3-{2-[2-tert-Butoxycarbonylamino-3-(1H-indol-3-yl)-propionylamino]-4-methylsulfanyl-butyrylamino}-N-(1-carbamoyl-2-phenyl-ethyl)-succinamic acid

ID: ALA64605

Chembl Id: CHEMBL64605

Cas Number: 5235-21-2

PubChem CID: 13178389

Max Phase: Preclinical

Molecular Formula: C34H44N6O8S

Molecular Weight: 696.83

Molecule Type: Protein

Names and Identifiers

Canonical SMILES:  CSCC[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)OC(C)(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(N)=O

Standard InChI:  InChI=1S/C34H44N6O8S/c1-34(2,3)48-33(47)40-26(17-21-19-36-23-13-9-8-12-22(21)23)31(45)37-24(14-15-49-4)30(44)39-27(18-28(41)42)32(46)38-25(29(35)43)16-20-10-6-5-7-11-20/h5-13,19,24-27,36H,14-18H2,1-4H3,(H2,35,43)(H,37,45)(H,38,46)(H,39,44)(H,40,47)(H,41,42)/t24-,25-,26-,27-/m0/s1

Standard InChI Key:  DDROKKYSSQPXQO-FWEHEUNISA-N

Alternative Forms

1. Parent:

   

   ALA64605

   Boc-trp-met-asp-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: 696.83

Molecular Weight (Monoisotopic): 696.2941

AlogP: 2.01

#Rotatable Bonds: 17

Polar Surface Area: 221.81

Molecular Species: ACID

HBA: 8

HBD: 7

#RO5 Violations: 2

HBA (Lipinski): 14

HBD (Lipinski): 8

#RO5 Violations (Lipinski): 3

CX Acidic pKa: 4.00

CX Basic pKa: ┄

CX LogP: 1.92

CX LogD: -1.24

Aromatic Rings: 3

Heavy Atoms: 49

QED Weighted: 0.11

Np Likeness Score: -0.28

References

1. Shiosaki K, Lin CW, Kopecka H, Craig RA, Bianchi BR, Miller TR, Witte DG, Stashko M, Nadzan AM..  (1992)  Development of potent and selective CCK-A receptor agonists from Boc-CCK-4: tetrapeptides containing Lys(N epsilon)-amide residues.,  35  (11): [PMID:1375964] [10.1021/jm00089a010]

2. Shiosaki K, Lin CW, Kopecka H, Craig R, Wagenaar FL, Bianchi B, Miller T, Witte D, Nadzan AM..  (1990)  Development of CCK-tetrapeptide analogues as potent and selective CCK-A receptor agonists.,  33  (11): [PMID:1700123] [10.1021/jm00173a006]

3. Bellier B, Million ME, DaNascimento S, Meudal H, Kellou S, Maigret B, Garbay C..  (2000)  Replacement of glycine with dicarbonyl and related moieties in analogues of the C-terminal pentapeptide of cholecystokinin: CCK(2) agonists displaying a novel binding mode.,  43  (20): [PMID:11020275] [10.1021/jm0000416]

4. Holladay MW, Lin CW, May CS, Garvey DS, Witte DG, Miller TR, Wolfram CA, Nadzan AM..  (1991)  trans-3-n-propyl-L-proline is a highly favorable, conformationally restricted replacement for methionine in the C-terminal tetrapeptide of cholecystokinin. Stereoselective synthesis of 3-allyl- and 3-n-propyl-L-proline derivatives from 4-hydroxy-L-proline.,  34  (1): [PMID:1992147] [10.1021/jm00105a068]

5. Horwell DC, Beeby A, Clark CR, Hughes J..  (1987)  Synthesis and binding affinities of analogues of cholecystokinin-(30-33) as probes for central nervous system cholecystokinin receptors.,  30  (4): [PMID:3560164] [10.1021/jm00387a027]

6. Shiosaki K, Lin CW, Leanna M, Morton HE, Miller TR, Witte D, Stashko M, Nadzan AM.  (1993)  Toward developing peptidomimetics: Successful replacement of backbone amide bonds in tetrapeptide-based CCK-A receptor agonists,  3  (5): [10.1016/S0960-894X(00)80680-0]

7. Herrero S, Suarez-Gea M, Gonzalez-Muniz R, Garcia-Lopez M, Herranz R, Ballaz S, Barber A, Fortuno A, Del Rio J.  (1997)  Pseudopeptide CCK-4 analogues incorporating the [CH(CN)NH] peptide bond surrogate,  7  (7): [10.1016/S0960-894X(97)00107-8]

8. Martín-Martínez M, De la Figuera N, Latorre M, García-López MT, Cenarruzabeitia E, Del Río J, González-Muñiz R..  (2005)  Conformationally constrained CCK4 analogues incorporating IBTM and BTD beta-turn mimetics.,  48  (24): [PMID:16302807] [10.1021/jm050689o]

9. Kumari S,Carmona AV,Tiwari AK,Trippier PC.  (2020)  Amide Bond Bioisosteres: Strategies, Synthesis, and Successes.,  63  (21.0): [PMID:32686940] [10.1021/acs.jmedchem.0c00530]

Source

Source(1):

• Scientific Literature