ID: ALA3989843

Max Phase: Approved

First Approval: 1961

Molecular Formula: C18H22N2

Molecular Weight: 266.39

Molecule Type: Small molecule

Representations

Synonyms (2): Tranylcypromine | NSC-80664
Synonyms from Alternative Forms(2):

Canonical SMILES:  N[C@@H]1C[C@H]1c1ccccc1.N[C@H]1C[C@@H]1c1ccccc1

Standard InChI:  InChI=1S/2C9H11N/c2*10-9-6-8(9)7-4-2-1-3-5-7/h2*1-5,8-9H,6,10H2/t2*8-,9+/m10/s1

Standard InChI Key:  IGLYMJRIWWIQQE-QUOODJBBSA-N

Molecule Features

Natural Product: No

Oral: Yes

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: Yes

Chirality: No

Availability: Yes

Prodrug: No

Properties

Molecular Weight: 266.39

Molecular Weight (Monoisotopic): 266.1783

AlogP:

#Rotatable Bonds:

Polar Surface Area:

Molecular Species:

HBA:

HBD:

#RO5 Violations:

HBA (Lipinski):

HBD (Lipinski):

#RO5 Violations (Lipinski):

CX Acidic pKa:

CX Basic pKa:

CX LogP:

CX LogD:

Aromatic Rings:

Heavy Atoms:

QED Weighted:

Np Likeness Score:

References

1. Cozzini P, Fornabaio M, Marabotti A, Abraham DJ, Kellogg GE, Mozzarelli A..  (2002)  Simple, intuitive calculations of free energy of binding for protein-ligand complexes. 1. Models without explicit constrained water.,  45  (12): [PMID:12036355] [10.1021/jm0200299]

2. Ishchenko AV, Shakhnovich EI..  (2002)  SMall Molecule Growth 2001 (SMoG2001): an improved knowledge-based scoring function for protein-ligand interactions.,  45  (13): [PMID:12061879] [10.1021/jm0105833]

3. Butler DE, Poschel BP, Marriott JG..  (1981)  Cognition-activating properties of 3-(Aryloxy)pyridines.,  24  (3): [PMID:7265121] [10.1021/jm00135a020]

4. Butler DE, Nordin IC, L'Italien YJ, Zweisler L, Poschel PH, Marriott JG..  (1984)  Amnesia-reversal activity of a series of N-[(disubstituted-amino)alkyl] -2-oxo-1-pyrrolidineacetamides, including pramiracetam.,  27  (5): [PMID:6716406] [10.1021/jm00371a023]

5. Santana L, González-Díaz H, Quezada E, Uriarte E, Yáñez M, Viña D, Orallo F..  (2008)  Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.,  51  (21): [PMID:18834112] [10.1021/jm800656v]

6. Lucas S, Heim R, Negri M, Antes I, Ries C, Schewe KE, Bisi A, Gobbi S, Hartmann RW..  (2008)  Novel aldosterone synthase inhibitors with extended carbocyclic skeleton by a combined ligand-based and structure-based drug design approach.,  51  (19): [PMID:18763754] [10.1021/jm800683c]

7. Cho SJ, Jensen NH, Kurome T, Kadari S, Manzano ML, Malberg JE, Caldarone B, Roth BL, Kozikowski AP..  (2009)  Selective 5-hydroxytryptamine 2C receptor agonists derived from the lead compound tranylcypromine: identification of drugs with antidepressant-like action.,  52  (7): [PMID:19284718] [10.1021/jm801354e]

8. Matsumoto M, Hashizume H, Tomishige T, Kawasaki M, Tsubouchi H, Sasaki H, Shimokawa Y, Komatsu M..  (2006)  OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice.,  3  (11): [PMID:17132069] [10.1371/journal.pmed.0030466]

9. Heim R, Lucas S, Grombein CM, Ries C, Schewe KE, Negri M, Müller-Vieira U, Birk B, Hartmann RW..  (2008)  Overcoming undesirable CYP1A2 inhibition of pyridylnaphthalene-type aldosterone synthase inhibitors: influence of heteroaryl derivatization on potency and selectivity.,  51  (16): [PMID:18672861] [10.1021/jm800377h]

10. Lucas S, Heim R, Ries C, Schewe KE, Birk B, Hartmann RW..  (2008)  In vivo active aldosterone synthase inhibitors with improved selectivity: lead optimization providing a series of pyridine substituted 3,4-dihydro-1H-quinolin-2-one derivatives.,  51  (24): [PMID:19049427] [10.1021/jm800888q]

11. Casero RA, Woster PM..  (2009)  Recent advances in the development of polyamine analogues as antitumor agents.,  52  (15): [PMID:19534534] [10.1021/jm900187v]

12. Boppana K, Dubey PK, Jagarlapudi SA, Vadivelan S, Rambabu G..  (2009)  Knowledge based identification of MAO-B selective inhibitors using pharmacophore and structure based virtual screening models.,  44  (9): [PMID:19321235] [10.1016/j.ejmech.2009.02.031]

13. Marchais-Oberwinkler S, Wetzel M, Ziegler E, Kruchten P, Werth R, Henn C, Hartmann RW, Frotscher M..  (2011)  New drug-like hydroxyphenylnaphthol steroidomimetics as potent and selective 17β-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of estrogen-dependent diseases.,  54  (2): [PMID:21189020] [10.1021/jm1009082]

14. Kumar S, Bawa S, Drabu S, Gupta H, Machwal L, Kumar R..  (2011)  Synthesis, antidepressant and antifungal evaluation of novel 2-chloro-8-methylquinoline amine derivatives.,  46  (2): [PMID:21194811] [10.1016/j.ejmech.2010.12.002]

15. Fourches D, Barnes JC, Day NC, Bradley P, Reed JZ, Tropsha A..  (2010)  Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.,  23  (1): [PMID:20014752] [10.1021/tx900326k]

16. Lucas S, Negri M, Heim R, Zimmer C, Hartmann RW..  (2011)  Fine-tuning the selectivity of aldosterone synthase inhibitors: structure-activity and structure-selectivity insights from studies of heteroaryl substituted 1,2,5,6-tetrahydropyrrolo[3,2,1-ij]quinolin-4-one derivatives.,  54  (7): [PMID:21384875] [10.1021/jm101470k]

17. Benelkebir H, Hodgkinson C, Duriez PJ, Hayden AL, Bulleid RA, Crabb SJ, Packham G, Ganesan A..  (2011)  Enantioselective synthesis of tranylcypromine analogues as lysine demethylase (LSD1) inhibitors.,  19  (12): [PMID:21382717] [10.1016/j.bmc.2011.02.017]

18. Benelkebir H, Hodgkinson C, Duriez PJ, Hayden AL, Bulleid RA, Crabb SJ, Packham G, Ganesan A..  (2011)  Enantioselective synthesis of tranylcypromine analogues as lysine demethylase (LSD1) inhibitors.,  19  (12): [PMID:21382717] [10.1016/j.bmc.2011.02.017]

19. Lohse B, Kristensen JL, Kristensen LH, Agger K, Helin K, Gajhede M, Clausen RP..  (2011)  Inhibitors of histone demethylases.,  19  (12): [PMID:21596573] [10.1016/j.bmc.2011.01.046]

20. Liu Z, Shi Q, Ding D, Kelly R, Fang H, Tong W..  (2011)  Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).,  7  (12): [PMID:22194678] [10.1371/journal.pcbi.1002310]

21. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P..  (2012)  Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.,  55  (10): [PMID:22541068] [10.1021/jm300212s]

22. Decarlo D, Hadden MK..  (2012)  Oncoepigenomics: making histone lysine methylation count.,  56  [PMID:22975593] [10.1016/j.ejmech.2012.08.010]

23. Gok S, Murat Demet M, Ozdemir A, Turan-Zitouni G.  (2010)  Evaluation of antidepressant-like effect of 2-pyrazoline derivatives,  19  (1): [10.1007/s00044-009-9176-x]

24. Byun Y, Park J, Hong SH, Han MH, Park S, Jung HI, Noh M..  (2013)  The opposite effect of isotype-selective monoamine oxidase inhibitors on adipogenesis in human bone marrow mesenchymal stem cells.,  23  (11): [PMID:23611731] [10.1016/j.bmcl.2013.03.117]

25. Sorna V, Theisen ER, Stephens B, Warner SL, Bearss DJ, Vankayalapati H, Sharma S..  (2013)  High-throughput virtual screening identifies novel N'-(1-phenylethylidene)-benzohydrazides as potent, specific, and reversible LSD1 inhibitors.,  56  (23): [PMID:24237195] [10.1021/jm400870h]

26. Mattsson C, Svensson P, Sonesson C..  (2014)  A novel series of 6-substituted 3-(pyrrolidin-1-ylmethyl)chromen-2-ones as selective monoamine oxidase (MAO) A inhibitors.,  73  [PMID:24393810] [10.1016/j.ejmech.2013.11.035]

27. Biour M, Ben Salem C, Chazouillères O, Grangé JD, Serfaty L, Poupon R..  (2004)  [Drug-induced liver injury; fourteenth updated edition of the bibliographic database of liver injuries and related drugs].,  28  (8-9): [PMID:15646539] [10.1016/s0399-8320(04)95062-2]

28. Sharma SK, Hazeldine S, Crowley ML, Hanson A, Beattie R, Varghese S, Senanayake TM, Hirata A, Hirata F, Huang Y, Wu Y, Steinbergs N, Murray-Stewart T, Bytheway I, Casero RA, Woster PM..  (2012)  Polyamine-based small molecule epigenetic modulators.,  3  (1): [PMID:23293738] [10.1039/c1md00220a]

29. Chen J, Levant B, Jiang C, Keck TM, Newman AH, Wang S..  (2014)  Tranylcypromine substituted cis-hydroxycyclobutylnaphthamides as potent and selective dopamine D₃ receptor antagonists.,  57  (11): [PMID:24848155] [10.1021/jm401798r]

30. Suchaud V, Bailly F, Lion C, Calmels C, Andréola ML, Christ F, Debyser Z, Cotelle P..  (2014)  Investigation of a novel series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones as human immunodeficiency virus type 1 integrase inhibitors.,  57  (11): [PMID:24793360] [10.1021/jm500109z]

31. Jones P.  (2012)  Development of second generation epigenetic agents,  3  (2): [10.1039/C1MD00199J]

32. Park EJ, Ahn YG, Jung SH, Bang HJ, Kim M, Hong DJ, Kim J, Suh KH, Kim YJ, Kim D, Kim EY, Lee K, Min KH..  (2014)  Discovery of novel pyrimidine and malonamide derivatives as TGR5 agonists.,  24  (17): [PMID:25082126] [10.1016/j.bmcl.2014.07.026]

33. Vianello P, Botrugno OA, Cappa A, Ciossani G, Dessanti P, Mai A, Mattevi A, Meroni G, Minucci S, Thaler F, Tortorici M, Trifiró P, Valente S, Villa M, Varasi M, Mercurio C..  (2014)  Synthesis, biological activity and mechanistic insights of 1-substituted cyclopropylamine derivatives: a novel class of irreversible inhibitors of histone demethylase KDM1A.,  86  [PMID:25173853] [10.1016/j.ejmech.2014.08.068]

34. Nowotarski SL, Pachaiyappan B, Holshouser SL, Kutz CJ, Li Y, Huang Y, Sharma SK, Casero RA, Woster PM..  (2015)  Structure-activity study for (bis)ureidopropyl- and (bis)thioureidopropyldiamine LSD1 inhibitors with 3-5-3 and 3-6-3 carbon backbone architectures.,  23  (7): [PMID:25725609] [10.1016/j.bmc.2015.01.049]

35. Kakizawa T, Ota Y, Itoh Y, Tsumoto H, Suzuki T..  (2015)  Histone H3 peptide based LSD1-selective inhibitors.,  25  (9): [PMID:25827526] [10.1016/j.bmcl.2015.03.030]

36. Rojas RJ, Edmondson DE, Almos T, Scott R, Massari ME..  (2015)  Reversible and irreversible small molecule inhibitors of monoamine oxidase B (MAO-B) investigated by biophysical techniques.,  23  (4): [PMID:25600407] [10.1016/j.bmc.2014.12.063]

37. Ma LY, Zheng YC, Wang SQ, Wang B, Wang ZR, Pang LP, Zhang M, Wang JW, Ding L, Li J, Wang C, Hu B, Liu Y, Zhang XD, Wang JJ, Wang ZJ, Zhao W, Liu HM..  (2015)  Design, synthesis, and structure-activity relationship of novel LSD1 inhibitors based on pyrimidine-thiourea hybrids as potent, orally active antitumor agents.,  58  (4): [PMID:25610955] [10.1021/acs.jmedchem.5b00037]

38. Valente S, Rodriguez V, Mercurio C, Vianello P, Saponara B, Cirilli R, Ciossani G, Labella D, Marrocco B, Monaldi D, Ruoppolo G, Tilset M, Botrugno OA, Dessanti P, Minucci S, Mattevi A, Varasi M, Mai A..  (2015)  Pure enantiomers of benzoylamino-tranylcypromine: LSD1 inhibition, gene modulation in human leukemia cells and effects on clonogenic potential of murine promyelocytic blasts.,  94  [PMID:25768700] [10.1016/j.ejmech.2015.02.060]

39. FDA drug approval package for Aliskiren hemifumarate, 

40. Stephens ES, Walsh AA, Scott EE..  (2012)  Evaluation of inhibition selectivity for human cytochrome P450 2A enzymes.,  40  (9): [PMID:22696418] [10.1124/dmd.112.045161]

41. Curran RE, Claxton CR, Hutchison L, Harradine PJ, Martin IJ, Littlewood P..  (2011)  Control and measurement of plasma pH in equilibrium dialysis: influence on drug plasma protein binding.,  39  (3): [PMID:21098647] [10.1124/dmd.110.036988]

42. Kutz CJ, Holshouser SL, Marrow EA, Woster PM..  (2014)  3,5-Diamino-1,2,4-triazoles as a novel scaffold for potent, reversible LSD1 (KDM1A) inhibitors.,  5  (12): [PMID:25580204] [10.1039/c4md00283k]

43. Zhan P, Itoh Y, Suzuki T, Liu X..  (2015)  Strategies for the Discovery of Target-Specific or Isoform-Selective Modulators.,  58  (19): [PMID:26086931] [10.1021/acs.jmedchem.5b00229]

44.  (2013)  Synthetic compounds and derivatives as modulators of smoking or nicotine ingestion and lung cancer, 

45. Kakizawa T, Mizukami T, Itoh Y, Hasegawa M, Sasaki R, Suzuki T..  (2016)  Evaluation of phenylcyclopropylamine compounds by enzymatic assay of lysine-specific demethylase 2 in the presence of NPAC peptide.,  26  (4): [PMID:26794039] [10.1016/j.bmcl.2016.01.036]

46. McAllister TE, England KS, Hopkinson RJ, Brennan PE, Kawamura A, Schofield CJ..  (2016)  Recent Progress in Histone Demethylase Inhibitors.,  59  (4): [PMID:26710088] [10.1021/acs.jmedchem.5b01758]

47. Billamboz M, Suchaud V, Bailly F, Lion C, Andréola ML, Christ F, Debyser Z, Cotelle P..  (2016)  2-hydroxyisoquinoline-1,3(2H,4H)-diones (HIDs) as human immunodeficiency virus type 1 integrase inhibitors: Influence of the alkylcarboxamide substitution of position 4.,  117  [PMID:27105029] [10.1016/j.ejmech.2016.03.083]

48. WHO Anatomical Therapeutic Chemical Classification, 

49. Hutchinson JH, Rowbottom MW, Lonergan D, Darlington J, Prodanovich P, King CD, Evans JF, Bain G..  (2017)  Small Molecule Lysyl Oxidase-like 2 (LOXL2) Inhibitors: The Identification of an Inhibitor Selective for LOXL2 over LOX.,  8  (4): [PMID:28435530] [10.1021/acsmedchemlett.7b00014]

50. Duan YC, Guan YY, Zhai XY, Ding LN, Qin WP, Shen DD, Liu XQ, Sun XD, Zheng YC, Liu HM..  (2017)  Discovery of resveratrol derivatives as novel LSD1 inhibitors: Design, synthesis and their biological evaluation.,  126  [PMID:27888721] [10.1016/j.ejmech.2016.11.035]

51. Metcalf B, Chuang C, Dufu K, Patel MP, Silva-Garcia A, Johnson C, Lu Q, Partridge JR, Patskovska L, Patskovsky Y, Almo SC, Jacobson MP, Hua L, Xu Q, Gwaltney SL, Yee C, Harris J, Morgan BP, James J, Xu D, Hutchaleelaha A, Paulvannan K, Oksenberg D, Li Z..  (2017)  Discovery of GBT440, an Orally Bioavailable R-State Stabilizer of Sickle Cell Hemoglobin.,  8  (3): [PMID:28337324] [10.1021/acsmedchemlett.6b00491]

52. Sartori L, Mercurio C, Amigoni F, Cappa A, Fagá G, Fattori R, Legnaghi E, Ciossani G, Mattevi A, Meroni G, Moretti L, Cecatiello V, Pasqualato S, Romussi A, Thaler F, Trifiró P, Villa M, Vultaggio S, Botrugno OA, Dessanti P, Minucci S, Zagarrí E, Carettoni D, Iuzzolino L, Varasi M, Vianello P..  (2017)  Thieno[3,2-b]pyrrole-5-carboxamides as New Reversible Inhibitors of Histone Lysine Demethylase KDM1A/LSD1. Part 1: High-Throughput Screening and Preliminary Exploration.,  60  (5): [PMID:28186755] [10.1021/acs.jmedchem.6b01018]

53. Chen M, Suzuki A, Thakkar S, Yu K, Hu C, Tong W..  (2016)  DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.,  21  (4): [PMID:26948801] [10.1016/j.drudis.2016.02.015]

54. Borrello MT, Schinor B, Bartels K, Benelkebir H, Pereira S, Al-Jamal WT, Douglas L, Duriez PJ, Packham G, Haufe G, Ganesan A..  (2017)  Fluorinated tranylcypromine analogues as inhibitors of lysine-specific demethylase 1 (LSD1, KDM1A).,  27  (10): [PMID:28390942] [10.1016/j.bmcl.2017.03.081]

55. Wang S, Zhao LJ, Zheng YC, Shen DD, Miao EF, Qiao XP, Zhao LJ, Liu Y, Huang R, Yu B, Liu HM..  (2017)  Design, synthesis and biological evaluation of [1,2,4]triazolo[1,5-a]pyrimidines as potent lysine specific demethylase 1 (LSD1/KDM1A) inhibitors.,  125  [PMID:27769034] [10.1016/j.ejmech.2016.10.021]

56. Jaiteh M, Zeifman A, Saarinen M, Svenningsson P, Bréa J, Loza MI, Carlsson J..  (2018)  Docking Screens for Dual Inhibitors of Disparate Drug Targets for Parkinson's Disease.,  61  (12): [PMID:29792714] [10.1021/acs.jmedchem.8b00204]

57. Unpublished dataset, 

58. Sutherland JJ, Yonchev D, Fekete A, Urban L..  (2023)  A preclinical secondary pharmacology resource illuminates target-adverse drug reaction associations of marketed drugs.,  14  (1): [PMID:37468498] [10.1038/s41467-023-40064-9]

Source

Source(5):

• Scientific Literature
• Clinical Candidates
• FDA Approval Packages
• BindingDB Database
• WHO Anatomical Therapeutic Chemical Classification