trans-4-{4-[3-(4-trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid

ID: ALA2397148

Chembl Id: CHEMBL2397148

Max Phase: Preclinical

Molecular Formula: C21H21F3N2O5

Molecular Weight: 438.40

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  O=C(Nc1ccc(OC(F)(F)F)cc1)N[C@H]1CC[C@H](Oc2ccc(C(=O)O)cc2)CC1

Standard InChI:  InChI=1S/C21H21F3N2O5/c22-21(23,24)31-18-11-5-15(6-12-18)26-20(29)25-14-3-9-17(10-4-14)30-16-7-1-13(2-8-16)19(27)28/h1-2,5-8,11-12,14,17H,3-4,9-10H2,(H,27,28)(H2,25,26,29)/t14-,17-

Standard InChI Key:  XDVFKCZZXOGEMN-CZIWCDLHSA-N

Alternative Forms

1. Parent:

   

   ALA2397148

   ---

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: 438.40

Molecular Weight (Monoisotopic): 438.1403

AlogP: 4.80

#Rotatable Bonds: 6

Polar Surface Area: 96.89

Molecular Species: ACID

HBA: 4

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 4.36

CX Basic pKa: ┄

CX LogP: 4.94

CX LogD: 2.02

Aromatic Rings: 2

Heavy Atoms: 31

QED Weighted: 0.60

Np Likeness Score: -0.93

References

1. 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]

2. Lee KS, Liu JY, Wagner KM, Pakhomova S, Dong H, Morisseau C, Fu SH, Yang J, Wang P, Ulu A, Mate CA, Nguyen LV, Hwang SH, Edin ML, Mara AA, Wulff H, Newcomer ME, Zeldin DC, Hammock BD..  (2014)  Optimized inhibitors of soluble epoxide hydrolase improve in vitro target residence time and in vivo efficacy.,  57  (16): [PMID:25079952] [10.1021/jm500694p]

3.  (2015)  Sorafenib derivatives as sEH inhibitors, 

4. 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]

5. Burmistrov V, Morisseau C, D'yachenko V, Karlov D, Butov GM, Hammock BD..  (2020)  Imidazolidine-2,4,5- and pirimidine-2,4,6-triones - New primary pharmacophore for soluble epoxide hydrolase inhibitors with enhanced water solubility.,  30  (3): [PMID:31870649] [10.1016/j.bmcl.2019.126908]

6. Burmistrov V,Morisseau C,Karlov D,Pitushkin D,Vernigora A,Rasskazova E,Butov GM,Hammock BD.  (2020)  Bioisosteric substitution of adamantane with bicyclic lipophilic groups improves water solubility of human soluble epoxide hydrolase inhibitors.,  30  (18.0): [PMID:32736212] [10.1016/j.bmcl.2020.127430]

7. Barnych B,Singh N,Negrel S,Zhang Y,Magis D,Roux C,Hua X,Ding Z,Morisseau C,Tantillo DJ,Siegel JB,Hammock BD.  (2020)  Development of potent inhibitors of the human microsomal epoxide hydrolase.,  193  [PMID:32203787] [10.1016/j.ejmech.2020.112206]

8. 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]

Source

Source(2):

• Scientific Literature
• BindingDB Database