Target Validation Information
Target ID T06046
Target Name Nitric-oxide synthase, endothelial
Target Type
Clinical Trial
Drug Potency against Target 4-Methyl-3,6-dihydro-1H-pyridin-(2Z)-ylideneamine Drug Info IC50 = 440 nM [526394]
3-Bromo-1H-indazole-7-carbonitrile Drug Info IC50 = 13000 nM [529494]
Thiazolidin-(2E)-ylideneamine Drug Info IC50 = 1100 nM [527210]
L-NAME Drug Info IC50 = 1000 nM [552681]
3-bromo-7-nitro-1H-indazole Drug Info IC50 = 2000 nM [529494]
1-(2-amino-benzothiazol-6-yl)-2-ethyl-isothiourea Drug Info IC50 = 9200 nM [528695]
4-Methyl-5,6-dihydro-1H-pyridin-(2Z)-ylideneamine Drug Info IC50 = 230 nM [526394]
5-Ethyl-3-methyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 5500 nM [527210]
2-Amino-5-(N-nitro-guanidino)-pentanoic acid Drug Info IC50 = 500 nM [534097]
5-Methyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 1900 nM [527210]
[1,4]Thiazepan-(5E)-ylideneamine Drug Info IC50 = 13400 nM [527266]
[1,4]Oxazepan-(3E)-ylideneamine Drug Info IC50 = 450 nM [527266]
Azepan-(2Z)-ylideneamine Drug Info IC50 = 15250 nM [526140]
4-Methyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 2600 nM [527210]
Hexahydro-cyclopenta[c]pyrrol-(1Z)-ylideneamine Drug Info IC50 = 4700 nM [527210]
7-Methyl-[1,4]thiazepan-(5E)-ylideneamine Drug Info IC50 = 5000 nM [527266]
N-(5-Amino-6-oxo-heptyl)-acetamidine Drug Info IC50 = 7900 nM [527210]
[1,3]Oxazinan-(2E)-ylideneamine Drug Info IC50 = 8200 nM [534097]
7-(2-Nitro-ethyl)-azepan-(2Z)-ylideneamine Drug Info IC50 = 2770 nM [526140]
5-Ethyl-4-methyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 520 nM [527210]
4-Ethyl-5-methyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 6300 nM [527210]
6-(3-Fluoropropyl)-4-methylpyridin-2-amine Drug Info IC50 = 1428 nM [530039]
4-Ethyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 14500 nM [527210]
(5S,6R)-[Octahydro-quinolin-(2E)-ylidene]amine Drug Info IC50 = 5500 nM [527502]
(5S,6S)-[Octahydro-quinolin-(2E)-ylidene]amine Drug Info IC50 = 12500 nM [527502]
3,4-Dimethyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 8700 nM [527210]
6-(2-Fluoropropyl)-4-methylpyridin-2-amine Drug Info IC50 = 1500 nM [530039]
(S)-6-Amino-2-(2-imino-ethylamino)-hexanoic acid Drug Info IC50 = 7900 nM [527266]
(S)-3-Propyl-[1,4]thiazepan-(5E)-ylideneamine Drug Info IC50 = 1000 nM [527266]
4-methyl-6-propylpyridin-2-amine Drug Info IC50 = 34 nM [529745]
Piperidin-(2E)-ylideneamine Drug Info IC50 = 630 nM [527502]
1-(2-amino-benzothiazol-5-yl)-2-ethyl-isothiourea Drug Info IC50 = 12000 nM [528695]
L-NIL Drug Info IC50 = 2500 nM [529159]
4-Ethyl-5,6-dihydro-1H-pyridin-(2Z)-ylideneamine Drug Info IC50 = 1500 nM [526394]
4-Methyl-piperidin-(2E)-ylideneamine Drug Info IC50 = 146 nM [527502]
[1,4]Thiazepan-(3E)-ylideneamine Drug Info IC50 = 10500 nM [527266]
L-NMMA Drug Info IC50 = 3000 nM [534283]
L-Nw-nitroarginine Drug Info Ki = 750 nM [531224]
THIOCITRULLINE Drug Info IC50 = 400 nM [527563]
6-isobutyl-4-methylpyridin-2-amine Drug Info IC50 = 150 nM [530039]
4-methylpyridin-2-amine Drug Info IC50 = 320 nM [529745]
(S)-2-Amino-5-(N-methyl-guanidino)-pentanoic acid Drug Info IC50 = 5900 nM [534097]
[1,3]Thiazinan-(2E)-ylideneamine Drug Info IC50 = 7100 nM [534097]
2-Methyl-[1,4]thiazepan-(5E)-ylideneamine Drug Info IC50 = 4100 nM [527266]
4,5-Dimethyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 600 nM [527210]
Pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 4600 nM [527210]
3-Methyl-pyrrolidin-(2Z)-ylideneamine Drug Info IC50 = 1800 nM [527210]
3-Methyl-[1,4]thiazepan-(5E)-ylideneamine Drug Info IC50 = 5000 nM [527266]
(5-Imino-[1,4]thiazepan-3-yl)-methanol Drug Info IC50 = 6000 nM [527266]
3-Ethyl-[1,4]thiazepan-(5E)-ylideneamine Drug Info IC50 = 1100 nM [527266]
Action against Disease Model L-NMMA We evaluated the contribution of endogenous and exogenous nitric oxide (NO) in ischaemia reperfusion (IR) injury and histamine release in the isolated guinea pig heart. Perfusion of the hearts with two inhibitors of the nitric oxide synthase pathway, namely N(G)-monomethyl-L-arginine (L-NMMA, 10(-4) M) or nitroarginine methylester (L-NAME, 10(-5) M) significantly enhanced histamine and LDH release; these effects were attenuated by co-infusion with L-arginine (10(-4) M) but not D-arginine (10(-4) M), while L-arginine (10(-4) M) alone had no effect. Perfusion of the heart with sodi uM nitroprusside (SNP), 3-morpholinosydnonimine (SIN-1), glyceryl trinitrate (GTN), all at 10(-5) M, reduced histamine release, LDH release, calci uM overload and MDA production induced by IR. [552208] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations Effect of ADMA infusion in knockout eNOS-/- mice:Plasma ADMA 1.9-2.8 mol/L;Speci?c phenotype:Increased medial thickening and perivascular ?brosis of coronary microvessels; Elevated blood pressure;Visceral obesity,impaired glucose tolerance [552208]
References
Ref 552208Cardioprotective activity of endogenous and exogenous nitric oxide on ischaemia reperfusion injury in isolated guinea pig hearts. Inflamm Res. 1999 Nov;48(11):561-8.
Ref 526394Bioorg Med Chem Lett. 2002 Sep 2;12(17):2291-4.Design and synthesis of orally bioavailable inhibitors of inducible nitric oxide synthase. Part 1: synthesis and biological evaluation of dihydropyridin-2-imines.
Ref 529494Bioorg Med Chem. 2008 Jun 1;16(11):5962-73. Epub 2008 Apr 26.Inhibitory effects of a series of 7-substituted-indazoles toward nitric oxide synthases: particular potency of 1H-indazole-7-carbonitrile.
Ref 527210Bioorg Med Chem Lett. 2004 Sep 6;14(17):4539-44.Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase.
Ref 552681A cell-based nitric oxide reporter assay useful for the identification and characterization of modulators of the nitric oxide/guanosine 3',5'-cyclic monophosphate pathway. Anal Biochem. 2007 Apr 15;363(2):219-27. Epub 2007 Feb 4.
Ref 529494Bioorg Med Chem. 2008 Jun 1;16(11):5962-73. Epub 2008 Apr 26.Inhibitory effects of a series of 7-substituted-indazoles toward nitric oxide synthases: particular potency of 1H-indazole-7-carbonitrile.
Ref 528695Bioorg Med Chem Lett. 2007 May 1;17(9):2540-4. Epub 2007 Feb 8.Novel 2-aminobenzothiazoles as selective neuronal nitric oxide synthase inhibitors.
Ref 526394Bioorg Med Chem Lett. 2002 Sep 2;12(17):2291-4.Design and synthesis of orally bioavailable inhibitors of inducible nitric oxide synthase. Part 1: synthesis and biological evaluation of dihydropyridin-2-imines.
Ref 527210Bioorg Med Chem Lett. 2004 Sep 6;14(17):4539-44.Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase.
Ref 534097J Med Chem. 1996 Feb 2;39(3):669-72.2-Iminopiperidine and other 2-iminoazaheterocycles as potent inhibitors of human nitric oxide synthase isoforms.
Ref 527210Bioorg Med Chem Lett. 2004 Sep 6;14(17):4539-44.Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase.
Ref 527266Bioorg Med Chem Lett. 2004 Dec 6;14(23):5907-11.Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases.
Ref 527266Bioorg Med Chem Lett. 2004 Dec 6;14(23):5907-11.Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases.
Ref 526140Bioorg Med Chem Lett. 2001 Oct 8;11(19):2651-3.Selective heterocyclic amidine inhibitors of human inducible nitric oxide synthase.
Ref 527210Bioorg Med Chem Lett. 2004 Sep 6;14(17):4539-44.Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase.
Ref 527210Bioorg Med Chem Lett. 2004 Sep 6;14(17):4539-44.Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase.
Ref 527266Bioorg Med Chem Lett. 2004 Dec 6;14(23):5907-11.Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases.
Ref 527210Bioorg Med Chem Lett. 2004 Sep 6;14(17):4539-44.Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase.
Ref 534097J Med Chem. 1996 Feb 2;39(3):669-72.2-Iminopiperidine and other 2-iminoazaheterocycles as potent inhibitors of human nitric oxide synthase isoforms.
Ref 526140Bioorg Med Chem Lett. 2001 Oct 8;11(19):2651-3.Selective heterocyclic amidine inhibitors of human inducible nitric oxide synthase.
Ref 527210Bioorg Med Chem Lett. 2004 Sep 6;14(17):4539-44.Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase.
Ref 527210Bioorg Med Chem Lett. 2004 Sep 6;14(17):4539-44.Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase.
Ref 530039J Med Chem. 2009 Apr 23;52(8):2443-53.Design and synthesis of 2-amino-4-methylpyridine analogues as inhibitors for inducible nitric oxide synthase and in vivo evaluation of [18F]6-(2-fluoropropyl)-4-methyl-pyridin-2-amine as a potential PET tracer for inducible nitric oxide synthase.
Ref 527210Bioorg Med Chem Lett. 2004 Sep 6;14(17):4539-44.Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase.
Ref 527502Bioorg Med Chem Lett. 2005 Apr 15;15(8):1997-2001.Bicyclic amidine inhibitors of nitric oxide synthase: discovery of perhydro-iminopyrindine and perhydro-iminoquinoline as potent, orally active inhibitors of inducible nitric oxide synthase.
Ref 527502Bioorg Med Chem Lett. 2005 Apr 15;15(8):1997-2001.Bicyclic amidine inhibitors of nitric oxide synthase: discovery of perhydro-iminopyrindine and perhydro-iminoquinoline as potent, orally active inhibitors of inducible nitric oxide synthase.
Ref 527210Bioorg Med Chem Lett. 2004 Sep 6;14(17):4539-44.Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase.
Ref 530039J Med Chem. 2009 Apr 23;52(8):2443-53.Design and synthesis of 2-amino-4-methylpyridine analogues as inhibitors for inducible nitric oxide synthase and in vivo evaluation of [18F]6-(2-fluoropropyl)-4-methyl-pyridin-2-amine as a potential PET tracer for inducible nitric oxide synthase.
Ref 527266Bioorg Med Chem Lett. 2004 Dec 6;14(23):5907-11.Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases.
Ref 527266Bioorg Med Chem Lett. 2004 Dec 6;14(23):5907-11.Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases.
Ref 529745Nat Chem Biol. 2008 Nov;4(11):700-7. Epub 2008 Oct 12.Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase.
Ref 527502Bioorg Med Chem Lett. 2005 Apr 15;15(8):1997-2001.Bicyclic amidine inhibitors of nitric oxide synthase: discovery of perhydro-iminopyrindine and perhydro-iminoquinoline as potent, orally active inhibitors of inducible nitric oxide synthase.
Ref 528695Bioorg Med Chem Lett. 2007 May 1;17(9):2540-4. Epub 2007 Feb 8.Novel 2-aminobenzothiazoles as selective neuronal nitric oxide synthase inhibitors.
Ref 529159Bioorg Med Chem Lett. 2008 Jan 1;18(1):336-43. Epub 2007 Oct 25.Discovery of a series of aminopiperidines as novel iNOS inhibitors.
Ref 526394Bioorg Med Chem Lett. 2002 Sep 2;12(17):2291-4.Design and synthesis of orally bioavailable inhibitors of inducible nitric oxide synthase. Part 1: synthesis and biological evaluation of dihydropyridin-2-imines.
Ref 527502Bioorg Med Chem Lett. 2005 Apr 15;15(8):1997-2001.Bicyclic amidine inhibitors of nitric oxide synthase: discovery of perhydro-iminopyrindine and perhydro-iminoquinoline as potent, orally active inhibitors of inducible nitric oxide synthase.
Ref 527266Bioorg Med Chem Lett. 2004 Dec 6;14(23):5907-11.Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases.
Ref 534283Br J Pharmacol. 1996 Nov;119(6):1101-8.2-Amino-4-methylpyridine as a potent inhibitor of inducible NO synthase activity in vitro and in vivo.
Ref 531224J Med Chem. 2010 Nov 11;53(21):7804-24.Exploration of the active site of neuronal nitric oxide synthase by the design and synthesis of pyrrolidinomethyl 2-aminopyridine derivatives.
Ref 527563Bioorg Med Chem Lett. 2005 Jun 2;15(11):2881-5. Epub 2005 Apr 25.Evaluation of 3-substituted arginine analogs as selective inhibitors of human nitric oxide synthase isozymes.
Ref 530039J Med Chem. 2009 Apr 23;52(8):2443-53.Design and synthesis of 2-amino-4-methylpyridine analogues as inhibitors for inducible nitric oxide synthase and in vivo evaluation of [18F]6-(2-fluoropropyl)-4-methyl-pyridin-2-amine as a potential PET tracer for inducible nitric oxide synthase.
Ref 529745Nat Chem Biol. 2008 Nov;4(11):700-7. Epub 2008 Oct 12.Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase.
Ref 534097J Med Chem. 1996 Feb 2;39(3):669-72.2-Iminopiperidine and other 2-iminoazaheterocycles as potent inhibitors of human nitric oxide synthase isoforms.
Ref 534097J Med Chem. 1996 Feb 2;39(3):669-72.2-Iminopiperidine and other 2-iminoazaheterocycles as potent inhibitors of human nitric oxide synthase isoforms.
Ref 527266Bioorg Med Chem Lett. 2004 Dec 6;14(23):5907-11.Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases.
Ref 527210Bioorg Med Chem Lett. 2004 Sep 6;14(17):4539-44.Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase.
Ref 527210Bioorg Med Chem Lett. 2004 Sep 6;14(17):4539-44.Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase.
Ref 527210Bioorg Med Chem Lett. 2004 Sep 6;14(17):4539-44.Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase.
Ref 527266Bioorg Med Chem Lett. 2004 Dec 6;14(23):5907-11.Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases.
Ref 527266Bioorg Med Chem Lett. 2004 Dec 6;14(23):5907-11.Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases.
Ref 527266Bioorg Med Chem Lett. 2004 Dec 6;14(23):5907-11.Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.