkenyl, \u2014(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R7 groups; or
(c) -phenyl, -naphthyl, \u2014(C14)aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R8 groups;
each R3 is independently:
(a) -halo, \u2014CN, \u2014OH, \u2014NO2, \u2014O(C1-C6)alkyl, or \u2014NH2;
(b) \u2014(C1-C10)alkyl, \u2014(C2-C10)alkenyl, \u2014(C2-C10)alkynyl, \u2014(C3-C10)cycloalkyl, \u2014(C8-C14)bicycloalkyl, \u2014(C8-C14)tricycloalkyl, \u2014(C5-C10)cycloalkenyl, \u2014(C8-C14)bicycloalkenyl, \u2014(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R7 groups; or
(c) -phenyl, -naphthyl, \u2014(C14)aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R8 groups;
R4 is \u2014H, \u2014(C1-C10)alkyl, \u2014C(O)R9, or \u2014C(O)NHR9;
R5 is \u2014H or \u2014(C1-C10)alkyl;
R6 is:
(a) \u2014(C1-C10)alkyl, \u2014(C2-C10)alkenyl, \u2014(C2-C10)alkynyl, \u2014(C3-C10)cycloalkyl, \u2014(C8-C14)bicycloalkyl, \u2014(C8-C14)tricycloalkyl, \u2014(C5-C10)cycloalkenyl, \u2014(C8-C14)bicycloalkenyl, \u2014(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R7 groups; or
(b) -phenyl, -naphthyl, \u2014(C14)aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R8 groups;
each R7 and R8 is independently \u2014(C1-C6)alkyl, \u2014(C2-C6)alkenyl, \u2014(C2-C6)alkynyl, \u2014(C3-C8)cycloalkyl, \u2014(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, \u2014C(halo)3, \u2014CH(halo)2, \u2014CH2(halo), \u2014CN, \u2014OH, -halo, \u2014N3, \u2014NO2, \u2014N(R10)2, \u2014CH\u2550NR10, \u2014NR10OH, \u2014OR10, \u2014COR10, \u2014(O)OR10, \u2014OC(O)R10, \u2014OC(O)OR10, \u2014SR10, \u2014S(O)R10, or \u2014S(O)2R10;
each R9 is independently \u2014H, \u2014(C1-C6)alkyl, \u2014(C2-C6)alkenyl, \u2014(C2-C6)alkynyl, \u2014(C3-C8)cycloalkyl, \u2014(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, \u2014C(halo)3, \u2014CH(halo)2, \u2014CH2(halo), \u2014OH, \u2014N(R10)2, \u2014CH\u2550NR10, \u2014NR10OH, \u2014OR10, or \u2014SR10;
each R10is independently \u2014H, \u2014(C1-C6)alkyl, \u2014(C2-C6)alkenyl, \u2014(C2-C6)alkynyl, \u2014(C3-C8)cycloalkyl, \u2014(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, \u2014C(halo)3, \u2014CH(halo)2, or \u2014CH2(halo);
each halo is independently \u2014F, \u2014Cl, \u2014Br, or \u2014I;
n is an integer ranging from 0 to 2; and
m is an integer ranging from 0 to 2.
135. The method of claim 134, wherein:
n is 0;
m is 0; and
R6 is phenyl.
136. The method of claim 135, wherein the R6 phenyl is unsubstituted or substituted at the para-position with a tert-butyl group, an iso-propyl group, or a \u2014CF3 group.
137. The method of claim 134, wherein:
n is 0;
mis 1;
R3 is methyl; and
R6 is phenyl.
138. The method of claim 137, wherein the R6 phenyl is unsubstituted or substituted at the para-position with a tert-butyl group, an iso-propyl group, or a \u2014CF3 group.
139. A method for treating pain, comprising administering to an animal in need thereof an effective amount of a compound or a pharmaceutically acceptable salt of the compound of formula I:
wherein:
R1 is -halo, \u2014CH3, \u2014NO2, \u2014CN, \u2014OH, \u2014OCH3, \u2014NH2, \u2014C(halo)3, \u2014CH(halo)2, or \u2014CH2(halo);
each R2 is independently:
(a) -halo, \u2014CN, \u2014OH, \u2014NO2, \u2014O(C1-C6)alkyl, or \u2014NH2;
(b) \u2014(C1-C10)akyl, \u2014(C2-C10)alkenyl, \u2014(C2-C10)alkynyl, \u2014(C3-C10)cycloalkyl, \u2014(C8-C14)bicycloalkyl, \u2014(C8-C14)tricycloalkyl, \u2014(C5-C10)cycloalkenyl, \u2014(C8-C14)bicycloalkenyl, \u2014(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R7 groups; or
(c) -phenyl, -naphthyl, \u2014(C14)aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R8 groups;
each R3 is independently:
(a) -halo, \u2014CN, \u2014OH, \u2014NO2, \u2014O(C1-C6)alkyl, or \u2014NH2;
(b) \u2014(C1-C10)alkyl, \u2014(C2-C10)alkenyl, \u2014(C2-C10)alkynyl, \u2014(C3-C10)cycloalkyl, \u2014(C8-C14)bicycloalkyl, \u2014(C8-C14)tricycloalkyl, \u2014(C5-C10)cycloalkenyl, \u2014(C8-C14)bicycloalkenyl, \u2014(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R7 groups; or
(c) -phenyl, -naphthyl, \u2014(C14)aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R8 groups;
R4 is \u2014H, \u2014(C1-C10)alkyl, \u2014C(O)R9, or \u2014C(O)NHR9;
R5 is \u2014H or \u2014(C1-C10)alkyl;
R6 is:
(a) \u2014(C1-C10)alkyl, \u2014(C2-C10)alkenyl, \u2014(C2-C10)alkynyl, \u2014(C3-C10)cycloalkyl, \u2014(C8-C14)bicycloalkyl, \u2014(C8-C14)tricycloalkyl, \u2014(C5-C10)cycloalkenyl, \u2014(C8-C14)bicycloalkenyl, \u2014(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R7 groups; or
(b) -phenyl, -naphthyl, \u2014(C14)aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R8 groups;
each R7 and R8 is independently \u2014(C1-C6)alkyl, \u2014(C2-C6)alkenyl, \u2014(C2-C6)alkynyl, \u2014(C3-C8)cycloalkyl, \u2014(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, \u2014C(halo)3, \u2014CH(halo)2, \u2014CH2(halo), \u2014CN, \u2014OH, -halo, \u2014N3, \u2014NO2, \u2014N(R10)2, \u2014CH\u2550NR10, \u2014NR10OH, \u2014OR10, \u2014COR10, \u2014C(O)OR10, \u2014OC(O)R10, \u2014OC(O)OR10, \u2014SR10, \u2014S(O)R10, or \u2014S(O)2R10;
each R9 is \u2014H, \u2014(C1-C6)alkyl, \u2014(C2-C6)alkenyl, \u2014(C2-C6)alkynyl, \u2014(C3-C8)cycloalkyl, \u2014(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, \u2014C(halo)3, \u2014CH(halo)2, \u2014CH2(halo), \u2014OH, \u2014N(R10)2, \u2014CH\u2550NR10, \u2014NR10OH, \u2014OR10, or \u2014SR10;
each R10 is independently \u2014H, \u2014(C1-C6)alkyl, \u2014(C2-C6)alkenyl, \u2014(C2-C6)alkynyl, \u2014(C3-C8)cycloalkyl, \u2014(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, \u2014C(halo)3, \u2014CH(halo)2, or \u2014CH2(halo);
each halo is independently \u2014F, \u2014Cl, \u2014Br, or \u2014I;
n is an integer ranging from 0 to 2; and
m is an integer ranging from 0 to 2.
140. The method of claim 139, wherein:
n is 0;
m is 0; and
R6 is phenyl.
141. The method of claim 140, wherein the R6 phenyl is unsubstituted or substituted at the para-position with a tert-butyl group, an iso-propyl group, or a \u2014CF3 group.
142. The method of claim 139, wherein:
nis 0;
m is 1;
R3 is methyl; and
R6 is phenyl.
143. The method of claim 142, wherein the R6 phenyl is unsubstituted or substituted at the para-position with a tert-butyl group, an iso-propyl group, or a \u2014CF3 group.
144. A method for inhibiting VR1 function in a cell, comprising contacting a cell capable of expressing VR1 with an effective amount of a compound or a pharmaceutically acceptable salt of the compound of formula VIIa:
wherein:
Ar1 is
\u2003Ar2 is
\u2003R1 is -halo, \u2014CH3, \u2014NO2, \u2014CN, \u2014OH, \u2014OCH3, \u2014NH2, \u2014C(halo)3, \u2014CH(halo)2, or \u2014CH2(halo);
each R2 is independently:
(a) -halo, \u2014CN, \u2014OH, \u2014NO2, \u2014O(C1-C6)alkyl, or \u2014NH2;
(b) \u2014(C1-C10)akyl, \u2014(C2-C10)alkenyl, \u2014(C2-C10)alkynyl, \u2014(C3-C10)cycloalkyl, \u2014(C8-C14)bicycloalkyl, \u2014(C8-C14)tricycloalkyl, \u2014(C5-C10)cycloalkenyl, \u2014(C8-C14)bicycloalkenyl, \u2014(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R7 groups; or
(c) -phenyl, -naphthyl, \u2014(C14)aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R8 groups;
each R3 is independently:
(a) -halo, \u2014CN, \u2014OH, \u2014NO2, \u2014O(C1-C6)alkyl, or \u2014NH2;
(b) \u2014(C1-C10)alkyl, \u2014(C2-C10)alkenyl, \u2014(C2-C10)alkynyl, \u2014(C3-C10)cycloalkyl, \u2014(C8-C14)bicycloalkyl, \u2014(C8-C14)tricycloalkyl, \u2014(C5-C10)cycloalkenyl, \u2014(C8-C14)bicycloalkenyl, \u2014(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R7 groups; or
(c) -phenyl, -naphthyl, \u2014(C14)aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R8 groups;
R4 is \u2014H, \u2014(C1-C10)alkyl, \u2014C(O)R9, or \u2014C(O)NHR9;
R5 is \u2014H or \u2014(C1-C10)alkyl;
each R7 and R8 is independently \u2014(C1-C6)alkyl, \u2014(C2-C6)alkenyl, \u2014(C2-C6)alkynyl, \u2014(C3-C8)cycloalkyl, \u2014(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, \u2014C(halo)3, \u2014CH(halo)2, \u2014CH2(halo), \u2014CN, \u2014OH, -halo, \u2014N3, \u2014NO2, \u2014N(R10)2, \u2014CH\u2550NR10, \u2014NR10OH, \u2014OR10, \u2014COR10, \u2014C(O)OR10, \u2014OC(O)R10, \u2014OC(O)OR10, \u2014SR10, \u2014S(O)R10, or \u2014S(O)2R10;
each R9 is \u2014H, \u2014(C1-C6)alkyl, \u2014(C2-C6)alkenyl, \u2014(C2-C6)alkynyl, \u2014(C3-C8)cycloalkyl, \u2014(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, \u2014C(halo)3, \u2014CH(halo)2, \u2014CH2(halo), \u2014OH, \u2014N(R10)2, \u2014CH\u2550NR10, \u2014NR10OH, \u2014OR10, or \u2014SR10;
each R10 is independently \u2014H, \u2014(C1-C6)alkyl, \u2014(C2-C6)alkenyl, \u2014(C2-C6)alkynyl, \u2014(C3-C8)cycloalkyl, \u2014(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, \u2014C(halo)3, \u2014CH(halo)2, or \u2014CH2(halo);
each R11 and R12 is independently \u2014(C1-C6)alkyl, \u2014(C2-C6)alkenyl, \u2014(C2-C6)alkynyl, \u2014(C3-C8)cycloalkyl, \u2014(C5-C8)cycloalkenyl, -phenyl, \u2014C(halo)3, \u2014CH(halo)2, \u2014CH2(halo), \u2014CN, \u2014OH, -halo, \u2014N3, \u2014NO2, \u2014N(R7)2, \u2014CH\u2550NR7, \u2014NR7OH, \u2014OR7, \u2014COR7, \u2014C(O)OR7, \u2014OC(O)R7, \u2014OC(O)OR7, \u2014SR7, \u2014S(O)R7, or \u2014S(O)2R7;
each R13 is independently \u2014(C1-C6)alkyl, \u2014(C2-C6)alkenyl, \u2014(C2-C6)alkynyl, \u2014(C3-C8)cycloalkyl, \u2014(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, \u2014C(halo)3, \u2014CH(halo)2, \u2014CH2(halo), or -halo;
each halo is independently \u2014F, \u2014Cl, \u2014Br, or \u2014I;
s is an integer ranging from 0 to 4;
o is an integer ranging from 0 to 4;
q is an integer ranging from 0 to 6;
r is an integer ranging from 0 to 5;
t is an integer ranging from 0 to 2;
p is an integer ranging from 0 to 2;
n is an integer ranging from 0 to 3;
m is an integer ranging from 0 to 2; and
x is the integer 0 or 1.
145. The method of claim 144, wherein Ar1 is a pyridyl group.
146. The method of claim 145, wherein Ar2 is a phenyl group.
147. The method of claim 146, wherein m is 0.
148. The method of claim 146, wherein m is 1 and R3 is a \u2014(C1-C10)alkyl group.
149. A method for treating pain, comprising administering to an animal in need thereof an effective amount of a compound or a pharmaceutically acceptable salt of the compound of formula VIIa:
wherein:
Ar1 is
\u2003Ar2 is
\u2003R1 is -halo, \u2014CH3, \u2014NO2, \u2014CN, \u2014OH, \u2014OCH3, \u2014NH2, \u2014C(halo)3, \u2014CH(halo)2, or \u2014CH2(halo);
each R2 is independently:
(a) -halo, \u2014CN, \u2014OH, \u2014NO2, \u2014O(C1-C6)alkyl, or \u2014NH2;
(b) \u2014(C1-C10)akyl, \u2014(C2-C10)alkenyl, \u2014(C2-C10)alkynyl, \u2014(C3-C10)cycloalkyl, \u2014(C8-C14)bicycloalkyl, \u2014(C8-C14)tricycloalkyl, \u2014(C5-C10)cycloalkenyl, \u2014(C8-C14)bicycloalkenyl, \u2014(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R7 groups; or
(c) -phenyl, -naphthyl, \u2014(C14)aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R8 groups;
each R3 is independently:
(a) -halo, \u2014CN, \u2014OH, \u2014NO2, \u2014O(C1-C6)alkyl, or \u2014NH2;
(b) \u2014(C1-C10)alkyl, \u2014(C2-C10)alkenyl, \u2014(C2-C10)alkynyl, \u2014(C3-C10)cycloalkyl, \u2014(C8-C14)bicycloalkyl, \u2014(C8-C14)tricycloalkyl, \u2014(C5-C10)cycloalkenyl, \u2014(C8-C14)bicycloalkenyl, \u2014(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R7 groups; or
(c) -phenyl, -naphthyl, \u2014(C14)aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R8 groups;
R4 is \u2014H, \u2014(C1-C10)alkyl, \u2014C(O)R9, or \u2014C(O)NHR9;
R5 is \u2014H or \u2014(C1-C10)alkyl;
each R7 and R8 is independently \u2014(C1-C6)alkyl, \u2014(C2-C6)alkenyl, \u2014(C2-C6)alkynyl, \u2014(C3-C8)cycloalkyl, \u2014(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, \u2014C(halo)3, \u2014CH(halo)2, \u2014CH2(halo), \u2014CN, \u2014OH, -halo, \u2014N3, \u2014NO2, \u2014N(R10)2, \u2014CH\u2550NR10, \u2014NR10OH, \u2014OR10, \u2014COR10, \u2014C(O)OR10, \u2014OC(O)R10, \u2014OC(O)OR10, \u2014SR10, \u2014S(O)R10, or \u2014S(O)2R10;
each R9 is \u2014H, \u2014(C1-C6)alkyl, \u2014(C2-C6)alkenyl, \u2014(C2-C6)alkynyl, \u2014(C3-C8)cycloalkyl, \u2014(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, \u2014C(halo)3, \u2014CH(halo)2, \u2014CH2(halo), \u2014OH, \u2014N(R10)2, \u2014CH\u2550NR10, \u2014NR10OH, \u2014OR10, or \u2014SR10;
each R10 is independently \u2014H, \u2014(C1-C6)alkyl, \u2014(C2-C6)alkenyl, \u2014(C2-C6)alkynyl, \u2014(C3-C8)cycloalkyl, \u2014(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, \u2014C(halo)3, \u2014CH(halo)2, or \u2014CH2(halo);
each R11 and R12 is independently \u2014(C1-C6)alkyl, \u2014(C2-C6)alkenyl, \u2014(C2-C6)alkynyl, \u2014(C3-C8)cycloalkyl, \u2014(C5-C8)cycloalkenyl, -phenyl, \u2014C(halo)3, \u2014CH(halo)2, \u2014CH2(halo), \u2014CN, \u2014OH, -halo, \u2014N3, \u2014NO2, \u2014N(R7)2, \u2014CH\u2550NR7, \u2014NR7OH, \u2014OR7, \u2014COR7, \u2014C(O)OR7, \u2014OC(O)R7, \u2014OC(O)OR7, \u2014SR7, \u2014S(O)R7, or \u2014S(O)2R7;
each R13 is independently \u2014(C1-C6)alkyl, \u2014(C2-C6)alkenyl, \u2014(C2-C6)alkynyl, \u2014(C3-C8)cycloalkyl, \u2014(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, \u2014C(halo)3, \u2014CH(halo)2, \u2014CH2(halo), or -halo;
each halo is independently \u2014F, \u2014Cl, \u2014Br, or \u2014I;
s is an integer ranging from 0 to 4;
o is an integer ranging from 0 to 4;
q is an integer ranging from 0 to 6;
r is an integer ranging from 0 to 5;
t is an integer ranging from 0 to 2;
p is an integer ranging from 0 to 2;
n is an integer ranging from 0 to 3;
m is an integer ranging from 0 to 2; and
x is the integer 0 or 1.
150. The method of claim 149, wherein Ar1 is a pyridyl group.
151. The method of claim 150, wherein Ar2 is a phenyl group.
152. The method of claim 151, wherein m is 0.
153. The method of claim 151, wherein m is 1 and R3 is a \u2014(C1-C10)alkyl group.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
What is claimed is:
1. A living body variable measuring device comprising a weight scale-like body having electrodes and a weight sensor equipped therewith, and a box-like display device, in which measuring device: said electrodes are used in measuring the bioelectrical impedance appearing between both feet; and said weight sensor measures the weight of a person, characterized in that said weight scale-like body has a storage section so sized and shaped as to accommodate said box-like display device.
2. A living body variable measuring device according to claim 1 wherein said weight scale-like body and said box-like display device are provided with connection terminals to be mated together for signal communication between said weight scale-like body and said box-like display device.
3. A living body variable measuring device according to claim 1 wherein said weight scale-like body and said box-like display device are provided with wireless communication means for signal communication between said weight scale-like body and said box-like display device.