1. Acyclic compound represented by General Formula (2):
wherein R1 is the same or different, and each represents a hydrogen atom or a protecting group for a hydroxy group; R2 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; R4 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; n is the same or different, and each represents an integer of 1 or more; and m is the same or different, and each represents an integer of 0 or more,
and wherein at least one \u2014(R4)m\u2014 is represented by General Formula (8):
wherein m\u2033 is 1, 2 or 3; and a ring of a repeating unit is a 6-membered heterocyclic aromatic ring having nitrogen.
2. A method for producing a carbon nanoring represented by General Formula (1):
wherein R2 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; R4 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; n is the same or different, and each represents an integer of 1 or more; and m is the same or different, and each represents an integer of 0 or more,
and wherein at least one \u2014(R4)m\u2014 is represented by General Formula (8):
wherein m\u2033 is 1, 2 or 3; and a ring of a repeating unit is a 6-membered heterocyclic aromatic ring having nitrogen,
the method comprising a conversion step of: converting cyclohexane rings of a cyclic compound represented by General Formula (2):
wherein R1 is the same or different, and each represents a hydrogen atom or a hydroxyl protecting group; and R2, R4, n and m are as defined above,
into benzene rings.
3. A method for producing a carbon nanoring represented by General Formula (1),
wherein R2 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; R4 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; n is the same or different, and each represents an integer of 1 or more; and m is the same or different, and each represents an integer of 0 or more,
the method comprising a coupling step of:
performing coupling reaction of a compound represented by General Formula (3):
wherein X is the same or different, and each represents a halogen atom; R1 is the same or different, and each represents a hydrogen atom or a hydroxyl protecting group; and R2, R4, n and m are as defined above,
and a compound represented by General Formula (4):
wherein Y is the same or different, and each represents a group represented by General Formula (9):
wherein R3 is the same or different, and each represents a hydrogen atom or a C1-C10 alkyl group; and R3 may be bonded to form a ring with adjacent \u2014O\u2014B\u2014O\u2014;
and R1, R2 and n are as defined above,
to form a cyclic compound represented by General Formula (2):
wherein R1, R2, R4, n and m are as defined above;
and a conversion step of converting cyclohexane rings of the cyclic compound into benzene rings.
4. A carbon nanoring represented by General Formula (1):
wherein R2 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; R4 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; n is the same or different, and each represents an integer of 1 or more; and m is the same or different, and each represents an integer of 0 or more,
and wherein at least one \u2014(R4)m\u2014 is represented by General Formula (8):
wherein m\u2033 is 1, 2 or 3; and a ring of a repeating unit is a 6-membered heterocyclic aromatic ring having nitrogen.
5. (canceled)
6. (canceled)
7. (canceled)
9. (canceled)
10. (canceled)
11. (canceled)
12. A method for producing a cyclic compound represented by General Formula (2):
wherein R1 is the same or different, and each represents a hydrogen atom or a protecting group for a hydroxy group; R2 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; R4 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; n is the same or different, and each represents an integer of 1 or more; and m is the same or different, and each represents an integer of 0 or more,
the method comprising a coupling step of performing coupling reaction of a compound represented by General Formula (3):
wherein X is the same or different, and each represents a halogen atom; and R1, R2, R4, n and m are as defined above,
and a compound represented by General Formula (4):
wherein Y is the same or different, and each represents a group represented by General Formula (9):
wherein R3 is the same or different, and each represents a hydrogen atom or a C1-C10 alkyl group; R3 may be bonded to form a ring with adjacent \u2014O\u2014B\u2014O\u2014,
and R1, R2 and n are as defined above,
to form the cyclic compound represented by General Formula (2).
13. A compound represented by General Formula (3):
wherein X is the same or different, and each represents a halogen atom; R1 is the same or different, and each represents a hydrogen atom or a protecting group for a hydroxy group; R2 each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; R4 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; n is an integer of 1 or more; and m is the same or different, and each represents an integer of 0 or more.
14. A method for producing a compound represented by General Formula (3):
wherein X is the same or different, and each represents a halogen atom; R1 is the same or different, and each represents a hydrogen atom or a protecting group for a hydroxy group; R2 each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; R4 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; n is an integer of 1 or more; and m is the same or different, and each represents an integer of 0 or more,
the method comprising a reaction step of reacting, in the presence of a palladium catalyst, a raw materials containing Compound (10) represented by General Formula (10):
wherein X and R1 are as defined above,
and Compound (11) represented by General Formula (11):
wherein R2 and n are as defined above; and Y is the same or different and each represents a group represented by General Formula (9):
wherein R3 is the same or different, and each represents a hydrogen atom or a C1-C10 alkyl group; and R2 may be bonded to form a ring with adjacent \u2014O\u2014B\u2014O\u2014.
15. A carbon nanoring represented by General Formula (1):
wherein R2 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; R4 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; n is the same or different, and each represents an integer of 1 or more; and m is the same or different, and each represents an integer of 0 or more,
and wherein at least one \u2014(R2)n\u2014 is represented by General Formula (5):
wherein n\u2032 is 1 or 2; and p is 1.
16. (canceled)
17. The carbon nanoring according to claim 4, wherein the total number of phenylene, R2, and R4 in the carbon nanoring is 13, 14, 15, 16, 17, 19 or 20.
18. A cyclic compound represented by General Formula (2):
wherein R1 is the same or different, and each represents a hydrogen atom or a protecting group for a hydroxy group; R2 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; R4 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; n is the same or different, and each represents an integer of 1 or more; and m is the same or different, and each represents an integer of 0 or more,
and wherein at least one \u2014(R2)n\u2014 is represented by General Formula (5):
wherein n\u2032 is 1 or 2; and p is 1.
19. A method for producing a carbon nanoring represented by General Formula (1):
wherein R2 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; R4 is the same or different, and each represents a bivalent aromatic hydrocarbon group, a bivalent heterocyclic group, or a derivative group thereof; n is the same or different, and each represents an integer of 1 or more; and m is the same or different, and each represents an integer of 0 or more,
wherein at least one \u2014(R2)n\u2014 is represented by General Formula (5):
wherein n\u2032 is 1 or 2; and p is 1,
the method comprising a conversion step of: converting cyclohexane rings of a cyclic compound represented by General Formula (2):
wherein R1 is the same or different, and each represents a hydrogen atom or a hydroxyl protecting group; and R2, R4, n and m are as defined above,
into benzene rings.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method of treating a brain or nerve disorder selected from the group consisting of cerebral ischemia, ischemic stroke, hemorrhagic stroke, Alzheimer’s disease, and epilepsy, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula (I):
wherein
R1 is hydrogen or alkyl;
each of R2 and R3 is independently selected from hydrogen, alkyl, \u2014COR6, \u2014SO2R7, or substituted or unsubstituted phenyl or benzyl, wherein R6 is alkyl, alkoxy, phenyl, phenyloxy or benzyloxy, each of which is unsubstituted or substituted with halogen, hydroxy, methoxy, ethoxy or nitro, and R7 is unsubstituted or substituted lower alkyl or aryl;
A is \u2014(CH2)n- or \u2014CH2CH\u2550CHCH2\u2014, wherein n is an integer selected from 2 to 4;
R4 is hydrogen and R5 is hydrogen or benzoyl unsubstituted or substituted with one or more of halogen, hydroxy, alkoxy or nitro in benzene ring or when R4 and R5 together with N form a ring,
R4 and R5 form a divalent moiety of
wherein R8 is hydrogen or alkyl;
each of l and m is independently an integer selected from 2 to 4; and
p is an integer of 0 or 1,
or a pharmaceutically acceptable salt thereof
2. The method of claim 1, wherein said disorder is an ischemic or hemorrhagic stroke.
3. The method of claim 1, wherein said disorder is Alzheimer’s disease.
4. The method of claim 1, wherein said disorder is epilepsy.
5. The method of claim 1, wherein:
R1 is hydrogen;
each of R2 and R3 is independently selected from hydrogen, C1-6 alkyl, \u2014COR6, \u2014SO2R7, or substituted or unsubstituted phenyl or benzyl, wherein R6 is alkyl, alkoxy, phenyl, phenyloxy or benzyloxy, each of which is unsubstituted or substituted with halogen, hydroxy, methoxy, ethoxy or nitro, and R7 is unsubstituted or substituted lower alkyl or aryl;
A is \u2014(CH2)n-or \u2014CH2CH\u2550CHCH2-, wherein n is an integer selected from 2 to 4;
R4 is hydrogen and R5 is hydrogen or benzoyl unsubstituted or substituted with one or more of halogen, hydroxy, alkoxy or nitro in benzene ring, or when R4 and R5 together with N form a ring,
R4 and R5 form a divalent moiety of
\u2003wherein R8 is hydrogen or alkyl;
each of l and m is independently an integer selected from 2 to 4; and
p is an integer of 0 or 1.
6. The method of claim 1 wherein the compound is selected from the group consisting of:
3-{3-4-(3-aminopropylamino)butylaminopropyl}-1H-quinazoline-2,4-dione;
3-(3-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminobutylamino}propyl)-1H-quinazoline-2,4-dione;
N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-N-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminobutyl}acetamide;
N-(4-{acetyl-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylamino}butyl)-N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylacetamide;
3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminobutyl}carbamic acid ethyl ester;
N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-N-(4-{3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylmethylamino}butyl)acetamide;
3-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminobutyl}-1 H-quinazoline-2,4-dione;
N-(3-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminobutylamino}propyl)-4-hydroxybenzamide;
3-{3-4-({N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-N-benzyl}amino)butyl aminopropyl}-1 H-quinazoline-2,4-dione;
N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-N-{4-3-(2,4-dioxo-1,4-dihydro-2H- quinazolin-3-yl)propylaminobutyl}benzamide;
3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminobutyl}carbamic acid tert-butyl ester;
N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-N-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminobutyl}methansulfonamide;
N-(4-{benzyl-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylamino}butyl)-N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylacetamide;
(4-{acetyl-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylamino}butyl)-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylcarbamic acid ethyl ester;
3-{3-(4-{N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-N-benzylamino}butyl)-N-benzylaminopropyl}-1H-quinazoline-2,4-dione;
3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-(4-{3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylethoxycarbonylamino}butyl)carbamic acid ethyl ester;
(4-{tert-butoxycarbonyl-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylamino}butyl)-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylcarbamic acid tert-butyl ester;
N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-N-(4-{3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylmethansulfonylamino}butyl)methansulfonamide;
N- 3-(acetyl-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminobutyl}amino) propyl-4-hydroxybenzamide;
N-3-(4-{acetyl-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylamino}butylamino) propyl-4-hydroxybenzamide;
N-{3-acetyl-(4-{acetyl-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylamino}butyl) aminopropyl}-4-hydroxybenzamide;
N-4-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)butyl-N-3-(2,4-dioxo-1,4-dihydro-2H- quinazolin-3-yl)propylacetamide;
3-(2-{3-2-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)ethylaminopropylamino }ethyl)-1H-quinazoline-2,4-dione;
3-(3-{3-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminopropylamino}propyl)-1H-quinazoline-2,4-dione;
3-(3-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylamino-2-butenylamino}propyl)-1H-quinazoline-2,4-dione;
(4-{tert-butoxycarbonyl- 3-(1-methyl-2,4-dioxo- 1,4-dihydro-2H-quinazolin-3-yl) propylamino}butyl)-3-(1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl) propylcarbamic acid tert-butyl ester;
1-methyl-3-(3-{4-3-(1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl) propylaminobutylamino}propyl)-1H-quinazoline-2,4-dione;
3-(3-{4-3-(1 ,3-dioxo-1,3-dihydro-isoindole-2-yl)propylaminobutylamino }propyl)-1 H-quinazoline-2,4-dione;
3-(3-{2-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminoethylamino}propyl)-1H-quinazoline-2,4-dione;
3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-(4-{3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylhexylamino }butyl)carbamic acid tert-butyl ester;
3-3-(4-{N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-N-hexylamino}butylamino)propyl-1H-quinazoline-2,4-dione;
(4-{tert-butoxycarbonyl-3-(1-hexyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylamino}butyl)-3-(1-hexyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylcarbamic acid tert-butyl ester;
1-hexyl-3-(3-{4-3-(1-hexyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl) propylaminobutylamino}propyl)-1H-quinazoline-2,4-dione;
3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-(4-{3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylheptanoylamino }butyl)carbamic acid tert-butyl ester;
3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminobutyl}heptanoic amide;
N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-N-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminobutyl}-2,2,2-trifluoroacetamide;
N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-N-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-(2,2,2-trifluoroacetyl)aminobutyl}-2,2,2-trifluoroacetamide;
N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-N-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminobutyl}-2-methoxyacetamide;
3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminobutyl}carbamic acid benzyl ester;
N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-N-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminobutyl}-4-methylbenzenesulfonamide;
N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-N-(4-{3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-4-methylbenzenesulfonylamino }butyl)-4-methylbenzenesulfonamide; and
3-(3-{4 3-(2,5-dioxo-pyrrolidine-1-yl)propylaminobutylamino }propyl)-1H-quinazoline-2,4-dione,
or a pharmaceutically acceptable salt thereof
7. The method of claim 1 wherein the compound is N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-N-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminobutyl}acetamide, or a pharmaceutically acceptable salt thereof.
8. The method of claim 1 wherein the compound is 3-{4-3-(2,4-dioxo-1,4 -dihydro-2H-quinazolin-3-yl)propylaminobutyl}-1H-quinazoline-2,4-dione, or a pharmaceutically acceptable salt thereof.
9. The method of claim 1 wherein the compound is 3-{3 4-({N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-N-benzyl}amino)butylaminopropyl}-1H- quinazoline-2,4-dione, or a pharmaceutically acceptable salt thereof.
10. The method of claim 1 wherein the compound is N-3-(acetyl-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminobutyl}amino)propyl-4-hydroxybenzamide, or a pharmaceutically acceptable salt thereof
11. The method of claim 1 wherein the compound is N-3-(4-{acetyl-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylamino}butylamino)propyl-4-hydroxybenzamide, or a pharmaceutically acceptable salt thereof.
12. The method of claim 1 wherein the compound is 3-(2-{3-2-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)ethylaminopropylamino}ethyl)-1H-quinazoline-2,4-dione, or a pharmaceutically acceptable salt thereof.
13. The method of claim 1 wherein the compound is 3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-(4-{3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylhexylamino} butyl) carbamic acid tert-butyl ester, or a pharmaceutically acceptable salt thereof.
14. The method of claim 1 wherein the compound is 3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminobutyl}carbamic acid benzyl ester, or a pharmaceutically acceptable salt thereof.
15. The method of claim 1 wherein the compound is N-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl-N-{4-3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylaminobutyl}-4-methylbenzenesulfonamide, or a pharmaceutically acceptable salt thereof.