Synthesis of 3-amino-4-hydroxy coumarin and dihydroxy-phenyl coumarins as novel anticoagulants

Abstract

Natural and synthetic coumarin derivatives have been shown to possess several beneficial pharmacological effects. The anticoagulation and antithrombotic activities of the 4-hydroxy coumarin derivatives are well known. In this study, besides the 4-hydroxy substituent phenyl and p-methylphenyl derivatives were synthesized and confirmed on the basis of their spectral data. 3-Amino-4-hydroxy coumarin, 5,7-dihydroxy-4-phenyl coumarin and 7,8-dihydroxy-3-(4-methylphenyl)coumarin were tested in rats to determine whether they had any effect on vitamin K inhibition by investigating the prothrombin time (PT). PT values of coumarin derivatives were compared with those of warfarin (CAS 81-81-2), which is the most commonly used anticoagulant. 7,8-Dihydroxy-3-(4-methylphenyl)coumarin increased PT when compared to saline treated control group and other coumarins synthesized, 3-amino-4-hydroxy coumarin and 5,7-dihydroxy-4-phenyl coumarin.

Investigation of HMG‐CoA reductase inhibitory and antioxidant effects of various hydroxycoumarin derivatives

“…3‐Phenylcoumarin derivatives ( I , II , III , and IV ) were prepared by the reaction of substituted hydroxybenzaldehydes with the corresponding arylacetic acids under the traditional Perkin conditions. [ 28–30 ] 4‐Phenylcoumarin derivative ( V ) was obtained by condensation of selected phenol with ethyl‐3,4‐dimethoxybenzoylacetate according to the Pechmann reaction. [ 13 ] Scheme 1 shows the scheme of synthesis and chemical structures of the coumarin derivatives.…”

Daphnetin, a Coumarin in Genus Stellera Chamaejasme Linn: Chemistry, Bioactivity and Therapeutic Potential

“…Natural products containing various heterocyclic skeletons and diverse bioactivities are important sources in drug discovery. [1][2][3][4][5][6] Coumarin (2H-1-benzopyran-2-one), a heterocyclic compound with fused phenolic benzene and α-pyrone rings, possessed various bioactivities including anti-microbial, [7][8][9][10] anti-viral, [11][12][13][14] anticancer, [15][16][17][18][19][20] anti-oxidant, [21][22][23] anti-coagulation, [24][25][26][27][28] anti-diabetic, [29][30][31][32] anti-inflammatory [33][34][35] and neuroprotective [36][37][38] activities, which offered them great potential for biomedical applications.…”

Effective Synthesis and Biological Evaluation of Functionalized 2,3-Dihydrofuro[3,2-c]coumarins via an Imidazole-Catalyzed Green Multicomponent Approach

“…Warfarin, brodifacoum, dicumarol, coumatetralyl, coumafuryl, and difenacoum are well-known examples of current drugs molecules that possess 4-hydroxy coumarin as a core structural moiety. − Moreover, wedelolactone, coumestrol, and neo-tanshinlactone are emerging potential candidates to this end that revealed promising activities (Figure ). , Recently, trans -2,3-dihydrofuro­[3,2- c ]­coumarins (DHFCs) (derivatives of 4-hydroxy coumarin) are of great interest among coumarins possessing a unique 4 H -furo ring fused with coumarin, which are well-known for their medicinal importance, therapeutic activities, and applications in myriad pharmaceutical ingredients. , Several drug candidates containing the furo­[3,2- c ]­coumarin and DHFC skeleton display an extremely wide range of biological activities such as anticoagulant, antibacterial, antifungal, antitumor, antiviral, anticonvulsant, anticancer, antimicrobial, antiprotozoal, insecticidal, fungicidal, antimycobacterial, antimutagenic, antioxidant, and anti-inflammatory. − For instance, natural products austocystin A and D and neo-tanshinlactone isolated from the maize meal cultures of Aspergillus ustus and Salvia miltiorrhiza, respectively, displayed potent antitumor activities and cytotoxicity against breast cancer. , In addition, naphthalene-functionalized DHFCs are known as antioxidant and anthelmintic agents …”

“… 7 , 8 Several drug candidates containing the furo[3,2- c ]coumarin and DHFC skeleton display an extremely wide range of biological activities such as anticoagulant, antibacterial, antifungal, antitumor, antiviral, anticonvulsant, anticancer, antimicrobial, antiprotozoal, insecticidal, fungicidal, antimycobacterial, antimutagenic, antioxidant, and anti-inflammatory. 9 − 22 For instance, natural products austocystin A and D and neo-tanshinlactone isolated from the maize meal cultures of Aspergillus ustus and Salvia miltiorrhiza, respectively, displayed potent antitumor activities and cytotoxicity against breast cancer. 23 , 24 In addition, naphthalene-functionalized DHFCs are known as antioxidant and anthelmintic agents.…”