(S)-3-(3-(3,5-Dimethyl-1H-pyrazol-1-yl)phenyl)-4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic Acid

ID: ALA4241824

PubChem CID: 86272865

Max Phase: Preclinical

Molecular Formula: C29H37N5O2

Molecular Weight: 487.65

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cc1cc(C)n(-c2cccc([C@H](CC(=O)O)CN3CC[C@@H](CCc4ccc5c(n4)NCCC5)C3)c2)n1

Standard InChI:  InChI=1S/C29H37N5O2/c1-20-15-21(2)34(32-20)27-7-3-5-24(16-27)25(17-28(35)36)19-33-14-12-22(18-33)8-10-26-11-9-23-6-4-13-30-29(23)31-26/h3,5,7,9,11,15-16,22,25H,4,6,8,10,12-14,17-19H2,1-2H3,(H,30,31)(H,35,36)/t22-,25-/m1/s1

Standard InChI Key:  ZMXBIIQMSGOIRZ-RCZVLFRGSA-N

Molfile:  

     RDKit          2D

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   42.5947  -10.5420    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.3797  -10.7690    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.8398  -10.0935    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   43.3368   -9.4462    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   42.5701   -9.7264    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.7367   -9.7306    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   40.4463   -9.3211    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   40.4435   -8.4985    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.7349   -8.0932    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.0286   -9.3216    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.0328   -8.5020    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.3290   -8.0910    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.6165   -8.4949    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.6124   -9.3145    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.3207   -9.7301    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   41.1547   -9.7286    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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   45.9040  -10.7369    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   44.7009  -11.4826    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   46.3345  -11.4314    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   47.1513  -11.4058    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   45.9483  -12.1516    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   43.8837  -11.5065    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.4975  -12.2259    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.9281  -12.9214    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   44.7491  -12.8931    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   45.1315  -12.1733    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   45.1821  -13.5861    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   44.8799  -14.3438    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   45.5059  -14.8691    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   46.1990  -14.4360    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   46.0012  -13.6432    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   46.9567  -14.7422    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   44.0875  -14.5432    0.0000 C   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  5  1  0
  5  1  1  0
 10  6  1  0
  6  7  2  0
  7  8  1  0
  8  9  2  0
  9 11  1  0
 10 11  2  0
 10 15  1  0
 11 12  1  0
 12 13  1  0
 13 14  1  0
 14 15  1  0
  7 16  1  0
 16 17  1  0
  5 17  1  1
  3 18  1  0
 18 19  1  0
 19 20  1  0
 19 21  1  1
 20 22  1  0
 22 23  1  0
 22 24  2  0
 21 25  2  0
 25 26  1  0
 26 27  2  0
 27 28  1  0
 28 29  2  0
 29 21  1  0
 28 30  1  0
 30 31  1  0
 31 32  2  0
 32 33  1  0
 33 34  2  0
 34 30  1  0
 33 35  1  0
 31 36  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4241824

   Integrin-antagonist-1

2. Alternative Forms:

   

   ALA4241824

   Integrin Antagonist 1 (hydrochloride)

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: 487.65

Molecular Weight (Monoisotopic): 487.2947

AlogP: 4.76

#Rotatable Bonds: 9

Polar Surface Area: 83.28

Molecular Species: ZWITTERION

HBA: 6

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 4.02

CX Basic pKa: 10.26

CX LogP: 1.35

CX LogD: 1.13

Aromatic Rings: 3

Heavy Atoms: 36

QED Weighted: 0.45

Np Likeness Score: -1.00

References

1. Procopiou PA, Anderson NA, Barrett J, Barrett TN, Crawford MHJ, Fallon BJ, Hancock AP, Le J, Lemma S, Marshall RP, Morrell J, Pritchard JM, Rowedder JE, Saklatvala P, Slack RJ, Sollis SL, Suckling CJ, Thorp LR, Vitulli G, Macdonald SJF..  (2018)  Discovery of ( S)-3-(3-(3,5-Dimethyl-1 H-pyrazol-1-yl)phenyl)-4-(( R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic Acid, a Nonpeptidic αvβ6 Integrin Inhibitor for the Inhaled Treatment of Idiopathic Pulmonary Fibrosis.,  61  (18): [PMID:30215258] [10.1021/acs.jmedchem.8b00959]

2. Procopiou PA, Anderson NA, Barrett J, Barrett TN, Crawford MHJ, Fallon BJ, Hancock AP, Le J, Lemma S, Marshall RP, Morrell J, Pritchard JM, Rowedder JE, Saklatvala P, Slack RJ, Sollis SL, Suckling CJ, Thorp LR, Vitulli G, Macdonald SJF..  (2018)  Discovery of ( S)-3-(3-(3,5-Dimethyl-1 H-pyrazol-1-yl)phenyl)-4-(( R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic Acid, a Nonpeptidic αvβ6 Integrin Inhibitor for the Inhaled Treatment of Idiopathic Pulmonary Fibrosis.,  61  (18): [PMID:30215258] [10.1021/acs.jmedchem.8b00959]

3. Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek.  (2020)  Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection,  [10.21203/rs.3.rs-23951/v1]

4. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]

5. Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen.  (2020)  Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort,  [10.6019/CHEMBL4495565]

6. Bernhard Ellinger, Justus Dick, Vanessa Lage-Rupprecht, Bruce Schultz, Andrea Zaliani, Marcin Namysl, Stephan Gebel, Ole Pless, Jeanette Reinshagen, Christian Ebeling, Alexander Esser, Marc Jacobs, Carsten Claussen, and Martin Hofmann-Apitius.  (2021)  HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators,  [10.6019/CHEMBL4808148]

Source

Source(3):

• Scientific Literature
• SARS-CoV-2 Screening Data 2020-21
• Fraunhofer HDAC6