6-Amino-2-((S)-2-{(R)-2-[2-amino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionylamino]-5-guanidino-1-oxo-pentylamino}-3-phenyl-propionylamino)-hexanoic acid amide

ID: ALA2181202

Chembl Id: CHEMBL2181202

Cas Number: 255861-98-4

PubChem CID: 9809562

Max Phase: Preclinical

Molecular Formula: C32H49N9O5

Molecular Weight: 639.80

Molecule Type: Protein

Names and Identifiers

Canonical SMILES:  Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCCN)C(N)=O

Standard InChI:  InChI=1S/C32H49N9O5/c1-19-15-22(42)16-20(2)23(19)18-24(34)29(44)40-26(12-8-14-38-32(36)37)30(45)41-27(17-21-9-4-3-5-10-21)31(46)39-25(28(35)43)11-6-7-13-33/h3-5,9-10,15-16,24-27,42H,6-8,11-14,17-18,33-34H2,1-2H3,(H2,35,43)(H,39,46)(H,40,44)(H,41,45)(H4,36,37,38)/t24-,25-,26+,27-/m0/s1

Standard InChI Key:  FIAKHZXVLBNZLW-NFGXINMFSA-N

Alternative Forms

1. Parent:

   

   ALA2181202

   (2S)-6-amino-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]hexanamide

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Protein

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 639.80

Molecular Weight (Monoisotopic): 639.3857

AlogP: -0.55

#Rotatable Bonds: 19

Polar Surface Area: 264.56

Molecular Species: BASE

HBA: 8

HBD: 10

#RO5 Violations: 2

HBA (Lipinski): 14

HBD (Lipinski): 14

#RO5 Violations (Lipinski): 3

CX Acidic pKa: 9.61

CX Basic pKa: 11.75

CX LogP: -0.52

CX LogD: -5.34

Aromatic Rings: 2

Heavy Atoms: 46

QED Weighted: 0.05

Np Likeness Score: 0.34

References

1. Balboni G, Cocco MT, Salvadori S, Romagnoli R, Sasaki Y, Okada Y, Bryant SD, Jinsmaa Y, Lazarus LH..  (2005)  From the potent and selective mu opioid receptor agonist H-Dmt-d-Arg-Phe-Lys-NH(2) to the potent delta antagonist H-Dmt-Tic-Phe-Lys(Z)-OH.,  48  (17): [PMID:16107162] [10.1021/jm0504959]

2. Novoa A, Van Dorpe S, Wynendaele E, Spetea M, Bracke N, Stalmans S, Betti C, Chung NN, Lemieux C, Zuegg J, Cooper MA, Tourwé D, De Spiegeleer B, Schiller PW, Ballet S..  (2012)  Variation of the net charge, lipophilicity, and side chain flexibility in Dmt(1)-DALDA: Effect on Opioid Activity and Biodistribution.,  55  (22): [PMID:23102273] [10.1021/jm3008079]

3. Ballet S, Betti C, Novoa A, Tömböly C, Nielsen CU, Helms HC, Lesniak A, Kleczkowska P, Chung NN, Lipkowski AW, Brodin B, Tourwé D, Schiller PW..  (2014)  In Vitro Membrane Permeation Studies and in Vivo Antinociception of Glycosylated Dmt(1)-DALDA Analogues.,  5  (4): [PMID:24839540] [10.1021/ml4004765]

4. Ballet S, Betti C, Novoa A, Tömböly C, Nielsen CU, Helms HC, Lesniak A, Kleczkowska P, Chung NN, Lipkowski AW, Brodin B, Tourwé D, Schiller PW..  (2014)  In Vitro Membrane Permeation Studies and in Vivo Antinociception of Glycosylated Dmt(1)-DALDA Analogues.,  5  (4): [PMID:24839540] [10.1021/ml4004765]

5. Turnaturi R, Aricò G, Ronsisvalle G, Parenti C, Pasquinucci L..  (2016)  Multitarget opioid ligands in pain relief: New players in an old game.,  108  [PMID:26656913] [10.1016/j.ejmech.2015.11.028]

6. Betti C, Starnowska J, Mika J, Dyniewicz J, Frankiewicz L, Novoa A, Bochynska M, Keresztes A, Kosson P, Makuch W, Van Duppen J, Chung NN, Vanden Broeck J, Lipkowski AW, Schiller PW, Janssens F, Ceusters M, Sommen F, Meert T, Przewlocka B, Tourwé D, Ballet S..  (2015)  Dual Alleviation of Acute and Neuropathic Pain by Fused Opioid Agonist-Neurokinin 1 Antagonist Peptidomimetics.,  6  (12): [PMID:26713106] [10.1021/acsmedchemlett.5b00359]

7. Cai Y, Lu D, Chen Z, Ding Y, Chung NN, Li T, Schiller PW..  (2016)  [Dmt(1)]DALDA analogues modified with tyrosine analogues at position 1.,  26  (15): [PMID:27301366] [10.1016/j.bmcl.2016.06.003]

8. Smith MT, Kong D, Kuo A, Imam MZ, Williams CM..  (2022)  Analgesic Opioid Ligand Discovery Based on Nonmorphinan Scaffolds Derived from Natural Sources.,  65  (3.0): [PMID:34995453] [10.1021/acs.jmedchem.0c01915]

Source

Source(1):

• Scientific Literature