(3S,7S,8S)-7-Hydroxy-8-(4-hydroxybenzyl)-3-isopropyl-1,4,9-triazacyclohenicosane-2,5,10-trione

ID: ALA4455141

PubChem CID: 155524560

Max Phase: Preclinical

Molecular Formula: C28H45N3O5

Molecular Weight: 503.68

Molecule Type: Unknown

This compound is available for customization.

Associated Items:

Bioactivity Summary Target Summary Assay Summary

Names and Identifiers

Canonical SMILES: CC(C)[C@@H]1NC(=O)C[C@H](O)[C@H](Cc2ccc(O)cc2)NC(=O)CCCCCCCCCCCNC1=O

Standard InChI: InChI=1S/C28H45N3O5/c1-20(2)27-28(36)29-17-11-9-7-5-3-4-6-8-10-12-25(34)30-23(24(33)19-26(35)31-27)18-21-13-15-22(32)16-14-21/h13-16,20,23-24,27,32-33H,3-12,17-19H2,1-2H3,(H,29,36)(H,30,34)(H,31,35)/t23-,24-,27-/m0/s1

Standard InChI Key: GPIQLEFFPFORMQ-DPZBCOQUSA-N

Molfile:

 
     RDKit          2D

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    5.4499   -1.4817    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.1411   -1.8779    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.8282   -1.4817    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.5152   -1.8779    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.1982   -1.4817    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.8853   -1.8779    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    4.7628   -2.6703    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5682   -3.0665    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5682   -3.9745    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.0757   -3.0665    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0757   -3.8590    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3887   -4.2593    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.7628   -4.2593    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
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    5.4499   -6.2404    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.1982   -5.4479    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.0792   -5.0765    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.1982   -6.2404    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.5152   -6.6366    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.8853   -6.6366    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0590   -5.4557    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.6477   -5.6554    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.0569   -6.2729    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3491   -6.6762    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3466   -7.4926    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0538   -7.9038    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.7649   -7.4927    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.7639   -6.6776    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0528   -8.7210    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
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 33 36  1  0
M  END

Associated Targets(Human)

CTSD Tchem Cathepsin D (3201 Activities)

Discover Target: CTSD

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

REN Tclin Renin (5251 Activities)

Discover Target: REN

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

BACE1 Tchem Beta-secretase 1 (15641 Activities)

Discover Target: BACE1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Associated Targets(non-human)

protease Protease (2551 Activities)

Discover Target: protease

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

PEP4 Saccharopepesin (34 Activities)

Discover Target: PEP4

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Natural Product: No	Oral: No	Chemical Probe: No	Parenteral: No
Molecule Type: Unknown	Topical: No	First In Class: No	Black Box: No
Chirality: No	Availability: No	Prodrug: No

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 503.68	Molecular Weight (Monoisotopic): 503.3359	AlogP: 3.34	#Rotatable Bonds: 3
Polar Surface Area: 127.76	Molecular Species: NEUTRAL	HBA: 5	HBD: 5
#RO5 Violations: 1	HBA (Lipinski): 8	HBD (Lipinski): 5	#RO5 Violations (Lipinski): 1
CX Acidic pKa: 9.50	CX Basic pKa: ┄	CX LogP: 3.60	CX LogD: 3.60
Aromatic Rings: 1	Heavy Atoms: 36	QED Weighted: 0.43	Np Likeness Score: 0.92

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]

(3S,7S,8S)-7-Hydroxy-8-(4-hydroxybenzyl)-3-isopropyl-1,4,9-triazacyclohenicosane-2,5,10-trione

Names and Identifiers

Alternative Forms

Associated Targets(Human)

Associated Targets(non-human)

Molecule Features

Drug Indications

Mechanisms of Action

Biocomponents

Calculated Properties

References

Source