(E)-3-[4-({1-[(3-Cyclopentyl-1-methyl-2-pyridin-2-yl-1H-indole-6-carbonyl)amino]cyclobutanecarbonyl}amino)phenyl]-acrylic Acid

ID: ALA2181776

Cas Number: 494856-61-0

PubChem CID: 56949326

Max Phase: Phase

Molecular Formula: C34H34N4O4

Molecular Weight: 562.67

Molecule Type: Small molecule

Names and Identifiers

Synonyms: BILB 1941 | Bilb-1941 | BILB-1941ZW | BILB 1941|BILB-1941|494856-61-0|UNII-3WV68DY85W|BILB1941|3WV68DY85W|BILB-1941ZW|CHEMBL2181776|BDBM50398052|AKOS040747979|HY-18079|CS-0007224|Q27258151|(2E)-3-(4-(((1-(((3-CYCLOPENTYL-1-METHYL-2-(2-PYRIDINYL)-1H-INDOL-6-YL)CARBONYL)AMINO)CYCLOBUTYL)CARBONYL)AMINO)PHENYL)-2-PROPENOIC ACID|2-PROPENOIC ACID, 3-(4-(((1-(((3-CYCLOPENTYL-1-METHYL-2-(2-PYRIDINYL)-1H-INDOL-6-YL)CARBONYL)AMINO)CYCLOBUTYL)CARBONYL)AMINO)PHENYL)-, (2E)-|N-(1-(((4-((E)-2-(CARBOXY)ETHENYLShow More⌵

Canonical SMILES:  Cn1c(-c2ccccn2)c(C2CCCC2)c2ccc(C(=O)NC3(C(=O)Nc4ccc(/C=C/C(=O)O)cc4)CCC3)cc21

Standard InChI:  InChI=1S/C34H34N4O4/c1-38-28-21-24(13-16-26(28)30(23-7-2-3-8-23)31(38)27-9-4-5-20-35-27)32(41)37-34(18-6-19-34)33(42)36-25-14-10-22(11-15-25)12-17-29(39)40/h4-5,9-17,20-21,23H,2-3,6-8,18-19H2,1H3,(H,36,42)(H,37,41)(H,39,40)/b17-12+

Standard InChI Key:  JBSNALXXNTWUEC-SFQUDFHCSA-N

Molfile:  

     RDKit          2D

 42 47  0  0  0  0  0  0  0  0999 V2000
   41.6189   -1.9395    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   42.2022   -1.3520    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   41.6147   -0.7686    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   41.0314   -1.3561    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.9632   -2.7628    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.7839   -2.7632    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.2678   -3.4315    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.2700   -2.0966    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   37.0163   -1.3115    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.0542   -2.3527    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.0495   -3.1774    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.7604   -3.5922    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.4764   -3.1832    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.4772   -2.3552    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.7657   -1.9442    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.0153   -4.2186    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.2305   -4.4729    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.2298   -5.2979    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.0143   -5.5536    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.4997   -4.8864    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   40.1919   -1.9432    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   40.9062   -2.3561    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   40.1924   -1.1181    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   42.3352   -2.3569    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.0499   -1.9449    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   42.3347   -3.1820    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   43.7642   -2.3578    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.7616   -3.1804    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   44.4751   -3.5933    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   45.1908   -3.1812    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   45.1886   -2.3518    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   44.4746   -1.9427    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   45.9056   -3.5932    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   46.6198   -3.1801    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   47.3346   -3.5921    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   48.0488   -3.1791    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   47.3352   -4.4171    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   35.5541   -2.0502    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.7342   -2.0495    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.3227   -2.7606    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.7372   -3.4739    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.5556   -3.4711    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  1  0
  4  1  1  0
  6  7  2  0
  7 11  1  0
 10  8  1  0
  8  6  1  0
  5  6  1  0
  8  9  1  0
 10 11  2  0
 11 12  1  0
 12 13  2  0
 13 14  1  0
 14 15  2  0
 15 10  1  0
 16 17  1  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 20 16  1  0
  7 16  1  0
 14 21  1  0
 21 22  1  0
 21 23  2  0
 22  1  1  0
  1 24  1  0
 24 25  1  0
 24 26  2  0
 25 27  1  0
 27 28  2  0
 28 29  1  0
 29 30  2  0
 30 31  1  0
 31 32  2  0
 32 27  1  0
 30 33  1  0
 33 34  2  0
 34 35  1  0
 35 36  1  0
 35 37  2  0
  5 38  2  0
 38 39  1  0
 39 40  2  0
 40 41  1  0
 41 42  2  0
 42  5  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA2181776

   BILB-1941

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: Yes

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 562.67

Molecular Weight (Monoisotopic): 562.2580

AlogP: 6.29

#Rotatable Bonds: 8

Polar Surface Area: 113.32

Molecular Species: ACID

HBA: 5

HBD: 3

#RO5 Violations: 2

HBA (Lipinski): 8

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.48

CX Basic pKa: 4.09

CX LogP: 5.31

CX LogD: 2.69

Aromatic Rings: 4

Heavy Atoms: 42

QED Weighted: 0.22

Np Likeness Score: -0.64

References

1. Beaulieu PL, Bös M, Cordingley MG, Chabot C, Fazal G, Garneau M, Gillard JR, Jolicoeur E, LaPlante S, McKercher G, Poirier M, Poupart MA, Tsantrizos YS, Duan J, Kukolj G..  (2012)  Discovery of the first thumb pocket 1 NS5B polymerase inhibitor (BILB 1941) with demonstrated antiviral activity in patients chronically infected with genotype 1 hepatitis C virus (HCV).,  55  (17): [PMID:22849725] [10.1021/jm3006788]

2. Beaulieu PL, Anderson PC, Bethell R, Bös M, Bousquet Y, Brochu C, Cordingley MG, Fazal G, Garneau M, Gillard JR, Kawai S, Marquis M, McKercher G, Poupart MA, Stammers T, Thavonekham B, Wernic D, Duan J, Kukolj G..  (2014)  Discovery of BI 207524, an indole diamide NS5B thumb pocket 1 inhibitor with improved potency for the potential treatment of chronic hepatitis C virus infection.,  57  (23): [PMID:25393851] [10.1021/jm501532z]

3. Beaulieu PL, Bolger G, Deon D, Duplessis M, Fazal G, Gagnon A, Garneau M, LaPlante S, Stammers T, Kukolj G, Duan J..  (2015)  Multi-parameter optimization of aza-follow-ups to BI 207524, a thumb pocket 1 HCV NS5B polymerase inhibitor. Part 2: Impact of lipophilicity on promiscuity and in vivo toxicity.,  25  (5): [PMID:25599836] [10.1016/j.bmcl.2014.12.078]

4. Unpublished dataset, 

5. Ganta NM, Gedda G, Rathnakar B, Satyanarayana M, Yamajala B, Ahsan MJ, Jadav SS, Balaraju T..  (2019)  A review on HCV inhibitors: Significance of non-structural polyproteins.,  164  [PMID:30639895] [10.1016/j.ejmech.2018.12.045]

6. Zhou Z, Zhang J, Zhou E, Ren C, Wang J, Wang Y..  (2022)  Small molecule NS5B RdRp non-nucleoside inhibitors for the treatment of HCV infection: A medicinal chemistry perspective.,  240  [PMID:35868125] [10.1016/j.ejmech.2022.114595]

Source

Source(2):

• Scientific Literature
• Clinical Candidates