N-((1S)-1-{[((1S)-3-Hydroxy-2-oxo-1-{[(3S)-2-oxopyrrolidin-3-yl]-methyl}propyl)amino]carbonyl}-3-methylbutyl)-4-methoxy-1H-indole-2-carboxamide

ID: ALA4777223

Cas Number: 870153-29-0

PubChem CID: 11561899

Product Number: P426549, Order Now?

Max Phase: Preclinical

Molecular Formula: C24H32N4O6

Molecular Weight: 472.54

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  COc1cccc2[nH]c(C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@@H]3CCNC3=O)C(=O)CO)cc12

Standard InChI:  InChI=1S/C24H32N4O6/c1-13(2)9-18(23(32)27-17(20(30)12-29)10-14-7-8-25-22(14)31)28-24(33)19-11-15-16(26-19)5-4-6-21(15)34-3/h4-6,11,13-14,17-18,26,29H,7-10,12H2,1-3H3,(H,25,31)(H,27,32)(H,28,33)/t14-,17-,18-/m0/s1

Standard InChI Key:  QDIMHKWNHMVDJB-WBAXXEDZSA-N

Molfile:  

 
     RDKit          2D

 35 37  0  0  0  0  0  0  0  0999 V2000
   25.1501  -12.7732    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.5670  -13.4827    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   25.5587  -12.0590    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   26.3800  -12.0542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.7844  -11.3399    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.7927  -12.7636    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.6141  -12.7588    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.0309  -13.4682    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.0226  -12.0445    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.6057  -11.3351    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   26.3716  -10.6305    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   28.0142  -10.6209    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.8355  -10.6161    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.2399   -9.9018    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.2483  -11.3255    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   27.5973   -9.9115    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.0059   -9.1972    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.8196   -9.1099    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.9847   -8.3055    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.2705   -7.9010    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   27.6624   -8.4515    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.8576   -8.2881    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   27.1819   -9.1913    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   30.0612   -9.8970    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   24.3288  -12.7781    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.8440  -12.1192    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.8518  -13.4481    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   23.0692  -13.1990    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.0683  -12.3795    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.3594  -11.9723    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.6507  -12.3834    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.6556  -13.2060    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.3651  -13.6095    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.3576  -11.1551    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   21.6490  -10.7480    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  1  3  1  0
  3  4  1  0
  4  5  1  0
  4  6  1  6
  6  7  1  0
  7  8  1  0
  7  9  1  0
  5 10  1  0
  5 11  2  0
 10 12  1  0
 12 13  1  0
 13 14  1  0
 13 15  2  0
 12 16  1  1
 16 17  1  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 20 21  1  0
 21 17  1  0
 21 22  2  0
 17 23  1  6
 14 24  1  0
  1 25  1  0
 25 26  2  0
 26 29  1  0
 28 27  1  0
 27 25  1  0
 28 29  2  0
 29 30  1  0
 30 31  2  0
 31 32  1  0
 32 33  2  0
 33 28  1  0
 30 34  1  0
 34 35  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4777223

   PF-00835231

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 472.54

Molecular Weight (Monoisotopic): 472.2322

AlogP: 0.89

#Rotatable Bonds: 11

Polar Surface Area: 149.62

Molecular Species: NEUTRAL

HBA: 6

HBD: 5

#RO5 Violations: ┄

HBA (Lipinski): 10

HBD (Lipinski): 5

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 12.46

CX Basic pKa: ┄

CX LogP: 0.32

CX LogD: 0.32

Aromatic Rings: 2

Heavy Atoms: 34

QED Weighted: 0.33

Np Likeness Score: 0.26

References

1. Hoffman RL,Kania RS,Brothers MA,Davies JF,Ferre RA,Gajiwala KS,He M,Hogan RJ,Kozminski K,Li LY,Lockner JW,Lou J,Marra MT,Mitchell LJ,Murray BW,Nieman JA,Noell S,Planken SP,Rowe T,Ryan K,Smith GJ,Solowiej JE,Steppan CM,Taggart B.  (2020)  Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19.,  63  (21): [PMID:33054210] [10.1021/acs.jmedchem.0c01063]

2. Vankadara S, Wong YX, Liu B, See YY, Tan LH, Tan QW, Wang G, Karuna R, Guo X, Tan ST, Fong JY, Joy J, Chia CSB..  (2021)  A head-to-head comparison of the inhibitory activities of 15 peptidomimetic SARS-CoV-2 3CLpro inhibitors.,  48  [PMID:34271072] [10.1016/j.bmcl.2021.128263]

3. Stille JK, Tjutrins J, Wang G, Venegas FA, Hennecker C, Rueda AM, Sharon I, Blaine N, Miron CE, Pinus S, Labarre A, Plescia J, Burai Patrascu M, Zhang X, Wahba AS, Vlaho D, Huot MJ, Schmeing TM, Mittermaier AK, Moitessier N..  (2022)  Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL^pro covalent inhibitors.,  229  [PMID:34995923] [10.1016/j.ejmech.2021.114046]

4. Gao S, Sylvester K, Song L, Claff T, Jing L, Woodson M, Weiße RH, Cheng Y, Schäkel L, Petry M, Gütschow M, Schiedel AC, Sträter N, Kang D, Xu S, Toth K, Tavis J, Tollefson AE, Müller CE, Liu X, Zhan P..  (2022)  Discovery and Crystallographic Studies of Trisubstituted Piperazine Derivatives as Non-Covalent SARS-CoV-2 Main Protease Inhibitors with High Target Specificity and Low Toxicity.,  65  (19.0): [PMID:36107752] [10.1021/acs.jmedchem.2c01146]

5. Hirose Y, Shindo N, Mori M, Onitsuka S, Isogai H, Hamada R, Hiramoto T, Ochi J, Takahashi D, Ueda T, Caaveiro JMM, Yoshida Y, Ohdo S, Matsunaga N, Toba S, Sasaki M, Orba Y, Sawa H, Sato A, Kawanishi E, Ojida A..  (2022)  Discovery of Chlorofluoroacetamide-Based Covalent Inhibitors for Severe Acute Respiratory Syndrome Coronavirus 2 3CL Protease.,  65  (20.0): [PMID:36229406] [10.1021/acs.jmedchem.2c01081]

6. Bai B, Arutyunova E, Khan MB, Lu J, Joyce MA, Saffran HA, Shields JA, Kandadai AS, Belovodskiy A, Hena M, Vuong W, Lamer T, Young HS, Vederas JC, Tyrrell DL, Lemieux MJ, Nieman JA..  (2021)  Peptidomimetic nitrile warheads as SARS-CoV-2 3CL protease inhibitors.,  12  (10.0): [PMID:34778773] [10.1039/D1MD00247C]

7. Gao S, Song L, Claff T, Woodson M, Sylvester K, Jing L, Weiße RH, Cheng Y, Sträter N, Schäkel L, Gütschow M, Ye B, Yang M, Zhang T, Kang D, Toth K, Tavis J, Tollefson AE, Müller CE, Zhan P, Liu X..  (2022)  Discovery and Crystallographic Studies of Nonpeptidic Piperazine Derivatives as Covalent SARS-CoV-2 Main Protease Inhibitors.,  65  (24.0): [PMID:36475694] [10.1021/acs.jmedchem.2c01716]

Source

Source(1):

• Scientific Literature