N-((S)-3-(3-fluorophenyl)-1-oxo-1-((S)-1-oxo-3-((S)-2-oxopyrrolidin-3-yl)propan-2-ylamino)propan-2-yl)-1H-indole-2-carboxamide

ID: ALA4764751

PubChem CID: 146672237

Max Phase: Preclinical

Molecular Formula: C25H25FN4O4

Molecular Weight: 464.50

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  O=C[C@H](C[C@@H]1CCNC1=O)NC(=O)[C@H](Cc1cccc(F)c1)NC(=O)c1cc2ccccc2[nH]1

Standard InChI:  InChI=1S/C25H25FN4O4/c26-18-6-3-4-15(10-18)11-21(24(33)28-19(14-31)12-17-8-9-27-23(17)32)30-25(34)22-13-16-5-1-2-7-20(16)29-22/h1-7,10,13-14,17,19,21,29H,8-9,11-12H2,(H,27,32)(H,28,33)(H,30,34)/t17-,19-,21-/m0/s1

Standard InChI Key:  HCRBVFBQANEDDM-CUWPLCDZSA-N

Molfile:  

 
     RDKit          2D

 35 38  0  0  0  0  0  0  0  0999 V2000
   17.9564  -10.9455    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.9553  -11.7728    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.6700  -12.1857    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.6682  -10.5327    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.3836  -10.9419    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.3885  -11.7683    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.1759  -12.0191    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   20.6579  -11.3476    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.1680  -10.6819    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.4827  -11.3427    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.8995  -12.0548    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   21.8911  -10.6259    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   22.7160  -10.6210    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.1242   -9.9042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.1327  -11.3331    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.9577  -11.3282    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.9492   -9.8993    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   24.3575   -9.1825    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.7076   -9.1922    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   25.1825   -9.1776    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.5992   -9.8895    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   23.9408   -8.4704    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.3491   -7.7536    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.1642   -7.6589    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.3310   -6.8509    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.6141   -6.4426    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   24.0043   -6.9983    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.1961   -6.8330    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   23.5202   -7.7497    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   24.3707  -12.0395    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.1950  -12.0350    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.6040  -11.3176    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.1829  -10.6033    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.3601  -10.6112    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.6113  -12.7472    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  6  2  0
  5  4  2  0
  4  1  1  0
  5  6  1  0
  6  7  1  0
  7  8  1  0
  8  9  2  0
  9  5  1  0
  8 10  1  0
 10 11  2  0
 10 12  1  0
 12 13  1  0
 13 14  1  0
 13 15  1  6
 15 16  1  0
 14 17  1  0
 17 18  1  0
 14 19  2  0
 18 20  1  0
 20 21  2  0
 18 22  1  1
 22 23  1  0
 23 24  1  0
 24 25  1  0
 25 26  1  0
 26 27  1  0
 27 23  1  0
 27 28  2  0
 23 29  1  6
 16 30  2  0
 30 31  1  0
 31 32  2  0
 32 33  1  0
 33 34  2  0
 34 16  1  0
 31 35  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4764751

   ---

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: 464.50

Molecular Weight (Monoisotopic): 464.1860

AlogP: 1.86

#Rotatable Bonds: 9

Polar Surface Area: 120.16

Molecular Species: NEUTRAL

HBA: 4

HBD: 4

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 4

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 12.57

CX Basic pKa: ┄

CX LogP: 1.35

CX LogD: 1.35

Aromatic Rings: 3

Heavy Atoms: 34

QED Weighted: 0.36

Np Likeness Score: -0.20

References

1. Liu Y,Liang C,Xin L,Ren X,Tian L,Ju X,Li H,Wang Y,Zhao Q,Liu H,Cao W,Xie X,Zhang D,Wang Y,Jian Y.  (2020)  The development of Coronavirus 3C-Like protease (3CL) inhibitors from 2010 to 2020.,  206  [PMID:32810751] [10.1016/j.ejmech.2020.112711]

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. Huff S, Kummetha IR, Tiwari SK, Huante MB, Clark AE, Wang S, Bray W, Smith D, Carlin AF, Endsley M, Rana TM..  (2022)  Discovery and Mechanism of SARS-CoV-2 Main Protease Inhibitors.,  65  (4.0): [PMID:34570513] [10.1021/acs.jmedchem.1c00566]

4. Cannalire R, Cerchia C, Beccari AR, Di Leva FS, Summa V..  (2022)  Targeting SARS-CoV-2 Proteases and Polymerase for COVID-19 Treatment: State of the Art and Future Opportunities.,  65  (4.0): [PMID:33186044] [10.1021/acs.jmedchem.0c01140]

5. Wang H, Pei R, Li X, Deng W, Xing S, Zhang Y, Zhang C, He S, Sun H, Xiao S, Xiong J, Zhang Y, Chen X, Wang Y, Guo Y, Zhang B, Shang L..  (2022)  The structure-based design of peptidomimetic inhibitors against SARS-CoV-2 3C like protease as Potent anti-viral drug candidate.,  238  [PMID:35635946] [10.1016/j.ejmech.2022.114458]

6. Yu W, Zhao Y, Ye H, Wu N, Liao Y, Chen N, Li Z, Wan N, Hao H, Yan H, Xiao Y, Lai M..  (2022)  Structure-Based Design of a Dual-Targeted Covalent Inhibitor Against Papain-like and Main Proteases of SARS-CoV-2.,  65  (24.0): [PMID:36503248] [10.1021/acs.jmedchem.2c00954]

7. Yang H, Yang J..  (2021)  A review of the latest research on M^pro targeting SARS-COV inhibitors.,  12  (7.0): [PMID:34355175] [10.1039/D1MD00066G]

8. La Monica G, Bono A, Lauria A, Martorana A..  (2022)  Targeting SARS-CoV-2 Main Protease for Treatment of COVID-19: Covalent Inhibitors Structure-Activity Relationship Insights and Evolution Perspectives.,  65  (19.0): [PMID:36169610] [10.1021/acs.jmedchem.2c01005]

9. Shagufta, Ahmad I..  (2021)  The race to treat COVID-19: Potential therapeutic agents for the prevention and treatment of SARS-CoV-2.,  213  [PMID:33486200] [10.1016/j.ejmech.2021.113157]

10. Zheng L, Zhang L, Huang J, Nandakumar KS, Liu S, Cheng K..  (2020)  Potential treatment methods targeting 2019-nCoV infection.,  205  [PMID:32771797] [10.1016/j.ejmech.2020.112687]

11. Gao K, Wang R, Chen J, Tepe JJ, Huang F, Wei GW..  (2021)  Perspectives on SARS-CoV-2 Main Protease Inhibitors.,  64  (23.0): [PMID:34798775] [10.1021/acs.jmedchem.1c00409]

12. Chen R, Gao Y, Liu H, Li H, Chen W, Ma J..  (2023)  Advances in research on 3C-like protease (3CL^pro) inhibitors against SARS-CoV-2 since 2020.,  14  (1): [PMID:36760740] [10.1039/d2md00344a]

13. Guo N, Huang C, Qiao J, Li Y, Wang Y, Xia A, Zhang G, Fang Z, You J, Li L..  (2023)  Discovery of 3-phenyl-1,2,4-oxadiazole derivatives as a new class of SARS-CoV-2 main protease inhibitors.,  86  [PMID:36924946] [10.1016/j.bmcl.2023.129238]

Source

Source(1):

• Scientific Literature