Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-11-28
2002-11-26
Solola, T. A. (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S219000, C514S428000, C514S475000, C514S539000, C514S617000, C514S622000, C546S205000, C548S568000, C549S545000, C558S414000, C560S008000, C564S342000
Reexamination Certificate
active
06486178
ABSTRACT:
TECHNICAL FIELD
The present invention relates to an indane derivative having bradycardia activity and is used for treating cardiac insufficiency in mammals inclusive of human being.
BACKGROUND OF THE TECHNOLOGY
Japanese Patent Application Laid-open No. Sho 63-264445 discloses that an indane derivative have strong affinity to an opiate-acceptor, especially &kgr;-acceptor and have neutral sadation property. Japanese Patent Application Laid-open No. Hei 2-141 discloses a certain kind of indane derivative which has an activity of loosing smooth muscle. However, the both publications do not refer to the possibility of treating the cardiac insufficiency on the basis of bradycardia activity.
The cardiac insufficiency which is in a state of insufficient function of heart is a disease which is based on the depression of contraction of heart muscles. As a treatment therefor, it has been clinically used medicines for reinforcing the contraction of cardiac muscles. However, these medicines have such a problem that heart muscles energy is excessively consumed on the basis of the increase of the heart rate and thus, they have had problems to be solved with respect to effects to improve life recuperation after administration of these medicines in a long period of time. It has been, therefore, desired to develop medicines which reduce load in consumption of heart muscle energy by reducing heart rate (i.e., bradycardia activity).
DISCLOSURE OF THE INVENTION
As a result that the present inventors have intensively studied indane derivatives, they found out that the compounds of the following formula (I) have strong bradycardia activity and they are useful as a medicine for treating insufficient cardiac disorders, whereby completing the present invention.
The present invention relates to indane derivatives of formula (I):
(wherein R
1
represents hydrogen atom, halogen atom, C
1-6
alkyl group (said alkyl group is unsubstituted or substituted by halogen atom, carboxyl group, C
1-6
alkoxy group, C
2-6
alkoxycarbonyl group, hydroxyl group, formyl group, cyano group or nitro group), C
1-6
alkoxy group {said alkoxy group is unsubstituted or substituted by halogen atom, carboxyl group, C
2-6
alkoxycarbonyl group, hydroxyl group, phenyl group (said phenyl group is unsubstituted or substituted by halogen atom, hydroxyl group, C
1-4
alkyl group or C
1-4
alkoxy group), formyl group, cyano group or nitro group}, C
3-6
cycloalkyl group {said cycloalkyl group is unsubstituted or substituted by halogen atom, carboxyl group, C
2-6
alkoxycarbonyl group, hydroxyl group, C
1-6
alkoxy group, phenyl group (said phenyl group is unsubstituted or substituted by halogen atom, hydroxyl group, C
1-4
alkyl group or C
1-4
alkoxy group), formyl group, cyano group or nitro group}, nitro group, cyano group, formyl group, carboxyl group, hydroxyl group, formamide group, cyanamide group, amino group, C
1-6
alkylamino group, di C
1-6
alkylamino group (said alkylamino group and di C
1-6
alkylamino group is unsubstituted or substituted by halogen atom, carboxyl group, C
2-6
alkoxycarbonyl group, hydroxyl group, formyl group, cyano group or nitro group), C
1-6
alkylcarbonylamino group, C
1-6
alkylsulfonylamino group, aminocarbonyl group, C
1-6
alkylaminocarbonyl group, di C
1-6
alkylaminocarbonyl group, C
1-6
alkylcarbony group, C
1-6
alkoxycarbonyl group, C
1-6
alkylcarbonyloxy group, C
1-6
alkylurea group, C
1-6
alkylthiourea group, aryl C
1-6
alkylamino group, di(aryl C
1-6
alkyl)amino group, arylcarbonylamino group, aryl C
1-6
alkylcarbonylamino group, arylsulfonylamino group, aryl C
1-6
alkylsulfonylamino group, aryl C
1-6
alkylaminocarbonyl group, di(aryl C
1-6
alkyl)aminocarbonyl group, arylcarbonyl group, aryl C
1-6
alkylcarbonyl group, aryloxycarbonyl group, aryl C
1-6
alkyloxycarbonyl group, arylcarbonyloxy group, aryl C
1-6
alkylcarbonyloxy group, arylurea group, aryl C
1-6
alkylurea group, arylthiourea group or aryl C
1-6
alkylthiourea group {all of said aryl C
1-6
alkylamino group, di(aryl C
1-6
alkyl)amino group, arylcarbonylamino group, aryl C
1-6
alkylcarbonylamino group, arylsulfonylamino group, aryl C
1-6
alkylsulfonylamino group, aryl C
1-6
alkylaminocarbonyl group, di(aryl C
1-6
alkyl)aminocarbonyl group, arylcarbonyl group, aryl C
1-6
alkylcarbonyl group, aryloxycarbonyl group, aryl C
1-6
alkyloxycarbonyl group, arylcarbonyloxy group, aryl C
1-6
alkylcarbonyloxy group, arylurea group, aryl C
1-6
alkylurea group, arylthiourea group and aryl C
1-6
alkylthiourea group are unsubstituted or substituted by halogen atom, carboxyl group, C
2-6
alkoxycarbonyl group, hydroxyl group, C
1-6
alkoxy group, phenyl group (said phenyl group is unsubstituted or substituted by halogen atom, hydroxyl group, C
1-4
alkyl group or C
1-4
alkoxy group), formyl group, cyano group or nitro group};
R
2
and R
3
each independently represent C
1-6
alkyl group (said alkyl group is unsubstituted or substituted by halogen atom, C
1-6
alkoxy group or hydroxyl group), or R
2
and R
3
taken together with the carbon atom to which they are bonded form C
3-6
cycloalkyl group;
R
4
represents hydroxyl group or C
1-6
alkylcarbonyloxy group, or form a bond together with R
5
, or represents oxygen atom together with R
5
;
R
5
represents hydrogen atom, or forms a bond together with R
4
, or represents oxygen atom together with R
4
;
R
6
represents hydrogen atom, hydroxyl group, C
1-6
alkoxy group, C
1-6
alkylcarbonyloxy group or NR
7
R
8
{said R
7
and R
8
each independently represent hydrogen atom, C
1-6
alkyl group, C
2-6
alkenyl group, C
2-6
alkynyl group, C
3-6
cycloalkyl group (all of said alkyl group, alkenyl group, alkynyl group and cycloalkyl group are unsubstituted or substituted by halogen atom, carboxyl group, C
2-6
alkoxycarbonyl group, hydroxyl group, C
1-6
alkoxy group, phenyl group (said phenyl group is unsubstituted or substituted by halogen atom, hydroxyl group, C
1-4
alkyl group, C
1-4
alkoxy group, formyl group, cyano group, nitro group, amino group, C
1-6
alkylamino group or di C
1-6
alkylamino group)) or phenyl group (said phenyl group is unsubstituted or substituted by halogen atom, hydroxyl group, C
1-4
alkyl group or C
1-4
alkoxy group), or
R
7
and R
8
taken together represents 1,4-butylene, 1,5-pentylene (said butylene and pentylene are each unsubstituted or substituted by C
1-4
alkyl group, phenyl group (said phenyl group is unsubstituted or substituted by halogen atom, hydroxyl group, C
1-4
alkyl group or C
1-4
alkoxy group), halogen atom, hydroxyl group, C
1-4
alkoxy group or C
1-6
alkylcarbonyloxy group) or (CH
2
)
1
X
1
(CH
2
)
p
(1 and p mean each 1, 2 or 3 while the sum of them becomes 3, 4 or 5; X
1
represents oxygen atom, sulfur atom or NR
14
(R
14
is unsubstituted or substituted by hydrogen atom, C
1-4
alkyl group or phenyl group (said phenyl group is unsubstituted or substituted by halogen atom, hydroxyl group, C
1-4
alkyl group or C
1-4
alkoxy group)), or
R
7
and R
8
taken together with nitrogen atom to which they are bonded form pyrrolyl group, pyrazolyl group, imidazolyl group, 1,2,3-triazolyl group, 1,2,4-triazolyl group or 1,2,3,4-tetrazolyl group which is unsubstituted or substituted by R
15
(R
15
has the same meanings as defined in R
10
};
n means 0 or an integer of 1 to 4;
X represents C═O, CH
2
, SO
2
or NR
16
(R
16
has the same meanings as defined in R
14
);
Y represents NR
17
(R
17
has the same meanings as defined in R
14
) when X is C═O, CH
2
or SO
2
and represents C═O when X is NR
16
;
Z is absent when Y represents NR
17
or represents NR
18
(R
18
has the same meanings as defined in R
14
) when Y is C═O;
W represents
{wherein R
9
represents hydrogen atom, halogen atom, C
1-6
alkyl group (said alkyl group is unsubstituted or substituted by halogen atom or C
1-6
alkoxy group), C
1-6
alkoxy group (said alkoxy group is unsubstituted or substituted by halogen atom), phenyl group (said phenyl group is unsubstituted or substituted by halog
Ohrai Kazuhiko
Sato Masayuki
Shigeta Yukihiro
Tanikawa Keizo
Yamashita Toru
Nissan Chemical Industries Ltd.
Oliff & Berridg,e PLC
Solola T. A.
Wright Sonya
LandOfFree
Indane derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Indane derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Indane derivatives will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2938322