ID: ALA137386

Max Phase: Preclinical

Molecular Formula: C22H38O5

Molecular Weight: 382.54

Molecule Type: Small molecule

Representations

Canonical SMILES:  CC(C)CC(C/C=C1\CC(CO)(COC(=O)C(C)(C)C)OC1=O)CC(C)C

Standard InChI:  InChI=1S/C22H38O5/c1-15(2)10-17(11-16(3)4)8-9-18-12-22(13-23,27-19(18)24)14-26-20(25)21(5,6)7/h9,15-17,23H,8,10-14H2,1-7H3/b18-9+

Standard InChI Key:  XKEOGEXDEKIDNA-GIJQJNRQSA-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: 382.54

Molecular Weight (Monoisotopic): 382.2719

AlogP: 4.28

#Rotatable Bonds: 9

Polar Surface Area: 72.83

Molecular Species: NEUTRAL

HBA: 5

HBD: 1

#RO5 Violations: 0

HBA (Lipinski): 5

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 0

CX Acidic pKa:

CX Basic pKa:

CX LogP: 5.59

CX LogD: 5.59

Aromatic Rings: 0

Heavy Atoms: 27

QED Weighted: 0.48

Np Likeness Score: 1.16

References

1. Choi Y, Kang JH, Lewin NE, Blumberg PM, Lee J, Marquez VE..  (2003)  Conformationally constrained analogues of diacylglycerol. 19. Synthesis and protein kinase C binding affinity of diacylglycerol lactones bearing an N-hydroxylamide side chain.,  46  (13): [PMID:12801241] [10.1021/jm030082c]

2. Lee J, Han KC, Kang JH, Pearce LL, Lewin NE, Yan S, Benzaria S, Nicklaus MC, Blumberg PM, Marquez VE..  (2001)  Conformationally constrained analogues of diacylglycerol. 18. The incorporation of a hydroxamate moiety into diacylglycerol-lactones reduces lipophilicity and helps discriminate between sn-1 and sn-2 binding modes to protein kinase C (PK-C). Implications for isozyme specificity.,  44  (25): [PMID:11728178] [10.1021/jm0103965]

3. Tamamura H, Sigano DM, Lewin NE, Peach ML, Nicklaus MC, Blumberg PM, Marquez VE..  (2004)  Conformationally constrained analogues of diacylglycerol (DAG). 23. Hydrophobic ligand-protein interactions versus ligand-lipid interactions of DAG-lactones with protein kinase C (PK-C).,  47  (20): [PMID:15369389] [10.1021/jm049723+]

4. Kang JH, Peach ML, Pu Y, Lewin NE, Nicklaus MC, Blumberg PM, Marquez VE..  (2005)  Conformationally constrained analogues of diacylglycerol (DAG). 25. Exploration of the sn-1 and sn-2 carbonyl functionality reveals the essential role of the sn-1 carbonyl at the lipid interface in the binding of DAG-lactones to protein kinase C.,  48  (18): [PMID:16134942] [10.1021/jm050352m]

5. Lee J, Kang JH, Han KC, Kim Y, Kim SY, Youn HS, Mook-Jung I, Kim H, Lo Han JH, Ha HJ, Kim YH, Marquez VE, Lewin NE, Pearce LV, Lundberg DJ, Blumberg PM..  (2006)  Branched diacylglycerol-lactones as potent protein kinase C ligands and alpha-secretase activators.,  49  (6): [PMID:16539391] [10.1021/jm0509391]

6. Ann J, Yoon S, Baek J, Kim DH, Lewin NE, Hill CS, Blumberg PM, Lee J..  (2015)  Design and synthesis of protein kinase C epsilon selective diacylglycerol lactones (DAG-lactones).,  90  [PMID:25437619] [10.1016/j.ejmech.2014.11.025]

7. Elhalem E, Bellomo A, Cooke M, Scravaglieri A, Pearce LV, Peach ML, Gandolfi Donadío L, Kazanietz MG, Comin MJ..  (2021)  Design, Synthesis, and Characterization of Novel sn-1 Heterocyclic DAG-Lactones as PKC Activators.,  64  (15.0): [PMID:34279947] [10.1021/acs.jmedchem.1c00739]

Source

Source(1):

• Scientific Literature