ID: ALA52330

Max Phase: Preclinical

Molecular Formula: C22H20F6N4O3

Molecular Weight: 502.42

Molecule Type: Small molecule

Representations

Canonical SMILES:  O=c1[nH]nc(CN2CCO[C@H](OCc3cc(C(F)(F)F)cc(C(F)(F)F)c3)[C@@H]2c2ccccc2)[nH]1

Standard InChI:  InChI=1S/C22H20F6N4O3/c23-21(24,25)15-8-13(9-16(10-15)22(26,27)28)12-35-19-18(14-4-2-1-3-5-14)32(6-7-34-19)11-17-29-20(33)31-30-17/h1-5,8-10,18-19H,6-7,11-12H2,(H2,29,30,31,33)/t18-,19+/m0/s1

Standard InChI Key:  OYKIXMQKLMUJEK-RBUKOAKNSA-N

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

Properties

Molecular Weight: 502.42

Molecular Weight (Monoisotopic): 502.1440

AlogP: 4.25

#Rotatable Bonds: 6

Polar Surface Area: 83.24

Molecular Species: ACID

HBA: 5

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 7

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 6.45

CX Basic pKa: 4.22

CX LogP: 4.66

CX LogD: 3.88

Aromatic Rings: 3

Heavy Atoms: 35

QED Weighted: 0.49

Np Likeness Score: -0.82

References

1. Hale JJ, Mills SG, MacCoss M, Shah SK, Qi H, Mathre DJ, Cascieri MA, Sadowski S, Strader CD, MacIntyre DE, Metzger JM..  (1996)  2(S)-((3,5-bis(trifluoromethyl)benzyl)-oxy)-3(S)-phenyl-4- ((3-oxo-1,2,4-triazol-5-yl)methyl)morpholine (1): a potent, orally active, morpholine-based human neurokinin-1 receptor antagonist.,  39  (9): [PMID:8627597] [10.1021/jm950654w]

2. Hale JJ, Mills SG, MacCoss M, Finke PE, Cascieri MA, Sadowski S, Ber E, Chicchi GG, Kurtz M, Metzger J, Eiermann G, Tsou NN, Tattersall FD, Rupniak NM, Williams AR, Rycroft W, Hargreaves R, MacIntyre DE..  (1998)  Structural optimization affording 2-(R)-(1-(R)-3, 5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4- (3-oxo-1,2,4-triazol-5-yl)methylmorpholine, a potent, orally active, long-acting morpholine acetal human NK-1 receptor antagonist.,  41  (23): [PMID:9804700] [10.1021/jm980299k]

3. Finke PE, Meurer LC, Levorse DA, Mills SG, Maccoss M, Sadowski S, Cascieri MA, Tsao KL, Chicchi GG, Metzger JM, Macintyre DE..  (2006)  Cyclopentane-based human NK1 antagonists. Part 1: discovery and initial SAR.,  16  (17): [PMID:16824752] [10.1016/j.bmcl.2006.06.035]

4. Hagmann WK..  (2008)  The many roles for fluorine in medicinal chemistry.,  51  (15): [PMID:18570365] [10.1021/jm800219f]

5. Wu YJ, Meanwell NA..  (2021)  Geminal Diheteroatomic Motifs: Some Applications of Acetals, Ketals, and Their Sulfur and Nitrogen Homologues in Medicinal Chemistry and Drug Design.,  64  (14.0): [PMID:34213340] [10.1021/acs.jmedchem.1c00790]

Source

Source(1):

• Scientific Literature