Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZUFI5)

• DTT Name: Nitric-oxide synthase brain (NOS1)
• Synonyms: Peptidyl-cysteine S-nitrosylase NOS1; Nitric oxide synthase, brain; Neuronal NOS; NOS, type I; NOS type I; NNOS; NC-NOS; N-NOS; BNOS
• Gene Name: NOS1
• DTT Type: Clinical trial target; [1]
• Related Disease:
  Headache [ICD-11: 8A80-8A84]
  Migraine [ICD-11: 8A80]
• BioChemical Class: Paired donor oxygen oxidoreductase
• UniProt ID: NOS1_HUMAN
• TTD ID: T16117
• EC Number: EC 1.14.13.39
• Sequence:
  MEDHMFGVQQIQPNVISVRLFKRKVGGLGFLVKERVSKPPVIISDLIRGGAAEQSGLIQA
  GDIILAVNGRPLVDLSYDSALEVLRGIASETHVVLILRGPEGFTTHLETTFTGDGTPKTI
  RVTQPLGPPTKAVDLSHQPPAGKEQPLAVDGASGPGNGPQHAYDDGQEAGSLPHANGLAP
  RPPGQDPAKKATRVSLQGRGENNELLKEIEPVLSLLTSGSRGVKGGAPAKAEMKDMGIQV
  DRDLDGKSHKPLPLGVENDRVFNDLWGKGNVPVVLNNPYSEKEQPPTSGKQSPTKNGSPS
  KCPRFLKVKNWETEVVLTDTLHLKSTLETGCTEYICMGSIMHPSQHARRPEDVRTKGQLF
  PLAKEFIDQYYSSIKRFGSKAHMERLEEVNKEIDTTSTYQLKDTELIYGAKHAWRNASRC
  VGRIQWSKLQVFDARDCTTAHGMFNYICNHVKYATNKGNLRSAITIFPQRTDGKHDFRVW
  NSQLIRYAGYKQPDGSTLGDPANVQFTEICIQQGWKPPRGRFDVLPLLLQANGNDPELFQ
  IPPELVLEVPIRHPKFEWFKDLGLKWYGLPAVSNMLLEIGGLEFSACPFSGWYMGTEIGV
  RDYCDNSRYNILEEVAKKMNLDMRKTSSLWKDQALVEINIAVLYSFQSDKVTIVDHHSAT
  ESFIKHMENEYRCRGGCPADWVWIVPPMSGSITPVFHQEMLNYRLTPSFEYQPDPWNTHV
  WKGTNGTPTKRRAIGFKKLAEAVKFSAKLMGQAMAKRVKATILYATETGKSQAYAKTLCE
  IFKHAFDAKVMSMEEYDIVHLEHETLVLVVTSTFGNGDPPENGEKFGCALMEMRHPNSVQ
  EERKSYKVRFNSVSSYSDSQKSSGDGPDLRDNFESAGPLANVRFSVFGLGSRAYPHFCAF
  GHAVDTLLEELGGERILKMREGDELCGQEEAFRTWAKKVFKAACDVFCVGDDVNIEKANN
  SLISNDRSWKRNKFRLTFVAEAPELTQGLSNVHKKRVSAARLLSRQNLQSPKSSRSTIFV
  RLHTNGSQELQYQPGDHLGVFPGNHEDLVNALIERLEDAPPVNQMVKVELLEERNTALGV
  ISNWTDELRLPPCTIFQAFKYYLDITTPPTPLQLQQFASLATSEKEKQRLLVLSKGLQEY
  EEWKWGKNPTIVEVLEEFPSIQMPATLLLTQLSLLQPRYYSISSSPDMYPDEVHLTVAIV
  SYRTRDGEGPIHHGVCSSWLNRIQADELVPCFVRGAPSFHLPRNPQVPCILVGPGTGIAP
  FRSFWQQRQFDIQHKGMNPCPMVLVFGCRQSKIDHIYREETLQAKNKGVFRELYTAYSRE
  PDKPKKYVQDILQEQLAESVYRALKEQGGHIYVCGDVTMAADVLKAIQRIMTQQGKLSAE
  DAGVFISRMRDDNRYHEDIFGVTLRTYEVTNRLRSESIAFIEESKKDTDEVFSS
• Function: In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body.
• KEGG Pathway:
  Arginine and proline metabolism (hsa00330)
  Metabolic pathways (hsa01100)
  Calcium signaling pathway (hsa04020)
  Phagosome (hsa04145)
  Circadian entrainment (hsa04713)
  Long-term depression (hsa04730)
  Salivary secretion (hsa04970)
  Alzheimer's disease (hsa05010)
  Amyotrophic lateral sclerosis (ALS) (hsa05014)
• Reactome Pathway:
  Nitric oxide stimulates guanylate cyclase (R-HSA-392154)
  ROS production in response to bacteria (R-HSA-1222556)
• BioCyc Pathway: MetaCyc:HS01647-MON

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NXN-188	DMMBAIH	Migraine	8A80	Phase 2	[2]
NXN-462	DMWVBS2	Headache	8A80-8A84	Phase 2	[1]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-NIL	DM6Y49D	N. A.	N. A.	Terminated	[3]

122 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
((E)-7-But-2-enyl)-azepan-(2Z)-ylideneamine	DMCW65Q	Discovery agent	N.A.	Investigative	[4]
(+/-)-2-Methyl-1-(1-phenylethyl)-1H-imidazole	DMJ6MPO	Discovery agent	N.A.	Investigative	[5]
(4S,5R)-4,5-Diethyl-oxazolidin-(2Z)-ylideneamine	DMM6QV5	Discovery agent	N.A.	Investigative	[6]
(4S,5R)-4,5-Dimethyl-oxazolidin-(2Z)-ylideneamine	DM0V9HB	Discovery agent	N.A.	Investigative	[6]
(4S,5S)-4,5-Diethyl-oxazolidin-(2Z)-ylideneamine	DM1VJUZ	Discovery agent	N.A.	Investigative	[6]
(5-Imino-[1,4]thiazepan-3-yl)-methanol	DMBKZDJ	Discovery agent	N.A.	Investigative	[7]
(5S,6R)-[Octahydro-quinolin-(2E)-ylidene]amine	DMT9CXD	Discovery agent	N.A.	Investigative	[8]
(5S,6S)-[Octahydro-quinolin-(2E)-ylidene]amine	DMP4UC1	Discovery agent	N.A.	Investigative	[8]
(6r,1'r,2's)-5,6,7,8 Tetrahydrobiopterin	DMOD9R7	Discovery agent	N.A.	Investigative	[9]
(R)-3-Propyl-[1,4]thiazepan-(5E)-ylideneamine	DM1Y9MZ	Discovery agent	N.A.	Investigative	[7]
(S)-2-Amino-5-(N-methyl-guanidino)-pentanoic acid	DMZSWDM	Discovery agent	N.A.	Investigative	[10]
(S)-3-Propyl-[1,4]thiazepan-(5E)-ylideneamine	DMIG9H3	Discovery agent	N.A.	Investigative	[7]
(S)-6-Amino-2-(2-imino-ethylamino)-hexanoic acid	DMG58HM	Discovery agent	N.A.	Investigative	[7]
1-(2-amino-benzothiazol-5-yl)-2-ethyl-isothiourea	DMAE8BF	Discovery agent	N.A.	Investigative	[11]
1-(2-amino-benzothiazol-6-yl)-2-ethyl-isothiourea	DMCSHRL	Discovery agent	N.A.	Investigative	[11]
1-(Benzhydrylamino)ethaniminium bromide	DMOJC9Z	Discovery agent	N.A.	Investigative	[5]
1-Benzyl-2-methyl-1H-imidazole	DMEVO6M	Discovery agent	N.A.	Investigative	[5]
1-[(3-Methoxybenzyl)amino]ethaniminium chloride	DM7U0XW	Discovery agent	N.A.	Investigative	[5]
1400W	DMLZT64	Discovery agent	N.A.	Investigative	[12], [5]
2'-Monophosphoadenosine 5'-Diphosphoribose	DME9S8M	Discovery agent	N.A.	Investigative	[9]
2-(2-Amino-ethyl)-7-imino-azepane	DM3JM7V	Discovery agent	N.A.	Investigative	[4]
2-amino-4,6-dimethylpyridine	DMVJXQ9	Discovery agent	N.A.	Investigative	[13]
2-amino-4-methylpyridine	DM1OED2	Discovery agent	N.A.	Investigative	[14]
2-Amino-5-(N-nitro-guanidino)-pentanoic acid	DMDUZ2H	Discovery agent	N.A.	Investigative	[10]
2-aminopyridine	DMQIC3L	Discovery agent	N.A.	Investigative	[13]
2-Aminothiazoline	DM9YCAH	Discovery agent	N.A.	Investigative	[15]
2-Methyl-[1,4]thiazepan-(5E)-ylideneamine	DMX1IC4	Discovery agent	N.A.	Investigative	[7]
3,4-Dihydro-1H-quinolin-(2E)-ylideneamine	DM0I6UT	Discovery agent	N.A.	Investigative	[8]
3,4-Dimethyl-pyrrolidin-(2Z)-ylideneamine	DMMO6QI	Discovery agent	N.A.	Investigative	[15]
3-(2-Amino-ethyl)-5-imino-[1,4]oxazepane	DM95R6O	Discovery agent	N.A.	Investigative	[4]
3-(2-Nitro-ethyl)-[1,4]oxazepan-(5Z)-ylideneamine	DMYXQ7L	Discovery agent	N.A.	Investigative	[4]
3-Bromo-1H-indazole-7-carbonitrile	DMZGWL2	Discovery agent	N.A.	Investigative	[16]
3-bromo-7-nitro-1H-indazole	DMM7DHB	Discovery agent	N.A.	Investigative	[9], [17]
3-Butyl-[1,4]thiazepan-(5E)-ylideneamine	DM6A80U	Discovery agent	N.A.	Investigative	[7]
3-Ethyl-[1,4]thiazepan-(5E)-ylideneamine	DMX2JKQ	Discovery agent	N.A.	Investigative	[7]
3-Isobutyl-[1,4]thiazepan-(5E)-ylideneamine	DMQXP7C	Discovery agent	N.A.	Investigative	[7]
3-Methyl-pyrrolidin-(2Z)-ylideneamine	DMHVUF8	Discovery agent	N.A.	Investigative	[15]
3-Methyl-[1,4]thiazepan-(5E)-ylideneamine	DMCOH46	Discovery agent	N.A.	Investigative	[7]
3-Propyl-[1,4]thiazepan-(5E)-ylideneamine	DMYACO7	Discovery agent	N.A.	Investigative	[7]
4,5,6,7-tetrafluoro-3-methyl-1H-indazole	DMTC7J2	Discovery agent	N.A.	Investigative	[17]
4,5-Dimethyl-pyrrolidin-(2Z)-ylideneamine	DMB9CJM	Discovery agent	N.A.	Investigative	[15]
4-bromo-1H-indazole	DM81D90	Discovery agent	N.A.	Investigative	[18]
4-Butyl-thiazolidin-(2E)-ylideneamine	DMKU4TR	Discovery agent	N.A.	Investigative	[15]
4-chloro-1H-indazole	DMHNSXP	Discovery agent	N.A.	Investigative	[18]
4-Ethyl-3-methyl-pyrrolidin-(2Z)-ylideneamine	DM5G3NU	Discovery agent	N.A.	Investigative	[15]
4-Ethyl-5-methyl-pyrrolidin-(2Z)-ylideneamine	DMOAQ1E	Discovery agent	N.A.	Investigative	[15]
4-Ethyl-oxazolidin-(2Z)-ylideneamine	DMG0Y3W	Discovery agent	N.A.	Investigative	[6]
4-Ethyl-pyrrolidin-(2Z)-ylideneamine	DMYIWAH	Discovery agent	N.A.	Investigative	[15]
4-iodo-1H-indazole	DMKZQ3I	Discovery agent	N.A.	Investigative	[18]
4-Isopropyl-pyrrolidin-(2Z)-ylideneamine	DMVTEOQ	Discovery agent	N.A.	Investigative	[15]
4-Methyl-5-propyl-pyrrolidin-(2Z)-ylideneamine	DMN8Z3C	Discovery agent	N.A.	Investigative	[15]
4-methyl-6-propylpyridin-2-amine	DMY04D1	Discovery agent	N.A.	Investigative	[14]
4-Methyl-oxazolidin-(2Z)-ylideneamine	DME7W0Q	Discovery agent	N.A.	Investigative	[6]
4-Methyl-piperidin-(2E)-ylideneamine	DMNMXCE	Discovery agent	N.A.	Investigative	[8]
4-Methyl-pyrrolidin-(2Z)-ylideneamine	DM0YS36	Discovery agent	N.A.	Investigative	[15]
4-[(2-Methyl-1H-imidazol-1-yl)methyl]pyridine	DM8BPTQ	Discovery agent	N.A.	Investigative	[5]
5-bromo-1H-indazole	DM2QPHE	Discovery agent	N.A.	Investigative	[18]
5-Bromomethyl-oxazolidin-(2Z)-ylideneamine	DMH908V	Discovery agent	N.A.	Investigative	[6]
5-chloro-1H-indazole	DMOCYDU	Discovery agent	N.A.	Investigative	[18]
5-Ethyl-3-methyl-pyrrolidin-(2Z)-ylideneamine	DMS9TFC	Discovery agent	N.A.	Investigative	[15]
5-Ethyl-4-methyl-pyrrolidin-(2Z)-ylideneamine	DMQWOIG	Discovery agent	N.A.	Investigative	[15]
5-Ethyl-4-propyl-pyrrolidin-(2Z)-ylideneamine	DMSA8X2	Discovery agent	N.A.	Investigative	[15]
5-Ethyl-oxazolidin-(2Z)-ylideneamine	DM8Y4G5	Discovery agent	N.A.	Investigative	[6]
5-iodo-1H-indazole	DM4NQY6	Discovery agent	N.A.	Investigative	[18]
5-Methyl-oxazolidin-(2Z)-ylideneamine	DMBQS31	Discovery agent	N.A.	Investigative	[6]
5-Methyl-pyrrolidin-(2Z)-ylideneamine	DM4QB3G	Discovery agent	N.A.	Investigative	[15]
5-N-Allyl-Arginine	DMOSKJ8	Discovery agent	N.A.	Investigative	[9]
6-(2-Fluoropropyl)-4-methylpyridin-2-amine	DME1JLM	Discovery agent	N.A.	Investigative	[19]
6-(3-Fluoropropyl)-4-methylpyridin-2-amine	DMTJPZU	Discovery agent	N.A.	Investigative	[19]
6-bromo-1H-indazole	DMU9WG0	Discovery agent	N.A.	Investigative	[18]
6-chloro-1H-indazole	DMKCBIL	Discovery agent	N.A.	Investigative	[18]
6-isobutyl-4-methylpyridin-2-amine	DM2XB68	Discovery agent	N.A.	Investigative	[19]
7-(2-Nitro-ethyl)-azepan-(2Z)-ylideneamine	DMK28IS	Discovery agent	N.A.	Investigative	[4]
7-bromo-1H-indazole	DMYBNCO	Discovery agent	N.A.	Investigative	[18]
7-Butyl-azepan-(2Z)-ylideneamine	DMVTK0A	Discovery agent	N.A.	Investigative	[4]
7-chloro-1H-indazole	DMX8DZM	Discovery agent	N.A.	Investigative	[18]
7-Methoxy-1H-indazole	DMTFBCU	Discovery agent	N.A.	Investigative	[20]
7-Methyl-[1,4]thiazepan-(5E)-ylideneamine	DMUCJA6	Discovery agent	N.A.	Investigative	[7]
7-nitro-1H-indazole	DMW4XKQ	Discovery agent	N.A.	Investigative	[17]
Acetate Ion	DMD08RH	Discovery agent	N.A.	Investigative	[9]
Alpha-D-Mannose	DMF5DLW	Discovery agent	N.A.	Investigative	[9]
AR-C102222	DMWVULN	Discovery agent	N.A.	Investigative	[14]
AR-C133057XX	DM71WQT	Discovery agent	N.A.	Investigative	[14]
Azepan-(2Z)-ylideneamine	DMZHV39	Discovery agent	N.A.	Investigative	[4]
Azocan-(2Z)-ylideneamine	DMQ13PZ	Discovery agent	N.A.	Investigative	[4]
Azonan-(2Z)-ylideneamine	DMTQSNK	Discovery agent	N.A.	Investigative	[10]
EUSYNSTYELAMIDE B	DMXBGSL	Discovery agent	N.A.	Investigative	[21]
Eusynstyelamide C	DM6ODAS	Discovery agent	N.A.	Investigative	[21]
Flavin-Adenine Dinucleotide	DM5S4GK	Discovery agent	N.A.	Investigative	[9]
Formic Acid	DMNFZC6	Discovery agent	N.A.	Investigative	[9]
Heme	DMGC287	Discovery agent	N.A.	Investigative	[12]
Hexahydro-cyclopenta[b]pyrrol-(2Z)-ylideneamine	DMNZLD6	Discovery agent	N.A.	Investigative	[15]
Hexahydro-cyclopenta[c]pyrrol-(1Z)-ylideneamine	DMG0UVT	Discovery agent	N.A.	Investigative	[15]
Hexahydro-pyrrolizin-(3E)-ylideneamine	DMIB3J2	Discovery agent	N.A.	Investigative	[15]
L-NIO	DME9FAV	Discovery agent	N.A.	Investigative	[22]
N*1*-(5-Methyl-2-nitro-phenyl)-butane-1,4-diamine	DM8JQEO	Discovery agent	N.A.	Investigative	[23]
N-(5-Amino-6-oxo-heptyl)-acetamidine	DM47XR8	Discovery agent	N.A.	Investigative	[15]
N-Butyl-N'-Hydroxyguanidine	DMKCX5N	Discovery agent	N.A.	Investigative	[9]
N-Isopropyl-N'-Hydroxyguanidine	DMIVO8P	Discovery agent	N.A.	Investigative	[9]
N-omega-allyl-L-arginine	DM0BPCT	Discovery agent	N.A.	Investigative	[22]
N-Omega-Hydroxy-L-Arginine	DMOXQ3N	Discovery agent	N.A.	Investigative	[9]
N-omega-propargyl-L-arginine	DM9X3B7	Discovery agent	N.A.	Investigative	[22]
N-Omega-Propyl-L-Arginine	DM4X0WY	Discovery agent	N.A.	Investigative	[9]
N5-(1-Imino-3-Butenyl)-L-Ornithine	DMY3O6N	Discovery agent	N.A.	Investigative	[9]
N5-(1-iminobut-3-enyl)-L-ornithine	DMB62OI	Discovery agent	N.A.	Investigative	[22]
N5-(1-iminobutyl)-L-ornithine	DMT893N	Discovery agent	N.A.	Investigative	[22]
N5-(1-iminopent-3-enyl)-L-ornithine	DM0TS21	Discovery agent	N.A.	Investigative	[22]
N5-(1-iminopropyl)-L-ornithine	DM05O7J	Discovery agent	N.A.	Investigative	[22]
Nitroarginine	DM7T80N	N. A.	N. A.	Investigative	[24]
Octahydro-isoindol-(1Z)-ylideneamine	DM4C70S	Discovery agent	N.A.	Investigative	[15]
Piperidin-(2E)-ylideneamine	DMN8OR2	Discovery agent	N.A.	Investigative	[8]
Pyrrolidin-(2Z)-ylideneamine	DMS4ZFU	Discovery agent	N.A.	Investigative	[15]
S-Ethyl-N-Phenyl-Isothiourea	DM6DT9Z	Discovery agent	N.A.	Investigative	[12]
S-Ethyl-N-[4-(Trifluoromethyl)Phenyl]Isothiourea	DM49AYM	Discovery agent	N.A.	Investigative	[12]
Tetrahydro-pyrimidin-2-ylideneamine	DMMU6WQ	Discovery agent	N.A.	Investigative	[10]
THIOCITRULLINE	DM7X8MH	Discovery agent	N.A.	Investigative	[25]
[1,3]Oxazinan-(2E)-ylideneamine	DMDX6W4	Discovery agent	N.A.	Investigative	[10]
[1,3]Thiazinan-(2E)-ylideneamine	DMOEIHC	Discovery agent	N.A.	Investigative	[10]
[1,4]Oxazepan-(3E)-ylideneamine	DMX58NK	Discovery agent	N.A.	Investigative	[7]
[1,4]Oxazepan-(5E)-ylideneamine	DMMUZVS	Discovery agent	N.A.	Investigative	[7]
[1,4]Thiazepan-(3E)-ylideneamine	DMCBFJQ	Discovery agent	N.A.	Investigative	[7]
[1,4]Thiazepan-(5E)-ylideneamine	DMFQ0Z4	Discovery agent	N.A.	Investigative	[7]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Asthma	CA23	Nasal and bronchial airway	5.20E-01	0.02	0.07
Sepsis with septic shock	1G41	Whole blood	1.03E-09	0.06	0.41

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Nitric oxide synthase brain (NOS1) DME Info
• Gene Name: NOS1

1 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[26]

References

• [1] ClinicalTrials.gov (NCT01748877) Efficacy, Tolerability, and Safety of NXN-462 in Patients With Post-Herpetic Neuralgia. U.S. National Institutes of Health.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Discovery of a series of aminopiperidines as novel iNOS inhibitors. Bioorg Med Chem Lett. 2008 Jan 1;18(1):336-43.
• [4] Selective heterocyclic amidine inhibitors of human inducible nitric oxide synthase. Bioorg Med Chem Lett. 2001 Oct 8;11(19):2651-3.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [10] 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.
• [11] Novel 2-aminobenzothiazoles as selective neuronal nitric oxide synthase inhibitors. Bioorg Med Chem Lett. 2007 May 1;17(9):2540-4.
• [12] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [13] 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.
• [14] Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase. Nat Chem Biol. 2008 Nov;4(11):700-7.
• [15] 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.
• [16] 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.
• [17] Fluorinated indazoles as novel selective inhibitors of nitric oxide synthase (NOS): synthesis and biological evaluation. Bioorg Med Chem. 2009 Sep 1;17(17):6180-7.
• [18] 4-substituted indazoles as new inhibitors of neuronal nitric oxide synthase. Bioorg Med Chem Lett. 2007 Jun 1;17(11):3177-80.
• [19] 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.
• [20] Inhibition of neuronal nitric oxide synthase by 7-methoxyindazole and related substituted indazoles. Bioorg Med Chem Lett. 2001 May 7;11(9):1153-6.
• [21] Eusynstyelamides A, B, and C, nNOS inhibitors, from the ascidian Eusynstyela latericius. J Nat Prod. 2009 Jun;72(6):1115-20.
• [22] Structure-activity relationship of novel and known inhibitors of human dimethylarginine dimethylaminohydrolase-1: alkenyl-amidines as new leads. Bioorg Med Chem. 2008 Dec 15;16(24):10205-9.
• [23] Nitroaromatic amino acids as inhibitors of neuronal nitric oxide synthase. J Med Chem. 1998 Jul 2;41(14):2636-42.
• [24] Crystal structure of nitric oxide synthase bound to nitro indazole reveals a novel inactivation mechanism. Biochemistry. 2001 Nov 13;40(45):13448-55.
• [25] 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.
• [26] The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. FASEB J. 2004 Apr;18(6):664-75.