4'-((2-((4-cyanophenyl)amino)pyrimidin-4-yl)amino)-3',5'-dimethyl-(1,1'-biphenyl)-4-carbonitrile

ID: ALA4174712

PubChem CID: 134816336

Max Phase: Preclinical

Molecular Formula: C26H20N6

Molecular Weight: 416.49

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cc1cc(-c2ccc(C#N)cc2)cc(C)c1Nc1ccnc(Nc2ccc(C#N)cc2)n1

Standard InChI:  InChI=1S/C26H20N6/c1-17-13-22(21-7-3-19(15-27)4-8-21)14-18(2)25(17)31-24-11-12-29-26(32-24)30-23-9-5-20(16-28)6-10-23/h3-14H,1-2H3,(H2,29,30,31,32)

Standard InChI Key:  RARAMGIQFJHXBX-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 32 35  0  0  0  0  0  0  0  0999 V2000
   11.4516   -7.1896    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.4505   -8.0091    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.1585   -8.4140    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.8682   -8.0087    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.8654   -7.1860    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.1568   -6.7766    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.5757   -6.7706    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.5726   -5.9534    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.7438   -6.7770    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.7436   -5.9598    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.4537   -5.5534    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.4538   -4.7370    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.7455   -4.3277    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.0355   -4.7409    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.0389   -5.5560    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2764   -5.5469    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2736   -4.7305    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5639   -4.3238    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.8554   -4.7394    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.8616   -5.5545    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.1606   -5.9634    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.3327   -5.9671    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5569   -3.5085    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5527   -2.6914    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.7433   -3.5139    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.4520   -3.1048    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.4511   -2.2883    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.7422   -1.8800    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.0328   -2.2900    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.0372   -3.1051    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.7438   -1.0656    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.7432   -0.2484    0.0000 N   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
  1  9  1  0
  9 10  1  0
 10 11  2  0
 11 12  1  0
 12 13  2  0
 13 14  1  0
 14 15  2  0
 15 10  1  0
  8 16  2  0
 16 17  1  0
 17 18  2  0
 18 19  1  0
 19 20  2  0
 20  8  1  0
 11 21  1  0
 15 22  1  0
 23 24  3  0
 18 23  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
 13 25  1  0
 31 32  3  0
 28 31  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4174712

   ---

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: 416.49

Molecular Weight (Monoisotopic): 416.1749

AlogP: 5.99

#Rotatable Bonds: 5

Polar Surface Area: 97.42

Molecular Species: NEUTRAL

HBA: 6

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 6

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 11.43

CX Basic pKa: 4.44

CX LogP: 6.59

CX LogD: 6.59

Aromatic Rings: 4

Heavy Atoms: 32

QED Weighted: 0.41

Np Likeness Score: -1.21

References

1. Jin K, Yin H, De Clercq E, Pannecouque C, Meng G, Chen F..  (2018)  Discovery of biphenyl-substituted diarylpyrimidines as non-nucleoside reverse transcriptase inhibitors with high potency against wild-type and mutant HIV-1.,  145  [PMID:29353724] [10.1016/j.ejmech.2018.01.016]

2. Sang Y, Han S, Pannecouque C, De Clercq E, Zhuang C, Chen F..  (2019)  Ligand-Based Design of Nondimethylphenyl-Diarylpyrimidines with Improved Metabolic Stability, Safety, and Oral Pharmacokinetic Profiles.,  62  (24): [PMID:31714780] [10.1021/acs.jmedchem.9b01446]

3. Ding L, Pannecouque C, De Clercq E, Zhuang C, Chen FE..  (2021)  Hydrophobic Pocket Occupation Design of Difluoro-Biphenyl-Diarylpyrimidines as Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors: from N-Alkylation to Methyl Hopping on the Pyrimidine Ring.,  64  (8.0): [PMID:33851529] [10.1021/acs.jmedchem.1c00128]

4. Ding L, Pannecouque C, De Clercq E, Zhuang C, Chen FE..  (2021)  Improving Druggability of Novel Diarylpyrimidine NNRTIs by a Fragment-Based Replacement Strategy: From Biphenyl-DAPYs to Heteroaromatic-Biphenyl-DAPYs.,  64  (14.0): [PMID:34197708] [10.1021/acs.jmedchem.1c00708]

Source

Source(1):

• Scientific Literature