4-(1-benzyl-4-(4-chlorobenzyl)piperidin-4-yl)-2-hydroxy-4-oxobut-2-enoic acid

ID: ALA463590

Cas Number: 1807796-13-9

PubChem CID: 6479291

Max Phase: Preclinical

Molecular Formula: C23H24ClNO4

Molecular Weight: 413.90

Molecule Type: Small molecule

Names and Identifiers

Synonyms: L-742001 | CHEMBL463590|(2z)-4-[1-Benzyl-4-(4-Chlorobenzyl)piperidin-4-Yl]-2-Hydroxy-4-Oxobut-2-Enoic Acid|4-(1-benzyl-4-(4-chlorobenzyl)piperidin-4-yl)-2-hydroxy-4-oxobut-2-enoic acid|177592-42-6|Q27451249|(Z)-4-(1-Benzyl-4-(4-chlorobenzyl)piperidin-4-yl)-2-hydroxy-4-oxobut-2-enoic acid|(Z)-4-[1-benzyl-4-[(4-chlorophenyl)methyl]-4-piperidyl]-2-hydroxy-4-oxo-but-2-enoic acid|1807796-13-9|2-Butenoic acid, 4-[4-[(4-chlorophenyl)methyl]-1-(phenylmethyl)-4-piperidinyl]-2-hydroxy-4-oxo-, (2Z)-

Canonical SMILES:  O=C(O)/C(O)=C/C(=O)C1(Cc2ccc(Cl)cc2)CCN(Cc2ccccc2)CC1

Standard InChI:  InChI=1S/C23H24ClNO4/c24-19-8-6-17(7-9-19)15-23(21(27)14-20(26)22(28)29)10-12-25(13-11-23)16-18-4-2-1-3-5-18/h1-9,14,26H,10-13,15-16H2,(H,28,29)/b20-14-

Standard InChI Key:  DGJZJCIAWLMRBY-ZHZULCJRSA-N

Molfile:  

     RDKit          2D

 29 31  0  0  0  0  0  0  0  0999 V2000
    5.7083  -14.7042    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.1167  -15.4167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.9333  -15.4193    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.3479  -14.7111    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.9395  -13.9986    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.1167  -13.9943    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.0583  -14.2917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.7768  -14.6972    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.0504  -13.4667    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.4872  -14.2778    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.2056  -14.6834    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.9161  -14.2640    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.2136  -15.5084    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.4792  -13.4529    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.0583  -15.1208    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.0587  -15.9458    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.3419  -16.3565    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.3419  -17.1807    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.0571  -17.5937    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.7738  -17.1765    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.7702  -16.3536    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.0586  -18.4187    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    4.8833  -14.7035    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4703  -15.4177    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6452  -15.4148    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2322  -16.1281    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6442  -16.8439    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4734  -16.8419    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8827  -16.1280    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  4  7  1  0
  4 15  1  0
  1  2  1  0
 15 16  1  0
  7  8  1  0
 16 17  2  0
  1  6  1  0
 17 18  1  0
  7  9  2  0
 18 19  2  0
  2  3  1  0
 19 20  1  0
  8 10  2  0
 20 21  2  0
 21 16  1  0
  3  4  1  0
 19 22  1  0
 10 11  1  0
  1 23  1  0
  4  5  1  0
 23 24  1  0
 11 12  1  0
 24 25  2  0
  5  6  1  0
 25 26  1  0
 11 13  2  0
 26 27  2  0
 27 28  1  0
 10 14  1  0
 28 29  2  0
 29 24  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA463590

   (2z)-4-[1-Benzyl-4-(4-Chlorobenzyl)piperidin-4-Yl]-2-Hydroxy-4-Oxobut-2-Enoic Acid

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

Calculated Properties

Molecular Weight: 413.90

Molecular Weight (Monoisotopic): 413.1394

AlogP: 4.26

#Rotatable Bonds: 7

Polar Surface Area: 77.84

Molecular Species: ACID

HBA: 4

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 5

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 2.53

CX Basic pKa: 8.43

CX LogP: 1.99

CX LogD: 1.96

Aromatic Rings: 2

Heavy Atoms: 29

QED Weighted: 0.52

Np Likeness Score: -0.23

References

1. Prado-Prado FJ, Martinez de la Vega O, Uriarte E, Ubeira FM, Chou KC, González-Díaz H..  (2009)  Unified QSAR approach to antimicrobials. 4. Multi-target QSAR modeling and comparative multi-distance study of the giant components of antiviral drug-drug complex networks.,  17  (2): [PMID:19112024] [10.1016/j.bmc.2008.11.075]

2. Baughman BM, Jake Slavish P, DuBois RM, Boyd VA, White SW, Webb TR..  (2012)  Identification of influenza endonuclease inhibitors using a novel fluorescence polarization assay.,  7  (3): [PMID:22211528] [10.1021/cb200439z]

3. Hastings JC, Selnick H, Wolanski B, Tomassini JE..  (1996)  Anti-influenza virus activities of 4-substituted 2,4-dioxobutanoic acid inhibitors.,  40  (5): [PMID:8723491] [10.1128/aac.40.5.1304]

4. Das K..  (2012)  Antivirals targeting influenza A virus.,  55  (14): [PMID:22612288] [10.1021/jm300455c]

5. Yan Z, Zhang L, Fu H, Wang Z, Lin J..  (2014)  Design of the influenza virus inhibitors targeting the PA endonuclease using 3D-QSAR modeling, side-chain hopping, and docking.,  24  (2): [PMID:24365156] [10.1016/j.bmcl.2013.12.026]

6. Fudo S, Yamamoto N, Nukaga M, Odagiri T, Tashiro M, Neya S, Hoshino T..  (2015)  Structural and computational study on inhibitory compounds for endonuclease activity of influenza virus polymerase.,  23  (17): [PMID:26252962] [10.1016/j.bmc.2015.07.046]

7. Pala N, Stevaert A, Dallocchio R, Dessì A, Rogolino D, Carcelli M, Sanna V, Sechi M, Naesens L..  (2015)  Virtual Screening and Biological Validation of Novel Influenza Virus PA Endonuclease Inhibitors.,  6  (8): [PMID:26288686] [10.1021/acsmedchemlett.5b00109]

8. Miyagawa M, Akiyama T, Mikamiyama-Iwata M, Hattori K, Kurihara N, Taoda Y, Takahashi-Kageyama C, Kurose N, Mikamiyama H, Suzuki N, Takaya K, Tomita K, Matsuo K, Morimoto K, Yoshida R, Shishido T, Yoshinaga T, Sato A, Kawai M..  (2016)  Discovery of novel 5-hydroxy-4-pyridone-3-carboxy acids as potent inhibitors of influenza Cap-dependent endonuclease.,  26  (19): [PMID:27568084] [10.1016/j.bmcl.2016.08.038]

9. Ju H, Zhang J, Huang B, Kang D, Huang B, Liu X, Zhan P..  (2017)  Inhibitors of Influenza Virus Polymerase Acidic (PA) Endonuclease: Contemporary Developments and Perspectives.,  60  (9): [PMID:28118010] [10.1021/acs.jmedchem.6b01227]

10. Credille CV, Dick BL, Morrison CN, Stokes RW, Adamek RN, Wu NC, Wilson IA, Cohen SM..  (2018)  Structure-Activity Relationships in Metal-Binding Pharmacophores for Influenza Endonuclease.,  61  (22): [PMID:30351002] [10.1021/acs.jmedchem.8b01363]

11. Ferro S, Gitto R, Buemi MR, Karamanou S, Stevaert A, Naesens L, De Luca L..  (2018)  Identification of influenza PA-Nter endonuclease inhibitors using pharmacophore- and docking-based virtual screening.,  26  (15): [PMID:30082105] [10.1016/j.bmc.2018.07.046]

12. Miyagawa M, Akiyama T, Taoda Y, Takaya K, Takahashi-Kageyama C, Tomita K, Yasuo K, Hattori K, Shano S, Yoshida R, Shishido T, Yoshinaga T, Sato A, Kawai M..  (2019)  Synthesis and SAR Study of Carbamoyl Pyridone Bicycle Derivatives as Potent Inhibitors of Influenza Cap-dependent Endonuclease.,  62  (17): [PMID:31386363] [10.1021/acs.jmedchem.9b00861]

13. Credille CV, Morrison CN, Stokes RW, Dick BL, Feng Y, Sun J, Chen Y, Cohen SM..  (2019)  SAR Exploration of Tight-Binding Inhibitors of Influenza Virus PA Endonuclease.,  62  (21): [PMID:31536340] [10.1021/acs.jmedchem.9b00747]

14. Credille CV, Chen Y, Cohen SM..  (2016)  Fragment-Based Identification of Influenza Endonuclease Inhibitors.,  59  (13): [PMID:27291165] [10.1021/acs.jmedchem.6b00628]

15. Zima V,Radilová K,Kožíšek M,Albiñana CB,Karlukova E,Brynda J,Fanfrlík J,Flieger M,Hodek J,Weber J,Majer P,Konvalinka J,Machara A.  (2020)  Unraveling the anti-influenza effect of flavonoids: Experimental validation of luteolin and its congeners as potent influenza endonuclease inhibitors.,  208  [PMID:32883638] [10.1016/j.ejmech.2020.112754]

Source

Source(1):

• Scientific Literature