133111-56-5

Basic information

• Product Name: 6-(4-Chlorophenyl)-2,3-Dihydro-2,2-DiMethyl-7-Phenyl-1H-Pyrrolizine
• Synonyms: 6-(4-Chlorophenyl)-2,3-Dihydro-2,2-DiMethyl-7-Phenyl-1H-Pyrrolizine;6-(4-Chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine;1H-Pyrrolizine,6-(4-chlorophenyl)-2,3-dihydro-2,2-diMethyl-7-phenyl-
• CAS NO: 133111-56-5
• Molecular Formula: C₂₁H₂₀ClN
• Molecular Weight: 321.8432
• Mol File: 133111-56-5.mol
• Article Data: 9

Chemical Properties

• Appearance: /
• Storage Temp.: 2-8°C
• CAS DataBase Reference: 6-(4-Chlorophenyl)-2,3-Dihydro-2,2-DiMethyl-7-Phenyl-1H-Pyrrolizine(CAS DataBase Reference)
• NIST Chemistry Reference: 6-(4-Chlorophenyl)-2,3-Dihydro-2,2-DiMethyl-7-Phenyl-1H-Pyrrolizine(133111-56-5)
• EPA Substance Registry System: 6-(4-Chlorophenyl)-2,3-Dihydro-2,2-DiMethyl-7-Phenyl-1H-Pyrrolizine(133111-56-5)

Safety Data

• Hazardous Substances Data: 133111-56-5(Hazardous Substances Data)

Usage

General Description

6-(4-Chlorophenyl)-2,3-Dihydro-2,2-DiMethyl-7-Phenyl-1H-Pyrrolizine, also known as TC-I 2014, is a chemical compound that belongs to the class of pyrrolizine derivatives. It is commonly used in research and pharmaceutical industries for its potential therapeutic properties. 6-(4-Chlorophenyl)-2,3-Dihydro-2,2-DiMethyl-7-Phenyl-1H-Pyrrolizine has been studied for its anti-inflammatory and anti-cancer activities, and has shown promise in preclinical studies. Its unique chemical structure and pharmacological properties make it a subject of interest for further research and potential drug development. However, its exact mechanisms of action and potential side effects are still under investigation.

InChI:InChI=1/C21H20ClN/c1-21(2)12-19-20(16-6-4-3-5-7-16)18(13-23(19)14-21)15-8-10-17(22)11-9-15/h3-11,13H,12,14H2,1-2H3

Synthetic route

4-chlorobenzoylmethyl bromide (536-38-9) + 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5)

Conditions	Yield
Stage #1: 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole With sodium hydrogencarbonate In methanol Stage #2: 4-chlorobenzoylmethyl bromide In methanol for 20h; Stage #3: With water at 40℃; for 1h;	84%
With sodium hydrogencarbonate In ethanol at 20℃; for 36h;	25%
With sodium hydrogencarbonate In ethanol; water at 20℃; for 36h;	25%

4-Chlorophenylboronic acid (1679-18-1) + 2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-6-yl trifluoromethanesulfonate (226900-28-3) → 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5)

Conditions	Yield
With potassium hydroxide; tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran 1) rt, overnight; 2) reflux, 24 h;	15%

(4-chlorphenyl)magnesium bromide (873-77-8) + N,N-diethyl 2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-6-yl carbamate (226900-31-8) → 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5)

Conditions	Yield
With Ni(aca)2 In tetrahydrofuran Heating; Yield given;

(4-chlorphenyl)magnesium bromide (873-77-8) + diethyl 2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-6-yl phosphate (226900-35-2) → 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5)

Conditions	Yield
With Ni(aca)2 In tetrahydrofuran Heating; Yield given;

1-chloro-3-phenyl-2-propyne (3355-31-5) + (1,2-dimethyl-3-zirconacyclopent-1-ene)(C5H5)2 → 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: 90 percent / aq. NaOH, NaI, n-Bu4NI / toluene / 24 h / 50 °C 2: 1.) Et3N, 2.) NaBH(OAc)3 / 1) CH2Cl2, rt, 15 min; 2) CH2Cl2, rt, 12 h 3: 68 percent / pivalic acid / 5 h / 150 °C 4: 1.) NaH / 1) THF, rt, 1 h; 2) THF, 0 deg C, 5 min, rt, 20 h 5: 15 percent / Pd(PPh3)4, aq. KOH / tetrahydrofuran / 1) rt, overnight; 2) reflux, 24 h View Scheme
Multi-step reaction with 5 steps 1: 90 percent / aq. NaOH, NaI, n-Bu4NI / toluene / 24 h / 50 °C 2: 1.) Et3N, 2.) NaBH(OAc)3 / 1) CH2Cl2, rt, 15 min; 2) CH2Cl2, rt, 12 h 3: 68 percent / pivalic acid / 5 h / 150 °C 4: 1.) NaH / 1) THF, rt, 1 h; 2) THF, 0 deg C, 5 min, rt, 20 h 5: Ni(aca)2 / tetrahydrofuran / Heating View Scheme
Multi-step reaction with 5 steps 1: 90 percent / aq. NaOH, NaI, n-Bu4NI / toluene / 24 h / 50 °C 2: 1.) Et3N, 2.) NaBH(OAc)3 / 1) CH2Cl2, rt, 15 min; 2) CH2Cl2, rt, 12 h 3: 68 percent / pivalic acid / 5 h / 150 °C 4: 1.) NaH / 1) THF, rt, 1 h; 2) THF, 0 deg C, 5 min, rt, 20 h 5: Ni(aca)2 / tetrahydrofuran / Heating View Scheme

2,2-dimethyl-5-phenylpent-4-ynal (197963-29-4) → 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) Et3N, 2.) NaBH(OAc)3 / 1) CH2Cl2, rt, 15 min; 2) CH2Cl2, rt, 12 h 2: 68 percent / pivalic acid / 5 h / 150 °C 3: 1.) NaH / 1) THF, rt, 1 h; 2) THF, 0 deg C, 5 min, rt, 20 h 4: 15 percent / Pd(PPh3)4, aq. KOH / tetrahydrofuran / 1) rt, overnight; 2) reflux, 24 h View Scheme
Multi-step reaction with 4 steps 1: 1.) Et3N, 2.) NaBH(OAc)3 / 1) CH2Cl2, rt, 15 min; 2) CH2Cl2, rt, 12 h 2: 68 percent / pivalic acid / 5 h / 150 °C 3: 1.) NaH / 1) THF, rt, 1 h; 2) THF, 0 deg C, 5 min, rt, 20 h 4: Ni(aca)2 / tetrahydrofuran / Heating View Scheme
Multi-step reaction with 4 steps 1: 1.) Et3N, 2.) NaBH(OAc)3 / 1) CH2Cl2, rt, 15 min; 2) CH2Cl2, rt, 12 h 2: 68 percent / pivalic acid / 5 h / 150 °C 3: 1.) NaH / 1) THF, rt, 1 h; 2) THF, 0 deg C, 5 min, rt, 20 h 4: Ni(aca)2 / tetrahydrofuran / Heating View Scheme

2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) → 2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-5,6-dihydro-pyrrolizin-3-one

Conditions	Yield
Stage #1: 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine With dipotassium peroxodisulfate; acetic acid; [2,2]bipyridinyl; palladium diacetate at 20 - 100℃; for 8h; Stage #2: With sodium carbonate In water pH=7;	88%

methanol (67-56-1) + 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) + trichloromethyl chloroformate (503-38-8) → 6-(4-chlorophenyl)-2,3-dihydro-2,2-dimethyl-7-phenyl-1H-pyrrolizine-5-carboxylic acid methyl ester (262426-69-7)

Conditions	Yield
Stage #1: 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine; trichloromethyl chloroformate With triethylamine In tetrahydrofuran at 20℃; for 7h; Stage #2: methanol In tetrahydrofuran at 20℃; for 12h;	84%

methyl 2-iodoacetate (5199-50-8) + 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) → methyl 2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl)acetate (1061179-20-1)

Conditions	Yield
With dihydrogen peroxide; iron(II) sulfate; dimethyl sulfoxide In water at 10 - 20℃; for 0.25h; Product distribution / selectivity; Cooling with cold water bath;	78%
With dihydrogen peroxide; iron(II) sulfate; dimethyl sulfoxide; sodium iodide at 10 - 20℃; for 0.333333h; Product distribution / selectivity; Cooling with cold water bath;	45%
With dihydrogen peroxide; iron(II) sulfate In dimethyl sulfoxide for 1h;

2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) + ethyl iodoacetae (623-48-3) → ethyl 2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl)acetate (156897-35-7)

Conditions	Yield
With dihydrogen peroxide; iron(II) sulfate In dimethyl sulfoxide for 1h;	78%
With dihydrogen peroxide; iron(II) sulfate; dimethyl sulfoxide In water; acetonitrile at 5 - 18℃; for 0.25h; Product distribution / selectivity; Cooling with cold water bath;	59%
With dihydrogen peroxide; iron(II) sulfate; dimethyl sulfoxide In water at 10 - 20℃; for 0.25 - 2h; Product distribution / selectivity; Cooling with cold water bath;	51%

ethyl bromoacetate (105-36-2) + 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) → ethyl 2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl)acetate (156897-35-7)

Conditions	Yield
With dihydrogen peroxide; iron(II) sulfate; sodium iodide In dimethyl sulfoxide for 1h;	75%

propionic acid anhydride (123-62-6) + 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) → 1-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)propan-1-one (1281816-31-6)

Conditions	Yield
With aluminum (III) chloride In diethyl ether at 20℃; Inert atmosphere;	73.2%

hexyl iodoacetate (5436-99-7) + 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) → hexyl 2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl)acetate

Conditions	Yield
With dihydrogen peroxide; iron(II) sulfate; dimethyl sulfoxide In water at 10 - 20℃; for 0.25h; Product distribution / selectivity; Cooling with cold water bath;	73%

iodoacetonitrile (624-75-9) + 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) → 2-[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl]acetonitrile (1061179-18-7)

Conditions	Yield
With dihydrogen peroxide; iron(II) sulfate In dimethyl sulfoxide for 4.5h;	65%
With dihydrogen peroxide; iron(II) sulfate; dimethyl sulfoxide In water at 10 - 20℃; for 0.25h; Product distribution / selectivity; Cooling with cold water bath;	65%

bromoacetic acid tert-butyl ester (5292-43-3) + 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) → [6-(4-chlorophenyl)-2,3-dihydro-2,2-dimethyl-7-phenyl-1H-pyrrolizin-5-yl]acetic acid tert-butyl ester (262426-70-0)

Conditions	Yield
With dihydrogen peroxide; iron(II) sulfate; sodium iodide In dimethyl sulfoxide; acetonitrile for 10h;	62%

t-butyl iodoacetate (49827-15-8) + 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) → [6-(4-chlorophenyl)-2,3-dihydro-2,2-dimethyl-7-phenyl-1H-pyrrolizin-5-yl]acetic acid tert-butyl ester (262426-70-0)

Conditions	Yield
With dihydrogen peroxide; iron(II) sulfate; dimethyl sulfoxide In water at 10 - 20℃; for 0.25 - 1.83333h; Product distribution / selectivity; Cooling with cold water bath;	60%
With dihydrogen peroxide; iron(II) sulfate In dimethyl sulfoxide for 10h;

chloroacetyl chloride (79-04-9) + 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) → 2-chloro-1-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)ethanone (1281816-34-9)

Conditions	Yield
With boron trifluoride diethyl etherate In diethyl ether at 20℃; Inert atmosphere;	59.3%
With boron trifluoride diethyl etherate at 20℃; for 3h; Inert atmosphere;	59%

bromoacetic acid methyl ester (96-32-2) + 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) → methyl 2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl)acetate (1061179-20-1)

Conditions	Yield
With dihydrogen peroxide; iron(II) sulfate; sodium iodide In dimethyl sulfoxide for 1h;	57%

n-hexanoic anhydride (2051-49-2) + 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) → 1-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)hexan-1-one (1281816-32-7)

Conditions	Yield
With boron trifluoride diethyl etherate In diethyl ether at 20℃; Inert atmosphere;	56.3%

2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) + dibenzoyl peroxide (94-36-0) → benzoic acid [2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl] ester

Conditions	Yield
Stage #1: 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine With tert.-butyl lithium In diethyl ether; pentane at -70 - 20℃; for 3h; Stage #2: dibenzoyl peroxide In diethyl ether; pentane at -70 - 20℃; for 16 - 29h;	53%

acetic anhydride (108-24-7) + 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) → 1-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)ethanone (1281816-29-2)

Conditions	Yield
With aluminum (III) chloride In diethyl ether at 20℃; Inert atmosphere;	43.2%

2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) + diazo-<2-(14)C>-acetic acid ethylester → C24(14)CH26ClNO2

Conditions	Yield
With copper In tetrahydrofuran for 1h; Heating;	26.5%

diazoacetic acid ethyl ester (623-73-4) + 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) → ethyl 2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl)acetate (156897-35-7)

Conditions	Yield
With copper In toluene for 0.25h; Heating;

2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) → licofelone (156897-06-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: Cu / toluene / 0.25 h / Heating 2: 75.5 percent / 10percent aq. NaOH / ethanol / 0.17 h / Heating View Scheme
Multi-step reaction with 2 steps 1.1: tetrahydrofuran / 10 - 15 °C 1.2: 0.33 h / 25 - 30 °C 2.1: hydrazine hydrate; potassium hydroxide / ethylene diglycol / 7 h / 85 - 145 °C View Scheme
Multi-step reaction with 3 steps 1: tetrahydrofuran / 10 - 15 °C 2: water / tetrahydrofuran / 0.33 h / 25 - 30 °C 3: hydrazine hydrate; potassium hydroxide / diethylene glycol / 7 h / 85 - 145 °C View Scheme
Multi-step reaction with 2 steps 1.1: tetrahydrofuran / 18 - 25 °C / Inert atmosphere 1.2: 0.33 h / 25 - 30 °C 2.1: hydrazine hydrate; potassium hydroxide / diethylene glycol / 50 - 145 °C View Scheme

oxalyl dichloride (79-37-8) + 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) → licofelone (156897-06-2)

Conditions	Yield
Stage #1: oxalyl dichloride; 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine In tetrahydrofuran at 10 - 25℃; for 0.5 - 0.75h; Stage #2: With water In tetrahydrofuran at 0 - 30℃; for 0.0833333 - 0.166667h; Stage #3: With hydrogenchloride; potassium hydroxide; hydrazine more than 3 stages;

Reaxys ID: 19180192 + 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5) → Reaxys ID: 19180191

Conditions	Yield
With dihydrogen peroxide; iron(II); dimethyl sulfoxide

Upstream product

• 1003-85-6 5.5-dimethyl-1,3,2-dioxathiane-2-oxide 
• 103804-80-4 3,3-dimethyl-4-hydroxy butyronitrile 
• 126-30-7 2,2-Dimethyl-1,3-propanediol 
• 116673-94-0 4-chloro-3,3-dimethylbutyronitrile 
• 100-44-7 benzyl chloride 
• 825-40-1 2-bromo-p-chloroacetophenone 
• 116673-95-1 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole 
• 536-38-9 4-chlorobenzoylmethyl bromide 
• 197963-30-7 methyl N-(2,2-dimethyl-5-phenylpent-4-ynyl)glycinate 
• 197963-31-8 2,2-dimethyl-7-phenyl-2,3,5,6-tetrahydro-1H-pyrrolizin-6-one 
• 197963-29-4 2,2-dimethyl-5-phenylpent-4-ynal 
• 3355-31-5 1-chloro-3-phenyl-2-propyne 
• 873-77-8 (4-chlorphenyl)magnesium bromide 
• 226900-35-2 diethyl 2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-6-yl phosphate 

Downstream Products

• 156897-06-2 licofelone 
• 262426-69-7 6-(4-chlorophenyl)-2,3-dihydro-2,2-dimethyl-7-phenyl-1H-pyrrolizine-5-carboxylic acid methyl ester 
• 1281816-32-7 1-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)hexan-1-one 
• 1281816-29-2 1-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)ethanone 
• 1281816-31-6 1-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)propan-1-one 
• 1281816-34-9 2-chloro-1-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)ethanone 
• 1281816-35-0 2-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)-2-oxoethyl formate 
• 1281816-36-1 2-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)-2-oxoethyl acetate 
• 1281816-37-2 2-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)-2-oxoethyl propionate 
• 1281816-39-4 2-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)-2-oxoethyl 4-chlorobenzoate 
• 1281816-41-8 2-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)-2-oxoethyl 4-methoxybenzoate 
• 1281816-43-0 2-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)-2-oxoethyl 4-methylbenzoate 
• 1281816-44-1 2-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)-2-oxoethyl 4-nitrobenzoate 
• 1281816-45-2 2-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)-2-oxoethyl 3-chlorobenzoate 

Relevant articles and documents

Investigations on cytotoxicity and anti-inflammatory potency of licofelone derivatives

A series of C5-substituted licofelone ([2,2-dimethyl-6-(4-chlorophenyl)-7- phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]acetic acid) derivatives were developed by a parallel synthesis approach and investigated for cytotoxicity against MCF-7 and MDA-MB-231 cells as well as for anti-inflammatory potency in vitro and in vivo. Dependent on the C5-substituent, the compounds showed high selectivity for MCF-7 cells. Especially 2-oxoethyl benzoate derivatives were inactive at the MDA-MB-231 cell line and as active as 5-FU at MCF-7 cells. C5-acetyl (8a), -2-oxoethyl formiate (8e), -2-oxoethyl acetate (8f) and -2-oxoethyl propionate (8g) derivatives showed growth inhibition at both cell lines, comparable with cisplatin. Modifications significantly reduced the inhibitory potency at COX-1 and COX-2 in vitro and in the xylene-induced ear swelling assay in mice. Only compound 8a was equipotent to licofelone, ibuprofen and celecoxibe in vivo.

Synthesis and biological evaluation of licofelone derivatives as anticancer and anti-inflammatory agents

Two C5-substituted licofelone derivatives were developed and investigated for cytotoxicity against mammary (MCF-7 and MDA-MB 231) as well as colon carcinoma (HT-29) cancer cells. Both compounds were at least 2-fold more active than 5-fluorouracil (5-FU) and licofelone against mammary carcinoma cells. At HT-29 cells, they were less active, but nevertheless distinctly as active as 5-FU and still 2-fold more active than licofelone. However, variation of the C5- carboxylic group results in an occasionally remarkable decrease of anti-inflammatory potency in in vitro and in vivo.

Arylpyrrolizines as inhibitors of microsomal prostaglandin E2 synthase-1 (mPGES-1) or as dual inhibitors of mPGES-1 and 5-lipoxygenase (5-LOX)

We synthesized and evaluated inhibitors for the microsomal prostaglandin E2 synthase-1 (mPGES-1), based on the arylpyrrolizine scaffold. In a cell free mPGES-1 assay several "sulfonimides" exceeded our leadML3000 (3) in potency. The most promising compound, the tolylsulfonimide 11f, revealed an IC50 of 2.1 μM and is equipotent to the literature reference molecule MK886 (1). Selected compounds also potently reduced 5-LOX product formation in intact cells. Inhibition of isolated COX was occasionally remarkably cut down.