[6-Fluoro-2-methyl-3-(4-methylsulfanyl-benzylidene)-3H-inden-1-yl]-acetic acid

ID: ALA18797

Cas Number: 49627-27-2

PubChem CID: 5352624

Product Number: S649952, Order Now?

Max Phase: Unknown

Molecular Formula: C20H17FO2S

Molecular Weight: 340.42

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Cis-sulindac sulfide | Sulindac related compound c | Sulindac sulfide | Sulindac sulfide, (z)- | Sulindac sulphide, (z)- | Z-sulindac sulfide | Sulindac sulfide|49627-27-2|Sulindac sulfide, (Z)-|32004-67-4|Z-sulindac sulfide|6UVA8S2DEY|Sulindac sulphide, (z)-|CHEMBL18797|DTXSID0049078|CHEBI:75408|cis-Sulindac sulfide|2-[(3Z)-6-fluoro-2-methyl-3-[(4-methylsulfanylphenyl)methylidene]inden-1-yl]acetic acid|NCGC00161601-01|DTXCID0029004|(Z)-Sulindac sulfide|MFCD00869764|Sulindac sulphide|(Z)-2-(3-(4Show More⌵

Canonical SMILES:  CSc1ccc(/C=C2/C(C)=C(CC(=O)O)c3cc(F)ccc32)cc1

Standard InChI:  InChI=1S/C20H17FO2S/c1-12-17(9-13-3-6-15(24-2)7-4-13)16-8-5-14(21)10-19(16)18(12)11-20(22)23/h3-10H,11H2,1-2H3,(H,22,23)/b17-9-

Standard InChI Key:  LFWHFZJPXXOYNR-MFOYZWKCSA-N

Molfile:  

     RDKit          2D

 24 26  0  0  0  0  0  0  0  0999 V2000
   -3.7688    0.2062    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.7701   -0.6212    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0571   -1.0342    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0591    0.6190    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3411    0.2103    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3405   -0.6212    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5495   -0.8777    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0611   -0.2047    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5504    0.4677    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2362   -0.2041    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2959    1.2524    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4891    1.4245    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2347    2.2092    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.0632    0.8117    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4836    0.6182    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2941   -1.6622    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8457   -2.2755    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6508   -2.1010    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2022   -2.7135    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9470   -3.4989    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1353   -3.6683    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5874   -3.0543    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4978   -4.1131    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   -4.3050   -3.9430    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 11 12  1  0
  2  3  1  0
 12 13  2  0
  3  6  2  0
 12 14  1  0
  1  2  2  0
  1 15  1  0
  5  4  2  0
  7 16  2  0
  6  7  1  0
 16 17  1  0
  7  8  1  0
 17 18  2  0
  8  9  2  0
 18 19  1  0
  9  5  1  0
 19 20  2  0
  4  1  1  0
 20 21  1  0
  8 10  1  0
 21 22  2  0
 22 17  1  0
  5  6  1  0
 20 23  1  0
  9 11  1  0
 23 24  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA18797

   Sulindac sulfide

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: 340.42

Molecular Weight (Monoisotopic): 340.0933

AlogP: 5.35

#Rotatable Bonds: 4

Polar Surface Area: 37.30

Molecular Species: ACID

HBA: 2

HBD: 1

#RO5 Violations: 1

HBA (Lipinski): 2

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 4.16

CX Basic pKa: ┄

CX LogP: 4.82

CX LogD: 1.76

Aromatic Rings: 2

Heavy Atoms: 24

QED Weighted: 0.76

Np Likeness Score: -0.74

References

1. Fan SS, Shen TY..  (1981)  Membrane effects of antiinflammatory agents. 1. Interaction of sulindac and its metabolites with phospholipid membrane, a magnetic resonance study.,  24  (10): [PMID:6276543] [10.1021/jm00142a015]

2. Karaguni IM, Glüsenkamp KH, Langerak A, Geisen C, Ullrich V, Winde G, Möröy T, Müller O..  (2002)  New indene-derivatives with anti-proliferative properties.,  12  (4): [PMID:11844707] [10.1016/s0960-894x(01)00839-3]

3. Armer RE, Ashton MR, Boyd EA, Brennan CJ, Brookfield FA, Gazi L, Gyles SL, Hay PA, Hunter MG, Middlemiss D, Whittaker M, Xue L, Pettipher R..  (2005)  Indole-3-acetic acid antagonists of the prostaglandin D2 receptor CRTH2.,  48  (20): [PMID:16190744] [10.1021/jm050519b]

4. Stock N, Munoz B, Wrigley JD, Shearman MS, Beher D, Peachey J, Williamson TL, Bain G, Chen W, Jiang X, St-Jacques R, Prasit P..  (2006)  The geminal dimethyl analogue of Flurbiprofen as a novel Abeta42 inhibitor and potential Alzheimer's disease modifying agent.,  16  (8): [PMID:16455248] [10.1016/j.bmcl.2006.01.033]

5. Iben LG, Olson RE, Balanda LA, Jayachandra S, Robertson BJ, Hay V, Corradi J, Prasad CV, Zaczek R, Albright CF, Toyn JH..  (2007)  Signal peptide peptidase and gamma-secretase share equivalent inhibitor binding pharmacology.,  282  (51): [PMID:17932033] [10.1074/jbc.m707002200]

6. Romeiro NC, Sant'Anna CM, Lima LM, Fraga CA, Barreiro EJ..  (2008)  NSAIDs revisited: putative molecular basis of their interactions with peroxisome proliferator-activated gamma receptor (PPARgamma).,  43  (9): [PMID:18222570] [10.1016/j.ejmech.2007.11.031]

7. Czirr E, Leuchtenberger S, Dorner-Ciossek C, Schneider A, Jucker M, Koo EH, Pietrzik CU, Baumann K, Weggen S..  (2007)  Insensitivity to Abeta42-lowering nonsteroidal anti-inflammatory drugs and gamma-secretase inhibitors is common among aggressive presenilin-1 mutations.,  282  (34): [PMID:17573346] [10.1074/jbc.m700618200]

8. Friesen RW, Mancini JA..  (2008)  Microsomal prostaglandin E2 synthase-1 (mPGES-1): a novel anti-inflammatory therapeutic target.,  51  (14): [PMID:18459759] [10.1021/jm800197b]

9. Felts AS, Siegel BS, Young SM, Moth CW, Lybrand TP, Dannenberg AJ, Marnett LJ, Subbaramaiah K..  (2008)  Sulindac derivatives that activate the peroxisome proliferator-activated receptor gamma but lack cyclooxygenase inhibition.,  51  (16): [PMID:18665581] [10.1021/jm700969c]

10. Walters MJ, Blobaum AL, Kingsley PJ, Felts AS, Sulikowski GA, Marnett LJ..  (2009)  The influence of double bond geometry in the inhibition of cyclooxygenases by sulindac derivatives.,  19  (12): [PMID:19427206] [10.1016/j.bmcl.2009.04.078]

11. Hieke M, Ness J, Steri R, Dittrich M, Greiner C, Werz O, Baumann K, Schubert-Zsilavecz M, Weggen S, Zettl H..  (2010)  Design, synthesis, and biological evaluation of a novel class of gamma-secretase modulators with PPARgamma activity.,  53  (12): [PMID:20503989] [10.1021/jm1003073]

12. Kurosumi M, Nishio Y, Osawa S, Kobayashi H, Iwatsubo T, Tomita T, Miyachi H..  (2010)  Novel Notch-sparing gamma-secretase inhibitors derived from a peroxisome proliferator-activated receptor agonist library.,  20  (17): [PMID:20650635] [10.1016/j.bmcl.2010.06.131]

13. Fogli S, Banti I, Stefanelli F, Picchianti L, Digiacomo M, Macchia M, Breschi MC, Lapucci A..  (2010)  Therapeutic potential of sulindac hydroxamic acid against human pancreatic and colonic cancer cells.,  45  (11): [PMID:20801552] [10.1016/j.ejmech.2010.08.019]

14. PubChem BioAssay data set, 

15. Schiefer IT, Abdul-Hay S, Wang H, Vanni M, Qin Z, Thatcher GR..  (2011)  Inhibition of amyloidogenesis by nonsteroidal anti-inflammatory drugs and their hybrid nitrates.,  54  (7): [PMID:21405086] [10.1021/jm101450p]

16. Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program. DrugMatrix in vitro pharmacology data, 

17. Liedtke AJ, Crews BC, Daniel CM, Blobaum AL, Kingsley PJ, Ghebreselasie K, Marnett LJ..  (2012)  Cyclooxygenase-1-selective inhibitors based on the (E)-2'-des-methyl-sulindac sulfide scaffold.,  55  (5): [PMID:22263894] [10.1021/jm201528b]

18. Oehlrich D, Berthelot DJ, Gijsen HJ..  (2011)  γ-Secretase modulators as potential disease modifying anti-Alzheimer's drugs.,  54  (3): [PMID:21141968] [10.1021/jm101168r]

19. Unpublished dataset, 

20. Nortcliffe A, Ekstrom AG, Black JR, Ross JA, Habib FK, Botting NP, O'Hagan D..  (2014)  Synthesis and biological evaluation of nitric oxide-donating analogues of sulindac for prostate cancer treatment.,  22  (2): [PMID:24387865] [10.1016/j.bmc.2013.12.014]

21. PubChem BioAssay data set, 

22. PubChem BioAssay data set, 

23. Brunell D, Sagher D, Kesaraju S, Brot N, Weissbach H..  (2011)  Studies on the metabolism and biological activity of the epimers of sulindac.,  39  (6): [PMID:21383205] [10.1124/dmd.110.037663]

24. Unpublished dataset, 

25. Huang F, Zeng Z, Zhang W, Yan Z, Chen J, Yu L, Yang Q, Li Y, Yu H, Chen J, Wu C, Zhang XK, Su Y, Zhou H..  (2021)  Design, synthesis, and biological evaluation of novel sulindac derivatives as partial agonists of PPARγ with potential anti-diabetic efficacy.,  222  [PMID:34118723] [10.1016/j.ejmech.2021.113542]

Source

Source(5):

• Scientific Literature
• PubChem BioAssays
• DrugMatrix
• Gene Expression Atlas Compounds
• Active Ingredient of a Prodrug