- Spiro[pyrrolidine-3,3′-oxindoles] as 5-HT7 receptor ligands
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Here we report the design and synthesis of spiro[pyrrolidine-3,3′-oxindole] derivatives representing a novel scaffold of 5-HT7 receptor ligands. The synthesized analogues were validated as low nanomolar ligands showing selectivity in a panel of
- Kelemen, ádám Andor,Sata?a, Grzegorz,Bojarski, Andrzej J.,Keser?, Gy?rgy M.
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supporting information
p. 2418 - 2421
(2018/06/18)
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- Novel aryl piperazines for alleviation of ‘andropause’ associated prostatic disorders and depression
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A series of seventeen piperazine derivatives have been synthesized and biologically evaluated for the management of andropause-associated prostatic disorders and depression. Five compounds 16, 19, 20, 21 and 22 significantly inhibited proliferation of and
- Gupta, Sonal,Pandey, Deepti,Mandalapu, Dhanaraju,Sharma, Vikas,Shukla, Mahendra,Singh, Seema,Singh, Nidhi,Yadav, Santosh Kumar,Tanpula, Dilip Kumar,Singh, Surabhi,Maikhuri, Jagdamba P.,Shukla, Shubha,Lal, Jawahar,Siddiqi, Mohammad I.,Gupta, Gopal,Sharma, Vishnu L.
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p. 204 - 218
(2017/04/03)
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- Syntheses, calcium channel antagonist and anticonvulsant activities of substituted 1,4-dihydro-3,5-pyridinedicarboxylates containing various 3-alkyl ester substituents
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A group of 3-alkyl-5-isopropyl 4-aryl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylates 10-20 containing an amine, quaternary ammonium, aryl(heteroaryl)alkenyl, 4-(4-fluorophenyl)-piperazin-1-yl or methoxy moiety in the C-3 alkyl ester R-substituent in combination with a C-4 phenyl ring bearing a 2,3-Cl2, 3-NO2, 3-NMe2, 4-NMe2 or 3,4,5-(OMe)3 X-substituent were prepared using the Hantzsch 1,4-dihydropyridine reaction. In vitro calcium channel antagonist activity (CCA) was determined using a guinea pig ileum longitudinal smooth muscle assay. In the C-4 3-nitrophenyl series of compounds, the C-3 ester R substituent was a determinant CCA activity where the relative potency order was -CH2CH2CH=C-(2-methylphenyl)2 ≤ -CH2CH2NMe2.HCl > -CH2CH2CH=C (3-methyl-2-thienyl)2 > -CH2CH2+NMe3I-. The position and nature of the C-4 phenyl X-substituent, were also determinants of CCA activity where the relative activity order was 3-NMe2>4-NMe2>3,4,5-(OMe)3. Anticonvulsant activities were determined in mice using the subcutaneous metrazol (scMet) and maximal electroshock (MES) screens. The compounds investigated were generally not effective for protecting against scMet induced seizures, except for 10 {X = 2,3-Cl2, R = 2-[4-(4-fluorophenyl)piperazin-1-yl]ethyl} and 14a (X = 3-NMe2.HCl, R = CH2CH2OMe), which exhibited modest activity. Compound 11a (X = 3-NO2, R = -CH2CH2NMe2.HCl) was the most effective agent in the MES screen. All of the compounds investigated, except for 11b (X = 3-NO2, R = -CH2CH2+NMe3 I-, Kp = 0.15) are lipophilic with n-octanol/aqueous phosphate buffer (pH = 7.4) partition coefficients (Kp) in the 121-424 range relative to the reference drug nimodipine (Kp = 187). The structure-activity relationship acquired reinforce the concept that calcium is only one of several factors that are involved in seizure generation.
- Yiu, Sai-Hay,Knaus, Edward E.
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- Substituted heterocyclylalkyl esters of 1,4-dihydropyridine-3,5-dicarboxylic acids
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Dihydropyridine derivatives and acid addition salts thereof which are of use as prophylactic or/and therapeutic drugs for cardiovascular diseases, said dihydropyridine derivatives having the formula STR1 wherein R1, R2 and R3 are the same or different and each is alkyl, cycloalkyl, cycloalkylalkyl or alkoxyalkyl; R4 and R5 are the same or different and each is hydrogen, halogen, nitro, trifluoromethyl, alkyl, cycloalkyl, alkoxy, cyano, alkoxycarbonyl or alkylthio; R6 is hydrogen, alkyl, cycloalkyl, aralkyl, aryl or a pyridyl; X is oxygen, sulfur, vinylene, azomethine or a group of the formula STR2 A is alkylene; Ar is aryl or a pyridyl; m is an integer of 1 to 3; n is an integer of 0 to 2.
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