2-Fluoro-N-{4-[4-(4-methoxyphenoxy)-2,6-dimethylphenyl]-thiazol-2-yl}isonicotinamide

ID: ALA3263869

Cas Number: 1334921-09-3

PubChem CID: 53389651

Max Phase: Preclinical

Molecular Formula: C24H20FN3O3S

Molecular Weight: 449.51

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  COc1ccc(Oc2cc(C)c(-c3csc(NC(=O)c4ccnc(F)c4)n3)c(C)c2)cc1

Standard InChI:  InChI=1S/C24H20FN3O3S/c1-14-10-19(31-18-6-4-17(30-3)5-7-18)11-15(2)22(14)20-13-32-24(27-20)28-23(29)16-8-9-26-21(25)12-16/h4-13H,1-3H3,(H,27,28,29)

Standard InChI Key:  JZGFZITYBNEDHQ-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 32 35  0  0  0  0  0  0  0  0999 V2000
    2.5079  -13.5290    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5068  -14.3486    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2148  -14.7575    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.9245  -14.3481    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.9217  -13.5254    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2130  -13.1202    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6293  -14.7582    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.7160  -15.5707    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.5157  -15.7394    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    5.9232  -15.0310    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.3753  -14.4246    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.2146  -15.5747    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6278  -13.1142    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.8001  -13.1206    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.7357  -14.9442    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.0669  -14.1971    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.8795  -14.1104    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5855  -13.5368    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.3568  -14.7707    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.1686  -14.6844    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5005  -13.9367    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.0145  -13.2745    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.2044  -13.3641    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.3430  -12.5262    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    1.0921  -11.8950    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7967  -12.3050    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5021  -11.8999    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5040  -11.0849    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7947  -10.6767    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0923  -11.0842    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7933   -9.8595    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.5003   -9.4497    0.0000 C   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
  7  8  2  0
  8  9  1  0
  9 10  1  0
 10 11  2  0
 11  7  1  0
  4  7  1  0
  3 12  1  0
  5 13  1  0
  1 14  1  0
 10 15  1  0
 15 16  1  0
 16 17  1  0
 16 18  2  0
 17 19  2  0
 19 20  1  0
 20 21  2  0
 21 22  1  0
 22 23  2  0
 23 17  1  0
 14 26  1  0
 22 24  1  0
 25 26  2  0
 26 27  1  0
 27 28  2  0
 28 29  1  0
 29 30  2  0
 30 25  1  0
 29 31  1  0
 31 32  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3263869

   2-Fluoro-N-[4-[4-(4-methoxyphenoxy)-2,6-dimethylphenyl]thiazol-2-yl]isonicotinamide

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: 449.51

Molecular Weight (Monoisotopic): 449.1209

AlogP: 6.01

#Rotatable Bonds: 6

Polar Surface Area: 73.34

Molecular Species: NEUTRAL

HBA: 6

HBD: 1

#RO5 Violations: 1

HBA (Lipinski): 6

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 10.26

CX Basic pKa: ┄

CX LogP: 6.13

CX LogD: 6.13

Aromatic Rings: 4

Heavy Atoms: 32

QED Weighted: 0.36

Np Likeness Score: -1.49

References

1. Lee YS, Chuang SH, Huang LY, Lai CL, Lin YH, Yang JY, Liu CW, Yang SC, Lin HS, Chang CC, Lai JY, Jian PS, Lam K, Chang JM, Lau JY, Huang JJ..  (2014)  Discovery of 4-aryl-N-arylcarbonyl-2-aminothiazoles as Hec1/Nek2 inhibitors. Part I: optimization of in vitro potencies and pharmacokinetic properties.,  57  (10): [PMID:24773549] [10.1021/jm401990s]

2. Chuang SH,Lee YE,Huang LYL,Chen CK,Lai CL,Lin YH,Yang JY,Yang SC,Chang LH,Chen CH,Liu CW,Lin HS,Lee YR,Huang KP,Fu KC,Jen HM,Lai JY,Jian PS,Wang YC,Hsueh WY,Tsai PY,Hong WH,Chang CC,Wu DZ,Wu J,Chen MH,Yu KM,Chern CY,Chang JM,Lau JYN,Huang JJ.  (2020)  Discovery of T-1101 tosylate as a first-in-class clinical candidate for Hec1/Nek2 inhibition in cancer therapy.,  191  [PMID:32113126] [10.1016/j.ejmech.2020.112118]

Source

Source(1):

• Scientific Literature