Heterocyclic compound
The present invention provides a compound having an MAGL inhibitory action, and expected to be useful as an agent for the prophylaxis or treatment of neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, glaucoma, multiple sclerosis etc.), anxiety disorder, pains (e.g., inflammatory pain, cancerous pain, neurogenic pain etc.), epilepsy, depression and the like. The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the description, or a salt thereof.
1. A compound represented by the formula (I):
wherein
A is an optionally substituted saturated cyclic group,
L is a bond or a C 1-3 alkylene group optionally substituted by halogen atom(s),
Ring D is a ring optionally further substituted by C 1-6 alkyl group(s) optionally substituted by halogen atom(s),
n is 1 or 2,
X is —O—, —CR 1 R 2 — or —NR 3 —,
R a and R b are each independently a hydrogen atom or a C 1-6 alkyl group optionally substituted by halogen atom(s), and
R 1 , R 2 and R 3 are each independently a hydrogen atom or a substituent,
or a salt thereof.
2. The compound or salt according to claim 1 , wherein A is a C 3-10 cycloalkyl group
substituted by 1 to 3 substituents selected from
(a) a C 6-14 aryloxy group optionally substituted by 1 to 4 substituents selected from
(i) a halogen atom, and
(ii) an optionally halogenated C 1-6 alkyl group,
(b) a C 6-14 aryloxy-C 1-6 alkyl group optionally substituted by 1 to 4 substituents selected from
(i) a halogen atom, and
(ii) an optionally halogenated C 1-6 alkyl group,
(c) a C 7-16 aralkyloxy group optionally substituted by 1 to 4 substituents selected from
(i) a halogen atom, and
(ii) an optionally halogenated C 1-6 alkyl group, and
(d) a C 7-16 aralkyloxy-C 1-6 alkyl group optionally substituted by 1 to 4 substituents selected from
(i) a halogen atom, and
(ii) an optionally halogenated C 1-6 alkyl group, and optionally further substituted by 1 to 3 C 1-6 alkyl groups;
L is bond or a C 1-3 alkylene group;
Ring D is a 4- or 5-membered nitrogen-containing heterocycle;
n is 1 or 2;
X is —O— or —CH 2 —; and
R a and R b are both hydrogen atoms.
3. The compound or salt according to claim 1 , wherein A is a cyclobutyl group substituted by one substituent selected from
(a) a phenoxy group substituted by 3 halogen atoms, and
(b) a phenoxymethyl group substituted by 3 halogen atoms;
L is bond;
Ring D is an azetidine ring;
n is 1;
X is —O—; and
R a and R b are both hydrogen atoms.
4. cis-3-((2,3,4-Trifluorophenoxy)methyl)cyclobutyl 6-oxo-7-oxa-2,5-diazaspiro[3.4]octane-2-carboxylate or a salt thereof.
5. cis-3-((2,4,6-Trifluorophenoxy)methyl)cyclobutyl 6-oxo-7-oxa-2,5-diazaspiro[3.4]octane-2-carboxylate or a salt thereof.
6. cis-3-(2,4,6-Trifluorophenoxy)cyclobutyl 6-oxo-7-oxa-2,5-diazaspiro[3.4]octane-2-carboxylate or a salt thereof.
7. A medicament comprising the compound or salt according to claim 1 .
8. The medicament according to claim 7 , which is a monoacylglycerol lipase inhibitor.
9. The medicament according to claim 7 , which is an agent for the prophylaxis or treatment of Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, anxiety disorder, pain, epilepsy or depression.
10. A method of inhibiting monoacylglycerol lipase in a mammal, which comprises administering an effective amount of the compound or salt according to claim 1 to the mammal.
11. A method for the prophylaxis or treatment of Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, anxiety disorder, pain, epilepsy or depression in a mammal, which comprises administering an effective amount of the compound or salt according to claim 1 to the mammal.
12. The compound or salt according to claim 1 for use in the prophylaxis or treatment of Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, anxiety disorder, pain, epilepsy or depression.