ID: ALA242459

Max Phase: Preclinical

Molecular Formula: C24H32N2O4

Molecular Weight: 412.53

Molecule Type: Small molecule

Representations

Canonical SMILES:  O=C(NC12CC3CC(CC(C3)C1)C2)N[C@H]1CC[C@H](Oc2ccc(C(=O)O)cc2)CC1

Standard InChI:  InChI=1S/C24H32N2O4/c27-22(28)18-1-5-20(6-2-18)30-21-7-3-19(4-8-21)25-23(29)26-24-12-15-9-16(13-24)11-17(10-15)14-24/h1-2,5-6,15-17,19,21H,3-4,7-14H2,(H,27,28)(H2,25,26,29)/t15?,16?,17?,19-,21-,24?

Standard InChI Key:  KNBWKJBQDAQARU-KSSCSKLYSA-N

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

Properties

Molecular Weight: 412.53

Molecular Weight (Monoisotopic): 412.2362

AlogP: 4.34

#Rotatable Bonds: 5

Polar Surface Area: 87.66

Molecular Species: ACID

HBA: 3

HBD: 3

#RO5 Violations: 0

HBA (Lipinski): 6

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 4.36

CX Basic pKa: 0.33

CX LogP: 3.58

CX LogD: 0.66

Aromatic Rings: 1

Heavy Atoms: 30

QED Weighted: 0.67

Np Likeness Score: -0.52

References

1. Hwang SH, Tsai HJ, Liu JY, Morisseau C, Hammock BD..  (2007)  Orally bioavailable potent soluble epoxide hydrolase inhibitors.,  50  (16): [PMID:17616115] [10.1021/jm070270t]

2. Hwang SH, Wagner KM, Morisseau C, Liu JY, Dong H, Wecksler AT, Hammock BD..  (2011)  Synthesis and structure-activity relationship studies of urea-containing pyrazoles as dual inhibitors of cyclooxygenase-2 and soluble epoxide hydrolase.,  54  (8): [PMID:21434686] [10.1021/jm2001376]

3. PubChem BioAssay data set, 

4. Scherman MS, North EJ, Jones V, Hess TN, Grzegorzewicz AE, Kasagami T, Kim IH, Merzlikin O, Lenaerts AJ, Lee RE, Jackson M, Morisseau C, McNeil MR..  (2012)  Screening a library of 1600 adamantyl ureas for anti-Mycobacterium tuberculosis activity in vitro and for better physical chemical properties for bioavailability.,  20  (10): [PMID:22522007] [10.1016/j.bmc.2012.03.058]

5. Hwang SH, Wecksler AT, Zhang G, Morisseau C, Nguyen LV, Fu SH, Hammock BD..  (2013)  Synthesis and biological evaluation of sorafenib- and regorafenib-like sEH inhibitors.,  23  (13): [PMID:23726028] [10.1016/j.bmcl.2013.05.011]

6. Morisseau C, Pakhomova S, Hwang SH, Newcomer ME, Hammock BD..  (2013)  Inhibition of soluble epoxide hydrolase by fulvestrant and sulfoxides.,  23  (13): [PMID:23684894] [10.1016/j.bmcl.2013.04.083]

7. Shihadih DS, Harris TR, Yang J, Merzlikin O, Lee KS, Hammock BD, Morisseau C..  (2015)  Identification of potent inhibitors of the chicken soluble epoxide hydrolase.,  25  (2): [PMID:25479771] [10.1016/j.bmcl.2014.11.053]

8.  (2015)  Sorafenib derivatives as sEH inhibitors, 

9. Kodani SD, Bhakta S, Hwang SH, Pakhomova S, Newcomer ME, Morisseau C, Hammock BD..  (2018)  Identification and optimization of soluble epoxide hydrolase inhibitors with dual potency towards fatty acid amide hydrolase.,  28  (4): [PMID:29366648] [10.1016/j.bmcl.2018.01.003]

10. Ammazzalorso A, Maccallini C, Amoia P, Amoroso R..  (2019)  Multitarget PPARγ agonists as innovative modulators of the metabolic syndrome.,  173  [PMID:31009912] [10.1016/j.ejmech.2019.04.030]

11. Codony S, Valverde E, Leiva R, Brea J, Isabel Loza M, Morisseau C, Hammock BD, Vázquez S..  (2019)  Exploring the size of the lipophilic unit of the soluble epoxide hydrolase inhibitors.,  27  (20): [PMID:31488357] [10.1016/j.bmc.2019.115078]

12. Han Y,Huang D,Xu S,Li L,Tian Y,Li S,Chen C,Li Y,Sun Y,Hou Y,Sun Y,Qin M,Gong P,Gao Z,Zhao Y.  (2021)  Ligand-based optimization to identify novel 2-aminobenzo[d]thiazole derivatives as potent sEH inhibitors with anti-inflammatory effects.,  212  [PMID:33248848] [10.1016/j.ejmech.2020.113028]

13. Codony S,Pujol E,Pizarro J,Feixas F,Valverde E,Loza MI,Brea JM,Saez E,Oyarzabal J,Pineda-Lucena A,Pérez B,Pérez C,Rodríguez-Franco MI,Leiva R,Osuna S,Morisseau C,Hammock BD,Vázquez-Carrera M,Vázquez S.  (2020)  2-Oxaadamant-1-yl Ureas as Soluble Epoxide Hydrolase Inhibitors: In Vivo Evaluation in a Murine Model of Acute Pancreatitis.,  63  (17): [PMID:32787085] [10.1021/acs.jmedchem.0c00310]

14. Codony S, Calvó-Tusell C, Valverde E, Osuna S, Morisseau C, Loza MI, Brea J, Pérez C, Rodríguez-Franco MI, Pizarro-Delgado J, Corpas R, Griñán-Ferré C, Pallàs M, Sanfeliu C, Vázquez-Carrera M, Hammock BD, Feixas F, Vázquez S..  (2021)  From the Design to the In Vivo Evaluation of Benzohomoadamantane-Derived Soluble Epoxide Hydrolase Inhibitors for the Treatment of Acute Pancreatitis.,  64  (9.0): [PMID:33945278] [10.1021/acs.jmedchem.0c01601]

15. Hartmann M, Bibli SI, Tews D, Ni X, Kircher T, Kramer JS, Kilu W, Heering J, Hernandez-Olmos V, Weizel L, Scriba GKE, Krait S, Knapp S, Chaikuad A, Merk D, Fleming I, Fischer-Posovszky P, Proschak E..  (2021)  Combined Cardioprotective and Adipocyte Browning Effects Promoted by the Eutomer of Dual sEH/PPARγ Modulator.,  64  (5.0): [PMID:33620196] [10.1021/acs.jmedchem.0c02063]

16. Wilt S, Kodani S, Valencia L, Hudson PK, Sanchez S, Quintana T, Morisseau C, Hammock BD, Kandasamy R, Pecic S..  (2021)  Further exploration of the structure-activity relationship of dual soluble epoxide hydrolase/fatty acid amide hydrolase inhibitors.,  51  [PMID:34794001] [10.1016/j.bmc.2021.116507]

17. Codony S, Entrena JM, Calvó-Tusell C, Jora B, González-Cano R, Osuna S, Corpas R, Morisseau C, Pérez B, Barniol-Xicota M, Griñán-Ferré C, Pérez C, Rodríguez-Franco MI, Martínez AL, Loza MI, Pallàs M, Verhelst SHL, Sanfeliu C, Feixas F, Hammock BD, Brea J, Cobos EJ, Vázquez S..  (2022)  Synthesis, In Vitro Profiling, and In Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors.,  65  (20.0): [PMID:36222708] [10.1021/acs.jmedchem.2c00515]

18. Tian Y, Li S, Yang P, Su X, Liu J, Lv X, Dong K, Yang T, Duan M, Hu G, Yue H, Sun Y, Sun Y, Zhang H, Du Z, Miao Z, Tong M, Hou Y, Gao Z, Zhao Y..  (2022)  Synthesis and biological evaluation of new series of benzamide derivatives containing urea moiety as sEH inhibitors.,  70  [PMID:35598794] [10.1016/j.bmcl.2022.128805]

19. Sharma S, Kumar D, Singh G, Monga V, Kumar B..  (2020)  Recent advancements in the development of heterocyclic anti-inflammatory agents.,  200  [PMID:32485533] [10.1016/j.ejmech.2020.112438]

Source

Source(3):

• Scientific Literature
• PubChem BioAssays
• BindingDB Database