(3S,7S,8S)-8-Benzyl-3-((R)-1-(benzyloxy)ethyl)-7-hydroxy-1,4,9-triazacyclohenicosane-2,5,10-trione

ID: ALA4591056

PubChem CID: 155568626

Max Phase: Preclinical

Molecular Formula: C34H49N3O5

Molecular Weight: 579.78

Molecule Type: Unknown

This compound is available for customization.

Associated Items:

Names and Identifiers

Canonical SMILES:  C[C@@H](OCc1ccccc1)[C@@H]1NC(=O)C[C@H](O)[C@H](Cc2ccccc2)NC(=O)CCCCCCCCCCCNC1=O

Standard InChI:  InChI=1S/C34H49N3O5/c1-26(42-25-28-19-13-10-14-20-28)33-34(41)35-22-16-8-6-4-2-3-5-7-15-21-31(39)36-29(30(38)24-32(40)37-33)23-27-17-11-9-12-18-27/h9-14,17-20,26,29-30,33,38H,2-8,15-16,21-25H2,1H3,(H,35,41)(H,36,39)(H,37,40)/t26-,29+,30+,33+/m1/s1

Standard InChI Key:  NVMKVRKXOYBACS-RZGHOXDUSA-N

Molfile:  

 
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M  END

Alternative Forms

  1. Parent:

    ALA4591056

    ---

Associated Targets(Human)

CTSD Tchem Cathepsin D (3201 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
REN Tclin Renin (5251 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
BACE1 Tchem Beta-secretase 1 (15641 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

protease Protease (2551 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PEP4 Saccharopepesin (34 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: NoOral: NoChemical Probe: NoParenteral: No
Molecule Type: UnknownTopical: NoFirst In Class: NoBlack Box: No
Chirality: NoAvailability: NoProdrug: No

Drug Indications

MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

Mechanisms of Action

Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

Biocomponents

Calculated Properties

Molecular Weight: 579.78Molecular Weight (Monoisotopic): 579.3672AlogP: 4.59#Rotatable Bonds: 6
Polar Surface Area: 116.76Molecular Species: NEUTRALHBA: 5HBD: 4
#RO5 Violations: 1HBA (Lipinski): 8HBD (Lipinski): 4#RO5 Violations (Lipinski): 1
CX Acidic pKa: 12.43CX Basic pKa: CX LogP: 4.75CX LogD: 4.75
Aromatic Rings: 2Heavy Atoms: 42QED Weighted: 0.40Np Likeness Score: 0.54

References

1. Houštecká R, Hadzima M, Fanfrlík J, Brynda J, Pallová L, Hánová I, Mertlíková-Kaiserová H, Lepšík M, Horn M, Smrčina M, Majer P, Mareš M..  (2020)  Biomimetic Macrocyclic Inhibitors of Human Cathepsin D: Structure-Activity Relationship and Binding Mode Analysis.,  63  (4): [PMID:32003991] [10.1021/acs.jmedchem.9b01351]
2. Dumas, J J and 8 more authors.  1999-09-06  Synthesis and structure activity relationships of novel small molecule cathepsin D inhibitors.  [PMID:10498202]
3. Ersmark, Karolina K and 9 more authors.  2004-01-01  Potent inhibitors of the Plasmodium falciparum enzymes plasmepsin I and II devoid of cathepsin D inhibitory activity.  [PMID:14695825]
4. Johansson, Per-Ola PO and 10 more authors.  2004-06-17  Design and synthesis of potent inhibitors of the malaria aspartyl proteases plasmepsin I and II. Use of solid-phase synthesis to explore novel statine motifs.  [PMID:15189032]
5. Johansson, Per-Ola PO and 8 more authors.  2005-06-30  Design and synthesis of potent inhibitors of plasmepsin I and II: X-ray crystal structure of inhibitor in complex with plasmepsin II.  [PMID:15974592]
6. Jennings, Lee D LD and 20 more authors.  2008-01-15  Acylguanidine inhibitors of beta-secretase: optimization of the pyrrole ring substituents extending into the S1' substrate binding pocket.  [PMID:18068983]
7. Clarke, Brian B and 26 more authors.  2008-02-01  BACE-1 inhibitors part 1: identification of novel hydroxy ethylamines (HEAs).  [PMID:18171614]
8. Charrier, Nicolas N and 24 more authors.  2008-06-12  Second generation of hydroxyethylamine BACE-1 inhibitors: optimizing potency and oral bioavailability.  [PMID:18457381]
9. and Ghosh, Arun K.  2009-04-23  Harnessing nature's insight: design of aspartyl protease inhibitors from treatment of drug-resistant HIV to Alzheimer's disease.  [PMID:19323561]
10. Charrier, Nicolas N and 23 more authors.  2009-07-01  Second generation of BACE-1 inhibitors. Part 1: The need for improved pharmacokinetics.  [PMID:19428244]
11. Charrier, Nicolas N and 21 more authors.  2009-07-01  Second generation of BACE-1 inhibitors part 2: Optimisation of the non-prime side substituent.  [PMID:19477642]
12. Orrling, Kristina M KM and 5 more authors.  2009-08-15  alpha-Substituted norstatines as the transition-state mimic in inhibitors of multiple digestive vacuole malaria aspartic proteases.  [PMID:19635672]
13. Kwan, Jason C; Eksioglu, Erika A; Liu, Chen; Paul, Valerie J and Luesch, Hendrik.  2009-09-24  Grassystatins A-C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation.  [PMID:19715320]
14. Malamas, Michael S MS and 13 more authors.  2010-02-11  Design and synthesis of 5,5'-disubstituted aminohydantoins as potent and selective human beta-secretase (BACE1) inhibitors.  [PMID:19968289]
15. Malamas, Michael S MS and 17 more authors.  2010-04-01  Novel pyrrolyl 2-aminopyridines as potent and selective human beta-secretase (BACE1) inhibitors.  [PMID:20223661]
16. Gupta, Deepak D, Yedidi, Ravikiran S RS, Varghese, Sheeba S, Kovari, Ladislau C LC and Woster, Patrick M PM.  2010-05-27  Mechanism-based inhibitors of the aspartyl protease plasmepsin II as potential antimalarial agents.  [PMID:20438064]
17. Clarke, Brian B and 21 more authors.  2010-08-01  BACE-1 hydroxyethylamine inhibitors using novel edge-to-face interaction with Arg-296.  [PMID:20579874]
18. Malamas, Michael S MS and 14 more authors.  2011-09-15  New pyrazolyl and thienyl aminohydantoins as potent BACE1 inhibitors: exploring the S2' region.  [PMID:21835615]
19. Monenschein, Holger H and 7 more authors.  2012-06-01  Structure guided P1' modifications of HEA derived β-secretase inhibitors for the treatment of Alzheimer's disease.  [PMID:22572583]
20. Ghosh, Arun K and 7 more authors.  2012-11-08  Structure-based design of highly selective β-secretase inhibitors: synthesis, biological evaluation, and protein-ligand X-ray crystal structure.  [PMID:22954357]
21. Liu, Yanxia Y and 13 more authors.  2012-12-13  Cyanobacterial peptides as a prototype for the design of potent β-secretase inhibitors and the development of selective chemical probes for other aspartic proteases.  [PMID:23181502]
22. Hunt, Kevin W KW and 25 more authors.  2013-04-25  Spirocyclic β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors: from hit to lowering of cerebrospinal fluid (CSF) amyloid β in a higher species.  [PMID:23537249]
23. Ghosh, Arun K and 10 more authors.  2015-02-01  Structure-based design, synthesis and biological evaluation of novel β-secretase inhibitors containing a pyrazole or thiazole moiety as the P3 ligand.  [PMID:25537272]
24. Chen, Jian Jeffrey JJ and 36 more authors.  2015-02-15  Development of 2-aminooxazoline 3-azaxanthenes as orally efficacious β-secretase inhibitors for the potential treatment of Alzheimer's disease.  [PMID:25613679]
25. Al-Awadhi, Fatma H; Ratnayake, Ranjala; Paul, Valerie J and Luesch, Hendrik.  2016-08-01  Tasiamide F, a potent inhibitor of cathepsins D and E from a marine cyanobacterium.  [PMID:27211244]
26. Al-Awadhi, Fatma H FH, Law, Brian K BK, Paul, Valerie J VJ and Luesch, Hendrik H.  2017-11-22  Grassystatins D-F, Potent Aspartic Protease Inhibitors from Marine Cyanobacteria as Potential Antimetastatic Agents Targeting Invasive Breast Cancer.  [PMID:29087712]
27. Low, Jonathan D JD and 14 more authors.  2017-06-01  Development of 2-aminooxazoline 3-azaxanthene β-amyloid cleaving enzyme (BACE) inhibitors with improved selectivity against Cathepsin D.  [PMID:30108829]
28. Zogota, Rimants R and 10 more authors.  2019-02-01  Peptidomimetic plasmepsin inhibitors with potent anti-malarial activity and selectivity against cathepsin D.  [PMID:30529637]
29. Pettus, Liping H and 14 more authors.  2020-03-12  Discovery of AM-6494: A Potent and Orally Efficacious β-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitor with in Vivo Selectivity over BACE2.  [PMID:31589043]
30. Goyal, Sandeep and 11 more authors.  2021-01-01  Identification and structure-activity relationship studies of small molecule inhibitors of the human cathepsin D.  [PMID:33271453]

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