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

General Information of Drug (ID: DMKE7FG)

• Drug Name: 1-(pyridin-2-yl)piperazine Drug Info
• Synonyms: 1-Pyridin-2-yl-piperazine

Indication

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

• Cross-matching ID:
  PubChem CID: 94459
  CAS Number: CAS 34803-66-2
  TTD Drug ID: DMKE7FG

Molecule-Related Drug Atlas

Drug(s) Targeting Adrenergic receptor alpha-2A (ADRA2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lofexidine	DM1WXA6	Heroin and opiate withdrawal	6C43	Approved	[3]
MOXONIDINE	DMGFB0E	Alcohol dependence	6C40.2	Approved	[4]
Connexyn	DMF29Q5	Attention deficit hyperactivity disorder	6A05.Z	Approved	[5]
Guanfacine	DMPN5IH	Attention deficit hyperactivity disorder	6A05.Z	Phase 4	[6]
A295	DM55GO2	Aggressive cancer	2A00-2F9Z	IND submitted	[7]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[8]
DSP-1200	DM4WSHG	Depression	6A70-6A7Z	Phase 1	[9]
MAZAPERTINE	DMRHYAU	N. A.	N. A.	Discontinued in Phase 2	[10]
NMI-870	DMU596F	Sexual dysfunction	HA00-HA01	Discontinued in Phase 2	[11]
SNAP-5089	DMROJEN	Heart arrhythmia	BC65	Terminated	[12]

Drug(s) Targeting Phospholipase D1 (PLD1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
US9127005, P2C	DMMT98V	N. A.	N. A.	Patented	[13]
US9453017, 1	DMVQ3IX	N. A.	N. A.	Patented	[14]
US9127005, P2B	DM3R7BT	N. A.	N. A.	Patented	[13]
ML272	DMNEY58	N. A.	N. A.	Patented	[14]
US9127005, P0L	DMKLYCV	N. A.	N. A.	Patented	[13]
US9453017, 2	DMPH05Y	N. A.	N. A.	Patented	[14]
HALOPEMIDE	DMF6V8W	Discovery agent	N.A.	Investigative	[15]
1-(pyridin-4-yl)piperazine	DM78AJ1	Discovery agent	N.A.	Investigative	[2]

Drug(s) Targeting Adrenergic receptor alpha-2B (ADRA2B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MOXONIDINE	DMGFB0E	Alcohol dependence	6C40.2	Approved	[4]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[8]
AGN-199981	DMP5Y1A	Neuropathic pain	8E43.0	Phase 2	[16]
INDORAMIN	DMNSJFD	Hypertension	BA00-BA04	Withdrawn from market	[17]
MAZAPERTINE	DMRHYAU	N. A.	N. A.	Discontinued in Phase 2	[10]
SNAP-5089	DMROJEN	Heart arrhythmia	BC65	Terminated	[12]
A-80426	DMBC3DG	N. A.	N. A.	Terminated	[18]
WB-4101	DMQU8B1	N. A.	N. A.	Terminated	[19]
SK&F-104078	DMRADBU	N. A.	N. A.	Terminated	[17]
(+/-)-nantenine	DM0L3GE	Discovery agent	N.A.	Investigative	[20]

Drug(s) Targeting Adrenergic receptor alpha-1D (ADRA1D)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxazosin	DM9PLRH	Benign prostatic hyperplasia	GA90	Approved	[21]
Armodafinil	DMGB035	Malignant glioma	2A00.0	Approved	[22]
Alfuzosin	DMZVMKF	Benign prostatic hyperplasia	GA90	Approved	[23]
Moxisylyte	DMFCLYW	Erectile dysfunction	HA01.1	Approved	[24]
Terazosin	DM3JCVS	Benign prostatic hyperplasia	GA90	Approved	[25]
Bunazosin	DM4I8O7	Glaucoma/ocular hypertension	9C61	Approved	[26]
Trimazosin	DM1QLST	Congestive heart failure	BD10	Approved	[27]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[8]
DL-017	DMM8GZT	Hypertension	BA00-BA04	Phase 1	[28]
PMID30124346-Compound-LDT8	DM5MUNG	Benign prostatic hyperplasia	GA90	Patented	[29]

Drug(s) Targeting Adrenergic receptor alpha-1A (ADRA1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SILODOSIN	DMJSBT6	Benign prostatic hyperplasia	GA90	Approved	[30]
NAFTOPIDIL	DMQ8R4E	Hypertension	BA00-BA04	Approved	[30]
Tamsulosin	DM5QF9V	Benign prostatic hyperplasia	GA90	Approved	[31]
Xatral	DMLHOA0	Benign prostatic hyperplasia	GA90	Approved	[32]
Dutasteride + tamsulosin	DM6P8HU	Benign prostatic hyperplasia	GA90	Phase 3	[33]
Besipirdine	DMLVNTA	Cognitive impairment	6D71	Phase 3	[34]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[8]
PMID30124346-Compound-LDT8	DM5MUNG	Benign prostatic hyperplasia	GA90	Patented	[29]
PMID30124346-Compound-LDT66	DMJMTNL	Benign prostatic hyperplasia	GA90	Patented	[29]
TIOSPIRONE	DME5QDP	N. A.	N. A.	Discontinued in Phase 3	[35]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor alpha-1A (ADRA1A)	TTNGILX	ADA1A_HUMAN	Inhibitor	[1]
Adrenergic receptor alpha-1D (ADRA1D)	TT34BHT	ADA1D_HUMAN	Inhibitor	[1]
Adrenergic receptor alpha-2A (ADRA2A)	TTWG9A4	ADA2A_HUMAN	Inhibitor	[1]
Adrenergic receptor alpha-2B (ADRA2B)	TTWM4TY	ADA2B_HUMAN	Inhibitor	[1]
Phospholipase D1 (PLD1)	TT3T17P	PLD1_HUMAN	Inhibitor	[2]

References

• [1] Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines. J Med Chem. 1984 Sep;27(9):1182-5.
• [2] Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part II. Identification of the 1,3,8-triazaspiro[4,5]decan-4-one privil... Bioorg Med Chem Lett. 2009 Apr 15;19(8):2240-3.
• [3] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [4] Synthesis and pharmacologic evaluation of 2-endo-amino-3-exo-isopropylbicyclo[2.2.1]heptane: a potent imidazoline1 receptor specific agent. J Med Chem. 1996 Mar 15;39(6):1193-5.
• [5] alpha2A-adrenergic receptors heterosynaptically regulate glutamatergic transmission in the bed nucleus of the stria terminalis. Neuroscience. 2009 Sep 29;163(1):339-51.
• [6] Scientific rationale for the use of alpha2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders. Mol Psychiatry. 2023 Apr 7:1-13.
• [7] Clinical pipeline report, company report or official report of Klus Pharma
• [8] A structure-activity relationship study of benzylic modifications of 4-[1-(1-naphthyl)ethyl]-1H-imidazoles on alpha 1- and alpha 2-adrenergic recep... J Med Chem. 1994 Jul 22;37(15):2328-33.
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] A new arylpiperazine antipsychotic with high D2/D3/5-HT1A/alpha 1A-adrenergic affinity and a low potential for extrapyramidal effects. J Med Chem. 1994 Apr 15;37(8):1060-2.
• [11] Female Sexual Dysfunction: Therapeutic Options and Experimental Challenges. Cardiovasc Hematol Agents Med Chem. 2009 October; 7(4): 260-269.
• [12] Design and synthesis of novel dihydropyridine alpha-1a antagonists. Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8.
• [13] Isoform selective phospholipase D inhibitors. US9127005.
• [14] Antiviral therapies with phospholipase D inhibitors. US9453017.
• [15] Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness. Nat Chem Biol. 2009 Feb;5(2):108-17.
• [16] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [17] Alpha- and beta-adrenoceptors: from the gene to the clinic. 1. Molecular biology and adrenoceptor subclassification. J Med Chem. 1995 Sep 1;38(18):3415-44.
• [18] Discovery of a new series of centrally active tricyclic isoxazoles combining serotonin (5-HT) reuptake inhibition with alpha2-adrenoceptor blocking... J Med Chem. 2005 Mar 24;48(6):2054-71.
• [19] alpha 2 adrenoceptors: classification, localization, mechanisms, and targets for drugs. J Med Chem. 1982 Dec;25(12):1389-401.
• [20] Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31.
• [21] The role of combination medical therapy in benign prostatic hyperplasia. Int J Impot Res. 2008 Dec;20 Suppl 3:S33-43.
• [22] Mechanisms of modafinil: A review of current research. Neuropsychiatr Dis Treat. 2007 June; 3(3): 349-364.
• [23] Alfuzosin: a review of the therapeutic use of the prolonged-release formulation given once daily in the management of benign prostatic hyperplasia. Drugs. 2002;62(4):633-53.
• [24] Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses. Eur J Clin Pharmacol. 1996;49(5):411-5.
• [25] Induction of prostate apoptosis by alpha1-adrenoceptor antagonists: mechanistic significance of the quinazoline component. Prostate Cancer Prostatic Dis. 2002;5(2):88-95.
• [26] Bunazosin, a selective alpha1-adrenoceptor antagonist, as an anti-glaucoma drug: effects on ocular circulation and retinal neuronal damage. Cardiovasc Drug Rev. 2005 Spring;23(1):43-56.
• [27] The hypotensive effect of trimazosin is not caused solely by alpha 1-adrenoceptor blockade. J Cardiovasc Pharmacol. 1984 Jan-Feb;6(1):142-50.
• [28] Antihypertensive action and blockade of alpha1-adrenoceptors by DL-017, a quinazoline derivative. J Cardiovasc Pharmacol. 2001 Dec;38(6):893-9.
• [29] 5-HT1A receptor ligands and their therapeutic applications: review of new patents.Expert Opin Ther Pat. 2018 Sep;28(9):679-689.
• [30] Pharmacophore identification of alpha(1A)-adrenoceptor antagonists. Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.
• [31] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [32] Pharma & Vaccines. Product Development Pipeline. April 29 2009.
• [33] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [34] Alpha-Adrenergic activity and cardiovascular effects of besipirdine HCl (HP 749) and metabolite P7480 in vitro and in the conscious rat and dog. J Pharmacol Exp Ther. 1997 Apr;281(1):337-46.
• [35] 3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents. J Med Chem. 1996 Jan 5;39(1):143-8.