trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid

ID: ALA242459

Chembl Id: CHEMBL242459

Max Phase: Preclinical

Molecular Formula: C24H32N2O4

Molecular Weight: 412.53

Molecule Type: Small molecule

Associated Items:

Names and Identifiers

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

Alternative Forms

  1. Parent:

    ALA242459

    ---

Associated Targets(Human)

EPHX2 Tchem Epoxide hydratase (3844 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Liver microsomes (16955 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PTGS2 Tclin Cyclooxygenase-2 (13999 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
RAN Tchem GTP-binding nuclear protein Ran/Importin subunit beta-1/Snurportin-1 (21853 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
POLI Tchem DNA polymerase iota (116820 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
GMNN Tbio Geminin (128009 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HUVEC (11049 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Huh-7 (12904 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HepG2 (196354 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
RAF1 Tclin Serine/threonine-protein kinase RAF (4169 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KDR Tclin Vascular endothelial growth factor receptor 2 (20924 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PDPK1 Tchem 3-phosphoinositide dependent protein kinase-1 (3758 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PDGFRB Tclin Platelet-derived growth factor receptor beta (5195 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PDGFRA Tclin Platelet-derived growth factor receptor alpha (5682 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MET Tclin Hepatocyte growth factor receptor (10718 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
GSK3A Tclin Glycogen synthase kinase-3 alpha (3764 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
FLT3 Tclin Tyrosine-protein kinase receptor FLT3 (13481 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
FLT1 Tclin Vascular endothelial growth factor receptor 1 (6262 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
FGFR2 Tclin Fibroblast growth factor receptor 2 (3405 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ABL2 Tchem Tyrosine-protein kinase ABL2 (1851 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
GNAS Tbio Guanine nucleotide-binding protein G(s), subunit alpha (103405 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Liver microsome (8277 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
FAAH Tchem Anandamide amidohydrolase (3465 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SH-SY5Y (11521 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ALOX5 Tclin Arachidonate 5-lipoxygenase (6568 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MT-CO2 Tchem Cytochrome c oxidase subunit 2 (250 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Ephx2 Epoxide hydratase (467 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Ephx2 Epoxide hydrolase 2 (342 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Canis familiaris (36305 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Mus musculus (284745 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PTGS1 Cyclooxygenase-1 (5266 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Rattus norvegicus (775804 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Plasmodium falciparum (966862 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Mycobacterium tuberculosis (203094 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Heart (1016 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: NoOral: NoChemical Probe: NoParenteral: No
Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
Chirality: NoAvailability: NoProdrug: No

Drug Indications

MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

Mechanisms of Action

Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

Calculated Properties

Molecular Weight: 412.53Molecular Weight (Monoisotopic): 412.2362AlogP: 4.34#Rotatable Bonds: 5
Polar Surface Area: 87.66Molecular Species: ACIDHBA: 3HBD: 3
#RO5 Violations: HBA (Lipinski): 6HBD (Lipinski): 3#RO5 Violations (Lipinski):
CX Acidic pKa: 4.36CX Basic pKa: 0.33CX LogP: 3.58CX LogD: 0.66
Aromatic Rings: 1Heavy Atoms: 30QED Weighted: 0.67Np 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]