2-[2-(2-{2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino}-4-methoxycarbonyl-butyrylamino)-3-cyclohexyl-propionylamino]-4,4-difluoro-butyric acid

ID: ALA421233

Chembl Id: CHEMBL421233

PubChem CID: 487905

Max Phase: Preclinical

Molecular Formula: C44H56F2N6O14

Molecular Weight: 930.96

Molecule Type: Protein

Names and Identifiers

Canonical SMILES:  CC(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1CCCCC1)C(=O)N[C@@H](CC(F)F)C(=O)O)C(c1ccccc1)c1ccccc1

Standard InChI:  InChI=1S/C44H56F2N6O14/c1-24(53)47-31(23-36(58)59)42(63)48-29(18-20-35(56)57)40(61)52-38(37(26-13-7-3-8-14-26)27-15-9-4-10-16-27)43(64)49-28(17-19-34(54)55)39(60)50-30(21-25-11-5-2-6-12-25)41(62)51-32(44(65)66)22-33(45)46/h3-4,7-10,13-16,25,28-33,37-38H,2,5-6,11-12,17-23H2,1H3,(H,47,53)(H,48,63)(H,49,64)(H,50,60)(H,51,62)(H,52,61)(H,54,55)(H,56,57)(H,58,59)(H,65,66)/t28-,29-,30-,31-,32-,38-/m0/s1

Standard InChI Key:  PPNHBWGLEUAQKU-BHTNCQBCSA-N

Alternative Forms

1. Parent:

   

   ALA421233

   2-[2-(2-{2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino}-4-methoxycarbonyl-butyrylamino)-3-cyclohexyl-propionylamino]-4,4-difluoro-butyric acid

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: 930.96

Molecular Weight (Monoisotopic): 930.3823

AlogP: 1.66

#Rotatable Bonds: 27

Polar Surface Area: 323.80

Molecular Species: ACID

HBA: 10

HBD: 10

#RO5 Violations: 2

HBA (Lipinski): 20

HBD (Lipinski): 10

#RO5 Violations (Lipinski): 3

CX Acidic pKa: 3.29

CX Basic pKa: ┄

CX LogP: 0.87

CX LogD: -11.84

Aromatic Rings: 2

Heavy Atoms: 66

QED Weighted: 0.06

Np Likeness Score: 0.12

References

1. Colarusso S, Koch U, Gerlach B, Steinkühler C, De Francesco R, Altamura S, Matassa VG, Narjes F..  (2003)  Phenethyl amides as novel noncovalent inhibitors of hepatitis C virus NS3/4A protease: discovery, initial SAR, and molecular modeling.,  46  (3): [PMID:12540231] [10.1021/jm025594q]

2. Narjes F, Koehler KF, Koch U, Gerlach B, Colarusso S, Steinkühler C, Brunetti M, Altamura S, De Francesco R, Matassa VG..  (2002)  A designed P1 cysteine mimetic for covalent and non-covalent inhibitors of HCV NS3 protease.,  12  (4): [PMID:11844705] [10.1016/s0960-894x(01)00842-3]

3. Colarusso S, Gerlach B, Koch U, Muraglia E, Conte I, Stansfield I, Matassa VG, Narjes F..  (2002)  Evolution, synthesis and SAR of tripeptide alpha-ketoacid inhibitors of the hepatitis C virus NS3/NS4A serine protease.,  12  (4): [PMID:11844706] [10.1016/s0960-894x(01)00843-5]

4. Meanwell NA..  (2011)  Synopsis of some recent tactical application of bioisosteres in drug design.,  54  (8): [PMID:21413808] [10.1021/jm1013693]

5. Meanwell NA..  (2018)  Fluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug Design.,  61  (14): [PMID:29400967] [10.1021/acs.jmedchem.7b01788]

6. Mei H, Han J, Klika KD, Izawa K, Sato T, Meanwell NA, Soloshonok VA..  (2020)  Applications of fluorine-containing amino acids for drug design.,  186  [PMID:31740056] [10.1016/j.ejmech.2019.111826]

7. Meanwell NA..  (2016)  2015 Philip S. Portoghese Medicinal Chemistry Lectureship. Curing Hepatitis C Virus Infection with Direct-Acting Antiviral Agents: The Arc of a Medicinal Chemistry Triumph.,  59  (16): [PMID:27501244] [10.1021/acs.jmedchem.6b00915]

Source

Source(1):

• Scientific Literature