(R)-2-((S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanamido)-N-((S)-2-(2-((3,5-bis(trifluoromethyl)benzyl)(methyl)amino)-2-oxoethyl)-3-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-4-yl)-5-guanidinopentanamide

ID: ALA1782141

Chembl Id: CHEMBL1782141

PubChem CID: 52937467

Max Phase: Preclinical

Molecular Formula: C39H46F6N8O5

Molecular Weight: 820.84

Molecule Type: Small molecule

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]1Cc2ccccc2CN(CC(=O)N(C)Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)C1=O

Standard InChI:  InChI=1S/C39H46F6N8O5/c1-21-11-28(54)12-22(2)29(21)17-30(46)34(56)50-31(9-6-10-49-37(47)48)35(57)51-32-15-24-7-4-5-8-25(24)19-53(36(32)58)20-33(55)52(3)18-23-13-26(38(40,41)42)16-27(14-23)39(43,44)45/h4-5,7-8,11-14,16,30-32,54H,6,9-10,15,17-20,46H2,1-3H3,(H,50,56)(H,51,57)(H4,47,48,49)/t30-,31+,32-/m0/s1

Standard InChI Key:  UXNDGPPTVKDIOD-QAXCHELISA-N

Alternative Forms

1. Parent:

   

   ALA1782141

   (R)-2-((S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanamido)-N-((S)-2-(2-((3,5-bis(trifluoromethyl)benzyl)(methyl)amino)-2-oxoethyl)-3-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-4-yl)-5-guanidinopentanamide

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

Calculated Properties

Molecular Weight: 820.84

Molecular Weight (Monoisotopic): 820.3495

AlogP: 3.39

#Rotatable Bonds: 14

Polar Surface Area: 206.97

Molecular Species: BASE

HBA: 7

HBD: 7

#RO5 Violations: 2

HBA (Lipinski): 13

HBD (Lipinski): 9

#RO5 Violations (Lipinski): 3

CX Acidic pKa: 9.74

CX Basic pKa: 11.75

CX LogP: 3.01

CX LogD: 0.73

Aromatic Rings: 3

Heavy Atoms: 58

QED Weighted: 0.06

Np Likeness Score: -0.40

References

1. Ballet S, Feytens D, Buysse K, Chung NN, Lemieux C, Tumati S, Keresztes A, Van Duppen J, Lai J, Varga E, Porreca F, Schiller PW, Vanden Broeck J, Tourwé D..  (2011)  Design of novel neurokinin 1 receptor antagonists based on conformationally constrained aromatic amino acids and discovery of a potent chimeric opioid agonist-neurokinin 1 receptor antagonist.,  54  (7): [PMID:21413804] [10.1021/jm1016285]

2. Guillemyn K, Kleczkowska P, Lesniak A, Dyniewicz J, Van der Poorten O, Van den Eynde I, Keresztes A, Varga E, Lai J, Porreca F, Chung NN, Lemieux C, Mika J, Rojewska E, Makuch W, Van Duppen J, Przewlocka B, Vanden Broeck J, Lipkowski AW, Schiller PW, Tourwé D, Ballet S..  (2015)  Synthesis and biological evaluation of compact, conformationally constrained bifunctional opioid agonist - neurokinin-1 antagonist peptidomimetics.,  92  [PMID:25544687] [10.1016/j.ejmech.2014.12.033]

3. 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]

Source

Source(1):

• Scientific Literature