Selected CGRP-antagonists process for preparing them and their use as pharmaceutical compositions

• US 20050227968A1
• Filed: 03/03/2005
• Published: 10/13/2005
• Est. Priority Date: 03/03/2004
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Arndt, Kirsten, Lustenberger, Philipp, Stenkamp, Dirk, Schaenzle, Gerhard, Doods, Henri, Rudolf, Klaus, Mueller, Stephan Georg
• Granted Patent: US 7,205,294 B2
• Time in Patent Office: Days
• US Class Current: 514/221
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: C07D 401/14 containing three or more hetero rings

Abstract

The present invention relates to substituted piperidines of general formula
wherein A, B, D, E, X, R¹ and R² are defined as in claim 1, the tautomers, the diastereomers, the enantiomers, the hydrates thereof, the mixtures thereof and the salts thereof and the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids, pharmaceutical compositions containing these compounds, the use thereof and processes for the preparation thereof.

Claims

1. A compound of the formula

2. A compound of the formula I according to claim 1, wherein

the combination of A, B, D and E denotes a group of formula

R¹ denotes a group of formula

and

R² denotes a group of formula

or a tautomer or salt thereof.

4. A physiologically acceptable salt of a compound according to claim 1, 2 or 3.

5. A pharmaceutical composition comprising a compound according to claim 1, 2 or 3, a physiologically acceptable salt thereof, together with one or more inert carriers and/or diluents.

6. A method for treating headaches, particularly migraine or cluster headaches, which comprises administering a therapeutically effective amount of a compound according to claim 1, 2 or 3, a physiologically acceptable salt thereof.

7. A method for treating non-insulin-dependent diabetes mellitus (NIDDM) which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound according to claim 1, 2 or 3, a physiologically acceptable salt thereof.

8. A method for treating cardiovascular diseases, morphine tolerance, diarrhoea caused by clostridium toxin, skin diseases, particularly thermal and radiation-induced skin damage including sunburn, inflammatory diseases, e.g. particularly inflammatory diseases of the joints such as arthritis, neurogenic inflammation of the oral mucosa, inflammatory lung diseases, allergic rhinitis, asthma, diseases accompanied by excessive vasodilatation and resultant reduced circulation of the blood, e.g. particularly shock and sepsis, for alleviating pain in general or for preventive or acute therapeutic treatment of the symptoms of hot flushes caused by vasodilatation and increased blood flow in menopausal oestrogen-deficient women and hormone-treated patients with prostate carcinoma, which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound according to claim 1, 2 or 3, a physiologically acceptable salt thereof.

3. A compound selected from the group consisting of:

(1) 1-(1,4′

-bipiperidinyl-1′

-yl)-2-(1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(2) 2-(1H-indazol-5-ylmethyl)-1-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(3) 1-(4,4′

-bipiperidinyl-1-yl)-2-(1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(4) 1-(4-dimethylamino-piperidin-1-yl)-2-(1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(5) (S)-2-(1H-indazol-5-yl methyl)-1-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(6) 2-(1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperazin-1-yl-piperidin-1-yl)-butane-1,4-dione,

(7) 2-(1H-indazol-5-ylmethyl)-1-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(8) 2-(1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperidin-4-yl-piperazin-1-yl)-butane-1,4-dione,

(9) 2-(1H-indazol-5-ylmethyl)-1-[4-(4-methyl-perhydro-1,4-diazepin-1-yl)-piperidin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(10) 2-(1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-perhydro-1,4-diazepin-1-yl-piperidin-1-yl)-butane-1,4-dione,

(11) 2-(1H-indazol-5-ylmethyl)-1-[4-(1-methyl-piperidin-4-yl)-perhydro-1,4-diazepin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(12) 2-(1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperidin-4-yl-perhydro-1,4-diazepin-1-yl)-butane-1,4-dione,

(13) 1-[4-(4-fluoro-phenyl)-piperazin-1-yl]-2-(1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(14) 1-[4-(4-fluoro-phenyl)-piperidin-1-yl]-2-(1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(15) 2-(1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-pyridin-4-yl-piperazin-1-yl)-butane-1,4-dione,

(16) methyl (1′

-{2-(1H-indazol-5-ylmethyl)-4-oxo-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butyryl}-4,4′

-bipiperidinyl-1-yl)-acetate,

(17) 2-(1H-indazol-5-ylmethyl)-1-(1′

-methanesulphonyl-4,4′

-bipiperidinyl-1-yl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(18) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(1,4′

-bipiperidinyl-1′

-yl)-1-(1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(19) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1H-indazol-5-ylmethyl)-2-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-2-oxo-ethyl]-amide,

(20) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(4,4′

-bipiperidinyl-1-yl)-1-(1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(21) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(4-dimethylamino-piperidin-1-yl)-1-(1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(22) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(1H-indazol-5-ylmethyl)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl}-amide,

(23) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperazin-1-yl-piperidin-1-yl)-ethyl]-amide,

(24) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(1H-indazol-5-ylmethyl)-2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-amide,

(25) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperidin-4-yl-piperazin-1-yl)-ethyl]-amide,

(26) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(1H-indazol-5-ylmethyl)-2-[4-(4-methyl-perhydro-1,4-diazepin-1-yl)-piperidin-1-yl]-2-oxo-ethyl}-amide,

(27) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1H-indazol-5-ylmethyl)-2-oxo-2-(4-perhydro-1,4-diazepin-1-yl-piperidin-1-yl)-ethyl]-amide,

(28) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(1H-indazol-5-ylmethyl)-2-[4-(1-methyl-piperidin-4-yl)-perhydro-1,4-diazepin-1-yl]-2-oxo-ethyl}-amide,

(29) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperidin-4-yl-perhydro-1,4-diazepin-1-yl)-ethyl]-amide,

(30) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-[4-(4-fluoro-phenyl)-piperazin-1-yl]-1-(1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(31) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-[4-(4-fluoro-phenyl)-piperidin-1-yl]-1-(1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(32) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1H-indazol-5-ylmethyl)-2-oxo-2-(4-pyridin-4-yl-piperazin-1-yl)-ethyl]-amide,

(33) methyl [1′

-(3-(1H-indazol-5-yl)-2-{[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyl]-amino}-propionyl)-4,4′

-bipiperidinyl-1-yl]-acetate,

(34) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1H-indazol-5-ylmethyl)-2-(1′

-methanesulphonyl-4,4′

-bipiperidinyl-1-yl)-2-oxo-ethyl]-amide,

(35) 1-(1,4′

-bipiperidinyl-1′

-yl)-2-(7-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(36) 1-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-2-(7-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(37) 1-(4,4′

-bipiperidinyl-1-yl)-2-(7-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(38) 1-(4-dimethylamino-piperidin-1-yl)-2-(7-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(39) 2-(7-methyl-1H-indazol-5-ylmethyl)-1-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(40) 2-(7-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperazin-1-yl-piperidin-1-yl)-butane-1,4-dione,

(41) 2-(7-methyl-1H-indazol-5-ylmethyl)-1-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(42) 2-(7-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperidin-4-yl-piperazin-1-yl)-butane-1,4-dione,

(43) 2-(7-methyl-1H-indazol-5-ylmethyl)-1-[4-(4-methyl-perhydro-1,4-diazepin-1-yl)-piperidin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(44) 2-(7-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-perhydro-1,4-diazepin-1-yl-piperidin-1-yl)-butane-1,4-dione,

(45) 2-(7-methyl-1H-indazol-5-ylmethyl)-1-[4-(1-methyl-piperidin-4-yl)-perhydro-1,4-diazepin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(46) 2-(7-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperidin-4-yl-perhydro-1,4-diazepin-1-yl)-butane-1,4-dione,

(47) 1-[4-(4-fluoro-phenyl)-piperazin-1-yl]-2-(7-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(48) 1-[4-(4-fluoro-phenyl)-piperidin-1-yl]-2-(7-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(49) 2-(7-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-pyridin-4-yl-piperazin-1-yl)-butane-1,4-dione,

(50) methyl (1′

-{2-(7-methyl-1H-indazol-5-ylmethyl)-4-oxo-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butyryl}-4,4′

-bipiperidinyl-1-yl)-acetate,

(51) 1-(1′

-methanesulphonyl-4,4′

-bipiperidinyl-1-yl)-2-(7-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(52) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(1,4′

-bipiperidinyl-1′

-yl)-1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(53) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(54) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(4,4′

-bipiperidinyl-1-yl)-1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(55) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(4-dimethylamino-piperidin-1-yl)-1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(56) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(7-methyl-1H-indazol-5-ylmethyl)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl}-amide,

(57) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperazin-1-yl-piperidin-1-yl)-ethyl]-amide,

(58) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(7-methyl-1H-indazol-5-ylmethyl)-2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-amide,

(59) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperidin-4-yl-piperazin-1-yl)-ethyl]-amide,

(60) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(7-methyl-1H-indazol-5-ylmethyl)-2-[4-(4-methyl-perhydro-1,4-diazepin-1-yl)-piperidin-1-yl]-2-oxo-ethyl}-amide,

(61) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-2-(4-perhydro-1,4-diazepin-1-yl-piperidin-1-yl)-ethyl]-amide,

(62) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(7-methyl-1H-indazol-5-ylmethyl)-2-[4-(1-methyl-piperidin-4-yl)-perhydro-1,4-diazepin-1-yl]-2-oxo-ethyl}-amide,

(63) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperidin-4-yl-perhydro-1,4-diazepin-1-yl)-ethyl]-amide,

(64) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-[4-(4-fluoro-phenyl)-piperazin-1-yl]-1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(65) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-[4-(4-fluoro-phenyl)-piperidin-1-yl]-1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(66) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-2-(4-pyridin-4-yl-piperazin-1-yl)-ethyl]-amide,

(67) methyl [1′

-(3-(7-methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyl]-amino}-propionyl)-4,4′

-bipiperidinyl-1-yl]-acetate,

(68) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(1′

-methanesulphonyl-4,4′

-bipiperidinyl-1-yl)-1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(69) 2-(1H-indazol-5-ylmethyl)-1-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-4-[4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidin-1-yl]-butane-1,4-dione,

(70) 1-(4,4′

-bipiperidinyl-1-yl)-2-(1H-indazol-5-ylmethyl)-4-[4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidin-1-yl]-butane-1,4-dione,

(71) 2-(1H-indazol-5-ylmethyl)-1-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-4-[4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidin-1-yl]-butane-1,4-dione,

(72) 2-(1H-indazol-5-ylmethyl)-4-[4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidin-1-yl]-1-(4-piperazin-1-yl-piperidin-1-yl)-butane-1,4-dione,

(73) 2-(1H-indazol-5-ylmethyl)-1-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-4-[4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidin-1-yl]-butane-1,4-dione,

(74) 2-(1H-indazol-5-ylmethyl)-4-[4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidin-1-yl]-1-(4-piperidin-4-yl-piperazin-1-yl)-butane-1,4-dione,

(75) 1-(1,4′

-bipiperidinyl-1′

-yl)-2-(1H-indazol-5-ylmethyl)-4-[4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidin-1-yl]-butane-1,4-dione,

(76) 1-(4-dimethylamino-piperidin-1-yl)-2-(1H-indazol-5-ylmethyl)-4-[4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidin-1-yl]-butane-1,4-dione,

(77) 4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidine-1-carboxylic acid [1-(1H-indazol-5-ylmethyl)-2-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-2-oxo-ethyl]-amide,

(78) 4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidine-1-carboxylic acid [2-(4,4′

-bipiperidinyl-1-yl)-1-(1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(79) 4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidine-1-carboxylic acid {1-(1H-indazol-5-ylmethyl)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl}-amide,

(80) 4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidine-1-carboxylic acid [1-(1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperazin-1-yl-piperidin-1-yl)-ethyl]-amide,

(81) 4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidine-1-carboxylic acid {1-(1H-indazol-5-ylmethyl)-2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-amide,

(82) 4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidine-1-carboxylic acid [1-(1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperidin-4-yl-piperazin-1-yl)-ethyl]-amide,

(83) 4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidine-1-carboxylic acid [2-(1,4′

-bipiperidinyl-1′

-yl)-1-(1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(84) 4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)-piperidine-1-carboxylic acid [2-(4-dimethylamino-piperidin-1-yl)-1-(1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(85) 2-(7-ethyl-1H-indazol-5-ylmethyl)-1-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(86) 1-(4,4′

-bipiperidinyl-1-yl)-2-(7-ethyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(87) 2-(7-ethyl-1H-indazol-5-ylmethyl)-1-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(88) 2-(7-ethyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperazin-1-yl-piperidin-1-yl)-butane-1,4-dione,

(89) 2-(7-ethyl-1H-indazol-5-ylmethyl)-1-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(90) 2-(7-ethyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperidin-4-yl-piperazin-1-yl)-butane-1,4-dione,

(91) 2-(7-chloro-1H-indazol-5-ylmethyl)-1-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(92) 1-(4,4′

-bipiperidinyl-1-yl)-2-(7-chloro-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(93) 2-(7-chloro-1H-indazol-5-ylmethyl)-1-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(94) 2-(7-chloro-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperazin-1-yl-piperidin-1-yl)-butane-1,4-dione,

(95) 2-(7-chloro-1H-indazol-5-ylmethyl)-1-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(96) 2-(7-chloro-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperidin-4-yl-piperazin-1-yl)-butane-1,4-dione,

(97) 2-(7-bromo-1H-indazol-5-ylmethyl)-1-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(98) 1-(4,4′

-bipiperidinyl-1-yl)-2-(7-bromo-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(99) 2-(7-bromo-1H-indazol-5-ylmethyl)-1-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(100) 2-(7-bromo-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperazin-1-yl-piperidin-1-yl)-butane-1,4-dione,

(101) 2-(7-bromo-1H-indazol-5-ylmethyl)-1-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(102) 2-(7-bromo-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperidin-4-yl-piperazin-1-yl)-butane-1,4-dione,

(103) 1-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-2-(7-trifluoromethyl-1H-indazol-5-ylmethyl)-butane-1,4-dione,

(104) 1-(4,4′

-bipiperidinyl-1-yl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-2-(7-trifluoromethyl-1H-indazol-5-ylmethyl)-butane-1,4-dione,

(105) 2-(7-methyl-1H-indazol-5-ylmethyl)-1-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(106) 4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperazin-1-yl-piperidin-1-yl)-2-(7-trifluoromethyl-1H-indazol-5-ylmethyl)-butane-1,4-dione,

(107) 1-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-2-(7-trifluoromethyl-1H-indazol-5-ylmethyl)-butane-1,4-dione,

(108) 4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperidin-4-yl-piperazin-1-yl)-2-(7-trifluoromethyl-1H-indazol-5-ylmethyl)-butane-1,4-dione,

(109) 1-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-2-(1-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(110) 1-(4,4′

-bipiperidinyl-1-yl)-2-(1-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(111) 2-(1-methyl-1H-indazol-5-ylmethyl)-1-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(112) 2-(1-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperazin-1-yl-piperidin-1-yl)-butane-1,4-dione,

(113) 2-(1-methyl-1H-indazol-5-ylmethyl)-1-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(114) 2-(1-methyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperidin-4-yl-piperazin-1-yl)-butane-1,4-dione,

(115) 2-(1,7-dimethyl-1H-indazol-5-ylmethyl)-1-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(116) 1-(4,4′

-bipiperidinyl-1-yl)-2-(1,7-dimethyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(117) 2-(1,7-dimethyl-1H-indazol-5-ylmethyl)-1-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(118) 2-(1,7-dimethyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperazin-1-yl-piperidin-1-yl)-butane-1,4-dione,

(119) 2-(1,7-dimethyl-1H-indazol-5-ylmethyl)-1-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(120) 2-(1,7-dimethyl-1H-indazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperidin-4-yl-piperazin-1-yl)-butane-1,4-dione,

(121) 2-(1H-benzotriazol-5-ylmethyl)-1-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(122) 2-(1H-benzotriazol-5-ylmethyl)-1-(4,4′

-bipiperidinyl-1-yl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(123) 2-(1H-benzotriazol-5-ylmethyl)-1-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(124) 2-(1H-benzotriazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperazin-1-yl-piperidin-1-yl)-butane-1,4-dione,

(125) 2-(1H-benzotriazol-5-ylmethyl)-1-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(126) 2-(1H-benzotriazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperidin-4-yl-piperazin-1-yl)-butane-1,4-dione,

(127) 2-(7-methyl-1H-benzotriazol-5-ylmethyl)-1-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(128) 1-(4,4′

-bipiperidinyl-1-yl)-2-(7-methyl-1H-benzotriazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(129) 2-(7-methyl-1H-benzotriazol-5-ylmethyl)-1-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(130) 2-(7-methyl-1H-benzotriazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperazin-1-yl-piperidin-1-yl)-butane-1,4-dione,

(131) 2-(7-methyl-1H-benzotriazol-5-ylmethyl)-1-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(132) 2-(7-methyl-1H-benzotriazol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperidin-4-yl-piperazin-1-yl)-butane-1,4-dione,

(133) 2-(1H-indol-5-ylmethyl)-1-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(134) 1-(4,4′

-bipiperidinyl-1-yl)-2-(1H-indol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(135) 2-(1H-indol-5-ylmethyl)-1-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(136) 2-(1H-indol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperazin-1-yl-piperidin-1-yl)-butane-1,4-dione,

(137) 2-(1H-indol-5-ylmethyl)-1-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(138) 2-(1H-indol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperidin-4-yl-piperazin-1-yl)-butane-1,4-dione,

(139) 1-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-2-(7-methyl-1H-indol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(140) 1-(4,4′

-bipiperidinyl-1-yl)-2-(7-methyl-1H-indol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(141) 2-(7-methyl-1H-indol-5-ylmethyl)-1-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(142) 2-(7-methyl-1H-indol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperazin-1-yl-piperidin-1-yl)-butane-1,4-dione,

(143) 2-(7-methyl-1H-indol-5-ylmethyl)-1-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butane-1,4-dione,

(144) 2-(7-methyl-1H-indol-5-ylmethyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-(4-piperidin-4-yl-piperazin-1-yl)-butane-1,4-dione,

(145) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-ethyl-1H-indazol-5-ylmethyl)-2-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-2-oxo-ethyl]-amide,

(146) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(4,4′

-bipiperidinyl-1-yl)-1-(7-ethyl-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(147) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(7-ethyl-1H-indazol-5-ylmethyl)-2-[4-[(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl}-amide,

(148) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-ethyl-1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperazin-1-yl-piperidin-1-yl)-ethyl]-amide,

(149) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(7-ethyl-1H-indazol-5-ylmethyl)-2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-amide,

(150) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-ethyl-1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperidin-4-yl-piperazin-1-yl)-ethyl]-amide,

(151) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-chloro-1H-indazol-5-ylmethyl)-2-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-2-oxo-ethyl]-amide,

(152) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(4,4′

-bipiperidinyl-1-yl)-1-(7-chloro-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(153) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(7-chloro-1H-indazol-5-ylmethyl)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl}-amide,

(154) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-chloro-1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperazin-1-yl-piperidin-1-yl)-ethyl]-amide,

(155) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(7-chloro-1H-indazol-5-ylmethyl)-2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-amide,

(156) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-chloro-1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperidin-4-yl-piperazin-1-yl)-ethyl]-amide,

(157) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-bromo-1H-indazol-5-ylmethyl)-2-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-2-oxo-ethyl]-amide,

(158) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(4,4′

-bipiperidinyl-1-yl)-1-(7-bromo-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(159) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(7-bromo-1H-indazol-5-ylmethyl)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl}-amide,

(160) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-bromo-1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperazin-1-yl-piperidin-1-yl)-ethyl]-amide,

(161) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(7-bromo-1H-indazol-5-ylmethyl)-2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-amide,

(162) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-bromo-1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperidin-4-yl-piperazin-1-yl)-ethyl]-amide,

(163) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-2-oxo-1-(7-trifluoromethyl-1H-indazol-5-ylmethyl)-ethyl]-amide,

(164) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(4,4′

-bipiperidinyl-1-yl)-2-oxo-1-(7-trifluoromethyl-1H-indazol-5-ylmethyl)-ethyl]-amide,

(165) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-1-(7-trifluoromethyl-1H-indazol-5-ylmethyl)-ethyl]-amide,

(166) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-oxo-2-(4-piperazin-1-yl-piperidin-1-yl)-1-(7-trifluoromethyl-1H-indazol-5-ylmethyl)-ethyl]-amide,

(167) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-1-(7-trifluoromethyl-1H-indazol-5-ylmethyl)-ethyl]-amide,

(168) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid (2-oxo-2-(4-piperidin-4-yl-piperazin-1-yl)-1-(7-trifluoromethyl-1H-indazol-5-ylmethyl)-ethyl]-amide,

(169) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-1-(1-methyl-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(170) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(4,4′

-bipiperidinyl-1-yl)-1-(1-methyl-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(171) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(1-methyl-1H-indazol-5-ylmethyl)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl}-amide,

(172) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1-methyl-1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperazin-1-yl-piperidin-1-yl)-ethyl]-amide,

(173) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(1-methyl-1H-indazol-5-ylmethyl)-2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-amide,

(174) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1-methyl-1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperidin-4-yl-piperazin-1-yl)-ethyl]-amide,

(175) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1,7-dimethyl-1H-indazol-5-ylmethyl)-2-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-2-oxo-ethyl]-amide,

(176) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(4,4′

-bipiperidinyl-1-yl)-1-(1,7-dimethyl-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(177) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(1,7-dimethyl-1H-indazol-5-ylmethyl)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl}-amide,

(178) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1,7-dimethyl-1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperazin-1-yl-piperidin-1-yl)-ethyl]-amide,

(179) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(1,7-dimethyl-1H-indazol-5-ylmethyl)-2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-amide,

(180) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1,7-dimethyl-1H-indazol-5-ylmethyl)-2-oxo-2-(4-piperidin-4-yl-piperazin-1-yl)-ethyl]-amide,

(181) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1H-benzotriazol-5-ylmethyl)-2-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-2-oxo-ethyl]-amide,

(182) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1H-benzotriazol-5-ylmethyl)-2-(4,4′

-bipiperidinyl-1-yl)-2-oxo-ethyl]-amide,

(183) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(1H-benzotriazol-5-ylmethyl)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl}-amide,

(184) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1H-benzotriazol-5-ylmethyl)-2-oxo-2-(4-piperazin-1-yl-piperidin-1-yl)-ethyl]-amide,

(185) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(1H-benzotriazol-5-ylmethyl)-2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-amide,

(186) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1H-benzotriazol-5-ylmethyl)-2-oxo-2-(4-piperidin-4-yl-piperazin-1-yl)-ethyl]-amide,

(187) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-methyl-1H-benzotriazol-5-ylmethyl)-2-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-2-oxo-ethyl]-amide,

(188) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(4,4′

-bipiperidinyl-1-yl)-1-(7-methyl-1H-benzotriazol-5-ylmethyl)-2-oxo-ethyl]-amide,

(189) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(7-methyl-1H-benzotriazol-5-ylmethyl)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl}-amide,

(190) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-methyl-1H-benzotriazol-5-ylmethyl)-2-oxo-2-(4-piperazin-1-yl-piperidin-1-yl)-ethyl]-amide,

(191) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(7-methyl-1H-benzotriazol-5-ylmethyl)-2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-amide,

(192) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-methyl-1H-benzotriazol-5-ylmethyl)-2-oxo-2-(4-piperidin-4-yl-piperazin-1-yl)-ethyl]-amide,

(193) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1H-indol-5-ylmethyl)-2-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-2-oxo-ethyl]-amide,

(194) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(4,4′

-bipiperidinyl-1-yl)-1-(1H-indol-5-ylmethyl)-2-oxo-ethyl]-amide,

(195) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(1H-indol-5-ylmethyl)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl}-amide,

(196) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1H-indol-5-ylmethyl)-2-oxo-2-(4-piperazin-1-yl-piperidin-1-yl)-ethyl]-amide,

(197) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(1H-indol-5-ylmethyl)-2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-amide,

(198) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(1H-indol-5-ylmethyl)-2-oxo-2-(4-piperidin-4-yl-piperazin-1-yl)-ethyl]-amide,

(199) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(1′

-methyl-4,4′

-bipiperidinyl-1-yl)-1-(7-methyl-1H-indol-5-ylmethyl)-2-oxo-ethyl]-amide,

(200) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [2-(4,4′

-bipiperidinyl-1-yl)-1-(7-methyl-1H-indol-5-ylmethyl)-2-oxo-ethyl]-amide,

(201) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(7-methyl-1H-indol-5-ylmethyl)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl}-amide,

(202) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-methyl-1H-indol-5-ylmethyl)-2-oxo-2-(4-piperazin-1-yl-piperidin-1-yl)-ethyl]-amide,

(203) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid {1-(7-methyl-1H-indol-5-ylmethyl)-2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-amide,

(204) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid [1-(7-methyl-1H-indol-5-ylmethyl)-2-oxo-2-(4-piperidin-4-yl-piperazin-1-yl)-ethyl]-amide,

or a tautomer or salt thereof.