ID: ALA27006

Max Phase: Preclinical

Molecular Formula: C20H19F6NO

Molecular Weight: 403.37

Molecule Type: Small molecule

Representations

Synonyms (1): L-733060
Synonyms from Alternative Forms(1):

Canonical SMILES:  FC(F)(F)c1cc(CO[C@H]2CCCN[C@H]2c2ccccc2)cc(C(F)(F)F)c1

Standard InChI:  InChI=1S/C20H19F6NO/c21-19(22,23)15-9-13(10-16(11-15)20(24,25)26)12-28-17-7-4-8-27-18(17)14-5-2-1-3-6-14/h1-3,5-6,9-11,17-18,27H,4,7-8,12H2/t17-,18-/m0/s1

Standard InChI Key:  FCDRFVCGMLUYPG-ROUUACIJSA-N

Molecule Features

Natural Product: Yes

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: 403.37

Molecular Weight (Monoisotopic): 403.1371

AlogP: 5.73

#Rotatable Bonds: 4

Polar Surface Area: 21.26

Molecular Species: BASE

HBA: 2

HBD: 1

#RO5 Violations: 1

HBA (Lipinski): 2

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 1

CX Acidic pKa:

CX Basic pKa: 8.78

CX LogP: 5.49

CX LogD: 4.09

Aromatic Rings: 2

Heavy Atoms: 28

QED Weighted: 0.66

Np Likeness Score: -0.23

References

1. Mills SG, MacCoss M, Underwood D, Shah SK, Finke PE, Miller DJ, Budhu RJ, Cascieri MA, Sadowski S, Strader CD.  (1995)  1,2,3-Trisubstituted cyclohexyl substance P antagonists: significance of the ring nitrogen in piperidine-based NK-1 receptor antagonists,  5  (13): [10.1016/0960-894X(95)00220-N]

2. 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]

3. Elliott JM, Cascieri MA, Chicchi G, Davies S, Kelleher FJ, Kurtz M, Ladduwahetty T, Lewis RT, MacLeod AM, Merchant KJ, Sadowski S, Stevenson GI..  (1998)  Serine derived NK1 antagonists. 1: The effect of modifications to the serine substituents.,  8  (14): [PMID:9873445] [10.1016/s0960-894x(98)00320-5]

4. Harrison T, Owens A, Williams B, Swain C, Baker R, Hutson P, Sadowski S, Cascieri M.  (1995)  Piperidine-ether based hNK1 antagonists 2: Investigation of the effect of N-substitution,  5  (3): [10.1016/0960-894X(95)00009-I]

5. Harrison T, Williams B, Swain C, Ball R.  (1994)  Piperidine-ether based hNK1 antagonists 1: Determination of the relative and absolute stereochemical requirements,  4  (21): [10.1016/S0960-894X(01)80280-8]

6. Harrison T, Williams B, Swain C.  (1994)  Gem-disubstituted amino-ether based substance p antagonists,  4  (23): [10.1016/S0960-894X(01)80585-0]

7. Swain C, Williams B, Baker R, Cascieri M, Chicchi G, Forrest M, Herbert R, Keown L, Ladduwahetty T, Luell S, MacIntyre D, Metzger J, Morton S, Owens A, Sadowski S, Watt A.  (1997)  3-Benzyloxy-2-phenylpiperidine NK1 antagonists: the influence of alpha methyl substitution,  7  (23): [10.1016/S0960-894X(97)10118-4]

8. Takeuchi Y, Shands EF, Beusen DD, Marshall GR..  (1998)  Derivation of a three-dimensional pharmacophore model of substance P antagonists bound to the neurokinin-1 receptor.,  41  (19): [PMID:9733486] [10.1021/jm9700171]

9. Stevenson GI, Huscroft I, MacLeod AM, Swain CJ, Cascieri MA, Chicchi GG, Graham MI, Harrison T, Kelleher FJ, Kurtz M, Ladduwahetty T, Merchant KJ, Metzger JM, MacIntyre DE, Sadowski S, Sohal B, Owens AP..  (1998)  4,4-Disubstituted piperidine high-affinity NK1 antagonists: structure-activity relationships and in vivo activity.,  41  (23): [PMID:9804702] [10.1021/jm980376b]

10. Di Fabio R, Griffante C, Alvaro G, Pentassuglia G, Pizzi DA, Donati D, Rossi T, Guercio G, Mattioli M, Cimarosti Z, Marchioro C, Provera S, Zonzini L, Montanari D, Melotto S, Gerrard PA, Trist DG, Ratti E, Corsi M..  (2009)  Discovery process and pharmacological characterization of 2-(S)-(4-fluoro-2-methylphenyl)piperazine-1-carboxylic acid [1-(R)-(3,5-bis-trifluoromethylphenyl)ethyl]methylamide (vestipitant) as a potent, selective, and orally active NK1 receptor antagonist.,  52  (10): [PMID:19388677] [10.1021/jm900023b]

11. PubChem BioAssay data set, 

12. PubChem BioAssay data set, 

13. Di Fabio R, Alvaro G, Braggio S, Carletti R, Gerrard PA, Griffante C, Marchioro C, Pozzan A, Melotto S, Poffe A, Piccoli L, Ratti E, Tranquillini E, Trower M, Spada S, Corsi M..  (2013)  Identification, biological characterization and pharmacophoric analysis of a new potent and selective NK1 receptor antagonist clinical candidate.,  21  (21): [PMID:24075145] [10.1016/j.bmc.2013.09.001]

14. Mark Wenlock and Nicholas Tomkinson. Experimental in vitro DMPK and physicochemical data on a set of publicly disclosed compounds,  [10.6019/CHEMBL3301361]

15. Bernhard Ellinger, Justus Dick, Vanessa Lage-Rupprecht, Bruce Schultz, Andrea Zaliani, Marcin Namysl, Stephan Gebel, Ole Pless, Jeanette Reinshagen, Christian Ebeling, Alexander Esser, Marc Jacobs, Carsten Claussen, and Martin Hofmann-Apitius.  (2021)  HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators,  [10.6019/CHEMBL4808148]

16. 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(4):

• Scientific Literature
• PubChem BioAssays
• AstraZeneca Deposited Data
• Fraunhofer HDAC6