Agents for promoting the proliferation or differentiation of stem cells or neural progenitor cells

1 .- 32 . (canceled)

33 . A method for preventing or treating a central nervous system disease in a mammal, comprising administering a compound represented by Formula:

wherein R 1 and R 2 are same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group or R 1 and R 2 may be taken together with the adjacent carbon atom to form an optionally substituted 3- to 8-membered homocyclic or heterocyclic ring,

R 3 is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group,

is a single bond or a double bond,

W is (i) a group represented by Formula:

wherein Ring A is an optionally substituted benzene ring, Ring B is an optionally substituted 5- to 7-membered nitrogen-containing heterocyclic ring,

(ii) a group represented by Formula:

wherein R 4 is (1) an aliphatic hydrocarbon group which is substituted by an optionally substituted aromatic group and which may have a further substituent or (2) an optionally substituted aromatic ring-containing acyl group, R 5 is a hydrogen atom, a C 1-6 alkyl or an acyl group, or,

(iii) a group represented by Formula:

R 4c —X—  (Wc)

wherein R 4c is an optionally substituted aromatic group, an optionally substituted aliphatic hydrocarbon group or an acyl group, X is an oxygen atom or an optionally oxidized sulfur atom,

Y is an oxygen atom, an optionally oxidized sulfur atom or an optionally substituted imino,

Ring C is a benzene ring which may have a further substituent in addition to the group represented by W,

or a salt or prodrug thereof to the mammal in need of such treatment.

34 . The method according to claim 33 , wherein is a single bond.

35 . The method according to claim 33 , wherein Y is an oxygen atom.

36 . The method according to claim 33 , wherein W is a group represented by Formula (Wa).

37 . The method according to claim 36 , wherein each of R 1 and R 2 is a hydrogen atom or a C 1-6 alkyl group, R 3 is a hydrogen atom or a phenyl group which may have 1 to 3 substituents selected from C 1-6 alkyl and halogen, the Ring C is a benzene ring which may further have 1 to 3 substituents selected from C 1-6 alkyl and C 1-6 alkoxy, is a single bond, Y is an oxygen atom, the group represented by Formula (Wa) is a group represented by Formula:

wherein Ring A 1 is a benzene ring which may have 1 to 3 substituents selected from halogen, C 1-6 alkoxy and C 1-6 alkylenedioxy.

38 . The method according to claim 37 , wherein the group represented by Formula (Wa) is a substituent on the 5-position of the benzofuran ring.

39 . The method according to claim 33 , wherein the compound is

[1] 2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]isoindoline,

[2] 5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]isoindoline,

[3] 5,6-dimethoxy-2-[3-(4-isopropyl phenyl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl]isoindoline,

[4] 5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]-2H-isoindole,

[5] 6-[3-(4-isopropylphenyl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl]-6,7-dihydro-5H-[1,3]dioxolo[4,5-f]isoindole,

[6] 6-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]-6H-[1,3]dioxolo[4,5-f]isoindole,

[7] 6-(2,2,4,6,7-pentamethyl-3-phenyl-2,3-dihydro-1-benzofuran-5-yl)-6,7-dihydro-5H-[1,3]dioxolo[4,5-f]isoindole,

[8] (R)-5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]isoindoline or

[9] (R)-5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]isoindoline hydrochloride.

40 . The method according to claim 33 , wherein the compound is (R)-5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]isoindoline.

41 . The method according to claim 33 , wherein W is a group represented by Formula (Wb).

42 . The method according to claim 41 , wherein each of R 1 and R 2 is a methyl group, R 3 is a phenyl group which may have 1 to 3 substituents selected from fluorine, methyl and isopropyl, the Ring C is a benzene ring which may further have 1 to 3 substituents selected from C 1-6 alkyl and C 1-6 alkoxy, Y is an oxygen atom, R 4 is a benzyl or phenethyl group which may have 1 to 3 substituents selected from fluorine, methoxy and methylenedioxy and R 5 is a hydrogen atom or a methyl group.

43 . The method according to claim 33 , wherein the compound is

(1) N-(4-fluorobenzyl)-2,2,4,6,7-pentamethyl-3-phenyl-2,3-dihydro-1-benzofuran-5-amine,

(2) N-benzyl-3-(4-isopropylphenyl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-amine,

(3) 3-(4-isopropylphenyl)-N-(4-methoxybenzyl)-N,2,2,4,6,7-hexamethyl-2,3-dihydro-1-benzofuran-5-amine,

(4) 3-(4-isopropylphenyl)-N-[2-(4-methoxyphenyl)ethyl]-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-amine,

(5) N-(4-fluorobenzyl)-3-(4-isopropylphenyl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-amine,

(6) N-(1,3-benzodioxol-5-ylmethyl)-3-(4-isopropylphenyl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-amine,

(7) N-(4-fluorobenzyl)-3-(4-fluorophenyl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-amine,

(8) N-(4-methoxybenzyl)-2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-amine,

(9) N-(4-fluorobenzyl)-2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-amine,

(10) 3-(4-isopropylphenyl)-N-(4-methoxybenzyl)-2,4,6,7-tetramethyl-1-benzofuran-5-amine,

(11) N-(4-fluorobenzyl)-3-(4-isopropylphenyl)-2,4,6,7-tetramethyl-1-benzofuran-5-amine,

(12) N-(4-fluorobenzyl)-3-(4-fluorophenyl)-2,4,6,7-tetramethyl-1-benzofuran-5-amine,

(13) N-(4-fluorobenzyl)-3-(4-isopropylphenyl)-1′,4,6,7-tetramethylspiro[benzofuran-2(3H), 4′-piperidine]-5-amine or (14) (R)—N-(4-fluorobenzyl)-3-(4-isopropylphenyl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-amine hydrochloride.

44 . The method according to claim 33 , wherein W is a group represented by Formula (Wc).

45 . The method according to claim 44 , wherein the compound is represented by the Formula:

wherein each of R 1 and R 2 is C 1-6 alkyl which may have a phenyl-substituted 6-membered saturated cyclic amino, or R 1 and R 2 are taken together with the adjacent carbon atom to form a C 1-6 alkyl- or C 7-16 aralkyl-substituted piperidine;

R 3 is (i) a hydrogen atom, or,

(ii) phenyl which may have 1 to 3 substituents selected from (1) C 1-6 alkyl, (2) di-C 1-6 alkylamino and (3) 6-membered saturated cyclic amino which may have C 1-6 alkyl;

R 4c is (i) phenyl which may have 1 to 3 substituents selected from nitro and C 1-6 alkyl-carboxamide,

(ii) C 1-6 alkyl or C 2-6 alkenyl having 1 to 3 phenyl, quinolyl or pyridyl which may have 1 to 3 substituents selected from C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkoxy-carbonyl, C 1-6 alkylsulfonyl and C 1-6 alkylsulfinyl and optionally further having phenyl, carboxy or C 1-6 alkoxy-carbonyl as additional substituents, or,

(iii) acyl represented by Formula: —(C═O)—R 5″ wherein R 5″ is C 1-6 alkoxy-substituted phenyl; and,

the Ring C′ is a benzene ring which may further have 1 to 3 C 1-6 alkyl, or a salt or prodrug thereof.

46 . The method according to claim 33 , wherein the compound is

3-(4-isopropyl phenyl)-5-(4-methoxybenzyloxy)-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran,

3-(4-methylphenyl)-2,4,6,7-tetramethylbenzofuran-5-yl 4-methoxybenzoate,

3-(4-isopropylphenyl)-2,4,6,7-tetramethylbenzofuran-5-yl 4-methoxybenzoate,

3-(4-isopropylphenyl)-5-(4-methoxybenzyloxy)-2,4,6,7-tetramethylbenzofuran, or

3-(4-isopropylphenyl)-5-(4-methoxybenzyloxy)-1′,4,6,7-tetramethylspiro[benzofuran-2(3H), 4′-piperidine], or a salt thereof.

47 . The method according to claim 33 , wherein the central nervous system disease is a cognitive impairment or a memory impairment.

48 . The method according to claim 33 , wherein the central nervous system disease is a mild cognitive impairment or a mild memory impairment.