(S)-2'-(3,6-dihydro-2H-pyran-4-yl)-4'-fluoro-7'-(2-fluoropyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthen]-2-amine

ID: ALA3354718

PubChem CID: 45254900

Max Phase: Preclinical

Molecular Formula: C25H19F2N3O3

Molecular Weight: 447.44

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  NC1=N[C@@]2(CO1)c1cc(-c3cccnc3F)ccc1Oc1c(F)cc(C3=CCOCC3)cc12

Standard InChI:  InChI=1S/C25H19F2N3O3/c26-20-12-16(14-5-8-31-9-6-14)11-19-22(20)33-21-4-3-15(17-2-1-7-29-23(17)27)10-18(21)25(19)13-32-24(28)30-25/h1-5,7,10-12H,6,8-9,13H2,(H2,28,30)/t25-/m0/s1

Standard InChI Key:  UBJVRJGPVXTXQB-VWLOTQADSA-N

Molfile:  

     RDKit          2D

 33 38  0  0  0  0  0  0  0  0999 V2000
   17.3178  -15.4827    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.9795  -15.0025    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.7272  -14.2248    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   16.9096  -14.2243    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.6567  -15.0018    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.1909  -15.9022    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.1898  -16.7217    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.8978  -17.1307    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.8960  -15.4933    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.6046  -15.8986    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.6035  -16.7238    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.3136  -17.1351    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   18.0306  -15.9006    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.0293  -16.7217    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.7386  -17.1315    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.4497  -16.7215    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.4470  -15.8972    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.7371  -15.4911    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.4296  -13.5630    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.4852  -15.4939    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.4863  -14.6756    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.7793  -14.2673    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.0708  -14.6761    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.0736  -15.4975    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.7811  -15.9022    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.7383  -17.9487    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   15.1944  -14.2676    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   20.1532  -15.4861    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.8593  -15.8978    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.5634  -15.4901    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.5647  -14.6726    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   20.8557  -14.2643    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.1454  -14.6737    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  1
  2  3  1  0
  3  4  1  0
  4  5  2  0
  5  1  1  0
  6  7  2  0
  7  8  1  0
  8 11  2  0
 10  9  2  0
  9  6  1  0
 10 11  1  0
 10  1  1  0
 11 12  1  0
 12 14  1  0
 13  1  1  0
 13 14  2  0
 14 15  1  0
 15 16  2  0
 16 17  1  0
 17 18  2  0
 18 13  1  0
  4 19  1  0
 20 21  2  0
 21 22  1  0
 22 23  2  0
 23 24  1  0
 24 25  2  0
 25 20  1  0
  6 20  1  0
 15 26  1  0
 21 27  1  0
 17 28  1  0
 28 29  1  0
 28 33  2  0
 29 30  1  0
 30 31  1  0
 31 32  1  0
 32 33  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3354718

   (4s)-2'-(3,6-Dihydro-2h-Pyran-4-Yl)-4'-Fluoro-7'-(2-Fluoropyridin-3-Yl)spiro[1,3-Oxazole-4,9'-Xanthen]-2-Amine

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: 447.44

Molecular Weight (Monoisotopic): 447.1394

AlogP: 4.52

#Rotatable Bonds: 2

Polar Surface Area: 78.96

Molecular Species: NEUTRAL

HBA: 6

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 5.65

CX LogP: 3.92

CX LogD: 3.91

Aromatic Rings: 3

Heavy Atoms: 33

QED Weighted: 0.58

Np Likeness Score: 0.10

References

1. Epstein O, Bryan MC, Cheng AC, Derakhchan K, Dineen TA, Hickman D, Hua Z, Human JB, Kreiman C, Marx IE, Weiss MM, Wahl RC, Wen PH, Whittington DA, Wood S, Zheng XM, Fremeau RT, White RD, Patel VF..  (2014)  Lead optimization and modulation of hERG activity in a series of aminooxazoline xanthene β-site amyloid precursor protein cleaving enzyme (BACE1) inhibitors.,  57  (23): [PMID:25389560] [10.1021/jm501266w]

2. Chen JJ, Liu Q, Yuan C, Gore V, Lopez P, Ma V, Amegadzie A, Qian W, Judd TC, Minatti AE, Brown J, Cheng Y, Xue M, Zhong W, Dineen TA, Epstein O, Human J, Kreiman C, Marx I, Weiss MM, Hitchcock SA, Powers TS, Chen K, Wen PH, Whittington DA, Cheng AC, Bartberger MD, Hickman D, Werner JA, Vargas HM, Everds NE, Vonderfecht SL, Dunn RT, Wood S, Fremeau RT, White RD, Patel VF..  (2015)  Development of 2-aminooxazoline 3-azaxanthenes as orally efficacious β-secretase inhibitors for the potential treatment of Alzheimer's disease.,  25  (4): [PMID:25613679] [10.1016/j.bmcl.2014.12.092]

Source

Source(1):

• Scientific Literature