3-(5-Fluoro-1H-indol-3-yl)pyrrolidine-2,5-dione

ID: ALA4086143

Cas Number: 198474-05-4

PubChem CID: 23063810

Product Number: P175464, Order Now?

Max Phase: Phase

Molecular Formula: C12H9FN2O2

Molecular Weight: 232.21

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Pf-06840003 | PF-06840003 | 198474-05-4|PF-06840003|3-(5-Fluoro-1H-indol-3-yl)pyrrolidine-2,5-dione|PF06840003|2,5-Pyrrolidinedione, 3-(5-fluoro-1H-indol-3-yl)-|EOS200271|3-(5-fluoro-indol-3-yl)-pyrrolidine-2,5-dione|5K1FUI0T2C|PF 06840003|UNII-5K1FUI0T2C|AMY445|GTPL9565|SCHEMBL5463464|CHEMBL4086143|US9603836, Compound 1|US9603836, Compound 1a|DTXSID00630149|MXKLDYKORJEOPR-UHFFFAOYSA-N|BDBM309529|BCP17158|EX-A1186|MFCD25121820|NSC796100|s8657|AKOS027252536|CCG-266801|CS-6186|EOS-200271|NSC-79610Show More⌵

Canonical SMILES:  O=C1CC(c2c[nH]c3ccc(F)cc23)C(=O)N1

Standard InChI:  InChI=1S/C12H9FN2O2/c13-6-1-2-10-7(3-6)9(5-14-10)8-4-11(16)15-12(8)17/h1-3,5,8,14H,4H2,(H,15,16,17)

Standard InChI Key:  MXKLDYKORJEOPR-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 17 19  0  0  0  0  0  0  0  0999 V2000
   13.7297   -8.0765    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.7742   -8.7707    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.7742   -9.9518    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.6509  -10.3168    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.2859  -11.4401    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.9567   -9.3613    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.6509   -8.4058    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.2859   -7.2825    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.9802   -6.3269    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.2859   -5.3714    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.1626   -5.7364    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.1398   -5.1458    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.1169   -5.7364    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.1169   -6.9175    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.0940   -7.5080    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    9.1398   -7.5080    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.1626   -6.9175    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  4  1  0
  4  5  2  0
  6  4  1  0
  7  6  1  0
  2  7  1  0
  7  8  1  0
  8  9  2  0
  9 10  1  0
 11 10  1  0
 11 12  2  0
 12 13  1  0
 14 13  2  0
 14 15  1  0
 16 14  1  0
 17 16  2  0
 17 11  1  0
  8 17  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4086143

   PF-06840003

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: 232.21

Molecular Weight (Monoisotopic): 232.0648

AlogP: 1.44

#Rotatable Bonds: 1

Polar Surface Area: 61.96

Molecular Species: NEUTRAL

HBA: 2

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 4

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 9.96

CX Basic pKa: ┄

CX LogP: 0.92

CX LogD: 0.92

Aromatic Rings: 2

Heavy Atoms: 17

QED Weighted: 0.73

Np Likeness Score: -0.55

References

1. Crosignani S, Bingham P, Bottemanne P, Cannelle H, Cauwenberghs S, Cordonnier M, Dalvie D, Deroose F, Feng JL, Gomes B, Greasley S, Kaiser SE, Kraus M, Négrerie M, Maegley K, Miller N, Murray BW, Schneider M, Soloweij J, Stewart AE, Tumang J, Torti VR, Van Den Eynde B, Wythes M..  (2017)  Discovery of a Novel and Selective Indoleamine 2,3-Dioxygenase (IDO-1) Inhibitor 3-(5-Fluoro-1H-indol-3-yl)pyrrolidine-2,5-dione (EOS200271/PF-06840003) and Its Characterization as a Potential Clinical Candidate.,  60  (23): [PMID:29111717] [10.1021/acs.jmedchem.7b00974]

2. Weng T, Qiu X, Wang J, Li Z, Bian J..  (2018)  Recent discovery of indoleamine-2,3-dioxygenase 1 inhibitors targeting cancer immunotherapy.,  143  [PMID:29220788] [10.1016/j.ejmech.2017.11.088]

3. Coletti A, Greco FA, Dolciami D, Camaioni E, Sardella R, Pallotta MT, Volpi C, Orabona C, Grohmann U, Macchiarulo A..  (2017)  Advances in indoleamine 2,3-dioxygenase 1 medicinal chemistry.,  8  (7): [PMID:30108849] [10.1039/C7MD00109F]

4. Unpublished dataset, 

5. Winters M, DuHadaway JB, Pham KN, Lewis-Ballester A, Badir S, Wai J, Sheikh E, Yeh SR, Prendergast GC, Muller AJ, Malachowski WP..  (2019)  Diaryl hydroxylamines as pan or dual inhibitors of indoleamine 2,3-dioxygenase-1, indoleamine 2,3-dioxygenase-2 and tryptophan dioxygenase.,  162  [PMID:30469041] [10.1016/j.ejmech.2018.11.010]

6. Parr BT, Pastor R, Sellers BD, Pei Z, Jaipuri FA, Castanedo GM, Gazzard L, Kumar S, Li X, Liu W, Mendonca R, Pavana RK, Potturi H, Shao C, Velvadapu V, Waldo JP, Wu G, Yuen PW, Zhang Z, Zhang Y, Harris SF, Oh AJ, DiPasquale A, Dement K, La H, Goon L, Gustafson A, VanderPorten EC, Mautino MR, Liu Y..  (2020)  Implementation of the CYP Index for the Design of Selective Tryptophan-2,3-dioxygenase Inhibitors.,  11  (4): [PMID:32292562] [10.1021/acsmedchemlett.0c00004]

7. Peng YH, Liao FY, Tseng CT, Kuppusamy R, Li AS, Chen CH, Fan YS, Wang SY, Wu MH, Hsueh CC, Chang JY, Lee LC, Shih C, Shia KS, Yeh TK, Hung MS, Kuo CC, Song JS, Wu SY, Ueng SH..  (2020)  Unique Sulfur-Aromatic Interactions Contribute to the Binding of Potent Imidazothiazole Indoleamine 2,3-Dioxygenase Inhibitors.,  63  (4): [PMID:31961685] [10.1021/acs.jmedchem.9b01549]

8. 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]

9. 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]

10. Li Y, Zhang S, Wang R, Cui M, Liu W, Yang Q, Kuang C..  (2020)  Synthesis of novel tryptanthrin derivatives as dual inhibitors of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase.,  30  (11): [PMID:32247733] [10.1016/j.bmcl.2020.127159]

11. Hamilton MM, Mseeh F, McAfoos TJ, Leonard PG, Reyna NJ, Harris AL, Xu A, Han M, Soth MJ, Czako B, Theroff JP, Mandal PK, Burke JP, Virgin-Downey B, Petrocchi A, Pfaffinger D, Rogers NE, Parker CA, Yu SS, Jiang Y, Krapp S, Lammens A, Trevitt G, Tremblay MR, Mikule K, Wilcoxen K, Cross JB, Jones P, Marszalek JR, Lewis RT..  (2021)  Discovery of IACS-9779 and IACS-70465 as Potent Inhibitors Targeting Indoleamine 2,3-Dioxygenase 1 (IDO1) Apoenzyme.,  64  (15.0): [PMID:34292726] [10.1021/acs.jmedchem.1c00679]

12. He X, He G, Chu Z, Wu H, Wang J, Ge Y, Shen H, Zhang S, Shan J, Peng K, Wei Z, Zou Y, Xu Y, Zhu Q..  (2021)  Discovery of the First Potent IDO1/IDO2 Dual Inhibitors: A Promising Strategy for Cancer Immunotherapy.,  64  (24.0): [PMID:34854662] [10.1021/acs.jmedchem.1c01305]

13. Tang K, Wang B, Yu B, Liu HM..  (2022)  Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors and PROTAC-based degraders for cancer therapy.,  227  [PMID:34752953] [10.1016/j.ejmech.2021.113967]

14. Zhang Y, Li Y, Chen X, Chen X, Chen C, Wang L, Dong X, Wang G, Gu R, Li F, Han F, Chen D..  (2022)  Discovery of 1-(Hetero)aryl-β-carboline Derivatives as IDO1/TDO Dual Inhibitors with Antidepressant Activity.,  65  (16.0): [PMID:35938398] [10.1021/acs.jmedchem.2c00677]

15. Zhang Y, Hu Z, Zhang J, Ren C, Wang Y..  (2022)  Dual-target inhibitors of indoleamine 2, 3 dioxygenase 1 (Ido1): A promising direction in cancer immunotherapy.,  238  [PMID:35696861] [10.1016/j.ejmech.2022.114524]

Source

Source(3):

• Scientific Literature
• Clinical Candidates
• SARS-CoV-2 Screening Data 2020-21