2-((6S,9S,12S,15S,18S,21S,23aS,28aR)-6,15,18-tribenzyl-21-(3-guanidinopropyl)-9-methyl-5,8,11,14,17,20,23,28-octaoxooctacosahydrodipyrrolo[1,2-a:1',2'-d][1,4,7,10,13,16,19,22]octaazacyclotetracosin-12-yl)acetamide

ID: ALA3577981

Chembl Id: CHEMBL3577981

PubChem CID: 122178151

Max Phase: Preclinical

Molecular Formula: C50H64N12O9

Molecular Weight: 977.14

Molecule Type: Protein

Names and Identifiers

Canonical SMILES:  C[C@@H]1NC(=O)[C@H](CC(N)=O)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/C50H64N12O9/c1-30-42(64)60-38(28-33-18-9-4-10-19-33)48(70)62-25-13-22-40(62)49(71)61-24-12-21-39(61)47(69)56-34(20-11-23-54-50(52)53)43(65)57-35(26-31-14-5-2-6-15-31)45(67)58-36(27-32-16-7-3-8-17-32)46(68)59-37(29-41(51)63)44(66)55-30/h2-10,14-19,30,34-40H,11-13,20-29H2,1H3,(H2,51,63)(H,55,66)(H,56,69)(H,57,65)(H,58,67)(H,59,68)(H,60,64)(H4,52,53,54)/t30-,34-,35-,36-,37-,38-,39-,40+/m0/s1

Standard InChI Key:  MTKQTEXYJKPBQD-GNDHHEKASA-N

Alternative Forms

1. Parent:

   

   ALA3577981

   ---

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: 977.14

Molecular Weight (Monoisotopic): 976.4919

AlogP: -1.22

#Rotatable Bonds: 12

Polar Surface Area: 320.21

Molecular Species: BASE

HBA: 10

HBD: 10

#RO5 Violations: 2

HBA (Lipinski): 21

HBD (Lipinski): 12

#RO5 Violations (Lipinski): 3

CX Acidic pKa: 11.48

CX Basic pKa: 11.34

CX LogP: -1.82

CX LogD: -3.54

Aromatic Rings: 3

Heavy Atoms: 71

QED Weighted: 0.06

Np Likeness Score: 0.52

References

1. Ericson MD, Wilczynski A, Sorensen NB, Xiang Z, Haskell-Luevano C..  (2015)  Discovery of a β-Hairpin Octapeptide, c[Pro-Arg-Phe-Phe-Dap-Ala-Phe-DPro], Mimetic of Agouti-Related Protein(87-132) [AGRP(87-132)] with Equipotent Mouse Melanocortin-4 Receptor (mMC4R) Antagonist Pharmacology.,  58  (11): [PMID:25898270] [10.1021/acs.jmedchem.5b00184]

2. 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]

3. 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]

4. 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