Target Validation Information
TTD ID T16117
Target Name Nitric-oxide synthase brain (NOS1)
Type of Target
Clinical trial
Drug Potency against Target Drug Info Ki = 4550 nM [17]
((E)-7-But-2-enyl)-azepan-(2Z)-ylideneamine Drug Info IC50 = 3390 nM [2]
(+/-)-2-Methyl-1-(1-phenylethyl)-1H-imidazole Drug Info IC50 = 5000 nM [16]
(4S,5R)-4,5-Diethyl-oxazolidin-(2Z)-ylideneamine Drug Info IC50 = 1200 nM [3]
(4S,5R)-4,5-Dimethyl-oxazolidin-(2Z)-ylideneamine Drug Info IC50 = 1600 nM [3]
(4S,5S)-4,5-Diethyl-oxazolidin-(2Z)-ylideneamine Drug Info IC50 = 2500 nM [3]
(5-Imino-[1,4]thiazepan-3-yl)-methanol Drug Info IC50 = 2700 nM [5]
(5S,6R)-[Octahydro-quinolin-(2E)-ylidene]amine Drug Info IC50 = 530 nM [7]
(5S,6S)-[Octahydro-quinolin-(2E)-ylidene]amine Drug Info IC50 = 246 nM [7]
(R)-3-Propyl-[1,4]thiazepan-(5E)-ylideneamine Drug Info IC50 = 7100 nM [5]
(S)-2-Amino-5-(N-methyl-guanidino)-pentanoic acid Drug Info IC50 = 10000 nM [18]
(S)-3-Propyl-[1,4]thiazepan-(5E)-ylideneamine Drug Info IC50 = 440 nM [5]
(S)-6-Amino-2-(2-imino-ethylamino)-hexanoic acid Drug Info IC50 = 17500 nM [5]
1-(2-amino-benzothiazol-5-yl)-2-ethyl-isothiourea Drug Info IC50 = 4600 nM [9]
1-(2-amino-benzothiazol-6-yl)-2-ethyl-isothiourea Drug Info IC50 = 1400 nM [9]
1-(Benzhydrylamino)ethaniminium bromide Drug Info IC50 = 300 nM [16]
1-Benzyl-2-methyl-1H-imidazole Drug Info IC50 = 5000 nM [16]
1-[(3-Methoxybenzyl)amino]ethaniminium chloride Drug Info IC50 = 10000 nM [16]
1400W Drug Info IC50 = 7300 nM [16]
2-(2-Amino-ethyl)-7-imino-azepane Drug Info IC50 = 932 nM [2]
2-amino-4,6-dimethylpyridine Drug Info IC50 = 100 nM [15]
2-amino-4-methylpyridine Drug Info IC50 = 160 nM [12]
2-Amino-5-(N-nitro-guanidino)-pentanoic acid Drug Info IC50 = 500 nM [18]
2-aminopyridine Drug Info IC50 = 8700 nM [15]
2-Aminothiazoline Drug Info IC50 = 1800 nM [4]
2-Methyl-[1,4]thiazepan-(5E)-ylideneamine Drug Info IC50 = 830 nM [5]
3,4-Dihydro-1H-quinolin-(2E)-ylideneamine Drug Info IC50 = 4900 nM [7]
3,4-Dimethyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 610 nM [4]
3-(2-Amino-ethyl)-5-imino-[1,4]oxazepane Drug Info IC50 = 8390 nM [2]
3-(2-Nitro-ethyl)-[1,4]oxazepan-(5Z)-ylideneamine Drug Info IC50 = 6240 nM [2]
3-Bromo-1H-indazole-7-carbonitrile Drug Info IC50 = 2500 nM [11]
3-Butyl-[1,4]thiazepan-(5E)-ylideneamine Drug Info IC50 = 1200 nM [5]
3-Ethyl-[1,4]thiazepan-(5E)-ylideneamine Drug Info IC50 = 590 nM [5]
3-Isobutyl-[1,4]thiazepan-(5E)-ylideneamine Drug Info IC50 = 1900 nM [5]
3-Methyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 900 nM [4]
3-Methyl-[1,4]thiazepan-(5E)-ylideneamine Drug Info IC50 = 1800 nM [5]
3-Propyl-[1,4]thiazepan-(5E)-ylideneamine Drug Info IC50 = 2800 nM [5]
4,5-Dimethyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 130 nM [4]
4-Butyl-thiazolidin-(2E)-ylideneamine Drug Info IC50 = 13200 nM [4]
4-Ethyl-3-methyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 610 nM [4]
4-Ethyl-5-methyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 140 nM [4]
4-Ethyl-oxazolidin-(2Z)-ylideneamine Drug Info IC50 = 2800 nM [3]
4-Ethyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 2600 nM [4]
4-Isopropyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 10600 nM [4]
4-Methyl-5-propyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 4800 nM [4]
4-methyl-6-propylpyridin-2-amine Drug Info IC50 = 23 nM [12]
4-Methyl-oxazolidin-(2Z)-ylideneamine Drug Info IC50 = 9800 nM [3]
4-Methyl-piperidin-(2E)-ylideneamine Drug Info IC50 = 16 nM [7]
4-Methyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 800 nM [4]
4-[(2-Methyl-1H-imidazol-1-yl)methyl]pyridine Drug Info IC50 = 5000 nM [16]
5-Bromomethyl-oxazolidin-(2Z)-ylideneamine Drug Info IC50 = 400 nM [3]
5-Ethyl-3-methyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 2400 nM [4]
5-Ethyl-4-methyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 80 nM [4]
5-Ethyl-4-propyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 17300 nM [4]
5-Ethyl-oxazolidin-(2Z)-ylideneamine Drug Info IC50 = 1800 nM [3]
5-Methyl-oxazolidin-(2Z)-ylideneamine Drug Info IC50 = 1400 nM [3]
5-Methyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 3100 nM [4]
6-(2-Fluoropropyl)-4-methylpyridin-2-amine Drug Info IC50 = 490 nM [13]
6-(3-Fluoropropyl)-4-methylpyridin-2-amine Drug Info IC50 = 514 nM [13]
6-isobutyl-4-methylpyridin-2-amine Drug Info IC50 = 100 nM [13]
7-(2-Nitro-ethyl)-azepan-(2Z)-ylideneamine Drug Info IC50 = 339 nM [2]
7-Butyl-azepan-(2Z)-ylideneamine Drug Info IC50 = 850 nM [2]
7-Methoxy-1H-indazole Drug Info IC50 = 6300 nM [1]
7-Methyl-[1,4]thiazepan-(5E)-ylideneamine Drug Info IC50 = 1000 nM [5]
AR-C102222 Drug Info IC50 = 790 nM [12]
AR-C133057XX Drug Info IC50 = 6000 nM [12]
Azepan-(2Z)-ylideneamine Drug Info IC50 = 3500 nM [2]
Azocan-(2Z)-ylideneamine Drug Info IC50 = 10150 nM [2]
Azonan-(2Z)-ylideneamine Drug Info IC50 = 6800 nM [18]
EUSYNSTYELAMIDE B Drug Info IC50 = 4300 nM [14]
Eusynstyelamide C Drug Info IC50 = 5800 nM [14]
Hexahydro-cyclopenta[b]pyrrol-(2Z)-ylideneamine Drug Info IC50 = 9900 nM [4]
Hexahydro-cyclopenta[c]pyrrol-(1Z)-ylideneamine Drug Info IC50 = 310 nM [4]
Hexahydro-pyrrolizin-(3E)-ylideneamine Drug Info IC50 = 9600 nM [4]
L-NIL Drug Info IC50 = 6000 nM [10]
N*1*-(5-Methyl-2-nitro-phenyl)-butane-1,4-diamine Drug Info IC50 = 2500 nM [19]
N-(5-Amino-6-oxo-heptyl)-acetamidine Drug Info IC50 = 17500 nM [4]
Octahydro-isoindol-(1Z)-ylideneamine Drug Info IC50 = 660 nM [4]
ONO-1714 Drug Info IC50 = 15 nM [3]
Piperidin-(2E)-ylideneamine Drug Info IC50 = 240 nM [7]
Pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 9600 nM [4]
Tetrahydro-pyrimidin-2-ylideneamine Drug Info IC50 = 17000 nM [18]
THIOCITRULLINE Drug Info IC50 = 60 nM [8]
[1,3]Oxazinan-(2E)-ylideneamine Drug Info IC50 = 3700 nM [18]
[1,3]Thiazinan-(2E)-ylideneamine Drug Info IC50 = 3200 nM [18]
[1,4]Oxazepan-(3E)-ylideneamine Drug Info IC50 = 160 nM [5]
[1,4]Oxazepan-(5E)-ylideneamine Drug Info IC50 = 8700 nM [5]
[1,4]Thiazepan-(3E)-ylideneamine Drug Info IC50 = 2800 nM [5]
[1,4]Thiazepan-(5E)-ylideneamine Drug Info IC50 = 4300 nM [5]
Action against Disease Model GW274150 Drug Info GW274150 was effective in inhibiting LPS-induced plasma NO(x) levels in mice with an ED(50) of 3.2+/-0.7 mg kg(-1) after 14 h intraperitoneally (i.p.) and 3.8+/-1.5 mg kg(-1) after 14 h when administered orally. GW273629 showed shorter-lived effects on plasma NO(x) and an ED(50) of 9+/-2 mg kg(-1) after 2 h when administered i.p. 5 The effects of GW274150 and GW273629 in vivo were consistent with high selectivity for iNOS, as these inhibitors were of low potency against nNOS in the rat cerebell uM and did not cause significant effects on blood pressure in instr uMented mice. [6]
References
REF 1 Inhibition of neuronal nitric oxide synthase by 7-methoxyindazole and related substituted indazoles. Bioorg Med Chem Lett. 2001 May 7;11(9):1153-6.
REF 2 Selective heterocyclic amidine inhibitors of human inducible nitric oxide synthase. Bioorg Med Chem Lett. 2001 Oct 8;11(19):2651-3.
REF 3 4,5-Disubstituted-1,3-oxazolidin-2-imine derivatives: a new class of orally bioavailable nitric oxide synthase inhibitor. Bioorg Med Chem Lett. 2004 Jan 19;14(2):313-6.
REF 4 Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase. Bioorg Med Chem Lett. 2004 Sep 6;14(17):4539-44.
REF 5 Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases. Bioorg Med Chem Lett. 2004 Dec 6;14(23):5907-11.
REF 6 GW274150 and GW273629 are potent and highly selective inhibitors of inducible nitric oxide synthase in vitro and in vivo. Br J Pharmacol. 2005 Jun;145(3):301-12.
REF 7 Bicyclic amidine inhibitors of nitric oxide synthase: discovery of perhydro-iminopyrindine and perhydro-iminoquinoline as potent, orally active inh... Bioorg Med Chem Lett. 2005 Apr 15;15(8):1997-2001.
REF 8 Evaluation of 3-substituted arginine analogs as selective inhibitors of human nitric oxide synthase isozymes. Bioorg Med Chem Lett. 2005 Jun 2;15(11):2881-5.
REF 9 Novel 2-aminobenzothiazoles as selective neuronal nitric oxide synthase inhibitors. Bioorg Med Chem Lett. 2007 May 1;17(9):2540-4.
REF 10 Discovery of a series of aminopiperidines as novel iNOS inhibitors. Bioorg Med Chem Lett. 2008 Jan 1;18(1):336-43.
REF 11 Inhibitory effects of a series of 7-substituted-indazoles toward nitric oxide synthases: particular potency of 1H-indazole-7-carbonitrile. Bioorg Med Chem. 2008 Jun 1;16(11):5962-73.
REF 12 Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase. Nat Chem Biol. 2008 Nov;4(11):700-7.
REF 13 Design and synthesis of 2-amino-4-methylpyridine analogues as inhibitors for inducible nitric oxide synthase and in vivo evaluation of [18F]6-(2-fl... J Med Chem. 2009 Apr 23;52(8):2443-53.
REF 14 Eusynstyelamides A, B, and C, nNOS inhibitors, from the ascidian Eusynstyela latericius. J Nat Prod. 2009 Jun;72(6):1115-20.
REF 15 L337H mutant of rat neuronal nitric oxide synthase resembles human neuronal nitric oxide synthase toward inhibitors. J Med Chem. 2009 Jul 23;52(14):4533-7.
REF 16 N-Substituted acetamidines and 2-methylimidazole derivatives as selective inhibitors of neuronal nitric oxide synthase. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6495-9.
REF 17 Exploration of the active site of neuronal nitric oxide synthase by the design and synthesis of pyrrolidinomethyl 2-aminopyridine derivatives. J Med Chem. 2010 Nov 11;53(21):7804-24.
REF 18 2-Iminopiperidine and other 2-iminoazaheterocycles as potent inhibitors of human nitric oxide synthase isoforms. J Med Chem. 1996 Feb 2;39(3):669-72.
REF 19 Nitroaromatic amino acids as inhibitors of neuronal nitric oxide synthase. J Med Chem. 1998 Jul 2;41(14):2636-42.

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