6-Fluoro-2-{(5R)-5-Methyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl}quinazoline

ID: ALA1083358

PubChem CID: 24808514

Max Phase: Preclinical

Molecular Formula: C23H22FN7O

Molecular Weight: 431.48

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  C[C@@H]1CCN(c2ncc3cc(F)ccc3n2)CCN1C(=O)c1ccccc1-n1nccn1

Standard InChI:  InChI=1S/C23H22FN7O/c1-16-8-11-29(23-25-15-17-14-18(24)6-7-20(17)28-23)12-13-30(16)22(32)19-4-2-3-5-21(19)31-26-9-10-27-31/h2-7,9-10,14-16H,8,11-13H2,1H3/t16-/m1/s1

Standard InChI Key:  XBSMDANCGKSKGK-MRXNPFEDSA-N

Molfile:  

     RDKit          2D

 32 36  0  0  0  0  0  0  0  0999 V2000
    7.0397   -8.4238    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.0397   -9.2533    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7541   -9.6658    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7541   -8.0068    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.4732   -8.4238    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.4743   -9.2533    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.1892   -9.6650    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.9077   -9.2515    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.9066   -8.4220    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.1870   -8.0058    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.6216   -9.6645    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.7453  -11.1595    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.2672  -10.4853    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.0647   -9.7047    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.9135  -11.1555    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.4125  -10.5025    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.3391   -9.3411    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.0913  -10.5228    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.4709  -11.2553    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5359   -9.8279    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   13.0244  -11.9463    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.4034  -12.6783    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2283  -12.7162    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.6729  -12.0162    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2915  -11.2872    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.7841  -10.6245    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.6090  -10.6372    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.8761   -9.8567    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.2161   -9.3615    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.5414   -9.8361    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.1067  -11.9009    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.3243   -8.0130    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
 12 15  1  0
 16 11  1  0
 11 17  1  0
 17 14  1  0
 15 16  1  0
  5 10  2  0
 13 18  1  0
  6  7  2  0
 18 19  1  0
  7  8  1  0
 18 20  2  0
  8  9  2  0
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  9 10  1  0
 21 22  1  0
  5  6  1  0
 22 23  2  0
  8 11  1  0
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 24 25  2  0
 25 19  1  0
 26 27  1  0
  1  2  1  0
  1  4  2  0
  2  3  2  0
  3  6  1  0
  5  4  1  0
 27 28  2  0
 28 29  1  0
 29 30  2  0
 30 26  1  0
 25 26  1  0
 12 13  1  0
 12 31  1  6
 13 14  1  0
  1 32  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA1083358

   6-Fluoro-2-{(5R)-5-Methyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl}quinazoline

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: 431.48

Molecular Weight (Monoisotopic): 431.1870

AlogP: 3.09

#Rotatable Bonds: 3

Polar Surface Area: 80.04

Molecular Species: NEUTRAL

HBA: 7

HBD: ┄

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): ┄

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 2.82

CX LogP: 2.86

CX LogD: 2.86

Aromatic Rings: 4

Heavy Atoms: 32

QED Weighted: 0.50

Np Likeness Score: -1.73

References

1. Cox CD, Breslin MJ, Whitman DB, Schreier JD, McGaughey GB, Bogusky MJ, Roecker AJ, Mercer SP, Bednar RA, Lemaire W, Bruno JG, Reiss DR, Harrell CM, Murphy KL, Garson SL, Doran SM, Prueksaritanont T, Anderson WB, Tang C, Roller S, Cabalu TD, Cui D, Hartman GD, Young SD, Koblan KS, Winrow CJ, Renger JJ, Coleman PJ..  (2010)  Discovery of the dual orexin receptor antagonist [(7R)-4-(5-chloro-1,3-benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone (MK-4305) for the treatment of insomnia.,  53  (14): [PMID:20565075] [10.1021/jm100541c]

2. Roecker AJ, Mercer SP, Harrell CM, Garson SL, Fox SV, Gotter AL, Prueksaritanont T, Cabalu TD, Cui D, Lemaire W, Winrow CJ, Renger JJ, Coleman PJ..  (2014)  Discovery of dual orexin receptor antagonists with rat sleep efficacy enabled by expansion of the acetonitrile-assisted/diphosgene-mediated 2,4-dichloropyrimidine synthesis.,  24  (9): [PMID:24704030] [10.1016/j.bmcl.2014.03.052]

3. Roecker AJ, Mercer SP, Bergman JM, Gilbert KF, Kuduk SD, Harrell CM, Garson SL, Fox SV, Gotter AL, Tannenbaum PL, Prueksaritanont T, Cabalu TD, Cui D, Lemaire W, Winrow CJ, Renger JJ, Coleman PJ..  (2015)  Discovery of diazepane amide DORAs and 2-SORAs enabled by exploration of isosteric quinazoline replacements.,  25  (21): [PMID:25613676] [10.1016/j.bmcl.2014.12.081]

4. Roecker AJ, Cox CD, Coleman PJ..  (2016)  Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.,  59  (2): [PMID:26317591] [10.1021/acs.jmedchem.5b00832]

Source

Source(1):

• Scientific Literature