US 2010/0168156 A1 · Novel Benzoxathiine Derivative

Abstract

Disclosed is a compound represented by the formula (I) below and a pharmaceutically acceptable salt thereof. This compound is useful for treatment of obesity, diabetes and the like. [In the formula (I), Ar represents a benzene ring or the like; X1 represents a nitrogen atom, a sulfur atom or the like; R1 represents an aryl group or the like; X2 represents a group represented by the following formula (II): (wherein R4 and R5 respectively represent a lower alkyl group or the like, and m represents a number of 2-4) or the like; one of X and Y represents an oxygen atom and the other represents a sulfanyl group or the like; and X3-X6 respectively represent —CH—, a nitrogen atom or the like.

Claims21

Dependent claims

1-24. (canceled)

A compound of the formula (I):

wherein:
R1 represents a hydrogen atom, a lower alkyl group (wherein the lower alkyl group may be substituted with a lower alkoxy group or a halogen atom), a lower alkoxy group (wherein the lower alkoxy group may be substituted with a halogen atom), an aryl group (wherein the aryl group may be substituted with a lower alkyl group (wherein the lower alkyl group may be substituted with a halogen atom), a lower alkoxy group (wherein the lower alkoxy group may be substituted with a halogen atom) or a halogen atom), or a heteroaryl group (wherein the heteroaryl group may be substituted with a lower alkyl group (wherein the lower alkyl group may be substituted with a halogen atom), a lower alkoxy group (wherein the lower alkoxy group may be substituted with a halogen atom), or a halogen atom);
R2 each independently represents a hydrogen atom, an amino group, an alkylamino group, a dialkylamino group, a nitro group, a cyano group, a hydroxyl group, a lower alkylsulfonyl group, a halogen atom, a lower alkyl group (wherein the lower alkyl group may be substituted with a halogen atom), a cycloalkyl group (wherein the cycloalkyl group may be substituted with a lower alkyl group or a halogen atom), a lower alkoxy group (wherein the lower alkoxy group may be substituted with a halogen atom), a cycloalkoxy group, an aryloxy group, an aralkyloxy group, a heteroaryloxy group, a heteroarylalkyloxy group, an aryl group, a heteroaryl group, an arylcarbamoyl group, a heteroarylcarbamoyl group, an aralkylcarbamoyl group, a heteroarylalkylcarbamoyl group, a mono or di-lower alkylcarbamoyl group, an aryloxycarbonylamino group, an aralkyloxycarbonylamino group, a lower alkoxycarbonylamino group, an alkanoylamino group, an arylcarbonylamino group, a heteroarylcarbonylamino group, an aralkylcarbonylamino group, a heteroarylalkylcarbonylamino group, an alkanoyl group, an arylcarbonyl group, an aralkylcarbonyl group, a formyl group, an alkylthio group, an alkylsulfonylamino group, an arylsulfonylamino group, a mono or di-lower alkylsulfamoyl group, an arylsulfamoyl group, or an aralkyl group;
one of X and Y is an oxygen atom, and the other is a sulfanyl group, a sulfinyl group or a sulfonyl group;
Ar represents a divalent group derived from a benzene ring, a pyridine ring, a pyrimidine ring, a pyrazine ring or a pyridazine ring by removing two hydrogen atoms therefrom (wherein the divalent group may be substituted with a halogen atom, a lower alkoxy group (wherein the lower alkoxy group may be substituted with a halogen atom), a lower alkyl group (wherein the lower alkyl group may be substituted with a halogen atom), or a hydroxyl group);
X1 represents a carbon atom, a nitrogen atom, a sulfur atom or an oxygen atom;
X2 represents a group of a formula (II):
wherein R4 and R5 are the same or different, each representing a lower alkyl group (wherein the lower alkyl group may be substituted with a halogen atom), or a cycloalkyl group (wherein the cycloalkyl group may be substituted with a lower alkyl group or a halogen atom), or R4, R5 and the nitrogen atom to which they bond, taken together, form a 4- to 9-membered monocyclic ring or a 4- to 8-membered bicyclic ring (wherein the monocyclic ring or the bicyclic ring may be substituted with a lower alkyl group (wherein the lower alkyl group may be substituted with a halogen atom), a halogen atom, a hydroxyl group or an oxo group;
and the monocyclic ring may have, in the ring, still another hetero atom selected from a nitrogen atom, a sulfur atom and an oxygen atom, in addition to the nitrogen atom to which R4 and R5 bond), m indicates from 2 to 4;
a group of a formula (III):
wherein R6 represents a lower alkyl group (wherein the lower alkyl group may be substituted with a halogen atom), or a cycloalkyl group (wherein the cycloalkyl group may be substituted with a lower alkyl group or a halogen atom), n indicates from 0 to 4,
or a group of a formula (IV):
X3 to X6 each independently represent —CR2— or a nitrogen atom;
however, 3 or more of X3 to X6 are not nitrogen atoms at the same time;
the formula (V):
(V)
indicates a single bond or a double bond;
or a pharmaceutically acceptable salt thereof.

15 more elements

A compound which is selected from the group consisting of:

3-phenyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin,
3-phenyl-2-[4-[3-(1-piperidinyl)propoxy]phenyl]-1,4-benzoxathiin,
(2,3-cis)-2,3-dihydro-3-phenyl-2-[4-[3-(1-piperidinyl)propoxy]phenyl]-1,4-benzoxathiin,
(2,3-cis)-2,3-dihydro-3-phenyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin,
3-methyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin,
3-ethyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin,
(2,3-cis)-2,3-dihydro-3-methyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin,
(2,3-cis)-2,3-dihydro-3-ethyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin,
(2,3-cis)-2,3-dihydro-3-methyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin-4,4-dioxide,
(2,3-cis)-2,3-dihydro-3-ethyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin-4,4-dioxide,
(2,3-trans)-2,3-dihydro-3-methyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin,
(2,3-trans)-2,3-dihydro-3-ethyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin,
(2,3-trans)-2,3-dihydro-4,4-dioxido-3-methyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin,
(2,3-trans)-2,3-dihydro-3-ethyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin-4,4-dioxide,
(2,3-cis)-2,3-dihydro-3-methyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin-4-oxide,
(2,3-cis)-2,3-dihydro-3-ethyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin-4-oxide,
(2,3-cis)-2,3-dihydro-2-methyl-3-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin,
(2,3-cis)-2,3-dihydro-2-methyl-3-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin-4,4-dioxide,
2,3-dihydro-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin,
(2,3-trans)-2,3-dihydro-3-methyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin-4-oxide,
(2,3-trans)-2,3-dihydro-3-ethyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin-4-oxide,
(2,3-trans)-2,3-dihydro-3-ethyl-2-[4-[3-((3S)-3-methyl-1-piperidinyl)propoxy]phenyl]-1,4-benzoxathiin,
(2,3-trans)-2,3-dihydro-3-ethyl-2-[4-[(1-cyclobutylpiperidin-4-yl)oxy]phenyl]-1,4-benzoxathiin,
(2,3-trans)-2,3-dihydro-3-methyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-[1,4]oxathiino[3,2-b]pyridine,
(2,3-trans)-2,3-dihydro-3-ethyl-2-[4-[3-((3S)-3-methyl-1-piperidinyl)propoxy]phenyl]-1,4-benzoxathiin-4,4-dioxide,
(2,3-trans)-2,3-dihydro-3-ethyl-2-[4-[(1-cyclobutylpiperidin-4-yl)oxy]phenyl]-1,4-benzoxathiin-4,4-dioxide,
(2S,3S)-2,3-dihydro-3-methyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin-4,4-dioxide,
(2R,3R)-2,3-dihydro-3-methyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-1,4-benzoxathiin-4,4-dioxide,
(2,3-trans)-2,3-dihydro-3-methyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-[1,4]oxathiino[3,2-b]pyridine-4,4-dioxide,
(2,3-trans)-2,3-dihydro-3-methyl-2-[4-[(1-cyclobutylpiperidin-4-yl)oxy]phenyl]-1,4-benzoxathiin-4,4-dioxide,
(2,3-trans)-2,3-dihydro-3-methyl-2-[4-[3-((3S)-3-methyl-1-piperidinyl)propoxy]phenyl]-1,4-benzoxathiin-4,4-dioxide,
(2,3-trans)-2,3-dihydro-8-methoxy-3-methyl-2-[4-[(1-cyclobutylpiperidin-4-yl)oxy]phenyl]-1,4-benzoxathiin-4,4-dioxide,
1-[3-[4-[(2,3-trans)-2,3-dihydro-4,4-dioxido-8-methoxy-3-methyl-1,4-benzoxathiin-2-yl]phenoxy]propyl]-(3S)-3-methylpiperidine,
1-[3-[4-[(2,3-trans)-2,3-dihydro-4,4-dioxido-8-methoxy-3-methyl-1,4-benzoxathiin-2-yl]phenoxy]propyl]-pyrrolidine,
1-[3-[4-[(2,3-trans)-2,3-dihydro-4,4-dioxido-8-methoxy-3-methyl-1,4-benzoxathiin-2-yl]phenoxy]propyl]-piperidine,
1-[3-[4-[(2,3-trans)-2,3-dihydro-4,4-dioxido-5-methoxy-3-methyl-1,4-benzoxathiin-2-yl]phenoxy]propyl]-pyrrolidine,
1-[3-[4-[(2,3-trans)-2,3-dihydro-4,4-dioxido-5-methoxy-3-methyl-1,4-benzoxathiin-2-yl]phenoxy]propyl]-piperidine,
1-[3-[5-[(2,3-trans)-2,3-dihydro-4,4-dioxido-3-methyl-1,4-benzoxathiin-2-yl]pyridin-2-yloxy]propyl-pyrrolidine,
1-[3-[4-[(2,3-trans)-2,3-dihydro-4,4-dioxido-6-methoxy-3-methyl-1,4-benzoxathiin-2-yl]phenoxy]propyl]-pyrrolidine,
1-[3-[4-[(2,3-trans)-2,3-dihydro-4,4-dioxido-6-methoxy-3-methyl-1,4-benzoxathiin-2-yl]phenoxy]propyl]-piperidine,
1-[3-[4-[(2S,3S)-2,3-dihydro-4,4-dioxido-8-methoxy-3-methyl-1,4-benzoxathiin-2-yl]phenoxy]propyl]-pyrrolidine,
1-[3-[4-[(2R,3R)-2,3-dihydro-4,4-dioxido-8-methoxy-3-methyl-1,4-benzoxathiin-2-yl]phenoxy]propyl]-pyrrolidine,
(2S,3S)-2,3-dihydro-8-methoxy-3-methyl-2-[4-[(1-cyclobutylpiperidin-4-yl)oxy]phenyl]-1,4-benzoxathiin-4,4-dioxide,
(2R,3R)-2,3-dihydro-8-methoxy-3-methyl-2-[4-[(1-cyclobutylpiperidin-4-yl)oxy]phenyl]-1,4-benzoxathiin-4,4-dioxide,
1-[3-[4-[(2,3-trans)-2,3-dihydro-4,4-dioxido-7-methoxy-3-methyl-1,4-benzoxathiin-2-yl]phenoxy]propyl]-pyrrolidine,
1-[3-[4-[(2,3-trans)-2,3-dihydro-4,4-dioxido-7-methoxy-3-methyl-1,4-benzoxathiin-2-yl]phenoxy]propyl]-piperidine,
1-[3-[4-[(2,3-trans)-2,3-dihydro-4,4-dioxido-3-methyl-[1,4]oxathiino[3,2-b]pyridin-2-yl]phenoxy]propyl]-piperidine,
(2,3-trans)-2,3-dihydro-5-methoxy-3-methyl-2-[4-[(1-cyclobutylpiperidin-4-yl)oxy]phenyl]-1,4-benzoxathiin-4,4-dioxide,
(2S,3S)-2,3-dihydro-5-methoxy-3-methyl-2-[4-[(1-cyclobutylpiperidin-4-yl)oxy]phenyl]-1,4-benzoxathiin-4,4-dioxide,
(2R,3R)-2,3-dihydro-5-methoxy-3-methyl-2-[4-[(1-cyclobutylpiperidin-4-yl)oxy]phenyl]-1,4-benzoxathiin-4,4-dioxide,
(2S,3S)-2,3-dihydro-3-methyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-[1,4]oxathiino[3,2-b]pyridin-4,4-dioxide,
(2R,3R)-2,3-dihydro-3-methyl-2-[4-[3-(1-pyrrolidinyl)propoxy]phenyl]-[1,4]oxathiino[3,2-b]pyridin-4,4-dioxide,
1-[3-[4-[(2S,3S)-2,3-dihydro-4,4-dioxido-5-methoxy-3-methyl-1,4-benzoxathiin-2-yl]phenoxy]propyl]-piperidine,
1-[3-[4-[(2R,3R)-2,3-dihydro-4,4-dioxido-5-methoxy-3-methyl-1,4-benzoxathiin-2-yl]phenoxy]propyl]-piperidine,
(2R,3R)-2-{4-[(1-cyclobutylpiperidin-4-yl)oxy]phenyl}-3-methyl-2,3-dihydro[1,4]oxathiino[3,2-b]pyridine 4,4-dioxide,
(2S,3S)-2-{4-[(1-cyclobutylpiperidin-4-yl)oxy]phenyl}-3-methyl-2,3-dihydro[1,4]oxathiino[3,2-b]pyridine 4,4-dioxide,
1-[3-[4-[(2S,3S)-2,3-dihydro-4,4-dioxido-3-methyl-[1,4]oxathiino[3,2-b]pyridin-2-yl]phenoxy]propyl]-piperidine,
1-[3-[4-[(2R,3R)-2,3-dihydro-4,4-dioxido-3-methyl-[1,4]oxathiino[3,2-b]pyridin-2-yl]phenoxy]propyl]-piperidine,
(2S,3S)-3-methyl-2-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-2,3-dihydro[1,4]oxathiino[3,2-b]pyridine 4,4-dioxide,
(2R,3R)-3-methyl-2-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-2,3-dihydro[1,4]oxathiino[3,2-b]pyridine 4,4-dioxide,
(2S,3S)-2-{4-[(1-isopropylpiperidin-4-yl)oxy]phenyl}-3-methyl-2,3-dihydro[1,4]oxathiino[3,2-b]pyridine 4,4-dioxide,
(2R,3R)-2-{4-[(1-isopropylpiperidin-4-yl)oxy]phenyl}-3-methyl-2,3-dihydro[1,4]oxathiino[3,2-b]pyridine 4,4-dioxide,
(2S*,3S*)-2-[3-bromo-4-(3-pyrrolidin-1-ylpropoxy)phenyl]-3-methyl-2,3-dihydro[1,4]oxathiino[3,2-b]pyridine 4,4-dioxide,
1-(3-{2-bromo-4-[(2S*,3S*)-8-methoxy-3-methyl-4,4-dioxido-2,3-dihydro-1,4-benzoxathiin-2-yl]phenoxy}propyl)pyrrolidine,
1-{3-[4-(3-methyl-4,4-dioxido-1,4-benzoxathiin-2-yl)phenoxy]propyl}pyrrolidine,
1-{2-[4-(3-phenyl-1,4-benzoxathiin-2-yl)phenoxy]ethyl}pyrrolidine,
1-(2-{4-[(2,3-cis)-3-phenyl-2,3-dihydro-1,4-benzoxathiin-2-yl]phenoxy}ethyl)pyrrolidine,
1-{2-[4-(3-phenyl-1,4-benzoxathiin-2-yl)phenoxy]ethyl}piperidine, and
1-(2-{4-[(2,3-cis)-3-phenyl-2,3-dihydro-1,4-benzoxathiin-2-yl]phenoxy}ethyl)piperidine,
or a pharmaceutically acceptable salt thereof.

67 more elements

Dependencies are inferred from the claim text.

Facts

Application

12/084,017Filed 25 Oct 2006

Priority

JP 2005-31295627 Oct 2005

Published

1 Jul 2010

Term ends

Not estimatedThe source records don’t support an estimate.

Classification30 codes

C07D 327/06
One oxygen atom and one sulfur atom: six-membered rings
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 3/00
Drugs for disorders of the metabolism
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents

Novel Benzoxathiine Derivative

Life of this patent

Novel Benzoxathiine Derivative

Life of this patent

Abstract

Claims21