24526-64-5

Basic information

• Product Name: NOMIFENSINE MALEATE
• Synonyms: 1,2,3,4-tetrahydro-2-methyl-4-phenyl-8-isoquinolinamin;1,2,3,4-tetrahydro-8-amino-2-methyl-4-phenyl-isoquinolin;2-Methyl-4-phenyl-1,2,3,4-tetrahydro-8-isoquinolinamine;8-Amino-1,2,3,4-tetrahydro-2-methyl-4-phenylisoquinoline;8-Amino-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline;8-Isoquinolinamine, 1,2,3,4-tetrahydro-2-methyl-4-phenyl-;linamiphen;Nomifenison
• CAS NO: 24526-64-5
• Molecular Formula: C₁₆H₁₈N₂
• Molecular Weight: 238.32752
• Product Categories: Amines;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 24526-64-5.mol

Chemical Properties

• Melting Point: 179-181°
• Boiling Point: 370.93°C (rough estimate)
• Flash Point: 164°C
• Appearance: /
• Density: 0.9597 (rough estimate)
• Vapor Pressure: 6.28E-06mmHg at 25°C
• Refractive Index: 1.5000 (estimate)
• Storage Temp.: 2-8°C(protect from light)
• PKA: 7.85±0.40(Predicted)
• CAS DataBase Reference: NOMIFENSINE MALEATE(CAS DataBase Reference)
• NIST Chemistry Reference: NOMIFENSINE MALEATE(24526-64-5)
• EPA Substance Registry System: NOMIFENSINE MALEATE(24526-64-5)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38
• Safety Statements: 26-36
• RIDADR: 3249
• WGK Germany: 3
• RTECS: NX4912800
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 24526-64-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
NOMIFENSINE MALEATE is used as an antidepressant for treating depressive disorders. It is particularly effective due to its unique bicyclic structure, which distinguishes it from existing tricyclic and tetracyclic antidepressants. The compound's ability to inhibit the reuptake of NE, DA, and 5-HT contributes to its antidepressant activity, making it a valuable option for patients suffering from depression.
Additionally, NOMIFENSINE MALEATE has demonstrated potential in modulating various signaling pathways related to depression, which could further enhance its therapeutic effects. Its selectivity for inhibiting NE and DA uptake over binding to other receptors may also contribute to a more favorable side effect profile compared to other antidepressants.

Originator

Alival,Hoechst,W. Germany ,1976

Manufacturing Process

A solution of N-(2-aminobenzyl)-1-phenyl-2-methylaminoethanol-1 was prepared by the reaction of α-bromo-acetophenone and (2nitrobenzyl)methylamine, followed by hydrogenation of the nitro group by means of nickel on diatomaceous earth at room temperature and reduction of the CO group by means of sodium borohydride. The intermediate thus produced was dissolved in 100 ml of methylene chloride and introduced dropwise into 125 ml of sulfuric acid at 10° to 15°C. After a short standing, the reaction mixture was poured onto ice and rendered alkaline by means of a sodium hydroxide solution. By extraction with ether, there was obtained 1,2,3,4-tetrahydro-2-methyl-4-phenyl-8-amino-isoquinoline. The base is reacted with maleic acid to give the maleate; melting point of the maleate 199° to 201°C (from ethanol).

Therapeutic Function

Psychostimulant

World Health Organization (WHO)

Nomifensine, an antidepressant indicated for the treatment of a wide range of depressive illness, was introduced in 1976. Subsequently rare cases of haemolytic anaemia - sometimes fatal - thrombocytopenia, hepatotoxicity and fever were associated with the use of the drug. Following discussions with regulatory authorities in the United Kingdom and the Federal Republic of Germany the major manufacturer withdrew all preparations containing nomifensine worldwide in January 1986.

Safety Profile

Poison by ingestion andintravenous routes. Human systemic effects by ingestion:diffuse hepatitis, hemorrhage and decrease in the numberof blood platelets (thrombocytopenia). When heated todecomposition it emits toxic fumes of NOx.

InChI:InChI=1/C16H18N2/c1-18-10-14(12-6-3-2-4-7-12)13-8-5-9-16(17)15(13)11-18/h2-9,14H,10-11,17H2,1H3

Synthetic route

styrene oxide (96-09-3) + (2-nitrobenzyl)methylamine (56222-08-3) → nomifensine (24526-64-5)

Conditions	Yield
Yield given. Multistep reaction;

N-(2-Aminobenzyl)-2-(methylamino)-1-phenyl-1-ethanol (65514-97-8) → nomifensine (24526-64-5)

Conditions	Yield
With hydrogenchloride; sulfuric acid; zinc 1) EtOH, 0 - 5 deg C, 2) CH2Cl2, r.t., 10 - 12 h; Yield given. Multistep reaction;
With sulfuric acid In dichloromethane at 6 - 8℃; for 0.5h;
With sulfuric acid In dichloromethane at 0 - 20℃; for 0.333333h;

(2-nitrobenzyl)methylamine (56222-08-3) → nomifensine (24526-64-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 93 percent / triethylamine / diethyl ether / 4 h / 18 - 25 °C 2: 88 percent / NaBH4 / methanol; H2O / 4 h / Ambient temperature 3: 87 percent / H2 / Raney nickel / ethanol / 12 h / 760 Torr 4: conc. H2SO4 / CH2Cl2 / 0.5 h / 6 - 8 °C View Scheme

2-acetophenone (102436-67-9) → nomifensine (24526-64-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 88 percent / NaBH4 / methanol; H2O / 4 h / Ambient temperature 2: 87 percent / H2 / Raney nickel / ethanol / 12 h / 760 Torr 3: conc. H2SO4 / CH2Cl2 / 0.5 h / 6 - 8 °C View Scheme

α-bromoacetophenone (70-11-1) + KOH → nomifensine (24526-64-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 93 percent / triethylamine / diethyl ether / 4 h / 18 - 25 °C 2: 88 percent / NaBH4 / methanol; H2O / 4 h / Ambient temperature 3: 87 percent / H2 / Raney nickel / ethanol / 12 h / 760 Torr 4: conc. H2SO4 / CH2Cl2 / 0.5 h / 6 - 8 °C View Scheme

N-(2-Nitrobenzyl)-2-(methylamino)-1-phenyl-1-ethanol (85660-33-9) → nomifensine (24526-64-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 87 percent / H2 / Raney nickel / ethanol / 12 h / 760 Torr 2: conc. H2SO4 / CH2Cl2 / 0.5 h / 6 - 8 °C View Scheme

2-[(2-Amino-benzyl)-methyl-amino]-1-phenyl-ethanone (119810-30-9) → nomifensine (24526-64-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaBH4 / 3 h / Ambient temperature 2: 1) zinc, conc. HCl, 2) 98percent H2SO4 / 1) EtOH, 0 - 5 deg C, 2) CH2Cl2, r.t., 10 - 12 h View Scheme
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / ethanol / 1.5 h / 0 - 20 °C 2: sulfuric acid / dichloromethane / 0.33 h / 0 - 20 °C View Scheme

1-chloroacetophenone (532-27-4) → nomifensine (24526-64-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: methanol / Ambient temperature 2: NaBH4 / 3 h / Ambient temperature 3: 1) zinc, conc. HCl, 2) 98percent H2SO4 / 1) EtOH, 0 - 5 deg C, 2) CH2Cl2, r.t., 10 - 12 h View Scheme

2-amino-N-methylbenzylamine (1904-69-4) → nomifensine (24526-64-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: methanol / Ambient temperature 2: NaBH4 / 3 h / Ambient temperature 3: 1) zinc, conc. HCl, 2) 98percent H2SO4 / 1) EtOH, 0 - 5 deg C, 2) CH2Cl2, r.t., 10 - 12 h View Scheme
Multi-step reaction with 3 steps 1: methanol / 0.5 h / Ambient temperature 2: NaBH4 / 3 h / Ambient temperature 3: 1) zinc, conc. HCl, 2) 98percent H2SO4 / 1) EtOH, 0 - 5 deg C, 2) CH2Cl2, r.t., 10 - 12 h View Scheme
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: sodium tetrahydroborate / ethanol / 1.5 h / 0 - 20 °C 3: sulfuric acid / dichloromethane / 0.33 h / 0 - 20 °C View Scheme

α-bromoacetophenone (70-11-1) → nomifensine (24526-64-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: methanol / 0.5 h / Ambient temperature 2: NaBH4 / 3 h / Ambient temperature 3: 1) zinc, conc. HCl, 2) 98percent H2SO4 / 1) EtOH, 0 - 5 deg C, 2) CH2Cl2, r.t., 10 - 12 h View Scheme

2-nitro-benzaldehyde (552-89-6) → nomifensine (24526-64-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: NaBH4 / methanol; H2O / 1 h / Ambient temperature 2: methanol / Ambient temperature 3: NaBH4 / 3 h / Ambient temperature 4: 1) zinc, conc. HCl, 2) 98percent H2SO4 / 1) EtOH, 0 - 5 deg C, 2) CH2Cl2, r.t., 10 - 12 h View Scheme
Multi-step reaction with 4 steps 1: NaBH4 / methanol; H2O / 1 h / Ambient temperature 2: methanol / 0.5 h / Ambient temperature 3: NaBH4 / 3 h / Ambient temperature 4: 1) zinc, conc. HCl, 2) 98percent H2SO4 / 1) EtOH, 0 - 5 deg C, 2) CH2Cl2, r.t., 10 - 12 h View Scheme

2-aminobenzaldehyde (529-23-7) → nomifensine (24526-64-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: methanol; water / 0.33 h / 20 °C 2: sodium tetrahydroborate / methanol; water / 2.5 h / 0 - 20 °C 3: triethylamine / dichloromethane / 18 h / 20 °C 4: sodium tetrahydroborate / ethanol / 1.5 h / 0 - 20 °C 5: sulfuric acid / dichloromethane / 0.33 h / 0 - 20 °C View Scheme

(2-amino-benzylidene)-methyl-amine (66486-62-2) → nomifensine (24526-64-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium tetrahydroborate / methanol; water / 2.5 h / 0 - 20 °C 2: triethylamine / dichloromethane / 18 h / 20 °C 3: sodium tetrahydroborate / ethanol / 1.5 h / 0 - 20 °C 4: sulfuric acid / dichloromethane / 0.33 h / 0 - 20 °C View Scheme

nomifensine (24526-64-5) → 2-methyl-4-phenyl-1,2,3,4-tetrahydro-8-isoquinoline diazonium-bis

Conditions	Yield
With tetrafluoroboric acid; sodium nitrite In water at -5℃; for 2h;	96%

acetic anhydride (108-24-7) + nomifensine (24526-64-5) → N-(2-Methyl-4-phenyl-1,2,3,4-tetrahydro-8-isochinolyl)-acetamid (63806-80-4)

Conditions	Yield
	93%

nomifensine (24526-64-5) + chloroacetyl chloride (79-04-9) → 4-phenyl-8-<(chloroacetyl)amino>-2-methyl-1,2,3,4-tetrahydroisoquinoline (99633-72-4)

Conditions	Yield
With potassium carbonate In acetone for 0.5h; Heating;	87%

2-chloroacetylisocyanate (4461-30-7) + nomifensine (24526-64-5) → 8-(N'-chloroacetylureido)-4-phenyl-2-methyl-1,2,3,4-tetrahydroisoquinoline (129053-99-2)

Conditions	Yield
In tetrahydrofuran Ambient temperature; 1.) 10 min, 5 deg C; 2.) 24 h, roomtemperature;	73.8%

ammonium hydroxide (1336-21-6) + nomifensine (24526-64-5) + carbonochloridic acid, butyl ester (592-34-7) → 8-butoxycarbonyl-amino-4-phenyl-2-methyl-1,2,3,4-tetrahydro-isoquinoline

Conditions	Yield
In benzene	52.9%

β-chloro-ethyl-chloro-formiate + nomifensine (24526-64-5) → 8-β-chloroethoxycarbonyl-amino-4-phenyl-2-methyl-1,2,3,4-tetrahydro-isoquinoline

Conditions	Yield
With pyridine In ethanol; water; benzene	52%

chloroformic acid ethyl ester (541-41-3) + nomifensine (24526-64-5) → 8-<(ethoxycarbonyl)amino>-4-phenyl-2-methyl-1,2,3,4-tetrahydroisoquinoline

Conditions	Yield
With sodium hydroxide In water; benzene	37.5%

nomifensine (24526-64-5) + maleic acid (110-16-7) → 2-Methyl-4-phenyl-8-chlor-1,2,3,4-tetrahydroisochinolin hydrogenmaleat (118411-64-6)

Conditions	Yield
Yield given. Multistep reaction;

nomifensine (24526-64-5) + Ethoxycarbonyl isothiocyanate (16182-04-0) → N1-Aethoxycarbonyl-N2-(2-methyl-4-phenyl-1,2,3,4-tetrahydroisochinol-8-yl)thioharnstoff (80947-21-3)

Conditions	Yield
In dichloromethane for 2h; Ambient temperature;	61.5 g

nomifensine (24526-64-5) → 8-azido-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline

Conditions	Yield
With hydrogenchloride; sodium azide; sodium nitrite 1.) water, -5 deg C, 30 min; 2.) water, 0 deg C, 1 h; Yield given. Multistep reaction;

nomifensine (24526-64-5) → 8-hydroxy-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline (129010-60-2)

Conditions	Yield
With nitrosylsulfuric acid; cyclohexane; sodium hydrogencarbonate 1.) glacial acetic acid, 0 deg C to 10 deg C, 30 min; 2.) water, reflux 100 deg C, 30 min; Yield given. Multistep reaction;

nomifensine (24526-64-5) → (R)-(-)-2-Methyl-4-phenyl-8-amino-1,2,3,4-tetrahydroisochinolin (89664-20-0)

nomifensine (24526-64-5) → (S)-(+)-2-Methyl-4-phenyl-8-amino-1,2,3,4-tetrahydroisochinolin (89664-18-6)

nomifensine (24526-64-5) → 8-Amino-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-1-ol (122246-73-5)

Conditions	Yield
With Hg(II)-EDTA In ethanol Yield given;

nomifensine (24526-64-5) → 2-Methyl-1-oxo-4-phenyl-1,2-dihydro-8-isochinolylacetamid

Conditions	Yield
Multi-step reaction with 2 steps 1: 93 percent 2: 1.) Hg(II)-EDTA, 2.) OH(1-) / 1.) aq. EtOH, 2.) 6 h View Scheme

nomifensine (24526-64-5) → N-(1-Cyano-2-methyl-4-phenyl-1,2,3,4-tetrahydro-8-isochinolinyl)-acetamid

Conditions	Yield
Multi-step reaction with 3 steps 1: 93 percent 2: 1.) Hg(II)-EDTA, 2.) OH(1-) / 1.) aq. EtOH, 2.) 6 h 3: H2O View Scheme
Multi-step reaction with 3 steps 1: 93 percent 2: Hg(II)-EDTA / aq. ethanol 3: H2O View Scheme

nomifensine (24526-64-5) → 8-Acetamido-2-methyl-4-phenyl-3,4-dihydroisochinoliniumiodid

Conditions	Yield
Multi-step reaction with 3 steps 1: 93 percent 2: 1.) Hg(II)-EDTA, 2.) OH(1-) / 1.) aq. EtOH, 2.) 6 h 3: KI, 2percent aq. HCl View Scheme
Multi-step reaction with 3 steps 1: 93 percent 2: Hg(II)-EDTA / aq. ethanol 3: KI, 2percent aq. HCl View Scheme

nomifensine (24526-64-5) → 1,1'-Iminobis-(2-methyl-4-phenyl-1,2,3,4-tetrahydro-8-isochinolylacetamid)

Conditions	Yield
Multi-step reaction with 2 steps 1: 93 percent 2: 1.) Hg(II)-EDTA, 2.) conc. NH3 View Scheme

nomifensine (24526-64-5) → N-(1-Hydroxy-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-acetamide (122246-76-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 93 percent 2: 1.) Hg(II)-EDTA, 2.) OH(1-) / 1.) aq. EtOH, 2.) 6 h View Scheme
Multi-step reaction with 2 steps 1: 93 percent 2: Hg(II)-EDTA / aq. ethanol View Scheme

nomifensine (24526-64-5) → N-<2-(2-Chinolon-5-yl)-2-phenyl-ethyl>-N-methyl-acetamid

Conditions	Yield
Multi-step reaction with 4 steps 1: Hg(II)-EDTA / aq. ethanol 2: HClO4 3: pyridine / 0.25 h / Heating 4: pyridine / 6 h / Heating View Scheme

nomifensine (24526-64-5) → 8-Amino-2-methyl-4-phenyl-3,4-dihydroisochinoliniumperchlorat

Conditions	Yield
Multi-step reaction with 2 steps 1: Hg(II)-EDTA / aq. ethanol 2: HClO4 View Scheme

nomifensine (24526-64-5) → 4-Methyl-6-phenyl-2,3,3a,4,5,6-hexahydro-1,4-diazaphenalen-2-on

Conditions	Yield
Multi-step reaction with 3 steps 1: Hg(II)-EDTA / aq. ethanol 2: HClO4 3: pyridine / 0.25 h / Heating View Scheme

nomifensine (24526-64-5) → 2-Dimethylamino-N-(2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-acetamide; hydrochloride (99633-73-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 87 percent / K2CO3 / acetone / 0.5 h / Heating 2: benzene / 72 h / Ambient temperature 3: ethanolic HCl / ethanol View Scheme

Upstream product

• 96-09-3 styrene oxide 
• 56222-08-3 (2-nitrobenzyl)methylamine 
• 65514-97-8 N-(2-Aminobenzyl)-2-(methylamino)-1-phenyl-1-ethanol 
• 102436-67-9 2-acetophenone 
• 70-11-1 α-bromoacetophenone 
• 85660-33-9 N-(2-Nitrobenzyl)-2-(methylamino)-1-phenyl-1-ethanol 
• 119810-30-9 2-[(2-Amino-benzyl)-methyl-amino]-1-phenyl-ethanone 
• 532-27-4 1-chloroacetophenone 
• 1904-69-4 2-amino-N-methylbenzylamine 
• 552-89-6 2-nitro-benzaldehyde 
• 66486-62-2 (2-amino-benzylidene)-methyl-amine 
• 529-23-7 o-aminobenzaldehyde 

Downstream Products

• 63806-80-4 N-(2-Methyl-4-phenyl-1,2,3,4-tetrahydro-8-isochinolyl)-acetamid 
• 129053-99-2 8-(N'-chloroacetylureido)-4-phenyl-2-methyl-1,2,3,4-tetrahydroisoquinoline 
• 99633-72-4 4-phenyl-8-<(chloroacetyl)amino>-2-methyl-1,2,3,4-tetrahydroisoquinoline 
• 118411-64-6 2-Methyl-4-phenyl-8-chlor-1,2,3,4-tetrahydroisochinolin hydrogenmaleat 
• 129010-60-2 8-hydroxy-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline 
• 89664-20-0 (R)-(-)-2-Methyl-4-phenyl-8-amino-1,2,3,4-tetrahydroisochinolin 
• 89664-18-6 (S)-(+)-2-Methyl-4-phenyl-8-amino-1,2,3,4-tetrahydroisochinolin 
• 122246-73-5 8-Amino-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-1-ol 
• 122246-76-8 N-(1-Hydroxy-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-acetamide 
• 99633-73-5 2-Dimethylamino-N-(2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-acetamide; hydrochloride 
• 99633-74-6 2-Diethylamino-N-(2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-acetamide; hydrochloride 
• 99633-75-7 N-(2-Methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-2-pyrrolidin-1-yl-acetamide; hydrochloride 
• 99633-78-0 N-(2-Methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-2-(4-methyl-piperazin-1-yl)-acetamide; hydrochloride 
• 91454-31-8 N-(2-Methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-2-piperidin-1-yl-acetamide; compound with (Z)-but-2-enedioic acid 

Relevant articles and documents

4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors

Novel 4-phenyl tetrahydroisoquinolines that inhibit both dopamine and norepinephrine transporters were designed and prepared. In this Letter, we describe the synthesis, in vitro activity and associated structure-activity relationships of this series. We also report the ex vivo NET occupancy of a representative compound, 41.

A New Synthesis of 1,2,3,4-Tetrahydro-2-methyl-4-phenylisoquinolines

1,2,3,4-Tetrahydro-2-methyl-4-phenylisoquinolines 6 are obtained from aromatic aldehydes 1, methyl amine and α-haloacetophenones 2 in the presence of sodium borohydride followed by cyclization with sulfuric acid and zinc in methanol.

An Improved Synthesis of 8-Amino-2-methyl-4-phenyl-1,2,3,4-Tetrahydroisoquinoline

The regioselectivity of the reaction of 2-nitrobenzylmethylamine (1) and styrenoxide (2) leading to a mixture of the isomeric aminoalcohols 3a and 3b has been studied.The course of the reaction strongly depends on the type of the solvent used as reaction medium.The highest selectivity (3a:3b=9:1) was achieved with a combination of polar aprotic and protic solvents (DMFA and ethanol). 1H n.m.r. spectroscopy was used for identification of the isomers as well as for the determination of their ratio in the crude reaction mixtures.The isomer ratio remains unaffected during catalytic reduction (Ra-Ni) of 3a/3b to a mixture of the correspondi ng aminoalcohols 4a and 4b.Pure 3a, 4a and 4b were independently synthesized for comparison.Cyclodehydration of crude 4a/4b mixtures gives 5 in a very good yield.

Synthesis and Pharmacological Evaluation of Some New Tetrahydroisoquinoline Derivatives Inhibiting Dopamine Uptake and/or Possessing a Dopaminomimetic Property

As shown by structure-activity relationship studies in 8-(substituted-amino)-4-aryl-2-methyl-1,2,3,4-tetrahydroisoquinolines, the most important structural requirement for a marked antidepressant action is a presence of an ureido, (alkoxycarbonyl)amino, or amino group attached to the isoquinoline skeleton in position 8.In one of the biological test a significant difference was found between 8-amino-4-phenyl-2-methyl-1,2,3,4-tetrahydroisoquinoline (nomifensine) and the new compounds synthesized.Nearly all compounds substituted in the amino group either decrease the spontaneous motility in mice or exert no effect on it.Two syntheses have been elaborated for the preparation of the compounds represented by the general formulas II-V where R1 = hydrogen, halogen, or methyl; Y = CONHR, OCOR, or CO(CH2)nNHR, in which R = alkyl or aralkyl or NHR = cyclic amine and n = 1-2.The syntheses start either from the corresponding 8-amino-4-aryl-2-methyl-1,2,3,4-tetrahydroisoquinolines or from the corresponding noncyclized amino alcohols.Of the compounds, 4-(p-chlorophenyl)-8--2-methyl-1,2,3,4-tetrahydroisoquinoline was found to possess the highest activity.