ID: ALA4102048

Max Phase: Preclinical

Molecular Formula: C49H64N12O8

Molecular Weight: 949.13

Molecule Type: Small molecule

Representations

Canonical SMILES:  C[C@@H]1NC(=O)[C@H](CN)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O

Standard InChI:  InChI=1S/C49H64N12O8/c1-30-41(62)58-37(28-33-18-9-4-10-19-33)47(68)61-25-13-22-40(61)48(69)60-24-12-21-39(60)46(67)55-34(20-11-23-53-49(51)52)42(63)56-35(26-31-14-5-2-6-15-31)43(64)57-36(27-32-16-7-3-8-17-32)44(65)59-38(29-50)45(66)54-30/h2-10,14-19,30,34-40H,11-13,20-29,50H2,1H3,(H,54,66)(H,55,67)(H,56,63)(H,57,64)(H,58,62)(H,59,65)(H4,51,52,53)/t30-,34-,35-,36-,37-,38-,39-,40+/m0/s1

Standard InChI Key:  IJUWOYISGCBYSL-GNDHHEKASA-N

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

Properties

Molecular Weight: 949.13

Molecular Weight (Monoisotopic): 948.4970

AlogP: -1.14

#Rotatable Bonds: 11

Polar Surface Area: 303.14

Molecular Species: BASE

HBA: 10

HBD: 10

#RO5 Violations: 2

HBA (Lipinski): 20

HBD (Lipinski): 12

#RO5 Violations (Lipinski): 3

CX Acidic pKa: 11.52

CX Basic pKa: 11.37

CX LogP: -1.55

CX LogD: -4.02

Aromatic Rings: 3

Heavy Atoms: 69

QED Weighted: 0.06

Np Likeness Score: 0.51

References

1. Ericson MD, Freeman KT, Schnell SM, Fleming KA, Haskell-Luevano C..  (2017)  Structure-Activity Relationship Studies on a Macrocyclic Agouti-Related Protein (AGRP) Scaffold Reveal Agouti Signaling Protein (ASP) Residue Substitutions Maintain Melanocortin-4 Receptor Antagonist Potency and Result in Inverse Agonist Pharmacology at the Melanocortin-5 Receptor.,  60  (19): [PMID:28813605] [10.1021/acs.jmedchem.7b00856]

2. Koerperich ZM, Ericson MD, Freeman KT, Speth RC, Pogozheva ID, Mosberg HI, Haskell-Luevano C..  (2020)  Incorporation of Agouti-Related Protein (AgRP) Human Single Nucleotide Polymorphisms (SNPs) in the AgRP-Derived Macrocyclic Scaffold c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-dPro] Decreases Melanocortin-4 Receptor Antagonist Potency and Results in the Discovery of Melanocortin-5 Receptor Antagonists.,  63  (5): [PMID:31845801] [10.1021/acs.jmedchem.9b00860]

3. Ericson MD,Freeman KT,Haskell-Luevano C.  (2020)  Peptoid NPhe in AGRP-Based c[Pro-Arg-Phe-Phe-Xxx-Ala-Phe-DPro] Scaffolds Maintain Mouse MC4R Antagonist Potency.,  11  (10): [PMID:33062177] [10.1021/acsmedchemlett.9b00641]

Source

Source(1):

• Scientific Literature