ID: ALA3416733

Max Phase: Preclinical

Molecular Formula: C27H37N4O4P

Molecular Weight: 512.59

Molecule Type: Small molecule

Representations

Canonical SMILES:  CC(C)C[C@H](CP(=O)(O)[C@@H](N)CCc1ccccc1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(N)=O

Standard InChI:  InChI=1S/C27H37N4O4P/c1-18(2)14-21(17-36(34,35)25(28)13-12-19-8-4-3-5-9-19)27(33)31-24(26(29)32)15-20-16-30-23-11-7-6-10-22(20)23/h3-11,16,18,21,24-25,30H,12-15,17,28H2,1-2H3,(H2,29,32)(H,31,33)(H,34,35)/t21-,24+,25-/m1/s1

Standard InChI Key:  QKFOTLXPIIESQI-IEZKXTBUSA-N

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Properties

Molecular Weight: 512.59

Molecular Weight (Monoisotopic): 512.2552

AlogP: 3.53

#Rotatable Bonds: 13

Polar Surface Area: 151.30

Molecular Species: ZWITTERION

HBA: 4

HBD: 5

#RO5 Violations: 1

HBA (Lipinski): 8

HBD (Lipinski): 7

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 0.65

CX Basic pKa: 9.61

CX LogP: 1.77

CX LogD: 1.77

Aromatic Rings: 3

Heavy Atoms: 36

QED Weighted: 0.22

Np Likeness Score: 0.10

References

1. Papakyriakou A, Zervoudi E, Tsoukalidou S, Mauvais FX, Sfyroera G, Mastellos DC, van Endert P, Theodorakis EA, Vourloumis D, Stratikos E..  (2015)  3,4-diaminobenzoic acid derivatives as inhibitors of the oxytocinase subfamily of M1 aminopeptidases with immune-regulating properties.,  58  (3): [PMID:25635706] [10.1021/jm501867s]

2. Węglarz-Tomczak E, Vassiliou S, Mucha A..  (2016)  Discovery of potent and selective inhibitors of human aminopeptidases ERAP1 and ERAP2 by screening libraries of phosphorus-containing amino acid and dipeptide analogues.,  26  (16): [PMID:27390066] [10.1016/j.bmcl.2016.06.062]

3. Mpakali A, Giastas P, Deprez-Poulain R, Papakyriakou A, Koumantou D, Gealageas R, Tsoukalidou S, Vourloumis D, Mavridis IM, Stratikos E, Saridakis E..  (2017)  Crystal Structures of ERAP2 Complexed with Inhibitors Reveal Pharmacophore Requirements for Optimizing Inhibitor Potency.,  8  (3): [PMID:28337326] [10.1021/acsmedchemlett.6b00505]

4. Kokkala P, Mpakali A, Mauvais FX, Papakyriakou A, Daskalaki I, Petropoulou I, Kavvalou S, Papathanasopoulou M, Agrotis S, Fonsou TM, van Endert P, Stratikos E, Georgiadis D..  (2016)  Optimization and Structure-Activity Relationships of Phosphinic Pseudotripeptide Inhibitors of Aminopeptidases That Generate Antigenic Peptides.,  59  (19): [PMID:27606717] [10.1021/acs.jmedchem.6b01031]

5. Stamogiannos A, Papakyriakou A, Mauvais FX, van Endert P, Stratikos E..  (2016)  Screening Identifies Thimerosal as a Selective Inhibitor of Endoplasmic Reticulum Aminopeptidase 1.,  7  (7): [PMID:27437077] [10.1021/acsmedchemlett.6b00084]

6. Laura M, Ronan G, Vy LB, Valentin G, Omar CA, Virgyl C, Piveteau C, Melissa R, Charlotte F, Sandrine W, Julie C, Julie DR, Damien B, Florence L, Peter VE, Benoit D, Rebecca DP..  (2021)  Modulators of hERAP2 discovered by high-throughput screening.,  211  [PMID:33359953] [10.1016/j.ejmech.2020.113053]

7. Wilding B, Pasqua AE, E A Chessum N, Pierrat OA, Hahner T, Tomlin K, Shehu E, Burke R, Richards GM, Whitton B, Arwert EN, Thapaliya A, Salimraj R, van Montfort R, Skawinska A, Hayes A, Raynaud F, Chopra R, Jones K, Newton G, Cheeseman MD..  (2021)  Investigating the phosphinic acid tripeptide mimetic DG013A as a tool compound inhibitor of the M1-aminopeptidase ERAP1.,  42  [PMID:33887439] [10.1016/j.bmcl.2021.128050]

8. Deddouche-Grass S, Andouche C, Bärenz F, Halter C, Hohwald A, Lebrun L, Membré N, Morales R, Muzet N, Poirot M, Reynaud M, Roujean V, Weber F, Zimmermann A, Heng R, Basse N..  (2021)  Discovery and Optimization of a Series of Benzofuran Selective ERAP1 Inhibitors: Biochemical and In Silico Studies.,  12  (7.0): [PMID:34267884] [10.1021/acsmedchemlett.1c00235]

Source

Source(1):

• Scientific Literature