5470-22-4

Basic information

• Product Name: 4-Chloropyridine-2-carboxylic acid
• Synonyms: IFLAB-BB F1926-0017;4-CHLOROPICOLINIC ACID;4-CHLOROPYRIDINE-2-CARBOXYLIC ACID;4-CHLORO-2-PYRIDINECARBOXYLIC ACID;Chloropicolinicacid;4-Chloropyridine-2-carboxylic;4-CHLOROPICOLINIC ACID 99%;4-Chloropicolinic acid ,98%
• CAS NO: 5470-22-4
• Molecular Formula: C₆H₄ClNO₂
• Molecular Weight: 157.55
• EINECS: -0
• Product Categories: blocks;Carboxes;Pyridines;Pyridine series;Acids and Derivatives;Heterocycles;pharmacetical;Carboxylic Acids;Pyridine;Chloropyridines;Halopyridines;Carboxylic Acids
• Mol File: 5470-22-4.mol
• Article Data: 18

Chemical Properties

• Melting Point: 181°C
• Boiling Point: 308 °C at 760 mmHg
• Flash Point: 140.1 °C
• Appearance: /
• Density: 1.47 g/cm³
• Vapor Pressure: 0.000303mmHg at 25°C
• Storage Temp.: Keep Cold
• PKA: 3.27±0.10(Predicted)
• CAS DataBase Reference: 4-Chloropyridine-2-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Chloropyridine-2-carboxylic acid(5470-22-4)
• EPA Substance Registry System: 4-Chloropyridine-2-carboxylic acid(5470-22-4)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36/37/39
• HazardClass: IRRITANT
• Hazardous Substances Data: 5470-22-4(Hazardous Substances Data)

Usage

Chemical Properties

White solid

Uses

4-Chloropicolinic Acid is a reactant used in the synthesis of VU0431316, a negative allosteric modulator of mGlu5.

InChI:InChI=1/C6H4ClNO2/c7-4-1-2-8-5(3-4)6(9)10/h1-3H,(H,9,10)/p-1

Synthetic route

4-Chloro-pyridine-2-carboxylic acid methyl ester (24484-93-3) → 4-chloropicolinic acid (5470-22-4)

Conditions	Yield
With sodium hydroxide at 20℃; for 1h;	87%
Stage #1: 4-Chloro-pyridine-2-carboxylic acid methyl ester With methanol; sodium hydroxide; water at 20℃; for 0.25h; Stage #2: With hydrogenchloride; water pH=2;
Stage #1: 4-Chloro-pyridine-2-carboxylic acid methyl ester With methanol; sodium hydroxide; water at 0 - 20℃; for 0.25h; Stage #2: With hydrogenchloride; water pH=2;

4-chloro-pyridine-2-carbonitrile (19235-89-3) → 4-chloropicolinic acid (5470-22-4)

Conditions	Yield
With sodium carbonate; sodium sulfite In ice-water; sulfuric acid; water	54.9%

2-Picolinic acid (98-98-6) → 4-chloropicolinic acid (5470-22-4)

Conditions	Yield
Stage #1: 2-Picolinic acid With thionyl chloride; sodium bromide for 20h; Heating / reflux; Stage #2: With water at -2 - 2℃;	28%
Multi-step reaction with 2 steps 1: 1) SOCl2, DMF / 1) 40-45 deg C, 45 min; 45->72 deg C, 2 h; 72 deg C, 21 h, 2) toluene, room temperature, 1 h 2: 1) 57percent HI, aq. hypophosphorous acid, 2) aq. NaOH / 1) 107 deg C, 6 h, 2) 95 deg C, 30 min; room temperature, 1 h View Scheme
With thionyl chloride In N,N-dimethyl-formamide at 95℃; for 12h;

4-chIoro-2-methylpyridine (3678-63-5) → 4-chloropicolinic acid (5470-22-4)

Conditions	Yield
With potassium permanganate

4-chloro-pyridine-2-carbonyl chloride (53750-66-6) → 4-chloropicolinic acid (5470-22-4)

Conditions	Yield
With water
With water

4,4'-dichloro-2,2'-bipyridine (1762-41-0) → 4-chloropicolinic acid (5470-22-4)

Conditions	Yield
With potassium permanganate; sulfuric acid; water

2-picolinic acid hydrochloride (636-80-6) → 4-chloropicolinic acid (5470-22-4)

Conditions	Yield
With thionyl chloride; sulfur dioxide Behandeln des Reaktionsprodukts mit H2O;
With thionyl chloride In water at 0℃; Reflux;

methyl 4-chloropyridine-2-carboxylate hydrochloride → 4-chloropicolinic acid (5470-22-4) + 4-iodopicolinic acid hemi-hydroiodide

Conditions	Yield
With sodium hydroxide; hydrogen iodide; hypophosphorous acid 1) 107 deg C, 6 h, 2) 95 deg C, 30 min; room temperature, 1 h; Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts;

2-Picolinic acid (98-98-6) + thionyl chloride (7719-09-7) → 4-chloropicolinic acid (5470-22-4) + 4,6-dichloro-2-pyridinecarboxylic acid (88912-25-8) + 4,5,6-trichloropicolinic acid (496849-77-5)

Conditions	Yield
Irradiation;

2-Picolinic acid (98-98-6) → 4-chloropicolinic acid (5470-22-4) + 4-chloro-6-oxy-picolinic acid

Conditions	Yield
With phosphorus pentachloride at 250 - 270℃; im Rohr; Behandeln des Reaktionsprodukts mit Schwefelsaeure;

4-chloro-aniline (106-47-8) → 4-chloropicolinic acid (5470-22-4) + 4-chlorobenzonitrile (100-00-5) + bis-(4-chloro-phenyl)-diazene (1602-00-2) + n,n'-dichloroazobenzene

Conditions	Yield
With phosphate buffer; ozone In water for 0.416667h; pH=8; Formation of xenobiotics; Title compound not separated from byproducts;

[2,2]bipyridinyl (366-18-7) → 4-chloropicolinic acid (5470-22-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: aqueous H2O2; acetic acid 2: fuming H2SO4; aqueous HNO3 3: PCl3 / 60 °C 4: H2O; KMnO4; H2SO4 View Scheme

[2,2']bipyridinyl 1,1'-dioxide (7275-43-6) → 4-chloropicolinic acid (5470-22-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: fuming H2SO4; aqueous HNO3 2: PCl3 / 60 °C 3: H2O; KMnO4; H2SO4 View Scheme

4,4'-dinitro-2,2'-bipyridyl-N,N'-dioxide (51595-55-2) → 4-chloropicolinic acid (5470-22-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: PCl3 / 60 °C 2: H2O; KMnO4; H2SO4 View Scheme

4-chloro-2-pyridinecarbaldehyde (63071-13-6) → 4-chloropicolinic acid (5470-22-4)

Conditions	Yield
With potassium permanganate In water; acetonitrile

4-hydroxypyridine-2-carboxylic acid (22468-26-4) → 4-chloropicolinic acid (5470-22-4)

Conditions	Yield
With thionyl chloride In N,N-dimethyl-formamide at 120℃; for 6h;

4-chloropicolinic acid (5470-22-4) + dimethyl amine (124-40-3) → 3-(dimethylamino)picolinic acid

Conditions	Yield
In water at 150℃; for 2h; Sealed tube;	99%
In water at 100℃; for 5h; Sealed tube;	95%
In water for 2h; Sealed tube; Heating;	90%

4-chloropicolinic acid (5470-22-4) → 4-chloropicolinamide (99586-65-9)

Conditions	Yield
Stage #1: 4-chloropicolinic acid In thionyl chloride at 80℃; for 2h; Stage #2: With ammonia In methanol; thionyl chloride at 0 - 20℃; for 3.25h;	96%
Stage #1: 4-chloropicolinic acid With thionyl chloride at 80℃; for 2h; Stage #2: With ammonia In methanol at 0 - 20℃; for 3.25h;	96%
Stage #1: 4-chloropicolinic acid With thionyl chloride In toluene at 80℃; for 6h; Stage #2: With ammonium hydroxide In toluene at 20℃; for 1h; Cooling with ice;	94%

4-chloropicolinic acid (5470-22-4) + diazomethyl-trimethyl-silane (18107-18-1) → 4-Chloro-pyridine-2-carboxylic acid methyl ester (24484-93-3)

Conditions	Yield
Stage #1: 4-chloropicolinic acid; diazomethyl-trimethyl-silane With methanol In tetrahydrofuran at 0 - 20℃; Stage #2: With acetic acid In tetrahydrofuran; methanol; water	96%

4-chloropicolinic acid (5470-22-4) + N,O-dimethylhydroxylamine*hydrochloride (6638-79-5) → 4-chloropyridine-2-carboxylic acid N-methoxy-N-methylamide (757251-62-0)

Conditions	Yield
Stage #1: N,O-dimethylhydroxylamine*hydrochloride With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0℃; for 0.166667h; Stage #2: 4-chloropicolinic acid With N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 16h;	96%
With 4-methyl-morpholine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃;	46%

4-chloropicolinic acid (5470-22-4) + benzyl alcohol (100-51-6) → benzyl 4-chloropyridin-2-ylcarbamate (1073372-14-1)

Conditions	Yield
With trimethylsilylazide; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In tetrahydrofuran Curtius rearrangement; Reflux;	94%

4-chloropicolinic acid (5470-22-4) + ethanol (64-17-5) → Ethyl 4-ethoxypicolinate (71777-70-3)

Conditions	Yield
sulfuric acid for 48h; Heating / reflux;	93%
Stage #1: 4-chloropicolinic acid; ethanol With sulfuric acid for 48h; Reflux; Stage #2: With sodium hydroxide In ethanol pH=8 - 9;	93%
With sulfuric acid at 85℃; for 16h;	69%

methanol (67-56-1) + 4-chloropicolinic acid (5470-22-4) → 4-Chloro-pyridine-2-carboxylic acid methyl ester (24484-93-3)

Conditions	Yield
Stage #1: 4-chloropicolinic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; Stage #2: methanol at 20℃; for 0.5h;	92%
Stage #1: 4-chloropicolinic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 1.5h; Stage #2: methanol at 20℃; for 0.5h;	90%
Stage #1: 4-chloropicolinic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h; Stage #2: methanol at 20℃; for 16h;	74%

4-chloropicolinic acid (5470-22-4) + 4-Amino-1-cyclohexyl-3-methyl-1H-pyrazole-5-carboxamide (553671-80-0) → N-[5-(aminocarbonyl)-1-cyclohexyl-3-methyl-1H-pyrazol-4-yl]-4-chloro-2-pyridinecarboxamide (553671-89-9)

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; for 3h;	91%

4-chloropicolinic acid (5470-22-4) + 4,5-difluoroindoline hydrochloride (1158918-84-3) → (4-chloro-pyridin-2-yl)-(4,5-difluoro-2,3-dihydro-indol-1-yl)-methanone (1159010-09-9)

Conditions	Yield
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide at 20℃;	91%

4-chloropicolinic acid (5470-22-4) + methyl-d3-amine hydrochloride (7436-22-8) → 4-chloropyridinyl-2-(N-1',1',1'-trideuteromethylcarboxamide) (1189858-48-7)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 16h;	91%

4-chloropicolinic acid (5470-22-4) + ethanol (64-17-5) → ethyl 4-chloropyridine-2-carboxylate (64064-56-8)

Conditions	Yield
With sulfuric acid	90%
Stage #1: 4-chloropicolinic acid With thionyl chloride at 100℃; for 6h; Stage #2: ethanol at 20℃; for 20h;	89%
Stage #1: 4-chloropicolinic acid With thionyl chloride at 100℃; for 6h; Stage #2: ethanol at 0 - 20℃; for 8h;	85%
Stage #1: 4-chloropicolinic acid With thionyl chloride at 100℃; for 6h; Inert atmosphere; Stage #2: ethanol at 20℃; for 25.5h; Cooling with ice; Stage #3: With sodium hydrogencarbonate In water	83.6%
With sulfuric acid for 2h; Inert atmosphere; Reflux;	55.7%

4-chloropicolinic acid (5470-22-4) + (S)-tert-leucinol (112245-13-3) → C12H17ClN2O2 (1257527-15-3)

Conditions	Yield
Stage #1: 4-chloropicolinic acid With 4-methyl-morpholine; isobutyl chloroformate In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: (S)-tert-leucinol With 4-methyl-morpholine In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere;	90%

4-chloropicolinic acid (5470-22-4) + isopropyl alcohol (67-63-0) → isopropyl 4-chloropicolinate (874786-49-9)

Conditions	Yield
Stage #1: 4-chloropicolinic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane for 1.5h; Stage #2: isopropyl alcohol In dichloromethane Stage #3: With sodium hydrogencarbonate In dichloromethane	87%

4-chloropicolinic acid (5470-22-4) + zinc(II) acetate tetrahydrate → zinc 4-chloropicolinate

Conditions	Yield
In water	86.4%

1,4-dioxane (123-91-1) + 4-chloropicolinic acid (5470-22-4) → 4–chloro–2–(2–(2–chloroethoxy)ethoxy)pyridine

Conditions	Yield
With tert-butylhypochlorite; chloranil at 110℃; for 12h; Inert atmosphere;	86%

4-chloropicolinic acid (5470-22-4) + 5-fluoroindoline (2343-22-8) → (4-chloropyridin-2-yl)-(5-fluoro-2,3-dihydroindol-1-yl)-methanone (1159009-70-7)

Conditions	Yield
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide at 20℃;	85%

4-chloropicolinic acid (5470-22-4) + 4-(3,5-dichlorophenoxy)-2-(piperazin-1-yl)pyrimidine → (4-chloropyridin-2-yl)(4-(4-(3,5-dichlorophenoxy)pyrimidin-2-yl)piperazin-1-yl)methanone

Conditions	Yield
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 10h;	85%

4-chloropicolinic acid (5470-22-4) + 3-Trifluoromethylphenol (98-17-9) → 4-(3-(trifluoromethyl)phenoxy)-2-pyridinecarboxylic acid

Conditions	Yield
With sodium carbonate; copper(l) chloride In N,N-dimethyl-formamide at 140℃; for 8h;	84.5%

4-chloropicolinic acid (5470-22-4) + aniline (62-53-3) → 4-chloro-N-phenylpyridine-2-carboxamide (133928-61-7)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	84%
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 25℃; for 4h;	69%

1-methyl-piperazine (109-01-3) + 4-chloropicolinic acid (5470-22-4) → (4-chloro-2-pyridyl)-(4-methylpiperazin-1-yl)methanone

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.5h;	83%

4-chloropicolinic acid (5470-22-4) + cyclopentadienylruthenium(II) trisacetonitrile hexafluorophosphate + allyl alcohol (107-18-6) → [RuCp(η3-C3H5)(4-Cl-PA)]PF6, PA=picolinic acid

Conditions	Yield
In acetone at 20℃; Inert atmosphere; Schlenk technique;	82%

4-chloropicolinic acid (5470-22-4) + 1-amino-naphthalene (134-32-7) → 4-chloro-N-(naphth-1-yl)pyridine-2-amide

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 12h; Inert atmosphere; Sealed tube;	81%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere;

4-chloropicolinic acid (5470-22-4) + 2-(4-aminophenyl)benzothiazole (6278-73-5) → (4-benzothiazol-2-yl-phenyl)-pyridin-4-yl-amine

Conditions	Yield
In N,N-dimethyl-formamide at 160℃; for 3h;	80%
In N,N-dimethyl-formamide at 160℃; for 3h;	8%

4-chloropicolinic acid (5470-22-4) + diethylamine (109-89-7) → 4-chloro-N,N-diethylpicolinamide (851903-41-8)

Conditions	Yield
Stage #1: 4-chloropicolinic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 50℃; for 0.883333h; Inert atmosphere; Glovebox; Stage #2: diethylamine In N,N-dimethyl-formamide at 50℃; for 12h; Inert atmosphere; Schlenk technique;	80%

4-chloropicolinic acid (5470-22-4) + C17H28N4O4S*C2HF3O2 → C23H30ClN5O5S

Conditions	Yield
Stage #1: 4-chloropicolinic acid With N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 0℃; Inert atmosphere; Cooling with ice; Stage #2: C17H28N4O4S*C2HF3O2 With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0℃; Inert atmosphere; Cooling with ice;	80%

4-chloropicolinic acid (5470-22-4) + sodium cyclopropylsulfinate (910209-21-1) → 4-(cyclopropylsulfonyl)picolinic acid (1354558-38-5)

Conditions	Yield
With quinoline; copper(l) chloride In 1-methyl-pyrrolidin-2-one at 140℃; for 0.166667h; Microwave irradiation;	75%

4-chloropicolinic acid (5470-22-4) + benzene (71-43-2) → 4-chloro-2-phenyl-pyridine (57311-18-9)

Conditions	Yield
With tert-butylhypochlorite; potassium carbonate at 40℃; for 15h; Schlenk technique;	75%
With tert-butylhypochlorite; potassium carbonate at 60℃; for 20h;	75%

4-chloropicolinic acid (5470-22-4) + C14H12N4O → N-(3-((1H-indazol-5-yl)carbamoyl)phenyl)-4-chloropicolinamide

Conditions	Yield
Stage #1: 4-chloropicolinic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: C14H12N4O With dmap In N,N-dimethyl-formamide at 20℃; for 18h;	74.5%

4-chloropicolinic acid (5470-22-4) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 4-Chloro-pyridine-2-carboxylic acid methyl ester (24484-93-3)

Conditions	Yield
With oxalyl dichloride In methanol; dichloromethane at 0 - 20℃; for 18h;	74%

Upstream product

• 3678-63-5 4-chIoro-2-methylpyridine 
• 106-47-8 4-chloro-aniline 
• 63071-13-6 4-chloro-2-pyridinecarbaldehyde 
• 22468-26-4 4-hydroxypyridine-2-carboxylic acid 
• 24484-93-3 4-Chloro-pyridine-2-carboxylic acid methyl ester 
• 19235-89-3 4-chloro-pyridine-2-carbonitrile 
• 51595-55-2 4,4'-dinitro-2,2'-bipyridyl-N,N'-dioxide 
• 7275-43-6 [2,2']bipyridinyl 1,1'-dioxide 
• 366-18-7 [2,2]bipyridinyl 
• 98-98-6 2-Picolinic acid 
• 7719-09-7 thionyl chloride 
• 176977-85-8 methyl 4-chloropyridine-2-carboxylate hydrochloride 
• 1762-41-0 4,4'-dichloro-2,2'-bipyridine 
• 53750-66-6 4-chloro-pyridine-2-carbonyl chloride 

Downstream Products

• 22468-26-4 4-hydroxypyridine-2-carboxylic acid 
• 640296-30-6 4-{2-[(4-chloro-pyridine-2-carbonyl)-amino]-4-fluoro-phenoxy}-phthalic acid dimethyl ester 
• 64064-56-8 ethyl 4-chloropyridine-2-carboxylate 
• 2767-90-0 4-piperidinylpyridine 
• 220000-87-3 4-chloro-N-methylpicolinamide 
• 103878-75-7 t-butyl [2-(4-chloropyridine-2-carboxamido)ethyl]carbamate 
• 24484-93-3 4-Chloro-pyridine-2-carboxylic acid methyl ester 
• 1338247-10-1 4-(dimethylamino)picolinohydrazide 
• 1333386-17-6 4-(4-(3-(4-chloro-3-trifluoromethylphenyl)ureido)phenoxyl)-2-(N-1’,1’,1’-trideuteromethyl)pyridine amide p-toluenesulfonate 
• 1373441-72-5 4-(benzylsulfanyl)pyridine-2-carboxamide 
• 1373441-81-6 4-(3-trifluoromethylbenzylsulfanyl)pyridine-2-carboxamide 
• 1373441-82-7 4-(4-trifluoromethylbenzylsulfanyl)pyridin-2-carboxamide 
• 1373441-83-8 4-(3-cyanobenzylsulfanyl)pyridine-2-carboxamide 
• 1373441-84-9 4-(3-methoxybenzylsulfanyl)pyridine-2-carboxamide 

Relevant articles and documents

Discovery of potent c-MET inhibitors with new scaffold having different quinazoline, pyridine and tetrahydro-pyridothienopyrimidine headgroups

Cellular mesenchymal-epithelial transition factor (c-MET) is closely linked to human malignancies, which makes it an important target for treatment of cancer. In this study, a series of 3-methoxy-N-phenylbenzamide derivatives, N-(3-(tert-butyl)-1-phenyl-1H-pyrazol-5-yl) benzamide derivatives and N1-(3-fluoro-4-methoxyphenyl)-N3-(4-fluorophenyl) malonamide derivatives were designed and synthesized, some of them were identified as c-MET inhibitors. Among these compounds with new scaffolds having different quinazoline, pyridine and tetrahydro-pyridothienopyrimidine head groups, compound 11c, 11i, 13b, 13h exhibited both potent inhibitory activities against c-MET and high anticancer activity against tested cancer cell lines in vitro. In addition, kinase selectivity assay further demonstrated that both 13b and 13h are potent and selective c-MET inhibitors. Molecular docking supported that they bound well to c-MET and VEGFR2, which demonstrates that they are potential c-MET RTK inhibitors for cancer therapy.

Design and synthesis of novel 2-(4-(2-(dimethylamino)ethyl)-4H-1,2,4- triazol-3-yl)pyridines as potential antitumor agents

New 2-(4-(2-(dimethylamino)ethyl)-4H-1,2,4-triazol-3-yl)pyridine derivatives were synthesized and evaluated for their in vitro cytotoxicity against five cancer cell lines namely MKN-45, H460, HT-29, A549 and U87MG, as well as the normal cell line WI-38. Nearly all the compounds exhibited superior potency to sorafenib with a better selectivity towards the MKN-45, H460 and HT-29 cell lines. In addition, the enzymatic screening result demonstrated that the optimized compounds possessed potent Raf kinase inhibition as well as favorable enzyme selectivity. The most promising compound, 11f, showed high levels of cytotoxicity against MKN-45, H460 and HT-29 cells with IC50 values of 51, 72 and 130 nM, respectively, which are 45.5, 30.4 and 27.8 folds higher than the corresponding IC50 values for sorafenib against these cell lines. Structure-activity relationships revealed that the dimethylaminoethyl group was crucial for high activity.

ALLOSTERIC MODULATORS OF 5-HYDROXYTRYPTAMINE 2C RECEPTOR (5-HT2CR)

[000166] Embodiments of the invention are directed to methods of identifying, methods of synthesizing, and compositions identified as allosteric modulators of 5-HT2cR.