1-(2-chloro-5-(hydroxymethyl)pyridin-4-yl)-3-(3-(difluoromethyl)isothiazol-5-yl)urea

ID: ALA4293567

PubChem CID: 145986542

Max Phase: Preclinical

Molecular Formula: C11H9ClF2N4O2S

Molecular Weight: 334.74

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  O=C(Nc1cc(C(F)F)ns1)Nc1cc(Cl)ncc1CO

Standard InChI:  InChI=1S/C11H9ClF2N4O2S/c12-8-1-6(5(4-19)3-15-8)16-11(20)17-9-2-7(10(13)14)18-21-9/h1-3,10,19H,4H2,(H2,15,16,17,20)

Standard InChI Key:  AVHFGSYJGSZHIC-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 21 22  0  0  0  0  0  0  0  0999 V2000
   10.0608  -14.0697    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.0596  -14.8892    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.7677  -15.2982    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.4773  -14.8887    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.4745  -14.0661    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.7659  -13.6608    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.7634  -12.8436    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   12.1857  -15.2962    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.8927  -14.8865    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.6011  -15.2940    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.8915  -14.0693    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   14.3069  -14.0671    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   14.3098  -14.8808    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.0845  -15.1295    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.5605  -14.4695    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.0798  -13.8130    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.3777  -14.4665    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.7675  -16.1154    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.7888  -15.1728    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   16.7837  -13.7574    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   10.0597  -16.5238    0.0000 O   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
  6  7  1  0
  4  8  1  0
  8  9  1  0
  9 10  1  0
  9 11  2  0
 10 13  1  0
 12 13  1  0
 13 14  2  0
 14 15  1  0
 15 16  2  0
 16 12  1  0
 15 17  1  0
  3 18  1  0
 17 19  1  0
 17 20  1  0
 18 21  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4293567

   ---

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: 334.74

Molecular Weight (Monoisotopic): 334.0103

AlogP: 3.27

#Rotatable Bonds: 4

Polar Surface Area: 87.14

Molecular Species: NEUTRAL

HBA: 5

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 7.28

CX Basic pKa: 1.26

CX LogP: 1.64

CX LogD: 1.30

Aromatic Rings: 2

Heavy Atoms: 21

QED Weighted: 0.75

Np Likeness Score: -1.66

References

1. Papillon JPN, Nakajima K, Adair CD, Hempel J, Jouk AO, Karki RG, Mathieu S, Möbitz H, Ntaganda R, Smith T, Visser M, Hill SE, Hurtado FK, Chenail G, Bhang HC, Bric A, Xiang K, Bushold G, Gilbert T, Vattay A, Dooley J, Costa EA, Park I, Li A, Farley D, Lounkine E, Yue QK, Xie X, Zhu X, Kulathila R, King D, Hu T, Vulic K, Cantwell J, Luu C, Jagani Z..  (2018)  Discovery of Orally Active Inhibitors of Brahma Homolog (BRM)/SMARCA2 ATPase Activity for the Treatment of Brahma Related Gene 1 (BRG1)/SMARCA4-Mutant Cancers.,  61  (22): [PMID:30339381] [10.1021/acs.jmedchem.8b01318]

Source

Source(1):

• Scientific Literature