2-(1-{2-[2-amino-3-(4-hydroxyphenyl)propanoyl]-1,2,3,4-tetrahydro-3-isoquinolinylmethylamino}-2-phenylethylcarboxamido)-3-phenylpropanoic acid

ID: ALA191751

Chembl Id: CHEMBL191751

Cas Number: 146369-65-5

PubChem CID: 644210

Max Phase: Preclinical

Molecular Formula: C37H38N4O6

Molecular Weight: 634.73

Molecule Type: Protein

Names and Identifiers

Canonical SMILES:  N[C@@H](Cc1ccc(O)cc1)C(=O)N1Cc2ccccc2C[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)O

Standard InChI:  InChI=1S/C37H38N4O6/c38-30(19-26-15-17-29(42)18-16-26)36(45)41-23-28-14-8-7-13-27(28)22-33(41)35(44)39-31(20-24-9-3-1-4-10-24)34(43)40-32(37(46)47)21-25-11-5-2-6-12-25/h1-18,30-33,42H,19-23,38H2,(H,39,44)(H,40,43)(H,46,47)/t30-,31-,32-,33-/m0/s1

Standard InChI Key:  JYOUATXRHWNDDW-YRCZKMHPSA-N

Alternative Forms

1. Parent:

   

   ALA191751

   Tyrosyl-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-phenylalanyl-phenylalanine

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: 634.73

Molecular Weight (Monoisotopic): 634.2791

AlogP: 2.76

#Rotatable Bonds: 12

Polar Surface Area: 162.06

Molecular Species: ACID

HBA: 6

HBD: 5

#RO5 Violations: 1

HBA (Lipinski): 10

HBD (Lipinski): 6

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.83

CX Basic pKa: 7.72

CX LogP: 1.84

CX LogD: 1.69

Aromatic Rings: 4

Heavy Atoms: 47

QED Weighted: 0.16

Np Likeness Score: -0.08

References

1. Schiller PW, Weltrowska G, Nguyen TM, Wilkes BC, Chung NN, Lemieux C..  (1993)  TIPP[psi]: a highly potent and stable pseudopeptide delta opioid receptor antagonist with extraordinary delta selectivity.,  36  (21): [PMID:8230106] [10.1021/jm00073a020]

2. Schiller PW, Weltrowska G, Nguyen TM, Wilkes BC, Chung NN, Lemieux C..  (1993)  TIPP[psi]: a highly potent and stable pseudopeptide delta opioid receptor antagonist with extraordinary delta selectivity.,  36  (21): [PMID:8230106] [10.1021/jm00073a020]

3. Kumar V, Murray TF, Aldrich JV..  (2002)  Solid phase synthesis and evaluation of Tyr-Tic-Phe-Phe(p-NHCOCH(2)Br) ([Phe(p-bromoacetamide)(4)]TIPP), a potent affinity label for delta opioid receptors.,  45  (18): [PMID:12190304] [10.1021/jm020290p]

4. Maeda DY, Berman F, Murray TF, Aldrich JV..  (2000)  Synthesis and evaluation of isothiocyanate-containing derivatives of the delta-opioid receptor antagonist Tyr-Tic-Phe-Phe (TIPP) as potential affinity labels for delta-opioid receptors.,  43  (26): [PMID:11150176] [10.1021/jm000345s]

5. Kumar V, Murray TF, Aldrich JV..  (2000)  Extended TIP(P) analogues as precursors for labeled delta-opioid receptor ligands.,  43  (26): [PMID:11150177] [10.1021/jm000362h]

6. Tourwé D, Mannekens E, Diem TN, Verheyden P, Jaspers H, Tóth G, Péter A, Kertész I, Török G, Chung NN, Schiller PW..  (1998)  Side chain methyl substitution in the delta-opioid receptor antagonist TIPP has an important effect on the activity profile.,  41  (26): [PMID:9857087] [10.1021/jm981011u]

7. Tourwé D, Mannekens E, Diem TN, Verheyden P, Jaspers H, Tóth G, Péter A, Kertész I, Török G, Chung NN, Schiller PW..  (1998)  Side chain methyl substitution in the delta-opioid receptor antagonist TIPP has an important effect on the activity profile.,  41  (26): [PMID:9857087] [10.1021/jm981011u]

8. Van den Eynde I, Laus G, Schiller PW, Kosson P, Chung NN, Lipkowski AW, Tourwé D..  (2005)  A new structural motif for mu-opioid antagonists.,  48  (10): [PMID:15887972] [10.1021/jm0491795]

9. 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]

10. 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]

11. Berezowska I, Chung NN, Lemieux C, Wilkes BC, Schiller PW..  (2009)  Agonist vs antagonist behavior of delta opioid peptides containing novel phenylalanine analogues in place of Tyr(1).,  52  (21): [PMID:19827750] [10.1021/jm9004913]

12. Berezowska I, Lemieux C, Chung NN, Ding J, Schiller PW..  (2012)  Novel TIPP (H-Tyr-Tic-Phe-Phe-OH) analogues displaying a wide range of efficacies at the δ opioid receptor. Discovery of two highly potent and selective δ opioid agonists.,  22  (5): [PMID:22325949] [10.1016/j.bmcl.2012.01.063]

13. 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]

Source

Source(1):

• Scientific Literature