Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMKEFJ0)

• Drug Name: 5-chloro-3,4-dihydroquinazolin-2-amine Drug Info
• Synonyms: CHEMBL401541; 2-Amino-5-chlor-3,4-dihydrochinazolin; 109319-86-0

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 13702393
  TTD Drug ID: DMKEFJ0

Molecule-Related Drug Atlas

Drug(s) Targeting 5-HT 1D receptor (HTR1D)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[2]
Eletriptan	DMW649X	Migraine	8A80	Approved	[3]
Zolmitriptan	DM1IB4Q	Migraine	8A80	Approved	[3]
Frovatriptan	DM7RE8P	Migraine	8A80	Approved	[3]
Sumatriptan	DMVYXR8	Migraine	8A80	Approved	[4]
Rizatriptan	DMDJMA3	Migraine	8A80	Approved	[5]
Almogran	DM7I64Z	Migraine	8A80	Approved	[6]
Neu-P11	DMIQDFW	Alzheimer disease	8A20	Phase 2	[7]
FKB01MD	DM2O7NM	N. A.	N. A.	Phase 2	[8]
NXN-188	DMMBAIH	Migraine	8A80	Phase 2	[9]

Drug(s) Targeting 5-HT 5A receptor (HTR5A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[10]
(+/-)-nantenine	DM0L3GE	Discovery agent	N.A.	Investigative	[11]
Serotonin	DMOFCRY	Discovery agent	N.A.	Investigative	[12]
5-CT	DM260KD	Discovery agent	N.A.	Investigative	[13]
TFMPP	DMAC8TP	Discovery agent	N.A.	Investigative	[14]
5,6-dichloro-3,4-dihydroquinazolin-2-amine	DMN1S35	Discovery agent	N.A.	Investigative	[1]
MPDT	DMYX31S	Discovery agent	N.A.	Investigative	[15]
EDMT	DMS3AXK	Discovery agent	N.A.	Investigative	[15]
5-chloro-4-methyl-3,4-dihydroquinazolin-2-amine	DM7FZU2	Discovery agent	N.A.	Investigative	[1]
[3H]5-CT	DMEAHFZ	Discovery agent	N.A.	Investigative	[16]

Drug(s) Targeting 5-HT 2A receptor (HTR2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[17]
Zotepine	DMF3VXA	Anxiety disorder	6B00-6B0Z	Approved	[18]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[19]
Flibanserin	DM70DTN	Mood disorder	6A60-6E23	Approved	[20]
Lurasidone hydrochloride	DMCVPXO	Schizophrenia	6A20	Approved	[21]
Aniracetam	DMOIFW0	Cerebrovascular ischaemia	8B1Z	Approved	[22]
lumateperone tosylate	DMQ8HOJ	Schizophrenia	6A20	Approved	[23]
Sarpogrelate	DMGLP6S	Diabetic complication	5A2Y	Approved	[24]
Pimavanserin	DMR7IVC	Parkinson disease	8A00.0	Approved	[25]
Zicronapine	DMP8ESD	Schizophrenia	6A20	Phase 3	[26]

Drug(s) Targeting 5-HT 3A receptor (HTR3A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dolasetron	DMMG26Z	Nausea	MD90	Approved	[27]
Alosetron	DML2A03	Irritable bowel syndrome	DD91.0	Approved	[28]
Tropisetron	DMNSJ7V	Fibromyalgia	MG30.01	Approved	[29]
Palonosetron	DMBHMOX	Nausea	MD90	Approved	[30]
Levetiracetam	DMTGDN8	Epilepsy	8A60-8A68	Approved	[29]
Palonosetron + fosnetupitant	DMK2PBD	Chemotherapy-induced nausea	MD90	Approved	[31]
Procaine	DM4LSNE	Anaesthesia	9A78.6	Approved	[32]
Cilansetron	DMP0NGX	Irritable bowel syndrome	DD91.0	Phase 3	[33]
BEMESETRON	DMSPJX9	N. A.	N. A.	Discontinued in Phase 3	[34]
Norcisapride	DMJSKUI	Gastroesophageal reflux disease	DA22.Z	Discontinued in Phase 2	[35]

Drug(s) Targeting 5-HT 1A receptor (HTR1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Trazodone	DMK1GBJ	Depression	6A70-6A7Z	Approved	[3]
Buspirone	DMBS632	Anxiety disorder	6B00-6B0Z	Approved	[36]
OPC-34712	DMHG57U	Major depressive disorder	6A70.3	Approved	[37]
Vilazodone	DM4LECQ	Major depressive disorder	6A70.3	Approved	[38]
Flibanserin	DM70DTN	Mood disorder	6A60-6E23	Approved	[20]
Tertatolol	DM2L3D5	Hypertension	BA00-BA04	Approved	[39]
Urapidil	DMD59GI	Hypertension	BA00-BA04	Approved	[40]
Treximet	DMU54QB	Migraine	8A80	Approved	[41]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[42]
Eltoprazine	DMW6C81	Attention deficit hyperactivity disorder	6A05.Z	Phase 3	[43]

Drug(s) Targeting 5-HT 7 receptor (HTR7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RP5063	DMKUE8O	Schizophrenia	6A20	Phase 2	[8]
JNJ-18038683	DMV1T59	Major depressive disorder	6A70.3	Phase 2	[44]
AVN-101	DMOGFNI	Cognitive impairment	6D71	Phase 2	[45]
ATI-9242	DM6GKMU	Schizophrenia	6A20	Phase 1	[46]
PMID30124346-Compound-34TABLE4	DM2G3VE	Attention deficit hyperactivity disorder	6A05.Z	Patented	[47]
PMID30124346-Compound-13TABLE4	DMHTJVA	Attention deficit hyperactivity disorder	6A05.Z	Patented	[47]
Carbamide derivative 2	DMW5GI3	N. A.	N. A.	Patented	[48]
4-oxadiazole derivative 1	DMWFHKR	N. A.	N. A.	Patented	[48]
SB-269970	DM8WTGA	Sleep-wake disorder	7A00-7B2Z	Terminated	[49]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[50]

Drug(s) Targeting 5-HT 2C receptor (HTR2C)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[17]
Lorcaserin	DMG6OYJ	Obesity	5B81	Approved	[51]
Tramadol	DMRQD04	Pain	MG30-MG3Z	Approved	[52]
Mirtazapine	DML53ZJ	Depression	6A70-6A7Z	Approved	[53]
Nefazodone	DM4ZS8M	Major depressive disorder	6A70.3	Approved	[54]
Methysergide	DM1EF73	Migraine	8A80	Approved	[55]
Eltoprazine	DMW6C81	Attention deficit hyperactivity disorder	6A05.Z	Phase 3	[43]
M100907	DM7ZFBA	Sleep-wake disorder	7A00-7B2Z	Phase 3	[56]
SR46349B	DM1ODMR	Primary insomnia	7A00	Phase 3	[57]
Vabicaserin	DM9GZW6	Psychotic disorder	6A20-6A25	Phase 2	[58]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 1A receptor (HTR1A)	TTSQIFT	5HT1A_HUMAN	Inhibitor	[1]
5-HT 1D receptor (HTR1D)	TT6MSOK	5HT1D_HUMAN	Inhibitor	[1]
5-HT 2A receptor (HTR2A)	TTJQOD7	5HT2A_HUMAN	Inhibitor	[1]
5-HT 2C receptor (HTR2C)	TTWJBZ5	5HT2C_HUMAN	Inhibitor	[1]
5-HT 3A receptor (HTR3A)	TTPC4TU	5HT3A_HUMAN	Inhibitor	[1]
5-HT 5A receptor (HTR5A)	TTRUFDT	5HT5A_HUMAN	Inhibitor	[1]
5-HT 7 receptor (HTR7)	TTO9X1H	5HT7R_HUMAN	Inhibitor	[1]

References

• [1] Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: structure-activity relationship elucidation. Bioorg Med Chem Lett. 2008 Jan 1;18(1):256-61.
• [2] Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor. Mol Pharmacol. 1991 Aug;40(2):143-8.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs. 2001;61(3):317-32.
• [5] An introduction to migraine: from ancient treatment to functional pharmacology and antimigraine therapy. Proc West Pharmacol Soc. 2002;45:199-210.
• [6] Efficacy and tolerability of subcutaneous almotriptan for the treatment of acute migraine: a randomized, double-blind, parallel-group, dose-finding study. Clin Ther. 2001 Nov;23(11):1867-75.
• [7] Clinical pipeline report, company report or official report of Neurim Pharmaceuticals.
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Company report (NeurAxon)
• [10] Cloning and characterisation of the human 5-HT5A serotonin receptor. FEBS Lett. 1994 Dec 5;355(3):242-6.
• [11] Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31.
• [12] Identification of a potent, selective, and orally active leukotriene a4 hydrolase inhibitor with anti-inflammatory activity. J Med Chem. 2008 Jul 24;51(14):4150-69.
• [13] Expression of functional mouse 5-HT5A serotonin receptor in the methylotrophic yeast Pichia pastoris: pharmacological characterization and localization. FEBS Lett. 1995 Dec 27;377(3):451-6.
• [14] Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization. Mol Pharmacol. 1993 Mar;43(3):313-9.
• [15] 2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors. J Med Chem. 2000 Mar 9;43(5):1011-8.
• [16] Human 5-HT(5) receptors: the 5-HT(5A) receptor is functional but the 5-HT(5B) receptor was lost during mammalian evolution. Eur J Pharmacol. 2001 Apr 27;418(3):157-67.
• [17] Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors. Naunyn Schmiedebergs Arch Pharmacol. 2004 Aug;370(2):114-23.
• [18] Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501.
• [19] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [20] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [21] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [22] Anxiolytic effects of aniracetam in three different mouse models of anxiety and the underlying mechanism. Eur J Pharmacol. 2001 May 18;420(1):33-43.
• [23] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [24] Beneficial effects of sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, supplemented with pioglitazone on diabetic model mice. Endocr Res. 2009;34(1-2):18-30.
• [25] Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone, 2mg/day, but does not enhance efficacy of haloperidol, 2mg/day: comparison with reference dose risperidone, 6mg/day.Schizophr Res.2012 Nov;141(2-3):144-52.
• [26] Clinical pipeline report, company report or official report of Lundbeck.
• [27] Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, do... Lancet Oncol. 2009 Feb;10(2):115-24.
• [28] Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2009 Jul;104(7):1831-43; quiz 1844.
• [29] Emerging therapies for fibromyalgia. Expert Opin Emerg Drugs. 2008 Mar;13(1):53-62.
• [30] Management of postoperative nausea and vomiting: focus on palonosetron. Ther Clin Risk Manag. 2009 Feb;5(1):21-34.
• [31] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [32] Local anesthetics have different mechanisms and sites of action at recombinant 5-HT3 receptors. Reg Anesth Pain Med. 2007 Nov-Dec;32(6):462-70.
• [33] Cilansetron: a new serotonergic agent for the irritable bowel syndrome with diarrhoea.Expert Opin Investig Drugs.2005 Feb;14(2):185-93.
• [34] Zatosetron, a potent, selective, and long-acting 5HT3 receptor antagonist: synthesis and structure-activity relationships. J Med Chem. 1992 Jan 24;35(2):310-9.
• [35] mu-Opioid/5-HT4 dual pharmacologically active agents-efforts towards an effective opioid analgesic with less GI and respiratory side effects (Part I). Bioorg Med Chem Lett. 2009 Oct 1;19(19):5679-83.
• [36] Interactions between corticotropin-releasing hormone and serotonin: implications for the aetiology and treatment of anxiety disorders. Handb Exp Pharmacol. 2005;(169):181-204.
• [37] Effects of brexpiprazole, a novel serotonin-dopamine activity modulator, on phencyclidine-induced cognitive deficits in mice: a role for serotonin 5-HT1A receptors.Pharmacol Biochem Behav.2014 Sep;124:245-9.
• [38] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [39] Synthesis of new derivatives of 8-OH-DPAT: Influence of substitution on the aromatic ring on the pharmacological profile, Bioorg. Med. Chem. Lett. 3(10):2035-2038 (1993).
• [40] Urapidil. A reappraisal of its use in the management of hypertension. Drugs. 1998 Nov;56(5):929-55.
• [41] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [42] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
• [43] Clinical pipeline report, company report or official report of Jazz Pharmaceuticals.
• [44] Selective pharmacological blockade of the 5-HT7 receptor attenuates light and 8-OH-DPAT induced phase shifts of mouse circadian wheel running activity. Front Behav Neurosci. 2015 Jan 15;8:453.
• [45] AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders. J Alzheimers Dis. 2016 May 25;53(2):583-620.
• [46] Pharmacological characteristics of ATI-9242, a Novel Atypical Antipsychotic. FASEB J, April, 2010, 24(Meeting Abstract Supplement),773.12.
• [47] 5-HT1A receptor ligands and their therapeutic applications: review of new patents.Expert Opin Ther Pat. 2018 Sep;28(9):679-689.
• [48] Acyltransferase inhibitors: a patent review (2010-present).Expert Opin Ther Pat. 2015 Feb;25(2):145-58.
• [49] [(3)H]-SB-269970--A selective antagonist radioligand for 5-HT(7) receptors. Br J Pharmacol. 2000 May;130(2):409-17.
• [50] Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 rec... J Med Chem. 2010 Sep 9;53(17):6386-97.
• [51] Anti-obesity drugs. Expert Opin Pharmacother. 2008 Jun;9(8):1339-50.
• [52] The inhibitory effects of tramadol on 5-hydroxytryptamine type 2C receptors expressed in Xenopus oocytes. Anesth Analg. 2004 May;98(5):1401-6, table of contents.
• [53] Inverse agonist and neutral antagonist actions of antidepressants at recombinant and native 5-hydroxytryptamine2C receptors: differential modulatio... Mol Pharmacol. 2008 Mar;73(3):748-57.
• [54] Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. Therapie. 2005 Sep-Oct;60(5):441-60.
• [55] Spinal serotonin receptor activation modulates the exercise ventilatory response with increased dead space in goats. Respir Physiol Neurobiol. 2008 May 31;161(3):230-8.
• [56] Non-basic ligands for aminergic GPCRs: the discovery and development diaryl sulfones as selective, orally bioavailable 5-HT2A receptor antagonists ... Bioorg Med Chem Lett. 2010 Jun 15;20(12):3708-12.
• [57] SR46349-B, a 5-HT(2A/2C) receptor antagonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens. Neuropsychopharmacology. 2002 Sep;27(3):430-41.
• [58] Prediction of Efficacy of Vabicaserin, a 5-HT2C Agonist, for the Treatment of Schizophrenia Using a Quantitative Systems Pharmacology Model.CPT Pharmacometrics Syst Pharmacol.2014 Apr 23;3:e111.