trans-1-(4-(4-(Trifluoromethoxy)phenoxy)cyclohexyl)-3-(3-(trifluoromethyl)phenyl)urea

ID: ALA3100015

PubChem CID: 72793090

Max Phase: Preclinical

Molecular Formula: C21H20F6N2O3

Molecular Weight: 462.39

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  O=C(Nc1cccc(C(F)(F)F)c1)N[C@H]1CC[C@H](Oc2ccc(OC(F)(F)F)cc2)CC1

Standard InChI:  InChI=1S/C21H20F6N2O3/c22-20(23,24)13-2-1-3-15(12-13)29-19(30)28-14-4-6-16(7-5-14)31-17-8-10-18(11-9-17)32-21(25,26)27/h1-3,8-12,14,16H,4-7H2,(H2,28,29,30)/t14-,16-

Standard InChI Key:  SHLYFOJAJRGKND-KOMQPUFPSA-N

Molfile:  

     RDKit          2D

 32 34  0  0  0  0  0  0  0  0999 V2000
   -0.2068  -12.7199    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2057  -13.5470    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.5120  -13.9596    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2281  -13.5465    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2253  -12.7162    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.5102  -12.3073    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.9380  -12.3013    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.6537  -12.7109    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3663  -12.2958    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.6568  -13.5356    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.0820  -12.7056    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0828  -13.5333    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.7944  -13.9428    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.5095  -13.5313    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.5084  -12.7057    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.7922  -12.2916    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.2237  -13.9437    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.9378  -13.5313    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.6492  -13.9441    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3629  -13.5325    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3634  -12.7069    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.6441  -12.2946    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.9334  -12.7087    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.5118  -14.7843    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2057  -15.1964    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    1.2259  -15.1968    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    0.5040  -15.6063    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    9.0770  -12.2936    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.7917  -12.7049    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.5056  -12.2914    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    9.7929  -13.5299    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   10.5062  -13.1174    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  4  2  0
  4  5  1  0
  5  6  2  0
  6  1  1  0
  5  7  1  0
  7  8  1  0
  8  9  1  0
  8 10  2  0
 11  9  1  6
 11 12  1  0
 11 16  1  0
 12 13  1  0
 13 14  1  0
 14 15  1  0
 15 16  1  0
 14 17  1  1
 17 18  1  0
 18 19  2  0
 19 20  1  0
 20 21  2  0
 21 22  1  0
 22 23  2  0
 23 18  1  0
  3 24  1  0
 24 25  1  0
 24 26  1  0
 24 27  1  0
 21 28  1  0
 28 29  1  0
 29 30  1  0
 29 31  1  0
 29 32  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3100015

   1-[3-(Trifluoromethyl)phenyl]-3-[4beta-[4-(trifluoromethoxy)phenoxy]cyclohexane-1alpha-yl]urea

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: 462.39

Molecular Weight (Monoisotopic): 462.1378

AlogP: 6.12

#Rotatable Bonds: 5

Polar Surface Area: 59.59

Molecular Species: NEUTRAL

HBA: 3

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 5

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 13.30

CX Basic pKa: ┄

CX LogP: 6.16

CX LogD: 6.16

Aromatic Rings: 2

Heavy Atoms: 32

QED Weighted: 0.53

Np Likeness Score: -1.25

References

1. Chen T, Takrouri K, Hee-Hwang S, Rana S, Yefidoff-Freedman R, Halperin J, Natarajan A, Morisseau C, Hammock B, Chorev M, Aktas BH..  (2013)  Explorations of substituted urea functionality for the discovery of new activators of the heme-regulated inhibitor kinase.,  56  (23): [PMID:24261904] [10.1021/jm400793v]

2. Yefidoff-Freedman R, Fan J, Yan L, Zhang Q, Dos Santos GRR, Rana S, Contreras JI, Sahoo R, Wan D, Young J, Dias Teixeira KL, Morisseau C, Halperin J, Hammock B, Natarajan A, Wang P, Chorev M, Aktas BH..  (2017)  Development of 1-((1,4-trans)-4-Aryloxycyclohexyl)-3-arylurea Activators of Heme-Regulated Inhibitor as Selective Activators of the Eukaryotic Initiation Factor 2 Alpha (eIF2α) Phosphorylation Arm of the Integrated Endoplasmic Reticulum Stress Response.,  60  (13): [PMID:28590739] [10.1021/acs.jmedchem.7b00059]

Source

Source(1):

• Scientific Literature