Target Validation Information | |||||
---|---|---|---|---|---|
TTD ID | T84621 | ||||
Target Name | Steroid 11-beta-hydroxylase (CYP11B1) | ||||
Type of Target |
Successful |
||||
Drug Potency against Target | Metyrapone | Drug Info | Ki = 140 uM | [15] | |
Drug Info | IC50 = 422 nM | [11] | |||
Drug Info | IC50 = 522 nM | [11] | |||
Drug Info | IC50 = 373 nM | [6] | |||
Drug Info | IC50 = 7050 nM | [14] | |||
Drug Info | IC50 = 709 nM | [9] | |||
Drug Info | IC50 = 25 nM | [9] | |||
Drug Info | IC50 = 1515 nM | [1] | |||
Drug Info | IC50 = 130 nM | [9] | |||
Drug Info | IC50 = 7720 nM | [14] | |||
Drug Info | IC50 = 660 nM | [14] | |||
Drug Info | IC50 = 955 nM | [1] | |||
Drug Info | IC50 = 311 nM | [1] | |||
Drug Info | IC50 = 1291 nM | [5] | |||
Drug Info | IC50 = 320 nM | [1] | |||
Drug Info | IC50 = 1977 nM | [8] | |||
Drug Info | IC50 = 10000 nM | [13] | |||
Drug Info | IC50 = 304 nM | [1] | |||
Drug Info | IC50 = 287 nM | [11] | |||
(3-((1H-imidazol-1-yl)methyl)phenyl)methanol | Drug Info | IC50 = 206 nM | [9] | ||
(4-((1H-imidazol-1-yl)methyl)phenyl)methanol | Drug Info | IC50 = 695 nM | [9] | ||
1-(3,4-dihydronaphthalen-2-yl)-1H-imidazole | Drug Info | IC50 = 639 nM | [5] | ||
1-(3-Bromobenzyl)-1H-imidazole | Drug Info | IC50 = 143 nM | [9] | ||
1-(3-Chlorobenzyl)-1H-imidazole | Drug Info | IC50 = 151 nM | [9] | ||
1-(3-Fluorobenzyl)-1H-imidazole | Drug Info | IC50 = 206 nM | [9] | ||
1-(3-Methoxy-naphthalen-2-yl)-1H-imidazole | Drug Info | IC50 = 81 nM | [3] | ||
1-(4-Aminobenzyl)-1H-imidazole | Drug Info | IC50 = 236 nM | [9] | ||
1-(4-Bromobenzyl)-1H-imidazole | Drug Info | IC50 = 211 nM | [9] | ||
1-(4-Bromobenzyl)-5-phenyl-1H-imidazole | Drug Info | IC50 = 7 nM | [9] | ||
1-(4-Cyanobenzyl)-5-(2-fluorophenyl)-1H-imidazole | Drug Info | IC50 = 20 nM | [9] | ||
1-(4-Cyanobenzyl)-5-(2-methylphenyl)-1H-imidazole | Drug Info | IC50 = 5.7 nM | [9] | ||
1-(4-Cyanobenzyl)-5-(3-fluorophenyl)-1H-imidazole | Drug Info | IC50 = 32 nM | [9] | ||
1-(4-Cyanobenzyl)-5-(3-methylphenyl)-1H-imidazole | Drug Info | IC50 = 6.2 nM | [9] | ||
1-(4-Cyanobenzyl)-5-(4-fluorophenyl)-1H-imidazole | Drug Info | IC50 = 27 nM | [9] | ||
1-(4-Cyanobenzyl)-5-(4-pyridyl)-1H-imidazole | Drug Info | IC50 = 307 nM | [9] | ||
1-(4-Cyanobenzyl)-5-bromo-1H-imidazole | Drug Info | IC50 = 73 nM | [9] | ||
1-(4-Cyanobenzyl)-5-formyl-1H-imidazole | Drug Info | IC50 = 478 nM | [9] | ||
1-(4-Cyanobenzyl)-5-hydroxymethyl-1H-imidazole | Drug Info | IC50 = 285 nM | [9] | ||
1-(4-Cyanobenzyl)-5-methyl-1H-imidazole | Drug Info | IC50 = 141 nM | [9] | ||
1-(4-Cyanobenzyl)-5-phenyl-1H-imidazole | Drug Info | IC50 = 28 nM | [9] | ||
1-(4-fluorobenzyl)-1H-imidazole | Drug Info | IC50 = 494 nM | [9] | ||
1-(4-Fluorobenzyl)-5-phenyl-1H-imidazole | Drug Info | IC50 = 16 nM | [9] | ||
1-(4-Methoxybenzyl)-5-phenyl-1H-imidazole | Drug Info | IC50 = 11 nM | [9] | ||
1-(6-Methoxy-naphthalen-2-yl)-1H-imidazole | Drug Info | IC50 = 849 nM | [3] | ||
1-Benzyl-5-phenyl-1H-imidazole | Drug Info | IC50 = 4.8 nM | [9] | ||
1-Ethyl-3-imidazol-1-ylmethyl-1H-indole | Drug Info | IC50 = 10000 nM | [12] | ||
1-Naphthalen-2-yl-1H-imidazole | Drug Info | IC50 = 1317 nM | [3] | ||
2-Methyl-1,2-di-pyridin-3-yl-1-methoxypropane | Drug Info | IC50 = 7300 nM | [14] | ||
2-Methyl-1,2-di-pyridin-3-yl-propan-1-one oxime | Drug Info | IC50 = 4780 nM | [14] | ||
2-Methyl-1,2-di-pyridin-3-yl-propane | Drug Info | IC50 = 2640 nM | [14] | ||
2-Methyl-1,2-di-pyridin-3-yl-propylchloride | Drug Info | IC50 = 7250 nM | [14] | ||
2-Methyl-1,2-di-pyridin-3-yl-propyliodide | Drug Info | IC50 = 5360 nM | [14] | ||
2-Methyl-1-phenyl-2-pyridin-3-yl-propan-1-ol | Drug Info | IC50 = 1530 nM | [14] | ||
2-Methyl-1-phenyl-2-pyridin-3-yl-propan-1-one | Drug Info | IC50 = 3300 nM | [14] | ||
3-((1H-imidazol-1-yl)methyl)aniline | Drug Info | IC50 = 390 nM | [9] | ||
3-(1,2-dihydroacenaphthylen-3-yl)pyridine | Drug Info | IC50 = 2452 nM | [4] | ||
3-(1,2-dihydroacenaphthylen-5-yl)pyridine | Drug Info | IC50 = 2896 nM | [4] | ||
3-(1-Benzyl-1H-imidazol-5-yl)-1-propanol | Drug Info | IC50 = 181 nM | [9] | ||
3-(1-Chloro-7-methoxy-naphthalen-2-yl)-pyridine | Drug Info | IC50 = 2724 nM | [3] | ||
3-(1-ethyl-3,4-dihydronaphthalen-2-yl)-pyridine | Drug Info | IC50 = 2117 nM | [5] | ||
3-(1-methyl-3,4-dihydronaphthalen-2-yl)-pyridine | Drug Info | IC50 = 1268 nM | [5] | ||
3-(1H-inden-2-yl)pyridine | Drug Info | IC50 = 2391 nM | [5] | ||
3-(2,3-Dihydro-1,4-benzodioxin-6-yl)pyridine | Drug Info | IC50 = 13378 nM | [8] | ||
3-(2-Chloro-1,1-dimethyl-2-phenyl-ethyl)-pyridine | Drug Info | IC50 = 1630 nM | [14] | ||
3-(3,4-dihydronaphthalen-2-yl)pyridine | Drug Info | IC50 = 1729 nM | [5] | ||
3-(3-Benzyl-6-methoxynaphthalen-2-yl)pyridine | Drug Info | IC50 = 640 nM | [7] | ||
3-(3-Benzylnaphthalen-2-yl)pyridine | Drug Info | IC50 = 953 nM | [7] | ||
3-(3-methyl-3,4-dihydronaphthalen-2-yl)pyridine | Drug Info | IC50 = 503 nM | [5] | ||
3-(4-ethyl-3,4-dihydronaphthalen-2-yl)pyridine | Drug Info | IC50 = 1615 nM | [5] | ||
3-(5-Bromo-6-methoxy-naphthalen-2-yl)-pyridine | Drug Info | IC50 = 4481 nM | [3] | ||
3-(5-Chloro-6-methoxy-naphthalen-2-yl)-pyridine | Drug Info | IC50 = 2517 nM | [3] | ||
3-(5-methoxy-1H-inden-2-yl)pyridine | Drug Info | IC50 = 5684 nM | [5] | ||
3-(6-Bromo-naphthalen-2-yl)-pyridine | Drug Info | IC50 = 2939 nM | [3] | ||
3-(6-Ethoxy-naphthalen-2-yl)-pyridine | Drug Info | IC50 = 5419 nM | [3] | ||
3-(6-methoxy-3,4-dihydronaphthalen-2-yl)pyridine | Drug Info | IC50 = 578 nM | [6] | ||
3-(6-Methoxy-3-methylnaphthalen-2-yl)pyridine | Drug Info | IC50 = 1047 nM | [6] | ||
3-(6-Methoxynaphthalen-2-yl)-4-methylpyridine | Drug Info | IC50 = 114 nM | [6] | ||
3-(6-Methoxynaphthalen-2-yl)-5-phenylpyridine | Drug Info | IC50 = 151 nM | [6] | ||
3-(6-Methoxynaphthalen-2-yl)pyridin-4-amine | Drug Info | IC50 = 1521 nM | [6] | ||
3-(6-methoxynaphthalen-2-yl)pyridine | Drug Info | IC50 = 1577 nM | [7] | ||
3-(naphthalen-2-yl)pyridine | Drug Info | IC50 = 5826 nM | [7] | ||
3-Fluoro-4'-(pyridin-4-ylmethyl)biphenyl-4-ol | Drug Info | IC50 = 850 nM | [11] | ||
3-Imidazol-1-yl-quinoline | Drug Info | IC50 = 6338 nM | [3] | ||
3-Imidazol-1-ylmethyl-1H-indole | Drug Info | IC50 = 10000 nM | [12] | ||
3-Imidazol-1-ylmethyl-2-isopropyl-1H-indole | Drug Info | IC50 = 2000 nM | [12] | ||
3-Indan-(1E)-ylidenemethyl-pyridine | Drug Info | IC50 = 888 nM | [1] | ||
3-Indan-(1Z)-ylidenemethyl-pyridine | Drug Info | IC50 = 87 nM | [1] | ||
3-methoxy-5-(6-methoxynaphthalen-2-yl)pyridine | Drug Info | IC50 = 238 nM | [6] | ||
3-Phenanthren-9-yl-pyridine | Drug Info | IC50 = 7553 nM | [3] | ||
3-[(Z)-2-phenylvinyl]pyridine | Drug Info | IC50 = 288 nM | [5] | ||
3-[1-(4-Bromobenzyl)-1H-imidazol-5-yl]-1-propanol | Drug Info | IC50 = 18 nM | [9] | ||
3-[1-(4-Cyanobenzyl)-1H-imidazol-5-yl]-1-propanol | Drug Info | IC50 = 48 nM | [9] | ||
3-[3-(4-Methoxybenzyl)naphthalen-2-yl]pyridine | Drug Info | IC50 = 2804 nM | [7] | ||
3-[4-Chloro-indan-(1Z)-ylidenemethyl]-pyridine | Drug Info | IC50 = 657 nM | [1] | ||
3-[4-Fluoro-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | IC50 = 774 nM | [1] | ||
3-[4-Methyl-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | IC50 = 763 nM | [1] | ||
3-[5-Bromo-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | IC50 = 1937 nM | [1] | ||
3-[5-Chloro-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | IC50 = 1472 nM | [1] | ||
3-[5-Chloro-indan-(1Z)-ylidenemethyl]-pyridine | Drug Info | IC50 = 270 nM | [1] | ||
3-[5-Ethoxy-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | IC50 = 2368 nM | [1] | ||
3-[5-Ethoxy-indan-(1Z)-ylidenemethyl]-pyridine | Drug Info | IC50 = 2697 nM | [1] | ||
3-[5-Fluoro-indan-(1Z)-ylidenemethyl]-pyridine | Drug Info | IC50 = 125 nM | [1] | ||
3-[5-Methoxy-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | IC50 = 1448 nM | [1] | ||
3-[5-Methoxy-indan-(1Z)-ylidenemethyl]-pyridine | Drug Info | IC50 = 790 nM | [1] | ||
4'-(Pyridin-4-ylmethyl)biphenyl-3,4-diamine | Drug Info | IC50 = 902 nM | [11] | ||
4'-(Pyridin-4-ylmethyl)biphenyl-3,4-diol | Drug Info | IC50 = 1400 nM | [11] | ||
4-((1H-imidazol-1-yl)methyl)benzonitrile | Drug Info | IC50 = 368 nM | [9] | ||
4-((3',4'-Difluorobiphenyl-4-yl)methyl)pyridine | Drug Info | IC50 = 4742 nM | [11] | ||
4-(4'-Fluoro-biphenyl-4-ylmethyl)pyridine | Drug Info | IC50 = 928 nM | [11] | ||
4-(4-(thiophen-2-yl)benzyl)pyridine | Drug Info | IC50 = 415 nM | [11] | ||
4-(6-methoxy-3,4-dihydronaphthalen-2-yl)pyridine | Drug Info | IC50 = 2529 nM | [5] | ||
4-(6-Methoxy-3-methylnaphthalen-2-yl)isoquinoline | Drug Info | IC50 = 843 nM | [6] | ||
4-(6-Methoxynaphthalen-2-yl)isoquinoline | Drug Info | IC50 = 67 nM | [6] | ||
4-Indan-(1Z)-ylidenemethyl-pyridine | Drug Info | IC50 = 931 nM | [1] | ||
4-[(3'-Hydroxybiphenyl-4-yl)methyl]pyridine | Drug Info | IC50 = 342 nM | [11] | ||
4-[(4'-Hydroxybiphenyl-4-yl)methyl]pyridine | Drug Info | IC50 = 251 nM | [11] | ||
4-[5-Bromo-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | IC50 = 2640 nM | [1] | ||
4-[5-Bromo-indan-(1Z)-ylidenemethyl]-pyridine | Drug Info | IC50 = 484 nM | [1] | ||
4-[5-Chloro-indan-(1Z)-ylidenemethyl]-pyridine | Drug Info | IC50 = 301 nM | [1] | ||
4-[5-Fluoro-indan-(1E)-ylidenemethyl]-pyridine | Drug Info | IC50 = 1098 nM | [1] | ||
4-[5-Fluoro-indan-(1Z)-ylidenemethyl]-pyridine | Drug Info | IC50 = 34 nM | [1] | ||
5-(6-Methoxynaphthalen-2-yl)pyridin-3-ol | Drug Info | IC50 = 8925 nM | [6] | ||
5-Indan-(1E)-ylidenemethyl-1H-imidazole | Drug Info | IC50 = 25.9 nM | [2] | ||
5-Indan-(1Z)-ylidenemethyl-1H-imidazole | Drug Info | IC50 = 6.1 nM | [2] | ||
5-Naphthalen-2-yl-1H-imidazole | Drug Info | IC50 = 207 nM | [3] | ||
5-Naphthalen-2-yl-oxazole | Drug Info | IC50 = 805 nM | [3] | ||
5-Pyridin-3-yl-1,3-dihydro-2H-indol-2-one | Drug Info | IC50 = 5952 nM | [8] | ||
5-Pyridin-3-yl-2,3-dihydro-1H-inden-1-one | Drug Info | IC50 = 819 nM | [8] | ||
5-[4-(Pyridin-4-ylmethyl)phenyl]-1H-indole | Drug Info | IC50 = 469 nM | [11] | ||
5-[5-Bromo-indan-(1E)-ylidenemethyl]-1H-imidazole | Drug Info | IC50 = 26.2 nM | [2] | ||
5-[5-Bromo-indan-(1Z)-ylidenemethyl]-1H-imidazole | Drug Info | IC50 = 23.5 nM | [2] | ||
5-[5-Fluoro-indan-(1E)-ylidenemethyl]-pyrimidine | Drug Info | IC50 = 27 nM | [1] | ||
6-(4-Methylpyridin-3-yl)-2-naphthonitrile | Drug Info | IC50 = 52 nM | [6] | ||
6-(pyridin-3-yl)-2-naphthonitrile | Drug Info | IC50 = 691 nM | [6] | ||
6-Isoquinolin-4-yl-3,4-dihydroquinolin-2(1H)-one | Drug Info | IC50 = 33 nM | [8] | ||
6-Pyridin-3-yl-1,2,3,4-tetrahydronaphthalen-2-ol | Drug Info | IC50 = 4921 nM | [8] | ||
6-Pyridin-3-yl-3,4-dihydro-1H-quinolin-2-one | Drug Info | IC50 = 6746 nM | [8] | ||
6-Pyridin-3-yl-3,4-dihydronaphthalen-2(1H)-one | Drug Info | IC50 = 3964 nM | [8] | ||
6-Pyridin-3-yl-3,4-dihydroquinoline-2(1H)-thione | Drug Info | IC50 = 580 nM | [8] | ||
6-Pyridin-3-yl-naphthalen-2-ol | Drug Info | IC50 = 2671 nM | [3] | ||
6-[4-(Pyridin-4-ylmethyl)phenyl]naphthalen-2-ol | Drug Info | IC50 = 627 nM | [11] | ||
7-Pyridin-3-yl-2H-1,4-benzothiazin-3(4H)-one | Drug Info | IC50 = 525 nM | [8] | ||
ABIRATERONE | Drug Info | IC50 = 1610 nM | [10] | ||
Methyl 3-(1-Benzyl-1H-imidazol-5-yl)-propanoate | Drug Info | IC50 = 326 nM | [9] | ||
N-(4'-Isonicotinoylbiphenyl-3-yl)acetamide | Drug Info | IC50 = 307 nM | [11] | ||
R-fadrozole | Drug Info | IC50 = 119 nM | [9] | ||
References | |||||
REF 1 | Synthesis and evaluation of (pyridylmethylene)tetrahydronaphthalenes/-indanes and structurally modified derivatives: potent and selective inhibitor... J Med Chem. 2005 Mar 10;48(5):1563-75. | ||||
REF 2 | Synthesis and evaluation of imidazolylmethylenetetrahydronaphthalenes and imidazolylmethyleneindanes: potent inhibitors of aldosterone synthase. J Med Chem. 2005 Mar 24;48(6):1796-805. | ||||
REF 3 | Heteroaryl-substituted naphthalenes and structurally modified derivatives: selective inhibitors of CYP11B2 for the treatment of congestive heart fa... J Med Chem. 2005 Oct 20;48(21):6632-42. | ||||
REF 4 | Development and evaluation of a pharmacophore model for inhibitors of aldosterone synthase (CYP11B2). Bioorg Med Chem Lett. 2006 Jan 1;16(1):25-30. | ||||
REF 5 | Synthesis and evaluation of heteroaryl-substituted dihydronaphthalenes and indenes: potent and selective inhibitors of aldosterone synthase (CYP11B... J Med Chem. 2006 Apr 6;49(7):2222-31. | ||||
REF 6 | Overcoming undesirable CYP1A2 inhibition of pyridylnaphthalene-type aldosterone synthase inhibitors: influence of heteroaryl derivatization on pote... J Med Chem. 2008 Aug 28;51(16):5064-74. | ||||
REF 7 | Novel aldosterone synthase inhibitors with extended carbocyclic skeleton by a combined ligand-based and structure-based drug design approach. J Med Chem. 2008 Oct 9;51(19):6138-49. | ||||
REF 8 | In vivo active aldosterone synthase inhibitors with improved selectivity: lead optimization providing a series of pyridine substituted 3,4-dihydro-... J Med Chem. 2008 Dec 25;51(24):8077-87. | ||||
REF 9 | Synthesis, biological evaluation, and molecular modeling of 1-benzyl-1H-imidazoles as selective inhibitors of aldosterone synthase (CYP11B2). J Med Chem. 2010 Feb 25;53(4):1712-25. | ||||
REF 10 | Isopropylidene substitution increases activity and selectivity of biphenylmethylene 4-pyridine type CYP17 inhibitors. J Med Chem. 2010 Jul 8;53(13):5049-53. | ||||
REF 11 | Replacement of imidazolyl by pyridyl in biphenylmethylenes results in selective CYP17 and dual CYP17/CYP11B1 inhibitors for the treatment of prosta... J Med Chem. 2010 Aug 12;53(15):5749-58. | ||||
REF 12 | Selective thromboxane synthetase inhibitors. 2. 3-(1H-imidazol-1-ylmethyl)-2-methyl-1H-indole-1-propanoic acid and analogues. J Med Chem. 1986 Mar;29(3):342-6. | ||||
REF 13 | Selective thromboxane synthetase inhibitors. 1. 1-[(Aryloxy)alkyl]-1H-imidazoles. J Med Chem. 1985 Oct;28(10):1427-32. | ||||
REF 14 | Structure-activity relationship study of the inhibition of adrenal cortical 11 beta-hydroxylase by new metyrapone analogues. J Med Chem. 1984 Jan;27(1):15-9. | ||||
REF 15 | Mitochondrial cytochrome p450. A component of chick kidney 25-hydrocholecalciferol-1alpha-hydroxylase. J Biol Chem. 1974 May 25;249(10):3026-33. | ||||
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