(S)-2-[(R)-8-(2,4-Dichloro-phenyl)-2-hydroxy-octyl]-2-hydroxy-succinic acid

ID: ALA119628

Chembl Id: CHEMBL119628

PubChem CID: 10835222

Max Phase: Preclinical

Molecular Formula: C18H24Cl2O6

Molecular Weight: 407.29

Molecule Type: Small molecule

Names and Identifiers

Synonyms: SB-201076 | CHEMBL119628|SB-201076|(S)-2-((R)-8-(2,4-dichlorophenyl)-2-hydroxyoctyl)-2-hydroxysuccinic acid|SCHEMBL16111195|BDBM50066683|(2S)-2-[(2R)-8-(2,4-Dichlorophenyl)-2-hydroxyoctyl]-2-hydroxybutanedioic acid|(S)-2-[(R)-8-(2,4-Dichloro-phenyl)-2-hydroxy-octyl]-2-hydroxy-succinic acid

Canonical SMILES:  O=C(O)C[C@@](O)(C[C@H](O)CCCCCCc1ccc(Cl)cc1Cl)C(=O)O

Standard InChI:  InChI=1S/C18H24Cl2O6/c19-13-8-7-12(15(20)9-13)5-3-1-2-4-6-14(21)10-18(26,17(24)25)11-16(22)23/h7-9,14,21,26H,1-6,10-11H2,(H,22,23)(H,24,25)/t14-,18+/m1/s1

Standard InChI Key:  NPZOIISFQXTCQN-KDOFPFPSSA-N

Alternative Forms

1. Parent:

   

   ALA119628

   (S)-2-((R)-8-(2,4-dichlorophenyl)-2-hydroxyoctyl)-2-hydroxysuccinic acid

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: 407.29

Molecular Weight (Monoisotopic): 406.0950

AlogP: 3.53

#Rotatable Bonds: 12

Polar Surface Area: 115.06

Molecular Species: ACID

HBA: 4

HBD: 4

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 4

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 3.72

CX Basic pKa: ┄

CX LogP: 3.84

CX LogD: -1.33

Aromatic Rings: 1

Heavy Atoms: 26

QED Weighted: 0.39

Np Likeness Score: 0.36

References

1. Gribble AD, Ife RJ, Shaw A, McNair D, Novelli CE, Bakewell S, Shah VP, Dolle RE, Groot PH, Pearce N, Yates J, Tew D, Boyd H, Ashman S, Eggleston DS, Haltiwanger RC, Okafo G..  (1998)  ATP-Citrate lyase as a target for hypolipidemic intervention. 2. Synthesis and evaluation of (3R,5S)-omega-substituted-3-carboxy-3, 5-dihydroxyalkanoic acids and their gamma-lactone prodrugs as inhibitors of the enzyme in vitro and in vivo.,  41  (19): [PMID:9733484] [10.1021/jm980091z]

2. Gribble AD, Ife RJ, Shaw A, McNair D, Novelli CE, Bakewell S, Shah VP, Dolle RE, Groot PH, Pearce N, Yates J, Tew D, Boyd H, Ashman S, Eggleston DS, Haltiwanger RC, Okafo G..  (1998)  ATP-Citrate lyase as a target for hypolipidemic intervention. 2. Synthesis and evaluation of (3R,5S)-omega-substituted-3-carboxy-3, 5-dihydroxyalkanoic acids and their gamma-lactone prodrugs as inhibitors of the enzyme in vitro and in vivo.,  41  (19): [PMID:9733484] [10.1021/jm980091z]

3. Gribble AD, Ife RJ, Shaw A, McNair D, Novelli CE, Bakewell S, Shah VP, Dolle RE, Groot PH, Pearce N, Yates J, Tew D, Boyd H, Ashman S, Eggleston DS, Haltiwanger RC, Okafo G..  (1998)  ATP-Citrate lyase as a target for hypolipidemic intervention. 2. Synthesis and evaluation of (3R,5S)-omega-substituted-3-carboxy-3, 5-dihydroxyalkanoic acids and their gamma-lactone prodrugs as inhibitors of the enzyme in vitro and in vivo.,  41  (19): [PMID:9733484] [10.1021/jm980091z]

4. Li JJ, Wang H, Tino JA, Robl JA, Herpin TF, Lawrence RM, Biller S, Jamil H, Ponticiello R, Chen L, Chu CH, Flynn N, Cheng D, Zhao R, Chen B, Schnur D, Obermeier MT, Sasseville V, Padmanabha R, Pike K, Harrity T..  (2007)  2-hydroxy-N-arylbenzenesulfonamides as ATP-citrate lyase inhibitors.,  17  (11): [PMID:17383874] [10.1016/j.bmcl.2007.03.017]

5. Jain KS, Kathiravan MK, Somani RS, Shishoo CJ..  (2007)  The biology and chemistry of hyperlipidemia.,  15  (14): [PMID:17521912] [10.1016/j.bmc.2007.04.031]

6. Abramson HN..  (2011)  The lipogenesis pathway as a cancer target.,  54  (16): [PMID:21726077] [10.1021/jm2005805]

7. Jernigan FE, Hanai JI, Sukhatme VP, Sun L..  (2017)  Discovery of furan carboxylate derivatives as novel inhibitors of ATP-citrate lyase via virtual high-throughput screening.,  27  (4): [PMID:28129980] [10.1016/j.bmcl.2017.01.001]

8. Granchi C..  (2018)  ATP citrate lyase (ACLY) inhibitors: An anti-cancer strategy at the crossroads of glucose and lipid metabolism.,  157  [PMID:30195238] [10.1016/j.ejmech.2018.09.001]

Source

Source(1):

• Scientific Literature