1. A wiring structure comprising: an insulating layer having an upper surface, a lower surface, and a connection hole communicating between the upper and bottom surfaces, the connection hole including a bottom at the lower surface and an opening at the upper surface; a body to be wired that is placed below the lower surface or at the bottom inside the connection hole so as to expose at least a portion thereof from the bottom of the connection hole, and a conductive pattern that is patterned inside and outside of the connection hole and that has an electrode portion disposed inside the connection hole and connected to the body to be wired, wherein a cross-sectional area of the electrode portion increases toward the body to be wired and the electrode portion is disposed to contact at least a portion of an inner wall of the connection hole and so as to define a space region between the electrode portion and the inner wall of the connection hole in which at least a portion of the inner wall of the connection hole and the electrode portion are not in contact, and wherein an upper-most point of the electrode portion is below the opening of the connection hole.
2. The wiring structure according to claim 1, wherein a width of an upper portion of the electrode portion is smaller than an opening diameter of the connection hole.
3. The wiring structure according to claim 1, wherein the electrode portion is disposed so as to cover the entire exposed surface of the body to be wired that is exposed from the bottom of the connection hole.
4. The wiring structure according to claim 1, wherein the conductive pattern including the electrode portion is formed of Cu.
5. The wiring structure according to claim 1, wherein the conductive pattern including the electrode portion is formed by plating.
6. The wiring structure according to claim 1, wherein the electrode portion has a flat upper surface distal from the body to he wired, and the cross-sectional area of the electrode portion increases from the flat upper surface toward the body to be wired.
7. The wiring structure according to claim 1, wherein an upper portion of the electrode portion includes a flat upper surface and side surfaces, the flat upper surface is distal from the body to be wired, the upper portion has a trapezoidal cross section, and the sides are not in contact with the inner wall of the connection hole.
8. The wiring structure according to claim 2, wherein the electrode portion is disposed so as to cover the entire exposed surface of the body to be wired that is exposed from the bottom of the connection hole.
9. A printed wiring board comprising a plurality of wiring structures formed therein, the wiring structures each comprising: an insulating layer having an upper surface, a lower surface, and a connection hole communicating between the upper and bottom surfaces, the connection hole including a bottom at the lower surface and an opening at the upper surface; a body to be wired that is placed below or at the bottom inside the insulating layer so as to expose at least a portion from the bottom of the connection hole; and a conductive pattern that is patterned inside and outside of the connection hole and that has an electrode portion disposed inside the connection hole and connected to the body to be wired, wherein a cross-sectional area of the electrode portion increases toward the body to be wired, the electrode portion is disposed to contact at least a portion of an inner wall of the connection hole and so as to define a space region between the electrode portion and the inner wall of the connection hole in which at least a portion of the inner wall of the connection hole and the electrode portion are not in contact, and an upper-most point of the electrode portion is below the opening of the connection hole.
10. The printing wiring board according to claim 9, wherein the conductive pattern including the electrode portion is formed of Cu.
11. The printing wiring board according to claim 9, wherein the conductive pattern including the electrode portion is formed by plating.
12. The printing wiring board according to claim 9, wherein the electrode portion has a flat upper surface distal from the body to be wired, and the cross-sectional area of the electrode portion increases from the flat upper surface toward the body to be wired.
13. The printing wiring board according to claim 9, wherein an upper portion of the electrode portion includes a flat upper surface and side surfaces, the flat upper surface is distal from the body to be wired, the upper portion has a trapezoidal cross section, and the sides are not in contact with the inner wall of the connection hole.
14. A method for manufacturing a wiring structure, which comprises: an insulating layer formation step for forming an insulating layer on a body to be wired, the insulating layer having an upper surface and a lower surface, a connection hole formation step for forming at least one connection hole in the insulating layer so as to expose at least a portion of the body to be wired from the connection hole, the connection hole including a bottom at the lower surface and an opening at the upper surface and communicating between the upper and bottom surfaces, and
a conductive pattern formation step for forming, by patterning, a conductive pattern that is patterned inside and outside of the connection hole and that has an electrode portion disposed inside the connection hole and connected to the body to be wired, wherein in the conductive pattern formation step, the electrode portion is formed to have a cross-sectional area that increases toward the body to be wired inside the connection hole and in contact with at least a portion of an inner wall of the connection hole and to define a space region between the electrode portion and the inner wall of the connection hole in which an inner wall of the connection hole is not in contact with the electrode portion, and the electrode portion is formed to have an upper-most point below the opening of the connection hole.
15. The method according to claim 14, wherein the conductive pattern including the electrode portion is formed of Cu.
16. The method according to claim 14, wherein the conductive pattern including the electrode portion is formed by plating.
17. The method according to claim 14, wherein the electrode portion has a flat upper surface distal from the body to be wired, and the cross-sectional area of the electrode portion increases from the flat upper surface toward the body to be wired.
18. The method according to claim 14, wherein an upper portion of the electrode portion includes a fiat upper surface and side surfaces, the flat upper surface is distal from the body to be wired, the upper portion has a trapezoidal cross section, and the sides are not in contact with the inner wall of the connection hole.
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 compound selected from the group consisting of piperidine carboxylic acid amides of the formula (I)
wherein
W is a phenyl ring or a six-membered, non benzofused aromatic ring containing one to four nitrogen atoms, wherein said ring is substituted by V in para position;
V represents a bond; \u2014(CH2)r\u2014; -A-(CH2)s\u2014; \u2014CH2-A-(CH2)t\u2014; \u2014(CH2)s-A-; \u2014(CH2)2-A-(CH2)u\u2014; -A-(CH2)v\u2014B\u2014; \u2014CH2\u2014CH2\u2014CH2-A-CH2\u2014; -A-CH2\u2014CH2\u2014B\u2014CH2\u2014; \u2014CH2-A-CH2\u2014CH2\u2014B\u2014; \u2014CH2\u2014CH2\u2014CH2-A-CH2\u2014CH2\u2014; \u2014CH2\u2014CH2\u2014CH2\u2014CH2-A-CH2\u2014; -A-CH2\u2014CH2\u2014B\u2014CH2\u2014CH2\u2014; \u2014CH2-A-CH2\u2014CH2\u2014B\u2014CH2\u2014; \u2014CH2-A-CH2\u2014CH2\u2014CH2\u2014B\u2014; \u2014CH2\u2014CH2-A-CH2\u2014CH2\u2014B\u2014; \u2014O\u2014CH2\u2014CH(OCH3)\u2014CH2\u2014O\u2014; \u2014O\u2014CH2\u2014CH(CH3)\u2014CH2\u2014O\u2014; \u2014O\u2014CH2\u2014CH(CF3)\u2014CH2\u2014O\u2014; \u2014O\u2014CH2\u2014C(CH3)2\u2014CH2\u2014O\u2014; \u2014O\u2014CH2\u2014C(CH3)2\u2014O\u2014; \u2014O\u2014C(CH3)2\u2014CH2\u2014O\u2014; \u2014O\u2014CH2\u2014CH(CH3)\u2014O\u2014; \u2014O\u2014CH(CH3)\u2014CH2\u2014O\u2014; \u2014O\u2014CH2\u2014C(CH2CH2)\u2014O\u2014; or \u2014O\u2014C(CH2CH2)\u2014CH2\u2014O\u2014;
A and B independently represent \u2014O\u2014 or \u2014S\u2014;
U represents unsubstituted aryl; mono-, di-, tri- or tetra-substituted aryl wherein the substituents are independently selected from the group consisting of halogen, alkyl, alkoxy, and \u2014CF3; or mono-, di-, or tri-substituted heteroaryl wherein the substituents are independently selected from the group consisting of halogen, alkyl, alkoxy, and \u2014CF3;
Q represents methylene or ethylene;
M represents an aryl, quinolinyl, isoquinolinyl, dihydroquinolinyl or tetrahydroquinolinyl group wherein said groups can optionally be mono- or di-substituted with substituents independently selected from the group consisting of alkyl; alkoxy; \u2014OCF3; \u2014CF3; hydroxy-alkyl; halogen; alkyl-O\u2014(CH2)x\u2014CH2\u2014; alkyl-O\u2014(CH2)y\u2014O\u2014; R\u20322N\u2014(CH2)x\u2014CH2\u2014, wherein R\u2032 is independently selected from the group consisting of hydrogen, alkyl (optionally substituted by one, two or three fluorine atoms), cyclopropyl, cyclopropyl-methyl, \u2014C(\u2550O)O\u2014R\u2033, and \u2014C(\u2550O)\u2014R\u2033 wherein R\u2033 is C1-Cx-alkyl, \u2014CF3, \u2014CH2\u2014CF3 or cyclopropyl; and R\u2032\u2033NH\u2014C(\u2550O)\u2014(O)z\u2014(CH2)x\u2014CH2\u2014, wherein R\u2032\u2033 is alkyl or cyclopropyl;
R1 represents alkyl or cycloalkyl;
n is the integer 0 or 1;
r is the integer 3, 4, 5, or 6;
s is the integer 2, 3, 4, or 5;
t is the integer 1, 2, 3, or 4;
u is the integer 1, 2, or 3; and
v is the integer 2, 3, or 4;
x is the integer 0, 1, 2, 3, or 4;
v is the integer 2, 3, or 4;
z is the integer 0 or 1;
in free or pharmaceutically acceptable salt form.
2. A compound according to claim 1, wherein n is the integer 1 and the ring substituents (\u2014CON(R1)-Q-M) and (\u2014W\u2014V\u2014U) are trans to each other.
3. A compound according to claim 1, wherein n is the integer 0 and the configurations at positions 3 and 4 of the piperidine ring of formula (I) are 3R and 4S, respectively.
4. A compound according to claim 1, wherein M represents an aryl, quinolinyl, isoquinolinyl, dihydroquinolinyl or tetrahydroquinolinyl group wherein said groups can optionally be mono- or di-substituted with substituents independently selected from the group consisting of alkyl; alkoxy; \u2014OCF3; \u2014CF3; hydroxy-alkyl; halogen; alkyl-O\u2014(CH2)x\u2014CH2\u2014; alkyl-O\u2014(CH2)y\u2014O\u2014; and R\u20322N\u2014(CH2)x\u2014CH2\u2014, wherein R\u2032 is independently selected from the group consisting of hydrogen, alkyl, cyclopropyl, and \u2014C(\u2550O)\u2014R\u2033 wherein R\u2033 is C1-Cx-alkyl, \u2014CF3, \u2014CH2\u2014CF3 or cyclopropyl.
5. A compound according to claim 1, wherein M represents the following radical:
wherein R2 is methyl or chlorine, R3 is hydrogen, and R4 represents hydrogen, \u2014CH2CH2\u2014O\u2014CH3, \u2014CH2CH2CH2\u2014O\u2014CH3, or R\u2032NH\u2014(CH2)x\u2014CH2\u2014 wherein R\u2032 is \u2014CH2\u2014CHF2, \u2014CH2\u2014CF3, cyclopropyl, \u2014CO\u2014CH3, \u2014CO\u2014CH2\u2014CF3, \u2014CO\u2014CH2\u2014CH3, or cyclopropyl-carbonyl, with the proviso that in this case R4 is hydrogen, R3 represents methyl, methoxy, chlorine, or \u2014O\u2014CH2CH2\u2014O\u2014CH3.
6. A compound according to claim 1, wherein Q is methylene.
7. A compound according to claim 1, wherein W represents a phenyl ring substituted by V in para position or a heteroaryl containing one nitrogen atom.
8. A compound according to claim 1, wherein V represents
a.)(-A-(CH2)s, wherein A represents O, wherein s is 2 or 3 and wherein V is linked to U of formula (I) via A, or
b.) \u2014OCH2CH2O\u2014.
9. A compound according to claim 1, wherein U is a mono-, di-, or tri-substituted phenyl.
10. A compound according to claim 1, wherein R1 is cyclopropyl.
11. A compound according to claim 1, selected from the group consisting of:
(1R*,5S*,6R*,7S*)-7-{4-3-(2-chloro-3,6-difluoro-phenoxy)-propyl-phenyl}-3,9-diaza-bicyclo3.3.1nonane-6-carboxylic acid cyclopropyl-(2,3-dichloro-benzyl)-amide, in free or pharmaceutically acceptable salt form;
4-{4-3-(2-chloro-3,6-difluoro-phenoxy)-propyl-phenyl}-piperidine-3-carboxylic acid cyclopropyl-(3-methoxy-2-methyl-benzyl)-amide, in free or pharmaceutically acceptable salt form;
4-{4-3-(2,6-dichloro-4-methyl-phenoxy)-propyl-phenyl}-piperidine-3-carboxylic acid cyclopropyl-(3-methoxy-2-methyl-benzyl)-amide, in free or pharmaceutically acceptable salt form;
4-{4-3-(2,3,6-trifluoro-phenoxy)-propyl-phenyl} -piperidine-3-carboxylic acid cyclopropyl-(3-methoxy-2-methyl-benzyl)-amide, in free or pharmaceutically acceptable salt form;
4-{4-3-(2-chloro-3,6-difluoro-phenoxy)-propyl-phenyl}-piperidine-3-carboxylic acid cyclopropyl-(2,3-dimethyl-benzyl)-amide, in free or pharmaceutically acceptable salt form;
4-{4-3-(2,6-dichloro-4-methyl-phenoxy)-propyl-phenyl}-piperidine-3-carboxylic acid cyclopropyl-(2,3-dimethyl-benzyl)-amide, in free or pharmaceutically acceptable salt form;
4-{4-3-(2-chloro-6-fluoro-3-methyl-phenoxy)-propyl-phenyl}-piperidine-3-carboxylic acid cyclopropyl-(2,3-dimethyl-benzyl)-amide, in free or pharmaceutically acceptable salt form: and
4-{4-3-(2,3,6-trifluoro-phenoxy)-propyl-phenyl}-piperidine-3-carboxylic acid cyclopropyl-(2,3-dimethyl-benzyl)-amide in free or pharmaceutically acceptable salt form.
12. A compound according to claim 1, selected from the group consisting of:
(3R*,4S*)-4-{4-2-(2,6-dichloro-4-methylphenoxy)ethoxyphenyl}-piperidine-3-carboxylic acid cyclopropyl-(2,3-dimethylbenzyl)-amide, in free or pharmaceutically acceptable salt form,
(3R,4S)-4-{4-2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy-phenyl}-piperidine-3-carboxylic acid 2-chloro-5-(3-methoxy-propyl)-benzyl-cyclopropyl-amide, in free or pharmaceutically acceptable salt form:
(3R,4S)-4-{4-2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy-phenyl}-piperidine-3-carboxylic acid 2-chloro-5-(2-methoxy-ethyl)-benzyl-cyclopropyl-amide, in free or pharmaceutical acceptable salt form;
(3R,4S)-6-2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy-1\u2032,2\u2032,3\u2032,4\u2032,5\u2032,6\u2032-hexahydro-3,4\u2032bipyridinyl-3\u2032-carboxylic acid 2-chloro-5-(3-methoxy-propyl)-benzyl-cyclopropyl-amide, in free or pharmaceutically acceptable salt form; and
(3R,4S)-6-2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy-1\u2032,2\u2032,3\u2032,4\u2032,5\u2032,6\u2032-3,4\u2032bipyridinyl-3\u2032-carboxylic acid 2-chloro-5-(2-methoxy-ethyl)-benzyl-cyclopropyl-amide in free or pharmaceutically acceptable salt form.
13. A compound according to claim 1, selected from the group consisting of:
(3R,4S)-4-{4-2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy-phenyl}-piperidine-3-carboxylic acid {2-chloro-5-(2,2-difluoro-ethylamino)-methyl-benzyl}-cyclopropyl-amide, in free or pharmaceutically acceptable salt form;
(3R,4S)-4-{4-2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy-phenyl}-piperidine-3-carboxylic acid {2-chloro-5-(3,3,3-trifluoro-propionylamino)-methyl-benzyl}-cyclopropyl-amide, in free or pharmaceutically acceptable salt form;
(3R,4S)-4-{4-2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy-phenyl}-piperidine-3-carboxylic acid {2-chloro-5-(cyclopropylmethyl-amino)-methyl-benzyl}-cyclopropyl-amide, in free or pharmaceutically acceptable salt form;
(3R,4S)-4-{4-2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy-phenyl}-piperidine-3-carboxylic acid 5-(acetylamino-methyl)-2-chloro-benzyl-cyclopropyl-amide, in free or pharmaceutically acceptable salt form;
(3R,4S)-4-{4-2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy-phenyl}-piperidine-3-carboxylic acid 2-chloro-5-(2-methylamino-ethyl)-benzyl-cyclopropyl-amide, in free or pharmaceutically acceptable salt form;
(3R,4S)-4-{4-2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy-phenyl}-piperidine-3-carboxylic acid (2-chloro-5-methylaminomethyl-benzyl)-cyclopropyl-amide, in free or pharmaceutically acceptable salt form;
(3R,4S)-4-{4-2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy-phenyl}-piperidine-3-carboxylic acid {2-chloro-5-2-(3,3,3-trifluoro-propionylamino)-ethyl-benzyl}-cyclopropyl-amide, in free or pharmaceutically acceptable salt form;
(3R,4S)-4-{4-2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy-phenyl}-piperidine-3-carboxylic acid 2-chloro-5-(2-ethylamino-ethyl)-benzyl-cyclopropyl-amide, in free or pharmaceutically acceptable salt form;
(3R,4S)-4-{4-2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy-phenyl}-piperidine-3-carboxylic acid 5-(2-acetylamino-ethyl)-2-chloro-benzyl-cyclopropyl-amide, in free or pharmaceutically acceptable salt form;
(3R,4S)-4-{4-2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy-phenyl}-piperidine-3-carboxylic acid {2-chloro-5-(2-fluoro-ethylamino)-methyl-benzyl}-cyclopropyl-amide, in free or pharmaceutically acceptable salt form;
(3R,4S)-4-{4-2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy-phenyl}-piperidine-3-carboxylic acid (2-chloro-5-ethylaminomethyl-benzyl)-cyclopropyl-amide, in free or pharmaceutically acceptable salt form;
(3R,4S)-4-{4-2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy-phenyl}-piperidine-3-carboxylic acid (2-chloro-5-cyclopropylaminomethyl-benzyl)-cyclopropyl-amide, in free or pharmaceutically acceptable salt form; and
(3R,4S)-4-{4-2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy-phenyl}-piperidine-3-carboxylic acid 2-chloro-5-(2-cyclopropylamino-ethyl)-benzyl-cyclopropyl-amide, in free or pharmaceutically acceptable salt form.
14. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier material.
15. A compound according to claim 1, for use as a medicament.
16. Use of a compound according to claim 1 for the preparation of a pharmaceutical composition for the treatment or prophylaxis of diseases such as or related to hypertension, congestive heart failure, pulmonary hypertension, renal insufficiency, renal ischemia, renal failure, renal fibrosis, cardiac insufficiency, cardiac hypertrophy, cardiac fibrosis, myocardial ischemia, cardiomyopathy, glomerulonephritis, renal colic, complications resulting from diabetes such as nephropathy, vasculopathy and neuropathy, glaucoma, elevated intra-ocular pressure, atherosclerosis, restenosis post angioplasty, complications following vascular or cardiac surgery, erectile dysfunction, hyperaldosteronism, lung fibrosis, scleroderma, anxiety, cognitive disorders, complications of treatments with immunosuppressive agents, and other diseases known to be related to the renin-angiotensin system.
17. A compound according to claim 14 for use as a medicament.