2,2-Dimethyl-propionic acid 2-hydroxymethyl-4-(3-isobutyl-5-methyl-hexylidene)-5-oxo-tetrahydro-furan-2-ylmethyl ester

ID: ALA137386

PubChem CID: 6520576

Max Phase: Preclinical

Molecular Formula: C22H38O5

Molecular Weight: 382.54

Molecule Type: Small molecule

Names and Identifiers

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

Molfile:  

     RDKit          2D

 27 27  0  0  0  0  0  0  0  0999 V2000
   -5.4804   -1.0955    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -6.1478   -1.5805    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.8929   -2.3651    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.0679   -2.3651    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.8129   -1.5805    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.5603   -0.8660    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.7311   -2.1638    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.5280   -1.9503    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -7.3853   -0.8660    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -7.7978   -0.1515    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -8.6228   -0.1515    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.3853    0.5629    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -9.0353    0.5629    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -9.0353   -0.8660    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -9.4478   -0.1515    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0283   -1.3255    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -4.5829   -3.0325    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.7965   -3.8294    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2131   -4.4127    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4266   -5.2096    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4162   -4.1992    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2027   -3.4023    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4058   -3.1888    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.7860   -2.8190    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8433   -5.7930    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0568   -6.5899    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0464   -5.5795    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  1  0
  4  5  1  0
  1  5  1  0
  2  6  1  0
  2  7  1  0
  7  8  1  0
  6  9  1  0
  9 10  1  0
 10 11  1  0
 10 12  2  0
 11 13  1  0
 11 14  1  0
 11 15  1  0
  5 16  2  0
  4 17  2  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 19 21  1  0
 21 22  1  0
 22 23  1  0
 22 24  1  0
 20 25  1  0
 25 26  1  0
 25 27  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA137386

   (E)-2-(2-(hydroxymethyl)-4-(3-isobutyl-5-methylhexylidene)-5-oxo-tetrahydrofuran-2-yl)ethyl pivalate

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: 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: ┄

HBA (Lipinski): 5

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: ┄

CX LogP: 5.59

CX LogD: 5.59

Aromatic Rings: ┄

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