1. A longitudinal magnetic recording medium having improved thermal stability and signal-to-medium noise ratio (\u201cSMNR\u201d), comprising:
(a) a non-magnetic substrate having at least one surface;
(b) a layer stack overlying said at least one surface, said layer stack comprising a plurality of vertically spaced-apart ferromagnetic layers, each vertically adjacent pair of said ferromagnetic layers being spaced-apart by a respective non-magnetic spacer layer, wherein:
(i) at least one of said plurality of vertically adjacent, spaced-apart pairs of ferromagnetic layers forms an anti-ferromagnetically coupled media (\u201cAFC\u201d) component of said magnetic recording medium, said AFC component comprising an upper and lower ferromagnetic layer wherein the lower ferromagnetic layer has a thickness less than that of the upper ferromagnetic layer; and
(ii) at least one of said plurality of vertically adjacent, spaced-apart pairs of ferromagnetic layers forms a laminated media (\u201cLM\u201d) component of said magnetic recording medium; and
(c) a protective overcoat layer directly on an upper surface of the uppermost ferromagnetic layer of said LM component.
2. The magnetic recording medium as in claim 1, wherein:
said at least one LM component (ii) is positioned in said layer stack (b) above said at least one AFC component (i).
3. The magnetic recording medium as in claim 1, wherein:
the thickness of the non-magnetic spacer layer of said at least one AFC component (i) is such that the anti-ferromagnetic coupling between the respective pair of vertically spaced-apart ferromagnetic layers are maximized; and
the thickness of the non-magnetic spacer layer of said at least one LM component (ii) is such that the energy of any magnetic coupling between the respective pair of vertically spaced-apart ferromagnetic layers is smaller than the magnetic energy of the magnetic grains in said ferromagnetic layers.
4. The magnetic recording medium as in claim 3, wherein:
the thickness of said non-magnetic spacer layer of said AFC component (i) is in the range from about 2 to about 20 \u212b; and
the thickness of said non-magnetic spacer layer of said LM component (ii) is in the range from about 4 to about 40 \u212b.
5. The magnetic recording medium as in claim 4, wherein:
the thickness of said non-magnetic spacer layer of said AFC component (i) is in the range from about 5 to about 10 \u212b; and
the thickness of said non-magnetic spacer layer of said LM component (ii) is in the range from about 10 to about 30 \u212b.
6. The magnetic recording medium as in claim 3, wherein:
each of said non-magnetic spacer layers comprises a material selected from the group consisting of Ru, Rh, Ir, Cr, Cu, Re, V, and their alloys.
7. The magnetic recording medium as in claim 3, further comprising: a ferromagnetic interface layer at at least one interface between the non-magnetic spacer layer and the respective pair of vertically spaced-apart ferromagnetic layers of said at least one AFC component (i) for increasing the coupling between the ferromagnetic layers.
8. The magnetic recording medium as in claim 7, wherein:
each of said ferromagnetic interface layers comprises an about 1 monolayer thick to an about 40 \u212b thick layer of a ferromagnetic material having a saturation magnetization value Ms>400 emucc.
9. The magnetic recording medium as in claim 8, wherein:
each of said ferromagnetic interface layers comprises at least one of Co and Fe or their alloys with at least one of Pt, Cr, B, Ni, Ru, Mo, Si, Ge, Nb, and Ta, wherein the concentration(s) of the at least one of Co and Fe in the alloy is (are) constant or varies (vary) across the thickness of the interface layer(s) from high near an interface with the non-magnetic spacer layer to low near an interface with a respective ferromagnetic layer.
10. The magnetic recording medium as in claim 1, wherein:
the thickness of the lower ferromagnetic layer of said at least one AFC component (i) proximal said at least one surface of said substrate (a) is in the range from about 2 to about 80 \u212b; and
the thickness of the upper ferromagnetic layer of said at least one AFC component (i) and of each of the pair of vertically spaced-apart ferromagnetic layers of said at least one LM component (ii) is in the range from about 30 to about 200 \u212b.
11. The magnetic recording medium as in claim 10, wherein:
each of said plurality of vertically adjacent, spaced-apart pairs of ferromagnetic layers of said layer stack (b) comprises a CoCr alloy or a CoCr alloy with at least one additional element selected from the group consisting of Pt, Ta, B, Mo, Ru, Si, Ge, Nb, Fe, and Ni.
12. The magnetic recording medium as in claim 1, further comprising:
(d) seed and underlayers between said at least one surface of said non-magnetic substrate (a) and said layer stack (b) for controlling the crystallographic texture of said ferromagnetic layers; and
(e) a lubricant topcoat layer provided on an upper surface of said protective overcoat.
13. The magnetic recording medium as in claim 10, wherein:
said seed layer is from about 10 to about 1,000 \u212b thick and comprises an amorphous or fine-grained material selected from the group consisting of Ni\u2014Al, Fe\u2014Al, Cr\u2014Ti, Cr\u2014Ta, Ta, Ta\u2014W, Ru\u2014Al, Co\u2014Ti, and TaN; and
said underlayer is from about 10 to about 300 \u212b thick and comprises a polycrystalline layer of Cr or a Cr-based alloy.
14. The magnetic recording medium as in claim 1, wherein said LM component of said magnetic recording medium comprises at least one single ferromagnetic layer that is not anti-ferromagnetically coupled with an adjacent ferromagnetic layer.
15. A method of forming a magnetic recording medium having improved thermal stability and signal-to-media noise ratio (\u201cSMNR\u201d), comprising steps of:
(a) providing a non-magnetic substrate having at least one surface adapted for layer formation thereover;
(b) forming a layer stack overlying said at least one surface, said layer stack comprising a plurality of vertically spaced-apart ferromagnetic layers, vertically adjacent pairs of said ferromagnetic layers being spaced-apart by respective non-magnetic spacer layers, wherein:
at least one of said plurality of vertically adjacent, spaced-apart pairs of ferromagnetic layers forms an anti-ferromagnetically coupled media (\u201cAFC\u201d) component of said magnetic recording medium, said AFC component comprising an upper and lower ferromagnetic layer wherein the lower ferromagnetic layer has a thickness less than that of the upper ferromagnetic layer; and
at least one of said plurality of vertically adjacent, spaced-apart pairs of ferromagnetic layers forms a laminated media (\u201cLM\u201d) component of said magnetic recording medium; and
(c) providing a protective overcoat layer directly on an upper surface of the uppermost ferromagnetic layer of said LM component.
16. The method according to claim 15, wherein step (b) comprises:
(b1) forming said layer stack such that said at least one LM component is positioned in said layer stack above said at least one AFC component;
(b2) forming the non-magnetic spacer layer of said at least one AFC component at a thickness such that the anti-ferromagnetic coupling between the respective pair of vertically spaced-apart ferromagnetic layers are maximized; and
(b3) forming the non-magnetic spacer layer of said at least one LM component at a thickness such that the energy of any magnetic coupling between the respective pair of vertically spaced-apart ferromagnetic layers is smaller than the magnetic energy of the magnetic grains in said ferromagnetic layers.
17. The method according to claim 16, wherein step (b) comprises:
(b2) forming said non-magnetic spacer layer of said AFC component at a thickness in the range from about 2 to about 20 \u212b; and
(b3) forming said non-magnetic spacer layer of said LM component at a thickness in the range from about 4 to about 40 \u212b, wherein:
each of said non-magnetic spacer layers of said layer stack comprises a material selected from the group consisting of Ru, Rh, Ir, Cr, Cu, Re, V, and their alloys.
18. The method according to claim 16, wherein step (b) further comprises:
(b4) forming a ferromagnetic interface layer at at least one interface between the non-magnetic spacer layer and the respective pair of vertically spaced-apart ferromagnetic layers of said at least one AFC component for increasing the RKKY-type coupling between the ferromagnetic layers, wherein:
each of said ferromagnetic interface layers comprises an about 1 monolayer thick to an about 40 \u212b thick layer of a ferromagnetic material having a saturation magnetization value Ms>400 emucc, said ferromagnetic material comprising at least one of Co and Fe or their alloys with at least one of Pt, Cr, B, Ni, Ru, Mo, Si, Ge, Nb, and Ta, wherein the concentration(s) of the at least one of Co and Fe in the alloy is (are) constant or varies (vary) across the thickness of the interface layer(s) from high near an interface with the non-magnetic spacer layer to low near an interface with a respective ferromagnetic layer.
19. The method according to claim 15, wherein step (b) comprises:
(b5) forming the lower ferromagnetic layer of said at least one AFC component proximal said at least one surface of said substrate at a thickness in the range from about 2 to about 80 \u212b; and
(b6) forming the upper ferromagnetic layer of said at least one AFC component and each of the pair of vertically spaced-apart ferromagnetic layers of said at least one LM component at a thickness in the range from about 30 to about 200 \u212b; wherein:
each of said plurality of vertically adjacent, spaced-apart pairs of ferromagnetic layers of said layer stack comprises a CoCr alloy or a CoCr alloy with at least one additional element selected from the group consisting of Pt, Ta, B, Mo, Ru, Si, Ge, Nb, Fe, and Ni.
20. The method according to claim 15, further comprising steps of:
(d) forming seed and underlayers between said at least one surface of said non-magnetic substrate and said layer stack for controlling the crystallographic texture of said ferromagnetic layers; and
(e) forming a lubricant topcoat layer on an uppermost surface of said protective overcoat layer; wherein:
said seed layer is formed at a thickness from about 10 to about 1,000 \u212b and comprises an amorphous or fine-grained material selected from the group consisting of Ni\u2014Al, Fe\u2014Al, Cr\u2014Ti, Cr\u2014Ta, Ta, Ta\u2014W, Ru\u2014Al, Co\u2014Ti, and TaN; and
said underlayer is formed at a thickness from about 10 to about 300 \u212b and comprises a polycrystalline layer of Cr or a Cr-based alloy.
21. The magnetic recording medium as in claim 15, wherein said LM component of said magnetic recording medium comprises at least one single ferromagnetic layer that is not anti-ferromagnetically coupled with an adjacent ferromagnetic layer.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
What is claimed is:
1. An imidazole derivative represented by the following formula (1):
222
in which
n1 represents an integer of 1 to 4,
A represents hydrogen; straight-chain or branched C1-C10-alkyl which may be optionally substituted by C3-C7-cycloalkyl or lower alkoxy; or a radical selected from the following group:
223
wherein
R1 and R1 independently of one another represent hydrogen, halogen, cyano, nitro, hydroxycarbonyl, aminocarbonyl, aminothiocarbonyl, lower alkoxy, phenoxy, phenyl, benzyloxy, or lower alkyl which may be optionally substituted by C3-C6-cycloalkyl,
R2 represents hydrogen or lower alkyl, or represents -E-F wherein E is CH2, C(O) or S(O)2 and F is hydrogen; lower alkyl which may be optionally substituted by phenoxy or biphenyl; lower alkoxy which may be optionally substituted by aryl; phenyl; benzyl; benzyloxy; or amino which may be optionally substituted by lower alkyl, benzyl or C5-C6-cycloalkyl,
R3 represents hydrogen, lower alkyl or phenyl,
R4 represents a radical selected from the following group:
224
wherein
n2 and n3 independently of one another denote 0, 1, 2, 3 or 4,
R5 and R9 independently of one another represent hydrogen, lower alkyl, lower alkoxy, phenoxy, phenyl, hydroxy or halogen,
R6 and R8 independently of one another represent hydrogen, lower alkyl, lower alkoxy, phenoxy, phenyl, cyano, hydroxy or halogen,
R7 represents hydrogen; lower alkyl which may be optionally substituted by C3-C6-cycloalkyl; lower alkoxy; hydroxy; C3-C6-cycloalkyl; di(lower alkyl)amino; phenyl; phenoxy; or halogen,
R10 represents hydrogen, lower alkyl or lower alkoxy,
Y represents a radical selected from the following group:
225
wherein
X represents O or S,
B represents hydrogen, or lower alkyl which may be optionally substituted by hydroxy, mercapto, lower alkoxy, lower alkylthio or aryl,
C represents hydrogen, or lower alkyl which may be optionally substituted by aryl; or represents a radical selected from the following group:
226
wherein
R11 and R12 independently of one another represent hydrogen, lower alkyl, lower alkoxy, halogen, cyano, hydroxycarbonyl, aminocarbonyl, aminothiocarbonyl, hydroxy, phenyl or phenoxy,
R13 and R14 independently of one another represent hydrogen, lower alkyl, aryl or
227
wherein X is defined as previously described, n4 is an integer of 2 to 4 and R15 is lower alkyl,
D represents amino acid residue or lower alkyl ester of amino acid residue; or represents a radical selected from the following group:
228
wherein
R10 is defined as previously described,
Q represents O, S, SO or SO2,
Z represents O, S, SO, SO2, CO or CS, or represents CHR20 or NR20(wherein R20 is hydrogen, lower alkyl or hydroxy),
n5 denotes an integer of 1 to 3,
R16 and R17 independently of one another represents hydrogen; aryl; lower alkyl which may be optionally substituted by aryl or cyanoaryl; or
229
wherein n4, Q and R10 are defined as previously described,
R18 and R19 independently of one another represents hydrogen; halogen; hydroxy; cyano; lower alkyl; lower alkoxy; alkoxyalkyl; alkylthio; hydroxycarbonyl; aminocarbonyl; aminothiocarbonyl; alkylsulfonyl; alkylthioalkyl; alkylthioalkyloxy; aryl; or oxy, thio, sulfonyl or lower alkyl substituted by aryl,
G represents a radical selected by the following group:
230
wherein
R11 and R12 are defined as previously described,
I represents lower alkoxy, or represents a radical selected from the following group:
231
wherein
R16, R17 and Z are defined as previously described,
L represents a radical selected from the following group:
232
wherein Z and Q are defined as previously described,
provided that (1) n2 is other than 0 when R3 is hydrogen, and (2) Y is other than
233
when A is
234
or a pharmaceutically acceptable salt or isomer thereof.
2. The compound of claim 1 wherein
n1 represents an integer of 1 to 3,
A represents hydrogen; straight-chain or branched C1-C10-alkyl which may be optionally substituted by C3-C7-cycloalkyl or lower alkoxy; or a radical selected from the following group:
235
wherein
R1 and R1 independently of one another represent hydrogen, halogen, cyano, nitro, hydroxycarbonyl, aminocarbonyl, aminothiocarbonyl, lower alkoxy, phenoxy, phenyl, benzyloxy, or lower alkyl which may be optionally substituted by C3-C6-cycloalkyl,
R2 represents hydrogen or lower allyl, or represents -E-F wherein E is CH2, C(O) or S(O)2 and F is hydrogen; lower alkyl which may be optionally substituted by phenoxy or biphenyl; lower alkoxy which may be optionally substituted by aryl; phenyl; benzyl; benzyloxy; or amino which may be optionally substituted by lower alkyl, benzyl or C5-C6-cycloalkyl,
R3 represents hydrogen or lower alkyl,
R4 represents a radical selected from the following group:
236
wherein
n2 and n3 independently of one another denote 0, 1, 2, 3 or 4,
R5, R6, R8 and R9 independently of one another represent hydrogen, lower alkyl, lower alkoxy, hydroxy or halogen,
R7 represents hydrogen; lower alkyl which may be optionally substituted by C3-C6-cycloalkyl; lower alkoxy; hydroxy; C3-C6-cycloalkyl; or halogen,
R10 represents hydrogen, methyl or methoxy,
Y represents a radical selected from the following group:
237
wherein
X represents O or S,
B represents hydrogen, or lower alkyl which may be optionally substituted by lower alkoxy or aryl,
C represents hydrogen, or lower alkyl which may be optionally substituted by aryl; or represents a radical selected from the following group:
238
wherein
R11 and R12 independently of one another represent hydrogen, lower alkyl, lower alkoxy, halogen, cyano, aminocarbonyl, phenyl or phenoxy,
R13 and R14 independently of one another represent hydrogen, lower alkyl, aryl or
239
wherein X is defined as previously described, n4 is 2 and R15 is lower alkyl,
D represents amino acid residue or lower alkyl ester of amino acid residue; or represents a radical selected from the following group:
240
wherein
R10 is defined as previously described,
Q represents O, S, SO or SO2,
Z represents O, S, SO, SO2 or CO, or represents CHR20 or NR20 (wherein R20 is hydrogen, lower alkyl or hydroxy),
n5 denotes an integer of 1 to 3,
R16 and R17 independently of one another represents hydrogen; aryl; lower alkyl which may be optionally substituted by aryl or cyanoaryl; or
241
wherein n4, Q and R10 are defined as previously described,
R8 and R19 independently of one another represents hydrogen; halogen; hydroxy; cyano; lower alkyl; lower alkoxy; alkoxyalkyl; alkylthio; hydroxycarbonyl; aminocarbonyl; aminothiocarbonyl; alkylsulfonyl; alkylthioalkyl; alkylthioalkyloxy; aryl; or oxy, thio, sulfonyl or lower alkyl substituted by aryl,
G represents a radical selected by the following group:
242
wherein
R11 and R12 are defined as previously described,
I represents lower alkoxy, or represents a radical selected from the following group:
243
wherein
R16, R17 and Z are defined as previously described,
L represents a radical selected from the following group:
244
wherein Z and Q are defined as previously described,
provided that (1) n2 is other than 0 when R3 is hydrogen, and (2) Y is other than
245
when A is
246
3. The compound of claim 1 wherein Y represents
247
and C represents
248
4. The compound of claim 1 which is selected from a group consisting of:
3–(2-methoxyethyl)-N-methylcarbamoyl-1-1-(3,4-methylenedioxybenzyl)-1H-imidazol-5-ylmethyl-4-(naphthalen-1-yl)-1H-pyrrole(1),
1-1-(3,4-methylenedioxybenzyl)-1H-imidazol-5-ylmethyl-3-(morpholin-4-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(2),
1-1-(3,4-methylenedioxybenzyl)-1H-imidazol-5-ylmethyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(3),
3-N-2-(N,N-dimethylamino)ethyl-N-methylcarbamoyl-1-1-(3,4-methylendioxybenzyl)-1H-imidazol-5-ylmethyl-4-(naphthalen-1-yl)-1H-pyrrole(4),
3-N-(2-methoxyethyl)-N-methylcarbamoyl)-4-naphthalen-1-yl)-1-1-naphthalen-1-ylmethyl)-1H-imidazol-5-ylmethyl-1H-pyrrole(5),
3-(morpholin-4-yl)carbonyl-4-(naphthalen-1-yl)-1-1-naphthalen-1-ylmethyl)-1H -imidazol-5-ylmethyl-1H-pyrrole(6),
3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalen-1-yl)-1-1-(naphthalen-1-ylmethyl)-1H-imidazol-5-ylmethyl-1H-pyrrole(7),
3-N-(2-methoxyethyl)-N-methylcarbamoyl-1-1-((R)–methylbenzyl)-1H-imidazol-5-ylmethyl-4-(naphthalen-1-yl)-1H-pyrrole(8),
1-1-((R)–methylbenzyl)-1H-imidazol-5-ylmethyl-3-(morpholin-4-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(9),
1-1-((R)–methylbenzyl)-1H-imidazol-5-ylmethyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(10),
3-N-(2-methoxyethyl)-N-methylcarbamoyl-1-1-((S)–methylbenzyl)-1H-imidazol-5-ylmethyl-4-(naphthalen-1-yl)-1H-pyrrole(1H),
1-1-((S)–methylbenzyl)-1H-imidazol-5-ylmethyl-3-(morpholin-4-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(12),
1–((S)–methylbenzyl)-1H-imidazol-5-ylmethyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(13),
3-N-(2-methoxyethyl)-N-methylcarbamoyl)-4-(naphthalen-1-yl)-1-1-(phenethyl)-1H-imidazol-5-ylmethyl-1H-pyrrole(14),
3-(morpholin-4-yl)carbonyl-4-(naphthalen-1-yl)-1-l-(phenethyl)-1H-imidazol-5-ylmethyl-1H-pyrrole(15),
3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalen-1-yl)-1-1-(phenethyl)-1H-imidazol-5-ylmethyl)-1H-pyrrole(16),
3-N-(2-methoxyethyl)-N-methylcarbamoyl-1-1-(2-methoxy)phenethyl-1H-imidazol-5-ylmethyl-4-(naphthalen-1-yl)-1H-pyrrole(17),
1-1-(2-methoxy)phenethyl-1H-imidazol-5-ylmethyl-3-4-methylpiperazin-1-ylcarbonyl-4-(naphthalen-1-yl)-1H-pyrrole(18),
3-N-(2-methoxyethyl)-N-methylcarbamoyl-1-1-(4-methoxy)phenethyl-1H-imidazol-5-ylmethyl-4-(naphthalen-1-yl)-1H-pyrrole(19),
1-1-(4-methoxy)phenethyl-1H-imidazol-5-ylmethyl-3-4-methylpiperazin-1-ylcarbonyl-4-(naphthalen-1-yl)-1H-pyrrole(20),
1-1-(2-fluoro)phenethyl-1H-imidazol-5-ylmethyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(21),
1-1-(2-fluoro)phenethyl-1H-imidazol-5-ylmethyl-3-4-methylpiperazin-1-ylcarbonyl-4-(naphthalen-1-yl)-1H-pyrrole(22),
1–(2-chloro)phenethyl-1H-imidazol-5-ylmethyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(23),
1-1-(2-chloro)phenethyl-1H-imidazol-5-ylmethyl-3-4-methylpiperazin-1-ylcarbonyl-4-(naphthalen-1-yl)-1H-pyrrole(24),
1-1-(3-chloro)phenethyl-1H-imidazol-5-ylmethyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(25),
1-1-(3-chloro)phenethyl-1H-imidazol-5-ylmethyl-3-4-methylpiperazin-1-ylcarbonyl-4-(naphthalen-1-yl)-1H-pyrrole(26),
3-N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1-1-(3-phenyl)propyl-1H-imidazol-5-ylmethyl-1H-pyrrole(27),
3-4-methylpiperazin-1-ylcarbonyl-4-naphthalen-1-yl)–1-(3-phenyl)propyl-1H-imidazol-5-ylmethyl-1H-pyrrole(28),
3-N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1-1-(naphthalen-2-yl)methyl-1H-imidazol-5-ylmethyl-1H-pyrrole(29),
3-4-methylpiperazin-1-ylcarbonyl-4-(naphthalen-1-yl)-1-1-naphthalen-2-yl)methyl-1H-imidazol-5-ylmethyl-1H-pyrrole(30),
3-N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1-1-2-(naphthalen-1-yl)ethyl-1H-imidazol-5-ylmethyl-1H-pyrrole(31),
3-4-methylpiperazin-1-ylcarbonyl-4-(naphthalen-1-yl)-1-1-2-(naphthalen-1-yl)ethyl-1H-imidazol-5-ylmethyl-1H-pyrrole(32),
1-1-(4-bromo)phenethyl-1H-imidazol-5-ylmethyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(33),
1-1-(4-bromo)phenethyl-1H-imidazol-5-ylmethyl-3-4-methylpiperazin-1-ylcarbonyl-4-(naphthalen-1-yl)-1H-pyrrole(34),
1-1-(4-fluoro)phenethyl-1H-imidazol-5-ylmethyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl)-4-(naphthalen-1-yl)-1H-pyrrole(35),
1-1-(4-fluoro)phenethyl-1H-imidazol-5-ylmethyl-3-4-methylpiperazin-1-ylcarbonyl-4-(naphthalen-1-yl)-1H-pyrrole(36),
3-N-(2-methoxyethyl)-N-methylcarbamoyl-1-1-(4-methyl)phenethyl-1H-imidazol-5-ylmethyl-4-(naphthalen-1-yl)-1H-pyrrole(37),
1-1-(4-methyl)phenethyl-1H-imidazol-5-ylmethyl-3-4-methylpiperazin-1-ylcarbonyl-4-(naphthalen-1-yl)-1H-pyrrole(38),
1–(4-chloro)phenethyl-1H-imidazol-5-ylmethyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(39),
1-1-(4-chloro)phenethyl-1H-imidazol-5-ylmethyl-3-4-methylpiperazin-1-ylcarbonyl-4-(naphthalen-1-yl)-1H-pyrrole(40),
3-N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1-1-2-(naphthalen-2-yl)ethyl-1H-imidazol-5-ylmethyl-1H-pyrrole(41),
3-4-methylpiperazin-1-ylcarbonyl-4-(naphthalen-1-yl)-1-1-2-(naphthalen-2-yl)ethyl-1H-imidazol-5-ylmethyl-1H-pyrrole(42),
1-1-(4-hydroxy)phenethyl-1H-imidazol-5-ylmethyl-3-4-methylpiperazin-1-ylcarbonyl-4-(naphthalen-1-yl)-1H-pyrrole(43),
1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-3-(thiophen-2-yl)carbonyl-1H-pyrrole(44),
1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-3-(thiophen-3-yl)carbonyl-1H-pyrrole(45),
3-benzoyl-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(46),
3-(2-bromobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(47),
3-(3-bromobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(48),
3-(4-bromobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(49),
1-(1H-imidazol-4-yl)methyl-3-(2-methylbenzoyl)-4-naphthalen-1-yl)-1H-pyrrole(50),
1-(1H-imidazol-4-yl)methyl-3-(3-methylbenzoyl)-4-(naphthalen-1-yl)-1H-pyrrole(51),
1-(1H-imidazol-4-yl)methyl-3-(4-methylbenzoyl)-4-(naphthalen-1-yl)-1H-pyrrole(52),
1-(1H-imidazol-4-yl)methyl-3-(3-methoxybenzoyl)-4-(naphthalen-1-yl)-1H-pyrrole(53),
1-(1H-imidazol-4-yl)methyl-3-(4-methoxybenzoyl)-4-(naphthalen-1-yl)-1H-pyrrole(54),
3-(2-chlorobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(55),
3-(4-chlorobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(56),
3-(2,4-dichlorobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(57),
3-(4-fluorobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(58),
3-(2,4-difluorobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(59),
3-(4-cyanobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(60),
1-(1H-imidazol-4-yl)methyl-3-(4-methylthiomethyl-benzoyl)-4-(naphthalen-1-yl)-1H-pyrrole(61),
1-(1H-imidazol-4-yl)methyl-3-4-(2-methylthioethyl)benzoyl-4-(naphthalen-1-yl)-1H-pyrrole(62),
1-(1H-imidazol-4-yl)methyl-3-4-(2-methylthioethoxy)benzoyl-4-(naphthalen-1-yl)-1H-pyrrole(63),
1-(1H-imidazol-4-yl)methyl-3-(3-methylthiomethyl-benzoyl)-4-(naphthalen-1-yl)-1H-pyrrole(64),
1-(1H-imidazol-4-yl)methyl)-4-(naphthalen-1-yl)-3-(3-phenylbenzoyl)-1H-pyrrole(65),
1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-3-(4-phenylbenzoyl)-1H-pyrrole(66),
1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-3-(4-phenoxybenzoyl)-1H-pyrrole(67),
3-(4-benzylbenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(68),
1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-3-(naphthalen-1-yl)carbonyl-1H-pyrrole(69),
1-(1H-imidazol-4-yl)methyl-3-(4-methylbenzoyl)-4-(N-methylindol-3-yl)-1H-pyrrole(70),
5-n-butyl-3-(2,4-dichlorobenzoyl)-1-(1H-imidazol)methyl-4-(naphthalen-1-yl)-1H-pyrrole(71),
5-benzyl-3-(2,4-dichlorobenzoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(72),
1-1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl-4-(naphthalen-1-yl)-3-(thiophen-2-yl)carbonyl-1H-pyrrole(73),
1-1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl-4-(naphthalen-1-yl)-3-(thiophen-3-yl)carbonyl-1H-pyrrole(74),
3-benzoyl-1-1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl-4-(naphthalen-1-yl)-1H-pyrrole(75),
3-(3-bromobenzoyl)-1-1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl-4-(naphthalen-1-yl)-1H-pyrrole(76),
3-(4-bromobenzoyl)-1-1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl(naphthalen-1-yl)-1H-pyrrole(77),
3-(4-fluorobenzoyl)-1-(1-methyl-1H-imidazol-4-yl)methyl-4naphthalen-1-yl)-1H-pyrrole(78),
1-(1-methyl-1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-3-(4-phenoxybenzoyl)-1H-pyrrole(79),
(S)-1-(1H-imidazol-4-yl)methyl-3-N-(1-methoxycarbonyl-3-methylthio)propylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(80),
(S)-3-N-(1-hydroxycarbonyl-3-methylthio)propylcarbamoyl-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(81),
1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-3-(N-phenylcarbamoyl)-1H-pyrrole(82),
3-(N-benzylcarbamoyl)-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(83),
1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-3-(piperidin-1-yl)carbonyl-1H-pyrrole(84),
1-(1H-imidazol-4-yl)methyl-3-(morpholin-4-yl)carbonyl-4-(naphthalen-1-yl)-H-pyrrole(85),
1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-3-(thiomorpholin-4-yl)carbonyl)-1H-pyrrole(86),
1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-3-(S,S -dioxothiomorpholin-4-yl)carbonyl-1H-pyrrole(87),
1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-3-(piperazin-1-yl)carbonyl-1H-pyrrole(88),
1-(1H-imidazol-4-yl)methyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(89),
1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-3-(thiazolidin-3-yl)carbonyl-1H-pyrrole(90),
3-(4-hydroxypiperidin-1-yl)carbonyl-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(91),
1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-3-(4-oxopiperidin-1-yl)carbonyl-1H-pyrrole(92),
3-N-(2-hydroxyethyl)carbamoyl-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(93),
3-N-(2-hydroxyethyl)-N-methylcarbamoyl-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(94),
1-(1H-imidazol-4-yl)methyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(95),
1-(1H-imidazol-4-yl)methyl-3-(morpholin-4-yl)carbonyl-4-(quinolin-4-yl)-1H-pyrrole(96),
4-(1,2-dihydroacenaphthylen-5-yl)-1-(1H-imidazol-4-yl)methyl-3-(morpholin-4-yl)carbonyl-1H-pyrrole(97),
3-N-(4-cyanobenzyl)carbamoyl-1-(1H-imidazol-4-yl)methyl-4-(naphthalen-1-yl)-1H-pyrrole(98),
1-(1-methyl-1H-imidazol-5-yl)methyl-3-(morpholin-4-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(99),
(S)-1-1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl-3-N-(1-methoxycarbonyl-3-methylthio)propylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(100),
(S)-1-1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl-3-N-(1-hydroxycarbonyl-3-methylthio)propylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(101),
(S)-1-1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl-3-N-(1-methyoxycarbonyl-3-methyl)butylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(102),
(S)-1-1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl-3-N-(1-hydroxycarbonyl-3-methyl)butylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(103)
1-1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl-3-(morpholin-4-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(104),
1-1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(105),
1-2-(1H-imidazol-1-yl)ethyl-3-(morpholin-4-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(106),
(S)-1-3-(1H-imidazol-4-yl)propyl-3-N-(1-methoxycarbonyl-3-methylthio)propylcarbamoyl)-4-(naphthalen-1-yl)-1H-pyrrole(107),
(S)-3-N-(1-hydroxycarbonyl-3-methylthio)propylcarbamoyl-1-3-(1H-imidazol-4-yl)propyl-4-(naphthalen-1-yl)-1H-pyrrole(108),
1-3-(1H-imidazol-4-yl)propyl-3-(morpholin-4-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(109),
1-1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl)-4-(naphthalen-1-yl)-1H-pyrrole(110),
1-1-(4-bromobenzyl)-1H-imidazol-5-ylmethyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(114),
1-1-(4-bromobenzyl)-1H-imidazol-5-ylmethyl-3-(morpholin-4-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(112),
1-1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl-3-(morpholin-4-yl)thiocarbonyl4-(naphthalen-1-yl)-1H-pyrrole(113),
3-N-(2-methoxyethyl)-N-methylcarbamoyl-1-(1-methyl-1H-imidazol-5-ylmethyl-4-(naphthalen-1-yl)-1H-pyrrole(114),
1-(1-isobutyl-1H-imidazol-5-yl)methyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(115),
1-(1-cyclohexylmethyl-1H-imidazol-5-yl)methyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(116),
3-N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1-(1-pentyl-1H-imidazol-5-yl)methyl-1H-pyrrole(117),
3-N-(2-methoxyethyl)-N-methylcarbamoyl)-4-(naphthalen-1-yl)-1-(1-octyl-1H-imidazol-5-yl)methyl-1H-pyrrole(118),
1-(1-decyl-1H-imidazol-5-yl)methyl-3-(N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(119),
3-N-(2-methoxyethyl)-N-methylcarbamoyl-1-1-(3-methylbutyl)-1H-imidazol-5-ylmethyl-4-(naphthalen-1-yl)-1H-pyrrole(120),
1-1-(2-methoxyethyl)-1H-imidazol-5-ylmethyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl)-4-(naphthalen-1-yl)-1H-pyrrole(121),
3-N-(2-methoxyethyl)-N-methylcarbamoyl-1-1-(3-methoxypropyl)-1H-imidazol-5-ylmethyl-4-(naphthalen-1-yl)-1H-pyrrole(122),
1-1-(3-ethoxypropyl)-1H-imidazol-5-ylmethyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl)-4-(naphthalen-1-yl)-1H-pyrrole(123),
1-1-(3-isopropoxypropyl)-1H-imidazol-5-ylmethyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(124),
1-1-(4-bromobenzyl)-1H-imidazol-5-ylmethyl-3-4-methylpiperazin-1-ylcarbonyl-4-(naphthalen-1-yl)-1H-pyrrole(125),
1–(4-chlorobenzyl)-1H-imidazol-5-ylmethyl-3-4-methylpiperazin-1-ylcarbonyl)-4-(naphthalen-1-yl)-1H-pyrrole(126),
1-1-(4-fluorobenzyl)-1H-imidazol-5-ylmethyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(127),
1-1-(4-fluorobenzyl)-1H-imidazol-5-ylmethyl-3-4-methylpiperazin-1-ylcarbonyl-4-(naphthalen-1-yl)-1H-pyrrole(128),
1-1-(4-methoxybenzyl)-1H-imidazol-5-ylmethyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl)-4-(naphthalen-1-yl)-1H-pyrrole(129),
1-1-(4-methoxybenzyl)-1H-imidazol-5-ylmethyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(130),
1-1-(3-chlorobenzyl)-1H-imidazol-5-ylmethyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(131),
1-1-(3-chlorobenzyl)-1H-imidazol-5-ylmethyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl)-4-(naphthalen-1-yl)-1H-pyrrole(132),
1-1-(2-chlorobenzyl)-1H-imidazol-5-ylmethyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(133),
1-1-(2-chlorobenzyl)-1H-imidazol-5-ylmethyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl-4-(naphthalen-1-yl)-1H-pyrrole(134),
1-1-(2-fluorobenzyl)-1H-imidazol-5-ylmethyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(135),
1-1-(4-methylbenzyl)-1H-imidazol-5-ylmethyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(136),
1-1-(4-methylbenzyl)-1H-imidazol-5-ylmethyl-3-(morpholin-4-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(137),
1-1-(3-methylbenzyl)-1H-imidazol-5-ylmethyl-3-(4-methylpiperazin-1-yl)carbonyl-4-(naphthalen-1-yl)-1H-pyrrole(138),
1-1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl-3-(naphthalen-1-yl)carbonyl-1H-pyrrole(139),
1-1-(4-bromobenzyl)-1H-imidazol-5-ylmethyl-3-(naphthalen-1-yl)carbonyl-1H-pyrrole(140),
1-1-(4-bromobenzyl)-1H-imidazol-5-ylmethyl-3-N-(2-methoxyethyl)-N-methylcarbamoyl)-4-(naphthalen-1-yl)carbonyl-1H-pyrrole(141),
4-ethoxycarbonyl-2-(1H-imidazol-5-ylmethyl)-5-(naphthalen-1-yl)oxazole(142),
2-(1H-imidazol-5-ylmethyl)-4-(morpholin-4-yl)carbonyl-5-(naphthalen-1-yl)oxazole(143),
4-ethoxycarbonyl-2-(1H-imidazol-5-ylmethyl)-5-(naphthalen-1-yl)thiazole(144),
2-1-(4-chlorobenzyl)-1H-imidazol-5-ylmethyl4-methoxycarbonyl-5-(naphthalen-1-yl)thiazole(145),
2-1-(4-chlorobenzyl)-1H-imidazol-5-ylmethyl-4-(morpholin-4-yl)carbonyl-5-(naphthalen-1-yl)thiazole(146),
2-1-(4-chlorobenzyl)-1H-imidazol-5-ylmethyl-4-N-(2-methoxy)ethyl-N-methylcarbamoyl-5-(naphthalen-1-yl)thiazole(147),
2-1-(4-chlorobenzyl)-1H-imidazol-5-ylmethyl-5-methoxycarbonyl-4-(naphthalen-1-yl)thiazole(148),
2-1-(4-chlorobenzyl)-1H-imidazol-5-ylmethyl-5-(morpholin-4-yl)carbonyl-4-(naphthalen-1-yl)thiazole(149),
2-1-1-(benzyloxycarbonyl)piperidin-4-ylmethyl-1H-imidazol-5-ylmethyl-5-methoxycarbonyl-4-(naphthalen-1-yl)thiazole(150),
2-1-1-(benzyloxycarbonyl)piperidin-4-ylmethyl-1H-imidazol-5-ylmethyl-5-N-(2-methoxy)ethyl-N-methylcarbamoyl-4-(naphthalen-1-yl)thiazole(151),
1-1-(1-benzyloxycarbonyl-piperidin-4-ylmethyl)-1H-imidazol-5-ylmethyl-4-N-(2-methoxyethyl)-N-methylcarbamoyl-3-(naphthalen-1-yl)-1H-pyrazole(152),
1-1-(1-methoxycarbonylpiperidin-4-ylmethyl)-1H-imidazole-5-ylmethyl-4-N-(2-methoxyethyl)-N-methylcarbamoyl-3-(naphthalen-1-yl)-1H-pyrazole(153),
1–(4-bromobenzyl)-1H-imidazol-5-ylmethyl-4-N-(2-methoxyethyl)-N-methylcarbamoyl-3-(naphthalen-1-yl) 1H-pyrazole(154),
1-1-(4-chlorobenzyl)-1H-imidazol-5-ylmethyl-N-(2-methoxyethyl)-N-methylcarbamoyl-3-(naphthalen-1-yl)-1H-pyrazole(155),
1–(4-cyanobenzyl)-1H-imidazol-5-ylmethyl-4-N-(2-methoxyethyl)-N-methylcarbamoyl-3-(naphthalen-1-yl)-1H-pyrazole(156),
1-1-methyl-1H-imidazol-5-ylmethyl-4-N-(2-methoxyethyl)-N-methylcarbamoyl-3-(naphthalen-1-yl)-1H-pyrazole(157),
1-1-(1-benzyloxycarbonyl-piperidin-4-ylmethyl)-1H-imidazol-5-ylmethyl-4-(morpholin-4-yl)carbonyl-3-(naphthalen-1-yl)-1H-pyrazole(158),
1-1-(1-methoxycarbonylpiperidin-4-ylmethyl)-1H-imidazol-5-ylmethyl-4-(morpholin-4-yl)carbonyl-3(naphthalen-1-yl)-1H-pyrazole(159),
1-1-(4-bromobenzyl)-1H-imidazol-5-ylmethyl-4-(morpholin-4-yl)carbonyl-3-(naphthalen-1-yl)-1H-pyrazole(160),
1-1-(4-chlorobenzyl)-1H-imidazol-5-ylmethyl-4-(morpholin-4-yl)carbonyl-3-(naphthalen-1-yl)-1H-pyrazole(161),
1-1-(4-cyanobenzyl)-1H-imidazol-5-ylmethyl-4-(morpholin-4-yl)carbonyl-3-(naphthalen-1-yl)-1H-pyrazole(162), and
1-(1-methyl-1H-imidazol-5-ylmethyl)-4-(morpholin-4-yl)carbonyl-3-(naphthalen-1-yl)-1H-pyrazole(163).
5. A process for preparing an imidazole derivative of formula (1) as defined in claim 1 characterized in that
(a) a compound represented by the following formula (2):
249
wherein n1 is defined as claim 1 and Tr represents trityl, is reacted in a solvent in the presence of a base with a compound represented by the following formula (3):
250
wherein B, C, D and X are defined as claim 1, then the trityl group in the product thus obtained is eliminated in the presence of trifluoroacetic acid to produce a compound represented by the following formula (1a):
251
wherein n1, B, C, D and X are defined as claim 1; or
(b) a compound represented by the following formula (4):
252
wherein n1 and A are defined as claim 1, is reacted in a solvent in the presence of a base with the compound of formula (3) to produce a compound represented by the following formula (1b):
253
wherein n1, A, B, C, D and X are defined as claim 1, or
(c) a compound represented by the following formula (5):
254
is reacted in a solvent in the presence of a base with the compound of formula (3), the trityl group in the product thus obtained is eliminated in the presence of trifluoroacetic acid to produce a compound represented by the following formula (6):
255
wherein B, C, D and X are defined as claim 1, and then hydrogenation reaction is carried out to produce a compound represented by the following formula (1c):
256
wherein B, C, D and X are defined as claim 1; or
(d) a compound represented by the following formula (7):
257
wherein n1, A, B and C are defined as claim 1, is hydrolyzed to produce a compound represented by the following formula (8):
258
wherein n1, A, B and C are defined as claim 1, which is then reacted with a compound represented by the following formula (9):
HNR16R17 (9)
wherein R16 and R17 are defined as claim 1, in the presence of a coupling agent to produce a compound represented by the following formula (1d):
259
wherein n1, A, B, C, R16 and R17 are defined as claim 1; or
(e) the carbonyl group in a compound represented by the following formula (1e):
260
wherein n1, A, B, C and D are defined as claim 1, is converted into the thiocarbonyl group in the presence of a sulfurizing agent to produce a compound represented by the following formula (1f):
261
wherein n1, A, B, C and D are defined as claim 1; or
(f) a compound represented by the following formula (1g):
262
wherein B, C, D and X are defined as claim 1, is coupled in a solvent with a compound represented by the following formula (10);
R2T (10)
wherein R2 is defined as claim 1 and T represents hydroxy or reactive leaving group, to produce a compound represented by the following formula (1h):
263
wherein R2, B, C, D and X are defined as claim 1; or
(g) a compound represented by the following formula (11):
264
wherein A, G and I are defined as claim 1, is cyclized in an inert solvent to produce a compound represented by the following formula (1i):
265
wherein A, G and I are defined as claim 1; or
(h) the amide group in the compound of formula (11H) is converted into the thioamide group to produce a compound represented by the following formula (12):
266
wherein A, G and I are defined as claim 1, which is then cyclized in an inert solvent to produce a compound represented by the following formula (1j):
267
wherein A, G and I are defined as claim 1; or
(i) a compound represented by the following formula (13):
268
wherein A is defined as claim 1, is reacted in a solvent with a compound represented by the following formula (14a):
269
wherein G and I are defined as claim 1, to produce the compound of formula (1j); or
(j) the compound of formula (13) is reacted in a solvent with a compound represented by the following formula (14b):
270
wherein G and I are defined as claim 1, to produce a compound represented by the following formula (1k):
271
wherein A, G and I are defined as claim 1; or
(k) a compound represented by the following formula (1l):
272
wherein A and G are defined as claim 1 and I represents lower alkoxy, is hydrolyzed in the presence of a base and the product thus obtained is reacted in a solvent in the presence of a coupling agent with a compound represented by the following formula (15):
IH (15)
wherein I is identical with I except that lower alkoxy is not included, to produce a compound represented by the following formula (1m):
273
wherein A and G are defined as claim 1 and I are defined as above; or
(l) a compound represented by the following formula (16):
274
wherein A is defined as claim 1, is reacted in a solvent in the presence of a base with a compound represented by the following formula (17):
275
wherein G and L are defined as claim 1, to produce a compound represented by the following formula (1n):
276
wherein A, G and L are defined as claim 1; or
(m) a compound represented by the following formula (18):
277
wherein Cbz represents benzyloxycarbonyl, is reacted in a solvent in the presence of a base with the compound of formula (17) and deprotected to produce a compound represented by the following formula (1o):
278
wherein G and L are defined as claim 1, which is then coupled with a compound represented by the following formula (19):
T-E-F (19)
wherein E and F are defined as claim 1, to produce a compound represented by the following formula (1p):
279
wherein E, F, G and L are defined as claim 1.
6. A compound represented by the following formula (3):
280
wherein B, C, D and X are defined as claim 1.
7. A compound represented by the following formula (8):
281
wherein n1, A, B and C are defined as claim 1.
8. A pharmaceutical composition comprising as active ingredient a therapeutically effective amount of a compound of formula (1) as defined in claim 1 or a pharmaceutically acceptable salt or isomer thereof together with a pharmaceutically acceptable carrier.
9. The pharmaceutical composition of claim 8 useful for preventing and treating cancer.
10. The pharmaceutical composition of claim 8 useful for preventing and treating restenosis.
11. The pharmaceutical composition of claim 8 useful for preventing and treating atherosclerosis.
12. The pharmaceutical composition of claim 8 useful for preventing and treating infections from hepatitis delta and related viruses.