em 1-Benzhydryl-4-methyl-piperazine (Cyclizine) I /em This compound was prepared under a published method (16-19) after some required modification. continued for a longer period by II and III comparing to I, as discussed above. In addition, the data on vascular permeability in xylene-induced ear edema and acetic acid-induced to peritoneal cavity confirmed that substitutions on cyclizine molecule were more effective and could decrease the vascular permeability and acute inflammation. However, the results from the cotton pellet-induced granuloma formation in rats exposed that none of the medicines (I-III) were effective to reduce the reactions and intermediates of chronic swelling. strong class=”kwd-title” KEY PHRASES: Cyclizine, Piperazine derivative, H1-antihistamine, Acute and chronic, Anti-inflammation Intro Cyclizine (1-benzhydryl-4-methyl-piperazine, CAS 82-92-8, CYC, Number 1) is definitely a piperazine derivative which belongs to H1- antihistamine group of medicines (1). In addition to the antihistamine effects, their H1-receptor antagonists display such pharmacological properties as anti-inflammatory and anti-allergic effects, antiplatelet activities, and suppression of respiratory burst of professional phagocytes that are not uniformly distributed among this class of medicines (2-5). Open in a separate window Number 1 Structure formulas of Cyclizine (Cycl, I), 1-ethyl-4-[( em p /em -isopropylphenyl)( em p /em -tolyl) methyl]-piperazine (Cycl-1, II) and 1-(3, 4-dichlorophenyl)-4-[( em p /em -isopropylphenyl)( em p /em -tolyl) methyl]-piperazine (Cycl-2, III Most H1-antihistamines show an onset of action within 1 to 2 2 h after the administration and 24 h duration of action after a single dose. Maps for pharmacokinetic/pharmacodynamic relationship in H1-antihistamines define plasma concentration/activity relationship in these medications (6). Recently, our knowledge on histamine functions in specific activation or blockade of the receptor subtypes, both in physiology and pathology, has been dramatically increased. Among the four subtypes, histamine H1-receptor has been an attractive target to drug finding for several years. H1-receptor antagonists have been proved to be effective therapeutic providers in many diseases; hence, they may ZCL-278 be incorporated into an important class of available medicines (7). Inflammation is usually a disorder involving localized increase in numbers of leukocytes and varieties of complex mediator molecules (8). Prostaglandins are ubiquitous substances that demonstrate and modulate cell and tissue responses involved in inflammation. Their biosynthesis has also been implicated in the pathophysiology of cardiovascular diseases, cancer, colonic adenomas and Alzheimer (9). In this paper, two new (II and III) derivatives and intermediates (compounds 1-4) of I were synthesized to evaluate their acute and chronic anti-inflammatory activities using some known pharmacological procedures (10-15). Experimental em General /em 1-methyl piperazine, 1-ethyl piperazine, 1-(3,4-dichlorophenyl) piperazine, Magnesium turning, Diethyl ether, 4-bromo toluene, Benzaldehyde, 4-methyl Benzaldehyde, 4-isopropyl Benzaldehyde, Thionyl chloride and all other chemicals, were purchased from Merck chemical Co. (Darmstadt, Germany). Melting points (uncorrected) were decided with a digital electrothermal melting point apparatus (model 9100, Electrothermal Engineering Ltd., Essex, UK). 1H and 13C NMR spectra were recorded with a Bruker 300 MHz (model AMX, Karlsruhe, Germany) spectrometer (Internal Reference: TMS). IR spectra were recorded with a Thermo Nicolet FT-IR (model Nexus-870, Nicolet Instrument Corp, Madison, Wisconsin, U.S.A.) spectrometer. Mass spectra were also recorded with an Agilent Technologies 5973, Mass Selective Detector (MSD) spectrometer (Wilmigton, USA). Column chromatographic separations were performed over Acros silica gel (No.7631-86-9 particle size 35-70 micrometer, Geel, Belgium). Thirty-two adult male Wistar rats (Pasteur`s Institute, Tehran) weighing 250-300 g were subjected to the pharmacological testing. em Preparations ( /em Figures 1 em – /em ?33 em ) /em Open in a separate window Figure 3 Synthesis of intermediates 2 and 4 em Diphenylmethanol (Benzhydrol) (1) /em This compound was prepared under a published method (16, 17) after some required modification. Phenyl magnesium bromide was added drop-wise to the solution of benzaldehyde (10.6 g, 0.1 mol) in THF (50 mL), (prepared from 15.7 g bromobenzene and 2.43 g of Mg in 50 mL of dry ether) and refluxed for additional 118 h, poured into ice-NH4Cl, before the organic layer was separated, brine-washed, re-extracted with diethyl ether, dried over MgSO4 and evaporated under vacuum. A solid compound (m.p., 64-66C) was obtained (Physique 2). Open in a separate window Physique 2 Synthesis of intermediates 1 and 3 em Chlorodiphenylmethane (Benzhydryl chloride) (2) /em This compound was prepared under a published method (16, 17) after some required modification. The alcohol (1, 10.5 g, 0.05 mol) dissolved in dichloromethane (250 mL) and SOCl2 (8 mL, 0.11 mol) was added to the solution. The reaction mixture was refluxed for additional 210 h. The solvent was evaporated under vacuum. An obtained oily brown compound was used in the next step without further purification (highly sensitive to light) (Physique 3). em 1-Benzhydryl-4-methyl-piperazine (Cyclizine) I.Evidences suggest that H1-antihistamines generate anti-inflammatory and immune- modulatory activities that are too extensive to be explained by H1-receptor blockade (21, 22). confirmed that substitutions on cyclizine molecule were more effective and could decrease the vascular permeability and acute inflammation. However, the results from the cotton pellet-induced granuloma formation in rats revealed that none of the drugs (I-III) were effective to reduce the reactions and intermediates of chronic inflammation. strong class=”kwd-title” Key Words: Cyclizine, Piperazine derivative, H1-antihistamine, Acute and chronic, Anti-inflammation Introduction Cyclizine (1-benzhydryl-4-methyl-piperazine, CAS 82-92-8, CYC, Physique 1) is usually a piperazine derivative which belongs to H1- antihistamine group of drugs (1). In addition to the antihistamine effects, their H1-receptor antagonists show such pharmacological properties as anti-inflammatory and anti-allergic effects, antiplatelet activities, and suppression of respiratory burst of professional phagocytes that are not uniformly distributed among this class of drugs (2-5). Open in a separate window Physique 1 Structure formulas of Cyclizine (Cycl, I), 1-ethyl-4-[( em p /em -isopropylphenyl)( em p /em -tolyl) methyl]-piperazine (Cycl-1, II) and 1-(3, 4-dichlorophenyl)-4-[( em p /em -isopropylphenyl)( em p /em -tolyl) methyl]-piperazine (Cycl-2, III Most H1-antihistamines exhibit an onset of action within 1 to 2 2 h after the administration and 24 h duration of action after a single dose. Maps for pharmacokinetic/pharmacodynamic relationship in H1-antihistamines define plasma concentration/activity relationship in these medications (6). Recently, our knowledge on histamine roles in specific activation or blockade of the receptor subtypes, both in physiology and pathology, has been dramatically increased. Among the four subtypes, histamine H1-receptor has been an attractive target to drug discovery for several years. H1-receptor antagonists have been proved to be effective therapeutic brokers in many diseases; hence, they are incorporated into an important class of available drugs (7). Inflammation is usually a disorder involving localized increase in numbers of leukocytes and varieties of complex mediator molecules (8). Prostaglandins are ubiquitous substances that demonstrate and modulate cell and tissue responses involved in inflammation. Their biosynthesis has also been implicated in the pathophysiology of cardiovascular diseases, cancer, colonic adenomas and ZCL-278 Alzheimer (9). In this paper, two new (II and III) derivatives and intermediates (compounds 1-4) of I were synthesized to evaluate their acute and chronic anti-inflammatory activities using some known pharmacological procedures (10-15). Experimental em General /em 1-methyl piperazine, 1-ethyl piperazine, 1-(3,4-dichlorophenyl) piperazine, Magnesium turning, Diethyl ether, 4-bromo toluene, Benzaldehyde, 4-methyl Benzaldehyde, 4-isopropyl Benzaldehyde, Thionyl chloride and all other chemicals, were bought from Merck chemical substance Co. (Darmstadt, Germany). Melting factors (uncorrected) were established with an electronic electrothermal melting stage equipment (model 9100, Electrothermal Executive Ltd., Essex, UK). 1H and 13C NMR spectra had been recorded having a Bruker 300 MHz (model AMX, Karlsruhe, Germany) spectrometer (Internal Research: TMS). IR spectra had been recorded having a Thermo Nicolet FT-IR (model Nexus-870, Nicolet Device Corp, Madison, Wisconsin, U.S.A.) spectrometer. Mass spectra had been also documented with an Agilent Systems 5973, Mass Selective Detector (MSD) spectrometer (Wilmigton, USA). Column chromatographic separations had been performed over Acros silica gel (No.7631-86-9 particle size 35-70 micrometer, Geel, Belgium). Thirty-two adult man Wistar rats (Pasteur`s Institute, Tehran) weighing 250-300 g had been put through the pharmacological tests. em Arrangements ( /em Numbers 1 em – /em ?33 em ) /em Open up in another windowpane Figure 3 Synthesis of intermediates 2 and 4 em Diphenylmethanol (Benzhydrol) (1) /em This chemical substance was prepared less than a posted method (16, 17) following some needed modification. Phenyl magnesium bromide was added drop-wise to the perfect solution is of benzaldehyde (10.6 g, 0.1 mol) in THF (50 mL), (ready from 15.7 g bromobenzene and 2.43 g of Mg in 50 mL of dried out ether) and refluxed for more 118 h, poured into ice-NH4Cl, prior to the organic layer was separated, brine-washed, re-extracted with diethyl ether, dried over MgSO4 and evaporated under vacuum. A good substance (m.p., 64-66C) was acquired (Shape 2). Open up in another.Animals received free usage of water and regular lab rat chow (Pars Business, Tehran, Iran). cyclizine molecule had been more effective and may reduce the vascular permeability and severe inflammation. Nevertheless, the outcomes from the natural cotton pellet-induced granuloma development in rats exposed that none from the medicines (I-III) had been effective to lessen the reactions and intermediates of chronic swelling. strong course=”kwd-title” KEY PHRASES: Cyclizine, Piperazine derivative, H1-antihistamine, Acute and persistent, Anti-inflammation Intro Cyclizine (1-benzhydryl-4-methyl-piperazine, CAS 82-92-8, CYC, Shape 1) can be a piperazine derivative which belongs to H1- antihistamine band of medicines (1). As well as the antihistamine results, their H1-receptor antagonists display such pharmacological properties as anti-inflammatory and anti-allergic results, antiplatelet actions, and suppression of respiratory burst of professional phagocytes that aren’t uniformly distributed among this course of medicines (2-5). Open up in another window Shape 1 Framework formulas of Cyclizine (Cycl, I), 1-ethyl-4-[( em p /em -isopropylphenyl)( em p /em -tolyl) methyl]-piperazine (Cycl-1, II) and 1-(3, 4-dichlorophenyl)-4-[( em p /em -isopropylphenyl)( em p /em -tolyl) methyl]-piperazine (Cycl-2, III Many H1-antihistamines show an starting point of actions within one to two 2 h following the administration and 24 h duration of actions after an individual dosage. Maps for pharmacokinetic/pharmacodynamic romantic relationship in H1-antihistamines define plasma focus/activity romantic relationship in these medicines (6). Lately, our understanding on histamine tasks in particular activation or blockade from the receptor subtypes, both in physiology and pathology, continues to be dramatically improved. Among the four subtypes, histamine H1-receptor continues to be an attractive focus on to drug finding for quite some time. H1-receptor antagonists have already been became effective therapeutic real estate agents in many illnesses; hence, they may be incorporated into a significant class of obtainable medicines (7). Inflammation can be a disorder concerning localized upsurge in amounts of leukocytes and types of complicated mediator substances (8). Prostaglandins are ubiquitous chemicals that demonstrate and modulate cell and cells responses involved with swelling. Their biosynthesis in addition has been implicated in the pathophysiology of cardiovascular illnesses, tumor, colonic adenomas and Alzheimer (9). With this paper, two fresh (II and III) derivatives and intermediates (substances 1-4) of I had been synthesized to judge their severe and chronic anti-inflammatory actions using some known pharmacological techniques (10-15). Experimental em General /em 1-methyl piperazine, 1-ethyl piperazine, 1-(3,4-dichlorophenyl) piperazine, Magnesium turning, Diethyl ether, 4-bromo toluene, Benzaldehyde, 4-methyl Benzaldehyde, 4-isopropyl Benzaldehyde, Thionyl chloride and all the chemicals, were bought from Merck chemical substance Co. (Darmstadt, Germany). Melting factors (uncorrected) were driven with an electronic electrothermal melting stage equipment (model 9100, Electrothermal Anatomist Ltd., Essex, UK). 1H and 13C NMR spectra had been recorded using a Bruker 300 MHz (model AMX, Karlsruhe, Germany) spectrometer (Internal Guide: TMS). IR spectra had been recorded using a Thermo Nicolet FT-IR (model Nexus-870, Nicolet Device Corp, Madison, Wisconsin, U.S.A.) spectrometer. Mass spectra had been also documented with an Agilent Technology 5973, Mass Selective Detector (MSD) spectrometer (Wilmigton, USA). Column chromatographic separations had been performed over Acros silica gel (No.7631-86-9 particle size 35-70 micrometer, Geel, Belgium). Thirty-two adult man Wistar rats (Pasteur`s Institute, Tehran) weighing 250-300 g had been put through the pharmacological examining. em Arrangements ( /em Statistics 1 em – /em ?33 em ) /em Open up in another screen Figure 3 Synthesis of intermediates 2 and 4 em Diphenylmethanol (Benzhydrol) (1) /em This chemical substance was prepared in a posted method (16, 17) following some necessary modification. Phenyl magnesium bromide was added drop-wise to the answer of benzaldehyde (10.6 g, 0.1 mol) in THF (50 mL), (ready from 15.7 g bromobenzene and 2.43 g of Mg in 50 mL of dried out ether) and refluxed for extra 118 h, poured into ice-NH4Cl, prior to the organic layer was separated, brine-washed, re-extracted with diethyl ether, dried over MgSO4 and evaporated under vacuum. A good substance (m.p., 64-66C) was attained (Amount 2). Open up in another window Amount 2 Synthesis of intermediates 1 and 3 em Chlorodiphenylmethane (Benzhydryl chloride) (2) /em This substance was ready under a released technique (16, 17) after some needed modification. The alcoholic beverages (1, 10.5 g, 0.05 mol) dissolved in dichloromethane (250 mL) and SOCl2 (8 mL, 0.11.The mix was refluxed for extra 280 h. xylene-induced hearing edema and acetic acid-induced to peritoneal cavity verified that substitutions on cyclizine molecule had been more effective and may reduce the vascular permeability and severe inflammation. Nevertheless, the outcomes from the natural cotton pellet-induced granuloma development in rats uncovered that none from the medications (I-III) had been effective to lessen the reactions and intermediates of chronic irritation. strong course=”kwd-title” KEY TERM: Cyclizine, Piperazine derivative, H1-antihistamine, Acute and persistent, Anti-inflammation Launch Cyclizine (1-benzhydryl-4-methyl-piperazine, CAS 82-92-8, CYC, Amount 1) is normally a piperazine derivative which belongs to H1- antihistamine band of medications (1). As well as the antihistamine results, their H1-receptor antagonists present such pharmacological properties as anti-inflammatory and anti-allergic results, antiplatelet actions, and suppression of respiratory burst of professional phagocytes that aren’t uniformly distributed among this course of medications (2-5). Open up in another window Amount 1 Framework formulas of Cyclizine (Cycl, I), 1-ethyl-4-[( em p /em -isopropylphenyl)( em p /em -tolyl) methyl]-piperazine (Cycl-1, II) and 1-(3, 4-dichlorophenyl)-4-[( em p /em -isopropylphenyl)( em p /em -tolyl) methyl]-piperazine (Cycl-2, III Many H1-antihistamines display an starting point of actions within one to two 2 h following the administration and 24 h duration of actions after an individual dosage. Maps for pharmacokinetic/pharmacodynamic romantic relationship in H1-antihistamines define plasma focus/activity romantic relationship in these medicines (6). Lately, our understanding on histamine assignments in particular activation or blockade from the receptor subtypes, both in physiology and pathology, continues to be dramatically elevated. Among the four subtypes, histamine H1-receptor continues to be an attractive focus on to drug breakthrough for quite some time. H1-receptor antagonists have already been became effective therapeutic realtors in many illnesses; hence, these are incorporated into a significant class of obtainable medications (7). Inflammation is normally a disorder regarding localized upsurge in amounts of leukocytes and types of complicated mediator substances (8). Prostaglandins are ubiquitous chemicals that demonstrate and modulate cell and tissues responses involved with irritation. Their biosynthesis in addition has been implicated in the pathophysiology of cardiovascular illnesses, cancer tumor, colonic adenomas and Alzheimer (9). Within this paper, two brand-new (II and III) derivatives and intermediates (substances 1-4) of I had been synthesized to judge their severe and chronic anti-inflammatory actions using some known pharmacological techniques (10-15). Experimental em General /em 1-methyl piperazine, 1-ethyl piperazine, 1-(3,4-dichlorophenyl) piperazine, Magnesium turning, Diethyl ether, 4-bromo toluene, Benzaldehyde, 4-methyl Benzaldehyde, 4-isopropyl Benzaldehyde, Thionyl chloride and all the chemicals, were bought from Merck chemical substance Co. (Darmstadt, Germany). Melting factors (uncorrected) were motivated with an electronic electrothermal melting stage equipment (model 9100, Electrothermal Anatomist Ltd., Essex, UK). 1H and 13C NMR spectra had been recorded using a Bruker 300 MHz (model AMX, Karlsruhe, Germany) spectrometer (Internal Guide: TMS). IR spectra had been recorded using a Thermo Nicolet FT-IR (model Nexus-870, Nicolet Device Corp, Madison, Wisconsin, U.S.A.) spectrometer. Mass spectra had been also documented with an Agilent Technology 5973, Mass Selective Detector (MSD) spectrometer (Wilmigton, USA). Column chromatographic separations had been performed over Acros silica gel (No.7631-86-9 particle size 35-70 micrometer, Geel, Belgium). Thirty-two adult man Wistar rats (Pasteur`s Institute, Tehran) weighing 250-300 g had been put through the pharmacological examining. em Arrangements ( /em Statistics 1 em – /em ?33 em ) /em Open up in another home window Figure 3 Synthesis of intermediates 2 and 4 em Diphenylmethanol (Benzhydrol) (1) /em This chemical substance Sh3pxd2a was prepared in a posted method (16, 17) following some necessary modification. Phenyl magnesium bromide was added drop-wise to the answer of benzaldehyde (10.6 g, 0.1 mol) in THF (50 mL), (ready from 15.7 g bromobenzene and 2.43 g of Mg in 50 mL of dried out ether) and refluxed for extra 118 h, poured into ice-NH4Cl, prior to the organic layer was separated, brine-washed, re-extracted with diethyl ether, dried over MgSO4 and evaporated under vacuum. A good substance (m.p., 64-66C) was attained (Body 2). Open up in another window Body 2 Synthesis of intermediates 1 and 3 em Chlorodiphenylmethane (Benzhydryl chloride) (2) /em This substance was ready under a released technique (16, 17) after some needed modification. The alcoholic beverages (1, 10.5 g, 0.05 mol) dissolved in dichloromethane (250 mL) and SOCl2 (8 mL, 0.11 mol) was put into the answer. The reaction mix was refluxed for extra 210 h. The solvent was evaporated under vacuum. An attained oily brown substance was found in the next phase without further purification (extremely delicate to light) (Body 3). em 1-Benzhydryl-4-methyl-piperazine (Cyclizine) I /em This substance was ready under a released technique (16-19) after some needed adjustment. The benzhydryl chloride (2, 8 g, 0.04 mol) was dissolved in acetonitrile (100 mL) to which 1-methyl piperazine (5,.IR spectra were recorded using a Thermo Nicolet FT-IR (model Nexus-870, Nicolet Device Corp, Madison, Wisconsin, U.S.A.) spectrometer. evaluating to I, as talked about above. Furthermore, the info on vascular permeability in xylene-induced hearing edema and acetic acid-induced to peritoneal cavity verified that substitutions on cyclizine molecule had been more effective and may reduce the vascular permeability and severe inflammation. Nevertheless, the outcomes from the natural cotton pellet-induced granuloma development in rats uncovered that none from the medications (I-III) had been effective to lessen the reactions and intermediates of chronic irritation. strong course=”kwd-title” KEY TERM: Cyclizine, Piperazine derivative, H1-antihistamine, Acute and persistent, Anti-inflammation Launch Cyclizine (1-benzhydryl-4-methyl-piperazine, CAS 82-92-8, CYC, Body 1) is certainly a piperazine derivative which belongs to H1- antihistamine band of medications (1). As well as the antihistamine results, their H1-receptor antagonists present such pharmacological properties as anti-inflammatory and anti-allergic results, antiplatelet actions, and suppression of respiratory burst of professional phagocytes that aren’t uniformly distributed among this course of medications (2-5). Open up in another window Body 1 Framework formulas of Cyclizine (Cycl, I), 1-ethyl-4-[( em p /em -isopropylphenyl)( em p /em -tolyl) methyl]-piperazine (Cycl-1, II) and 1-(3, 4-dichlorophenyl)-4-[( em p /em -isopropylphenyl)( em p /em -tolyl) methyl]-piperazine (Cycl-2, III Many H1-antihistamines display an starting point of actions within one to two 2 h following the administration and 24 h duration of actions after an individual dosage. Maps for pharmacokinetic/pharmacodynamic romantic relationship in H1-antihistamines define plasma focus/activity romantic relationship in these medicines (6). Lately, our understanding on histamine jobs in particular activation or blockade from the receptor subtypes, both in physiology and pathology, continues to be dramatically elevated. Among the four subtypes, histamine H1-receptor continues to be an attractive focus on to drug breakthrough for quite some time. H1-receptor antagonists have already been became effective therapeutic agencies in many illnesses; hence, these are incorporated into a significant class of obtainable medications (7). Inflammation is certainly a disorder regarding localized upsurge in amounts of leukocytes and types of complicated mediator substances (8). Prostaglandins are ubiquitous chemicals that demonstrate and modulate cell and tissues responses involved with irritation. Their biosynthesis in addition has been implicated in the pathophysiology of cardiovascular diseases, cancer, colonic adenomas and Alzheimer (9). In this paper, two new (II and III) derivatives and intermediates (compounds 1-4) of I were synthesized to evaluate their acute and chronic anti-inflammatory activities using some known pharmacological procedures (10-15). Experimental em General /em 1-methyl piperazine, 1-ethyl piperazine, 1-(3,4-dichlorophenyl) piperazine, Magnesium turning, Diethyl ether, 4-bromo toluene, Benzaldehyde, 4-methyl Benzaldehyde, 4-isopropyl Benzaldehyde, Thionyl chloride and all other chemicals, were purchased from Merck chemical Co. (Darmstadt, Germany). Melting points (uncorrected) were determined with a digital electrothermal melting point apparatus (model 9100, Electrothermal Engineering Ltd., Essex, UK). 1H and 13C NMR spectra were recorded with a Bruker 300 MHz (model AMX, Karlsruhe, Germany) spectrometer (Internal Reference: TMS). IR spectra were recorded with a Thermo Nicolet FT-IR (model Nexus-870, Nicolet Instrument Corp, Madison, Wisconsin, U.S.A.) spectrometer. Mass spectra were also recorded with an Agilent Technologies 5973, Mass Selective Detector (MSD) spectrometer (Wilmigton, USA). Column chromatographic separations were performed over Acros silica gel (No.7631-86-9 particle size 35-70 micrometer, Geel, Belgium). Thirty-two adult male Wistar rats (Pasteur`s Institute, Tehran) weighing 250-300 g were subjected to the pharmacological testing. em Preparations ( /em Figures 1 em – /em ?33 em ) /em Open in a separate window Figure 3 Synthesis of intermediates 2 and 4 em Diphenylmethanol (Benzhydrol) (1) /em This compound was prepared under a published method (16, 17) after some required modification. Phenyl magnesium bromide was added drop-wise to the solution of benzaldehyde (10.6 g, 0.1 mol) in THF (50 mL), (prepared from 15.7 g bromobenzene and 2.43 g of Mg in 50 mL of dry ether) and refluxed for additional 118 h, poured into ice-NH4Cl, before the organic layer was separated, brine-washed, re-extracted with diethyl ether, dried over MgSO4 and evaporated under vacuum. A solid compound (m.p., 64-66C) was obtained (Figure 2). Open in a separate window Figure 2 Synthesis of intermediates 1 and 3 em Chlorodiphenylmethane (Benzhydryl chloride) (2) /em This compound was prepared under a published method (16, 17) after some required modification. The alcohol (1, 10.5 g, 0.05 mol) dissolved in dichloromethane (250 mL) and SOCl2 (8 mL, 0.11 mol) was added to the solution. The reaction mixture was refluxed for additional 210 h. The solvent was evaporated under ZCL-278 vacuum. An obtained oily brown compound was used in the next step without further purification (highly sensitive to light) (Figure 3). em 1-Benzhydryl-4-methyl-piperazine (Cyclizine) I /em This compound was prepared under a published method (16-19) after some required modification. The benzhydryl chloride (2, 8 g, 0.04 mol) was dissolved in acetonitrile (100 mL) to which 1-methyl piperazine (5,.
em 1-Benzhydryl-4-methyl-piperazine (Cyclizine) I /em This compound was prepared under a published method (16-19) after some required modification