(S)-3-((S)-1-(2',4'-Difluoro-[1,1'-biphenyl]-4-yl)ethyl)-6-(4-fluorophenyl)-6-(2-hydroxyethyl)-1,3-oxazinan-2-one

ID: ALA1829763

Chembl Id: CHEMBL1829763

Cas Number: 1114065-09-6

PubChem CID: 53361128

Max Phase: Preclinical

Molecular Formula: C26H24F3NO3

Molecular Weight: 455.48

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  C[C@@H](c1ccc(-c2ccc(F)cc2F)cc1)N1CC[C@](CCO)(c2ccc(F)cc2)OC1=O

Standard InChI:  InChI=1S/C26H24F3NO3/c1-17(18-2-4-19(5-3-18)23-11-10-22(28)16-24(23)29)30-14-12-26(13-15-31,33-25(30)32)20-6-8-21(27)9-7-20/h2-11,16-17,31H,12-15H2,1H3/t17-,26-/m0/s1

Standard InChI Key:  SLSMHOGJKAPYQU-QLXKLKPCSA-N

Alternative Forms

1. Parent:

   

   ALA1829763

   (S)-3-((S)-1-(2',4'-difluorobiphenyl-4-yl)ethyl)-6-(4-fluorophenyl)-6-(2-hydroxyethyl)-1,3-oxazinan-2-one

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: 455.48

Molecular Weight (Monoisotopic): 455.1708

AlogP: 5.95

#Rotatable Bonds: 6

Polar Surface Area: 49.77

Molecular Species: NEUTRAL

HBA: 3

HBD: 1

#RO5 Violations: 1

HBA (Lipinski): 4

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 1

CX Acidic pKa: ┄

CX Basic pKa: ┄

CX LogP: 5.22

CX LogD: 5.22

Aromatic Rings: 3

Heavy Atoms: 33

QED Weighted: 0.50

Np Likeness Score: -0.28

References

1. Xu Z, Tice CM, Zhao W, Cacatian S, Ye YJ, Singh SB, Lindblom P, McKeever BM, Krosky PM, Kruk BA, Berbaum J, Harrison RK, Johnson JA, Bukhtiyarov Y, Panemangalore R, Scott BB, Zhao Y, Bruno JG, Togias J, Guo J, Guo R, Carroll PJ, McGeehan GM, Zhuang L, He W, Claremon DA..  (2011)  Structure-based design and synthesis of 1,3-oxazinan-2-one inhibitors of 11β-hydroxysteroid dehydrogenase type 1.,  54  (17): [PMID:21786805] [10.1021/jm2005354]

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

3.  (2013)  Cyclic inhibitors of 11BETA-hydroxysteroid dehydrogenase 1, 

4.  (2013)  Derivatives of [1,3]Oxazin-2-one useful for the treatment of metabolic diseases such as lipid disorders, 

5.  (2013)  Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1, 

6. Zhuang L, Tice CM, Xu Z, Zhao W, Cacatian S, Ye YJ, Singh SB, Lindblom P, McKeever BM, Krosky PM, Zhao Y, Lala D, Kruk BA, Meng S, Howard L, Johnson JA, Bukhtiyarov Y, Panemangalore R, Guo J, Guo R, Himmelsbach F, Hamilton B, Schuler-Metz A, Schauerte H, Gregg R, McGeehan GM, Leftheris K, Claremon DA..  (2017)  Discovery of BI 135585, an in vivo efficacious oxazinanone-based 11β hydroxysteroid dehydrogenase type 1 inhibitor.,  25  (14): [PMID:28528082] [10.1016/j.bmc.2017.04.033]

7. Chuanxin Z, Shengzheng W, Lei D, Duoli X, Jin L, Fuzeng R, Aiping L, Ge Z..  (2020)  Progress in 11β-HSD1 inhibitors for the treatment of metabolic diseases: A comprehensive guide to their chemical structure diversity in drug development.,  191  [PMID:32088493] [10.1016/j.ejmech.2020.112134]

Source

Source(3):

• Scientific Literature
• AstraZeneca Deposited Data
• BindingDB Database