3946-32-5

Basic information

• Product Name: SUBERIC ACID MONOMETHYL ESTER
• Synonyms: METHYL HYDROGEN SUBERATE;METHYL HYDROGEN OCTANE-1,8-DIOATE;SUBERIC ACID MONOMETHYL ESTER;OCTANEDIOIC ACID MONOMETHYL ESTER;MONOMETHYL OCTANE-1,8-DIOATE;MONOMETHYL SUBERATE;SUBERIC ACID METHYL ESTER;Monomethyl octanedioate
• CAS NO: 3946-32-5
• Molecular Formula: C₉H₁₆O₄
• Molecular Weight: 188.22
• EINECS: 1806241-263-5
• Product Categories: Linear hydrocarbon series;OLED materials,pharm chemical,electronic
• Mol File: 3946-32-5.mol
• Article Data: 22

Chemical Properties

• Melting Point: 17-19 °C(lit.)
• Boiling Point: 185-186 °C18 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: colorless low melting solid
• Density: 1.047 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.000208mmHg at 25°C
• Refractive Index: n20/D 1.444(lit.)
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO, Methanol
• PKA: 4.76±0.10(Predicted)
• CAS DataBase Reference: SUBERIC ACID MONOMETHYL ESTER(CAS DataBase Reference)
• NIST Chemistry Reference: SUBERIC ACID MONOMETHYL ESTER(3946-32-5)
• EPA Substance Registry System: SUBERIC ACID MONOMETHYL ESTER(3946-32-5)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-37/39
• WGK Germany: 3
• Hazardous Substances Data: 3946-32-5(Hazardous Substances Data)

Usage

Chemical Properties

colorless low melting solid

Uses

Different sources of media describe the Uses of 3946-32-5 differently. You can refer to the following data:
1. Suberic acid monomethyl ester was used in the synthetic preparation of Prostaglandin E1 (P838600), a primary prostaglandin and a peripheral vasodilator.
2. Monomethyl Suberate was used in the synthetic preparation of Prostaglandin E1 (P838600), a primary prostaglandin and a peripheral vasodilator.

General Description

The effects of suberic acid monomethyl ester (monomethyl suberate) on liver lactate metabolism was studied.

InChI:InChI=1/C9H16O4/c1-13-9(12)7-5-3-2-4-6-8(10)11/h2-7H2,1H3,(H,10,11)/p-1

Synthetic route

dimethyl subarate (1732-09-8) → suberic acid monomethyl ester (3946-32-5)

Conditions	Yield
With porcine liver esterase; sodium hydroxide; phosphate buffer for 6h;	87%
With sodium hydroxide; phosphate buffer for 1h; Ambient temperature; pig liver esterase;	87%
With sodium hydroxide; porcine pancreatic lipase In water Hydrolysis; Enzymatic reaction; pH 7;	85%

methanol (67-56-1) + oxonane-2,9-dione (10521-06-9) → suberic acid monomethyl ester (3946-32-5)

Conditions	Yield
for 3h; Reflux;	80%

methanol (67-56-1) + octane-1,8-dioic acid (505-48-6) → suberic acid monomethyl ester (3946-32-5) + dimethyl subarate (1732-09-8)

Conditions	Yield
With aluminum oxide at 25℃; for 48h; Green chemistry; chemoselective reaction;	A 72% B 11%
With sulfuric acid

methanol (67-56-1) + octane-1,8-dioic acid (505-48-6) → suberic acid monomethyl ester (3946-32-5)

Conditions	Yield
With acid	33%
With hydrogenchloride; water
With boron trifluoride methanol complex for 0.5h; Heating;

octane-1,8-dioic acid (505-48-6) + dimethyl subarate (1732-09-8) → suberic acid monomethyl ester (3946-32-5)

Conditions	Yield
With hydrogenchloride; dibutyl ether at 170℃;

diazomethane (186581-53-3, 908094-01-9) + octane-1,8-dioic acid (505-48-6) → suberic acid monomethyl ester (3946-32-5)

Conditions	Yield
With aluminum oxide In cyclohexane; N,N-dimethyl-formamide Product distribution; study of selectivity of methylation on alumina surface;

octane-1,8-dioic acid (505-48-6) + dimethyl sulfate (77-78-1) → suberic acid monomethyl ester (3946-32-5)

Conditions	Yield
aluminum oxide In cyclohexane for 2h; Heating; Yield given;

methanol (67-56-1) + 2-nitrocyclooctanone (13154-28-4) → suberic acid monomethyl ester (3946-32-5)

Conditions	Yield
With Oxone; potassium hydroxide; sodium hydroxide; disodium hydrogenphosphate; water 1.) 65 deg C, 4 h, 2.) r.t., 4 h; Yield given. Multistep reaction;

octane-1,8-dioic acid (505-48-6) → suberic acid monomethyl ester (3946-32-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 90 percent / H2SO4 / Heating 2: 34 percent / KOH / methanol / 4 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: Me3SiCl / methanol / 24 h / 20 °C 2: 85 percent / porcine pancreatic lipase; NaOH / H2O / Enzymatic reaction; pH 7 View Scheme
Multi-step reaction with 2 steps 1: sulfuric acid / methanol / 12 h 2: potassium hydroxide / methanol / 4 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: acetic anhydride / Heating 2: 3 h / Reflux View Scheme

dimethyl subarate (1732-09-8) → heptanedioic acid (111-16-0) + octane-1,8-dioic acid (505-48-6) + suberic acid monomethyl ester (3946-32-5)

Conditions	Yield
With Amberlyst 35 In water; acetic acid at 95℃; for 20h; Inert atmosphere; Overall yield = 0.41 g;	A 0.34 %Chromat. B 88.58%Chromat. C 10.6 %Chromat.

suberic acid monomethyl ester (3946-32-5) + (3-aminophenyl)carbamic acid tert-butyl ester (68621-88-5) → 7-(3-(tert-butoxycarbonylamino)phenylcarbamoyl)heptanoic acid methyl ester (1204005-96-8)

Conditions	Yield
Stage #1: suberic acid monomethyl ester With 4-methyl-morpholine; chloroformic acid ethyl ester In dichloromethane at 0℃; for 0.25h; Stage #2: (3-aminophenyl)carbamic acid tert-butyl ester In dichloromethane at 20℃;	100%
With pyridine; trichlorophosphate at 0℃;	46%
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 12h;

suberic acid monomethyl ester (3946-32-5) + C8H3NO3Re → tricarbonyl{methyl 8-[(η5-cyclopentadienyl)amino]-8-oxooctanoate}rhenium

Conditions	Yield
With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran at 20℃; for 17h; Inert atmosphere;	100%

suberic acid monomethyl ester (3946-32-5) + C8H3MnNO3 → tricarbonyl{methyl 8-[(η5-cyclopentadienyl)amino]-8-oxooctanoate}manganese

Conditions	Yield
With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran at 20℃; for 17h; Inert atmosphere;	100%

suberic acid monomethyl ester (3946-32-5) + N-(tert-butoxycarbonyl)-1,4-phenylenediamine (71026-66-9) + chloroformic acid ethyl ester (541-41-3) → methyl 8-((4-((tert-butoxycarbonyl)amino)phenyl)amino)-8-oxooctanoate

Conditions	Yield
Stage #1: suberic acid monomethyl ester; chloroformic acid ethyl ester With 4-methyl-morpholine In dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #2: N-(tert-butoxycarbonyl)-1,4-phenylenediamine In dichloromethane at 20℃; Inert atmosphere;	99%

suberic acid monomethyl ester (3946-32-5) + 2,3-dihydro-5-methoxy-1H-inden-1-amine (52372-95-9) → methyl 8-((5-methoxy-2,3-dihydro-1H-inden-1-yl)amino)-8-oxooctanoate

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃;	99%

suberic acid monomethyl ester (3946-32-5) + 6-methoxy-1-amino-1,2,3,4-tetrahydronaphthalene (52373-02-1) → methyl 8-((6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)amino)-8-oxooctanoate

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 20℃;	99%

5-bromo-2,3-dihydro-1H-inden-1-one oxime (185122-74-1) + suberic acid monomethyl ester (3946-32-5) → methyl 8-((5-bromo-2,3-dihydro-1H-inden-1-yl)amino)-8-oxooctanoate

Conditions	Yield
With 4-methyl-morpholine; dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃;	99%

suberic acid monomethyl ester (3946-32-5) → 8-hydroxyoctanoic acid methyl ester (20257-95-8)

Conditions	Yield
With borane-THF In tetrahydrofuran for 12h; Ambient temperature;	98%
With borane-THF In tetrahydrofuran at -15 - 20℃; for 24h;	90%

suberic acid monomethyl ester (3946-32-5) + aniline (62-53-3) → 7-phenylcarbamoyl heptanoic acid methyl ester (162853-41-0)

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; diisopropylamine In dichloromethane at 20℃; for 12h;	98%
Stage #1: suberic acid monomethyl ester; aniline With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide for 0.0833333h; Stage #2: With benzotriazol-1-ol at 25℃; for 4h;	94%
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 20℃; for 1.5h;	88.7%

PD 0332991 (571190-30-2) + suberic acid monomethyl ester (3946-32-5) → methyl 8-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)-8-oxooctanoate

Conditions	Yield
With 4-methyl-morpholine; 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane; N,N-dimethyl-formamide at 20℃;	98%

suberic acid monomethyl ester (3946-32-5) + tert–butyl (2–aminophenyl)carbamate (146651-75-4) → methyl 8-((2-((tert–butoxycarbonyl)amino)phenyl)amino)-8–oxooctanoate

Conditions	Yield
Stage #1: suberic acid monomethyl ester With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In chloroform at 20℃; for 0.5h; Inert atmosphere; Stage #2: tert–butyl (2–aminophenyl)carbamate In chloroform at 20℃; Inert atmosphere;	98%
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 12h;

suberic acid monomethyl ester (3946-32-5) + N-demethyltamoxifen (31750-47-7, 31750-48-8) → methyl (Z)-8-((2-(4-(1,2-diphenylbut-1-en-1-yl)phenoxy)ethyl)(methyl)amino)-8-oxooctanoate

Conditions	Yield
With 4-methyl-morpholine; 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;	97%

oxalyl dichloride (79-37-8) + suberic acid monomethyl ester (3946-32-5) → methyl 8-chloro-8-oxooctanoate (41624-92-4)

Conditions	Yield
With N,N-dimethyl-formamide In benzene 1.) 5 deg C, 15 min; 2.) 23 deg C, 2 h; 3.) 60 deg C, 1 h;	96%

suberic acid monomethyl ester (3946-32-5) + O-benzylhydoxylamine hydrochloride (2687-43-6) → methyl N-benzyloxysuberoylamide (149648-49-7)

Conditions	Yield
With bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; triethylamine In dichloromethane Substitution;	95%
With bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; N-ethyl-N,N-diisopropylamine In dichloromethane	95%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 4h; Inert atmosphere;

suberic acid monomethyl ester (3946-32-5) + 4-methoxy-aniline (104-94-9) + 9-fluorenyl hydroxy(methyl)carbamate (190656-07-6) → octanedioic acid hydroxy-methyl-amide (4-methoxy-phenyl)-amide

Conditions	Yield
Multistep reaction.;	94%

suberic acid monomethyl ester (3946-32-5) + 1-((2S,4S,5S)-4-(2-(4-aminophenyl)-1,3-dithian-2-yl)-5-(((tert-butyldimethylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione → methyl 8-((4-(2-((2S,3S,5S)-2-(((tert-butyldimethylsilyl)oxy)methyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yl)-1,3-dithian-2-yl)phenyl)amino)-8-oxooctanoate

Conditions	Yield
Stage #1: suberic acid monomethyl ester With bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; N-ethyl-N,N-diisopropylamine In dichloromethane Inert atmosphere; Stage #2: 1-((2S,4S,5S)-4-(2-(4-aminophenyl)-1,3-dithian-2-yl)-5-(((tert-butyldimethylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione In dichloromethane at 20℃; Inert atmosphere;	94%

suberic acid monomethyl ester (3946-32-5) + 4-hydroxy-6-methyl-2-pyrone → C15H20O6 (1402994-11-9)

Conditions	Yield
With dmap; diisopropyl-carbodiimide In toluene at 20 - 100℃; for 9h; Inert atmosphere;	93%

suberic acid monomethyl ester (3946-32-5) + 3-α-acetoxy-4-β-amino-24-norurs-12-ene (108015-89-0) → methyl 8-((3-α-acetoxy-24-norurs-12-en-4-yl)amino)-8-oxooctanoate

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In tetrahydrofuran at 0 - 20℃; for 16.5h;	93%

suberic acid monomethyl ester (3946-32-5) + N-benzyl-N-methoxyamine (20056-98-8) → C17H25NO4

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 14h; Inert atmosphere;	93%

(4-aminobenzyl)(methyl)carbamic acid tert-butyl ester (225240-83-5) + suberic acid monomethyl ester (3946-32-5) → methyl 8-((4-(((tert-butoxycarbonyl)(methyl)amino)methyl)phenyl)amino)-8-oxooctanoate

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 5h;	93%

furan (110-00-9) + suberic acid monomethyl ester (3946-32-5) + sodium carbonate (497-19-8) + Chloroacetic anhydride (541-88-8) → 8-(furan-2-yl)-8-oxooctanoic acid methyl ester (38199-47-2)

Conditions	Yield
In toluene	92.3%

suberic acid monomethyl ester (3946-32-5) + tert-butyl N-(6-aminohexyl)carbamate (51857-17-1) → methyl 8-((6-((tert-butoxycarbonyl)amino)hexyl)amino)-8-oxooctanoate

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 1h;	92%

suberic acid monomethyl ester (3946-32-5) → methyl 8-chloro-8-oxooctanoate (41624-92-4)

Conditions	Yield
With thionyl chloride for 6h; Heating;	91%
With thionyl chloride	90%
With oxalyl dichloride; N,N-dimethyl-formamide In toluene at 5 - 20℃; for 1.5h;	90%

suberic acid monomethyl ester (3946-32-5) + 2-Amino-1-phenylethanol (7568-93-6) → 7-(2-hydroxy-2-phenyl-ethylcarbamoyl)-heptanoic acid methyl ester (406726-57-6)

Conditions	Yield
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In tetrahydrofuran at 20℃; for 12h;	91%

suberic acid monomethyl ester (3946-32-5) + Chloroacetic anhydride (541-88-8) → 8-oxo-8-thiophen-2-yl-octanoic acid methyl ester (93568-18-4)

Conditions	Yield
In thiophene; 1,1-dichloroethane	91%

O-(1-isobutoxyethyl)hydroxylamine (860216-27-9) + suberic acid monomethyl ester (3946-32-5) → 7-(1-isobutoxy-ethoxycarbamoyl)-heptanoic acid methyl ester (914605-61-1)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In tetrahydrofuran; dichloromethane at 20℃;	91%

suberic acid monomethyl ester (3946-32-5) + Ethyl hydrogen suberate (14113-01-0) + 4-Aminobiphenyl (92-67-1) → 7-(Biphenyl-4-ylcarbamoyl)-heptanoic acid ethyl ester (406726-68-9)

Conditions	Yield
	91%

3-α-o-acetoxy-4β-amino-11-oxo-24-norurs-12-ene (872090-58-9) + suberic acid monomethyl ester (3946-32-5) → methyl 8-((3-α-acetoxy-11-oxo-24-norurs-12-en-4-yl)amino)-8-oxooctanoate

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In tetrahydrofuran at 0 - 20℃; for 16.5h;	91%

suberic acid monomethyl ester (3946-32-5) + di-tert-butyl 2-(4-aminophenyl)malonate (1006950-20-4) → di-tert-butyl 2-(4-(8-methoxy-8-oxooctanamido)phenyl)malonate (1350650-29-1)

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 16h; Cooling with ice;	90.1%

2-amino-1-(2-methoxyphenyl)ethan-1-one hydrochloride (34589-97-4) + suberic acid monomethyl ester (3946-32-5) → 7-[2-(2-methoxyphenyl)-2-oxoethylcarbamoyl]heptanoic acid methyl ester (847266-96-0)

Conditions	Yield
Stage #1: 2-amino-1-(2-methoxyphenyl)ethan-1-one hydrochloride; suberic acid monomethyl ester With triethylamine In dichloromethane at 0℃; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 22h;	88%

Upstream product

• 505-48-6 octane-1,8-dioic acid 
• 77-78-1 dimethyl sulfate 
• 67-56-1 methanol 
• 10521-06-9 oxonane-2,9-dione 
• 13154-28-4 2-nitrocyclooctanone 
• 186581-53-3 diazomethane 
• 1732-09-8 dimethyl subarate 

Downstream Products

• 5024-21-5 dimethyl tetradecanedioate 
• 76470-07-0 Tetradec-11-ynoic acid methyl ester 
• 1745-17-1 methyl hept-6-enoate 
• 137299-10-6 tert-butyl <8S,(S)R>-hydroxy-9-p-tolylsulfinyl nonanoate 
• 137299-09-3 tert-butyl <(S)R>-8-oxo-9-p-tolylsulfinyl nonanoate 
• 137324-60-8 <(8R)-(tert-butyldimethylsilyloxy)nonanyl> triphenyl phosphonium iodide 
• 406726-57-6 7-(2-hydroxy-2-phenyl-ethylcarbamoyl)-heptanoic acid methyl ester 
• 847266-96-0 7-[2-(2-methoxyphenyl)-2-oxoethylcarbamoyl]heptanoic acid methyl ester 
• 20257-95-8 8-hydroxyoctanoic acid methyl ester 
• 26825-92-3 methyl 8-bromooctanoate 
• 406726-70-3 7-[2-(1H-Benzoimidazol-2-yl)-ethylcarbamoyl]-heptanoic acid methyl ester 
• 1001329-52-7 C₁₉H₂₄N₂O₅ 
• 406726-61-2 methyl 8-oxo-8-(phenethylamino)octanoate 
• 406726-60-1 methyl 8-(benzylamino)-8-oxooctanoate 

Relevant articles and documents

TARGET PROTEIN EED DEGRADATION-INDUCING DEGRADUCER, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING DISEASES RELATED TO EED, EZH2, OR PRC2, COMPRISING SAME AS ACTIVE INGREDIENT

The present invention relates to a target protein degradation-inducing Degraducer, a preparation method thereof, and a pharmaceutical composition for preventing or treating diseases related to EED, EZH2, or PRC2 comprising same as an active ingredient. A novel compound represented by formula 1, according to the present invention is a Degraducer compound that induces degradation of a target protein, i.e., embryonic ectoderm development (EED) or polycomb repressive complex 2 (PRC2), utilizing cereblon E3 ubiquitin ligase, von Hippel-Lindau tumor suppressor (VHL) E3 ubiquitin ligase, mouse double minute 2 homolog (MDM2) E3 ubiquitin ligase, and cellular inhibitor of apoptosis protein 1 (cIAP) E3 ubiquitin ligase, wherein the compound has an aspect of remarkably achieving target protein degradation-inducing activity through a ubiquitin proteasome system (UPS), and therefore there is a useful effect in that it is possible to provide a pharmaceutical composition for preventing or treating diseases or conditions related to a target protein, and a functional health food composition for preventing or improving same, comprising said compound as an active ingredient.

PYRIDAZINE DERIVATIVES AS SMARCA2/4 DEGRADERS

The present invention provides pyridazine derivatives of formula (I), which are therapeutically useful as SMARCA2/4 degraders. These compounds are useful in the treatment and/or prevention of diseases or disorders dependent upon SMARCA2/4 in a mammal. The present invention also provides preparation of the compounds and pharmaceutical compositions comprising at least one of the pyridazine derivatives of formula (I) or a pharmaceutically acceptable salt, or a stereoisomer thereof.

Discovery, bioactivity and docking simulation of Vorinostat analogues containing 1,2,4-oxadiazole moiety as potent histone deacetylase inhibitors and antitumor agents

Abstract In our study, three series of hydroxamate, 2-aminobenzamide, and trifluoromethyl ketone analogues have been designed and synthesized. The synthesized compounds were investigated for their in vitro antiproliferative activities using the MTT-based assay against three human cancer cell lines including A549, NCI-H661, and U937. Most analogues exhibited higher antiproliferative activities against human acute myeloid leukemia cell U937 than the other two human lung cancer cell lines. Furthermore, the compounds were examined against HDAC1, 2, and 8 isoforms. Docking study of compounds 6h, 9b, and 10a suggested that they might bind tightly to the binding pocket of HDAC2 and/or HDAC8. The results suggest that these compounds might have potential as lead compounds for the development of anti-tumor drugs with HDACs inhibitory activities.