2-[(S)-2-Amino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionyl]-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [(S)-1-((S)-1-carbamoyl-2-phenyl-ethylcarbamoyl)-2-phenyl-ethyl]-amide

ID: ALA538700

Chembl Id: CHEMBL538700

PubChem CID: 45272750

Max Phase: Preclinical

Molecular Formula: C39H43N5O5

Molecular Weight: 661.80

Molecule Type: Protein

Names and Identifiers

Canonical SMILES:  Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N1Cc2ccccc2C[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1ccccc1)C(N)=O

Standard InChI:  InChI=1S/C39H43N5O5/c1-24-17-30(45)18-25(2)31(24)22-32(40)39(49)44-23-29-16-10-9-15-28(29)21-35(44)38(48)43-34(20-27-13-7-4-8-14-27)37(47)42-33(36(41)46)19-26-11-5-3-6-12-26/h3-18,32-35,45H,19-23,40H2,1-2H3,(H2,41,46)(H,42,47)(H,43,48)/t32-,33-,34-,35-/m0/s1

Standard InChI Key:  KYXSQGDWDGTJNF-BBACVFHCSA-N

Alternative Forms

1. Parent:

   

   ALA538700

   H-Tyr(2,6-diMe)-Tic-Phe-Phe-NH2

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: 661.80

Molecular Weight (Monoisotopic): 661.3264

AlogP: 2.77

#Rotatable Bonds: 12

Polar Surface Area: 167.85

Molecular Species: NEUTRAL

HBA: 6

HBD: 5

#RO5 Violations: 1

HBA (Lipinski): 10

HBD (Lipinski): 7

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 9.75

CX Basic pKa: 7.75

CX LogP: 4.33

CX LogD: 3.82

Aromatic Rings: 4

Heavy Atoms: 49

QED Weighted: 0.16

Np Likeness Score: -0.12

References

1. Schiller PW, Fundytus ME, Merovitz L, Weltrowska G, Nguyen TM, Lemieux C, Chung NN, Coderre TJ..  (1999)  The opioid mu agonist/delta antagonist DIPP-NH(2)[Psi] produces a potent analgesic effect, no physical dependence, and less tolerance than morphine in rats.,  42  (18): [PMID:10479285] [10.1021/jm980724+]

2. Tóth G, Ioja E, Tömböly C, Ballet S, Tourwé D, Péter A, Martinek T, Chung NN, Schiller PW, Benyhe S, Borsodi A..  (2007)  Beta-methyl substitution of cyclohexylalanine in Dmt-Tic-Cha-Phe peptides results in highly potent delta opioid antagonists.,  50  (2): [PMID:17228874] [10.1021/jm060721u]

3. Balboni G, Trapella C, Sasaki Y, Ambo A, Marczak ED, Lazarus LH, Salvadori S..  (2009)  Influence of the side chain next to C-terminal benzimidazole in opioid pseudopeptides containing the Dmt-Tic pharmacophore.,  52  (17): [PMID:19642675] [10.1021/jm900686q]

4. Lee YS, Qu HC, Davis P, Ma SW, Vardanyan R, Lai J, Porreca F, Hruby VJ..  (2013)  Chiral Effect of a Phe Residue in Position 3 of the Dmt(1)-L(or D)-Tic(2) Analogues on Opioid Functional Activities.,  4  (7): [PMID:24648867] [10.1021/ml400115n]

5. Weltrowska G, Nguyen TM, Chung NN, Wilkes BC, Schiller PW..  (2013)  N-terminal guanidinylation of TIPP (Tyr-Tic-Phe-Phe) peptides results in major changes of the opioid activity profile.,  23  (18): [PMID:23932788] [10.1016/j.bmcl.2013.07.036]

6. 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]

7. 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