共查询到20条相似文献,搜索用时 31 毫秒
1.
Srivastava BK Soni R Joharapurkar A Sairam KV Patel JZ Goswami A Shedage SA Kar SS Salunke RP Gugale SB Dhawas A Kadam P Mishra B Sadhwani N Unadkat VB Mitra P Jain MR Patel PR 《Bioorganic & medicinal chemistry letters》2008,18(3):963-968
Design, synthesis and conformational analysis of few imidazole and oxazole as bioisosters of 4S-(-)-3-(4-chlorophenyl)-N-methyl-N'-[(4-chlorophenyl)-sulfonyl]-4-phenyl-4,5-dihydro-1H-pyrazole-1-caboxamidine (SLV-319) 2 is reported. Computer assisted conformational analysis gave a direct clue for the loss of CB1 antagonistic activity of the ligands without a fine docking simulation for the homology model. 相似文献
2.
Biarylcarboxybenzamide derivatives as potent vanilloid receptor (VR1) antagonistic ligands 总被引:1,自引:0,他引:1
Park HG Choi JY Kim MH Choi SH Park MK Lee J Suh YG Cho H Oh U Kim HD Joo YH Shin SS Kim JK Jeong YS Koh HJ Park YH Jew SS 《Bioorganic & medicinal chemistry letters》2005,15(3):631-634
Seventeen biarylcarboxybenzamide derivatives were prepared for the study of their agonistic/antagonistic activities to the vanilloid receptor (VR1) in rat DRG neurons. The replacement of the piperazine moiety of the lead compound 1 with phenyl ring showed quite enhanced antagonistic activity. Among the prepared derivatives, N-(4-tert-butylphenyl)-4-pyridine-2-yl-benzamide (2, IC(50)=31 nM) and N-(4-tert-butylphenyl)-4-(3-methylpyridine-2-yl)benzamide (3g, IC(50)=31 nM), showed 5-fold higher antagonistic activity than 1 in (45)Ca(2+)-influx assay. 相似文献
3.
Based on [1-(1-mercaptocyclohexaneacetic acid),2-(O-ethyl-D-tyrosine),4-valine]-8-arginine-vasopressin as a model, five new analogues of arginine-vasopressin (AVP) were designed and synthesized. Four of them have in position 1 a large lipophilic substituent, whereas the fifth contains pchloro-D-phenylalanine at position 2. We found that the anti-antidiuretic potency with 1-mercapto-4-methycyclohexaneacetic acid is higher than with 1-mercaptocyclohexaneacetic acid (model peptide) in position 1 and this analogue is among the most potent antagonists of the antidiuretic response to AVP known to date. Upon further increase of the size of substituents, antagonistic potency was significantly decreased or totally eliminated. As for the substitution of p-chloro-D-phenylalanine in position 2, we conclude that this modification leads to substantial decrease of the V2 antagonistic potency. 相似文献
4.
Yamamoto S Matsunaga N Hitaka T Yamada M Hara T Miyazaki J Santou T Kusaka M Yamaoka M Kanzaki N Furuya S Tasaka A Hamamura K Ito M 《Bioorganic & medicinal chemistry》2012,20(1):422-434
A series of 4-phenylpyrrole derivatives D were designed, synthesized, and evaluated for their potential as novel orally available androgen receptor antagonists therapeutically effective against castration-resistant prostate cancers. 4-Phenylpyrrole compound 1 exhibited androgen receptor (AR) antagonistic activity against T877A and W741C mutant-type ARs as well as wild-type AR. An arylmethyl group incorporated into compound 1 contributed to enhancement of antagonistic activity. Compound 4n, 1-{[6-chloro-5-(hydroxymethyl)pyridin-3-yl]methyl}-4-(4-cyanophenyl)-2,5-dimethyl-1H-pyrrole-3-carbonitrile exhibited inhibitory effects on tumor cell growth against the bicalutamide-resistant LNCaP-cxD2 cell line as well as the androgen receptor-dependent JDCaP cell line in a mouse xenograft model. These results demonstrate that this series of pyrrole compounds are novel androgen receptor antagonists with efficacy against prostate cancer cells, including castration-resistant prostate cancers such as bicalutamide-resistant prostate cancer. 相似文献
5.
Chigaev A Wu Y Williams DB Smagley Y Sklar LA 《The Journal of biological chemistry》2011,286(7):5455-5463
Integrins are cell adhesion receptors that mediate cell-to-cell, or cell-to-extracellular matrix adhesion. They represent an attractive target for treatment of multiple diseases. Two classes of small molecule integrin inhibitors have been developed. Competitive antagonists bind directly to the integrin ligand binding pocket and thus disrupt the ligand-receptor interaction. Allosteric antagonists have been developed primarily for α(L)β(2)- integrin (LFA-1, lymphocyte function-associated antigen-1). Here we present the results of screening the Prestwick Chemical Library using a recently developed assay for the detection of α(4)β(1)-integrin allosteric antagonists. Secondary assays confirmed that the compounds identified: 1) do not behave like competitive (direct) antagonists; 2) decrease ligand binding affinity for VLA-4 ~2 orders of magnitude; 3) exhibit antagonistic properties at low temperature. In a cell based adhesion assay in vitro, the compounds rapidly disrupted cellular aggregates. In accord with reports that VLA-4 antagonists in vivo induce mobilization of hematopoietic progenitors into the peripheral blood, we found that administration of one of the compounds significantly increased the number of colony-forming units in mice. This effect was comparable to AMD3100, a well known progenitor mobilizing agent. Because all the identified compounds are structurally related, previously used, or currently marketed drugs, this result opens a range of therapeutic possibilities for VLA-4-related pathologies. 相似文献
6.
Protective effects of GLP-1 analogues exendin-4 and GLP-1(9-36) amide against ischemia-reperfusion injury in rat heart 总被引:3,自引:0,他引:3
Glucagon-Like Peptide-1 (GLP-1) is an incretin peptide secreted from intestinal L-cells, whose potent plasma glucose-lowering action has prompted intense efforts to develop GLP-1 receptor-targeting drugs for treatment of diabetic hyperglycemia. More recently, GLP-1 and its analogues have been shown to exert cardiovascular effects in a number of experimental models. Here we tested exendin-4 (Exe-4), a peptide agonist at GLP-1 receptors, and GLP-1(9-36) amide, the primary endogenous metabolite of GLP-1 (both in the concentration range 0.03-3.0 nM), for their protective effects against ischemia-reperfusion injury (IRI) in an isolated rat heart preparation. When administered, the agents were only present for the first 15 min of a 120 min reperfusion period (postconditioning protocol). Exe-4, but not GLP-1(9-36) amide, showed a strong infarct-limiting action (from 33.2% +/-2.7% to 14.5% +/-2.2% of the ischemic area, p<0.05). This infarct size-limiting effect of Exe-4 was abolished by exendin(9-39) (Exe(9-39)), a GLP-1 receptor antagonist. In contrast, both Exe-4 and GLP-1(9-36) amide were able to augment left ventricular performance (left ventricular developed pressure and rate-pressure product) during the last 60 min of reperfusion. These effects were only partially antagonized by Exe(9-39). We suggest that Exe-4, in addition to being currently exploited in treatment of diabetes, may present a suitable candidate for postconditioning trials in clinical settings of IRI. The divergent agonist effects of Exe-4 and GLP-1(9-36), along with correspondingly divergent antagonistic efficacy of Exe(9-39), seem consistent with the presence of more than one type of GLP-1 receptor in this system. 相似文献
7.
Suhagia BN Chhabria MT Makwana AG 《Journal of enzyme inhibition and medicinal chemistry》2006,21(6):681-691
A series of N1-(substituted)aryl-5,7-dimethyl-2-(substituted)pyrido(2,3-d)pyrimidin-4(3H)-one was designed on the basis of the triangular pharmacophoric requirement of histamine H1-receptor antagonists. The designed series was synthesized by cyclo-condensation of monoaryl thiourea with ethyl cyanoacetate in the presence of dry HCl gas to give N1-(substituted aryl)-2-mercaptopyrimidine-4(3H)-one, which on cyclo-condensation with acetylacetone gave the pyridopyrimidinone. Further methylation of the mercapto group at C-2 with methyl iodide followed by nucleophilic displacement of the methylmercapto group by various amines gave the targeted compounds. All the synthesized compounds were screened for histamine H1-receptor antagonistic activity by the in vitro method of inhibition of the isotonic contraction induced by histamine on isolated guinea pig ileum using cetirizine as a standard drug. All the compounds exhibited potent histamine H1-receptor antagonistic activity with pA2 values from 7.30- 9.75 (cetirizine, pA2 value 9.40). The potent compounds were screened for their in vivo antihistaminic activity by protection of animal from asphyxic shock. The sedative potential of potent compounds was checked on albino mice by photoactometer and they had comparative sedative potential to the standard drug cetirizine. None of the compound exhibited anticholinergic activity in the in vitro rat ileum model. 相似文献
8.
Micale N Colleoni S Postorino G Pellicanò A Zappalà M Lazzaro J Diana V Cagnotto A Mennini T Grasso S 《Bioorganic & medicinal chemistry》2008,16(5):2200-2211
In the search for AMPA receptor (AMPAR) antagonists, 2,3-benzodiazepines represent a family of specific noncompetitive antagonists with anticonvulsant and neuroprotective properties. We have previously shown that 2,3-benzodiazepin-4-ones possess marked anticonvulsant properties and high affinity for the noncompetitive binding site of the AMPAR complex. In this paper, we report the synthesis and pharmacological characterization of a full set of 2,3-benzodiazepin-4-ones in order to better define the structure-activity relationship (SAR) of this class of compounds. Binding assays and functional tests were performed to evaluate the antagonistic activity at the AMPARs. Through these results we have identified a potent AMPAR antagonist, 1-(4-amino-3-methylphenyl)-3,5-dihydro-7,8-ethylenedioxy-4H-2,3-benzodiazepin-4-one (5c). This compound noncompetitively inhibited AMPAR-mediated toxicity in primary mouse hippocampal cultures with an IC(50) of 1.6muM and blocked kainate-induced calcium influx in rat cerebellar granule cells with an IC(50) of 6.4muM. Thus, 5c has the in vitro potential as therapeutic drug in the treatment of various neurological disorders. 相似文献
9.
Klimaviciusa L Klusa V Duburs G Kaasik A Kalda A Zharkovsky A 《Cell biochemistry and function》2007,25(1):15-21
Our previous data obtained from in vivo experiments demonstrated high neuroprotective effects of three novel atypical neuronal non-calcium antagonistic 1,4-dihydropyridine (DHP) derivatives cerebrocrast, glutapyrone and tauropyrone. The present studies were carried out in vitro to clarify, at least in part, their mechanism of action in primary culture of cerebellar granule cells by use of 1-methyl-4-phenylpyridinium (MPP+) as a neurotoxic agent which causes dramatic oxidative stress. Cerebrocrast (highly lipophilic, with a classical two-ring structure) dose-dependently (0.01-10.0 microM, EC50 = 13 nM) reduced MPP+-induced cell death. At the same time, the calcium antagonist nimodipine (reference drug) protected cell death at much higher concentrations (EC50 = 12.4 microM). Cerebrocrast decreased also the generation of reactive oxygen species and loss of mitochondrial membrane potential. In contrast, low lipophilic amino acid-containing DHPs glutapyrone and tauropyrone (glutamate- and taurine-containing, correspondingly) were without significant effects indicating their distinct mode of action in comparison to cerebrocrast. We have demonstrated for the first time an ability of atypical non-calcium antagonistic DHP cerebrocrast (which has classical DHP structure elements and high lipophilicity) to protect MPP+-induced deterioration of mitochondrial bioenergetics. One may suggest mitochondria as an essential intracellular target for the neuroprotective action of cerebrocrast and indicate its usefulness in the treatment of Parkinson's disease. 相似文献
10.
11.
Alpha4beta1 integrin/ligand interaction inhibits alpha5beta1-induced stress fibers and focal adhesions via down-regulation of RhoA and induces melanoma cell migration
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We have studied the function of the Hep III fibronectin domain in the cytoskeletal response initiated by alpha5beta1 integrin-mediated adhesion. Melanoma cells formed stress fibers and focal adhesions on the RGD-containing FNIII7-10 fragment. Coimmobilization of FNIII4-5, a fragment spanning Hep III and containing the alpha4beta1 ligand H2 with FNIII7-10, or addition of soluble FNIII4-5 to cells preattached to FNIII7-10, inhibited stress fibers and induced cytoplasmic protrusions. This effect involved alpha4beta1 since: 1) mutations in H2 reverted the inhibition; 2) other alpha4beta1 ligands (CS-1, VCAM-1), an anti-alpha4 mAb, or alpha4 expression in HeLa cells inhibited stress fibers. This activity was apparently cryptic in fibronectin or large fibronectin fragments, but exposed upon proteolytic degradation. Indeed purified peptic fragments containing H2, inhibited stress fibers when mixed with FNIII7-10 or fibronectin. RhoA activation with LPA or transfection with V14RhoA reverted the inhibitory effect and induced stress fibers on FNIII7-10+FNIII4-5. Furthermore, addition of alpha4beta1 ligands to FNIII7-10, down-regulated RhoA and activated p190RhoGAP, which localized to cytoplasmic protrusions. alpha4beta1/ligand interaction induced cell migration, monitored by video microscopy and wound healing assays. These data indicate that alpha4beta1 provides an antagonistic signal to alpha5beta1 by interfering with the RhoA activation pathway and this leads to melanoma cell migration. 相似文献
12.
1,1-bis(4-Hydroxyphenyl)-2-phenylpent-1-ene (5) and 1,1,2-tris(4-hydroxyphenyl)pent-1-ene (6) derivatives with terminal CN (5a, 6a), NH(2) (5b, 6b), NHCOCH(3) (5c, 6c), NHCOC(2)H(5) (5d, 6d) groups at the C2-propyl chain were synthesized and assayed in vitro for estrogen receptor (ER) binding affinity (RBA) in a competition experiment with [3H]estradiol and for estrogenic and anti-estrogenic properties in a luciferase assay with ER-positive MCF-7-2a cells, stably transfected with the plasmid ERE(wtc)luc. The CN as well as the NH(2) group reduced the RBA-values (5: 2.09%; 5a: 1.50%; 5b: 0.07%; 6: 4.03%; 6a: 0.67%; 6b: 0.20%) and the antagonistic potency (5: IC(50)=0.05 microM; 5a: IC(50)=0.43 microM; 5b: IC(50)=1.50 microM; 6: IC(50)=0.07 microM; 6a: IC(50)=0.60 microM; 6b: IC(50)=2.00 microM). Derivatization of the amino function with acetic anhydride and propionic anhydride did not change the RBA-value but altered the antagonistic profile (5c: IC(50)=2.50 microM; 5d: IC(50)=not detectable; 6c: IC(50)=0.65 microM; 6d: IC(50)=1.00 microM). Agonistic effects were only detected for the amine 6b (34.2% activation of the luciferase expression). These data document that estrogen receptor binding and the antagonistic effects can be modified by terminal groups at the C2-propyl chain of the pure antagonists 5 and 6. The mode of action is unclear. However, it can be assumed that the elongation of the side chain causes a reorientation in the LBD in order to locate the side chain in a side pocket near the ligand binding domain. 相似文献
13.
Lee J Kang SU Lim JO Choi HK Jin MK Toth A Pearce LV Tran R Wang Y Szabo T Blumberg PM 《Bioorganic & medicinal chemistry》2004,12(2):371-385
We recently reported that N-(4-t-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl] thiourea (2) was a high affinity antagonist of the vanilloid receptor with a binding affinity of K(i)=63 nM and an antagonism of K(i)=53.9 nM in rat VR1 heterologously expressed in Chinese hamster ovary (CHO) cells (Mol. Pharmacol. 2002, 62, 947-956). In an effort to further improve binding affinity and antagonistic potency, we have modified the C-region of the lead 4-t-butylbenzyl group with diverse surrogates, such as araalkyl, alkyl, 4-alkynylbenzyl, indanyl, 3,3-diarylpropyl, 4-alkoxybenzyl, 4-substituted piperazine and piperidine. The lipophilic surrogates, arylalkyl and alkyl, conferred modest decreases in binding affinities and antagonistic potencies; the groups having heteroatoms resulted in dramatic decreases. Our findings indicate that 4-t-butylbenzyl is one of the most favorable groups for high receptor binding and potent antagonism to VR1 in this structural series. 相似文献
14.
15.
Gitto R Ficarra R Stancanelli R Guardo M De Luca L Barreca ML Pagano B Rotondo A Bruno G Russo E De Sarro G Chimirri A 《Bioorganic & medicinal chemistry》2007,15(16):5417-5423
Recently we identified (R,S)-2-acetyl-1-(4'-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (6) as a potent non-competitive AMPA receptor antagonist able to prevent epileptic seizures. We report here the optimized synthesis of compound 6, its resolution by chiral preparative HPLC, and the absolute configuration of (R)-enantiomer established by X-ray diffractometry. The biological tests of the single enantiomers revealed that higher anticonvulsant and antagonistic effects reside in (R)-enantiomer as also suggested by molecular modeling studies. 相似文献
16.
Zajdel P Marciniec K Maślankiewicz A Satała G Duszyńska B Bojarski AJ Partyka A Jastrzębska-Więsek M Wróbel D Wesołowska A Pawłowski M 《Bioorganic & medicinal chemistry》2012,20(4):1545-1556
Two series of arylpiperazinyl-alkyl quinoline-, isoquinoline-, naphthalene-sulfonamides with flexible (13-26) and semi-rigid (33-36) alkylene spacer were synthesized and evaluated for 5-HT(1A), 5-HT(2A), 5-HT(6), 5-HT(7) and selected compounds for D(2), D(3), D(4) receptors. The compounds with a mixed 5-HT and D receptors profile 16 (N-{4-[4-(3-chlorophenyl)-piperazin-1-yl]-butyl}-3-quinolinesulfonamide) and 36 (4-(4-{2-[4-(4-chloro-phenyl)-piperazin-1-yl]-ethyl}-piperidine-1-sulfonyl)-isoquinoline), displaying antagonistic activity at 5-HT(7), 5-HT(2A), D(2) postsynaptic sites, produced antidepressant-like effects in the forced swim test in mice and showed significant anxiolytic activity in the plus-maze test in rats. The lead compound 36, a multi-receptor 5-HT(2A)/5-HT(7)/D(2)/D(3)/D(4) agent, also displayed significant antipsychotic properties in the MK-801-induced hyperlocomotor activity in mice. 相似文献
17.
Peterson JA Sheibani N David G Garcia-Pardo A Peters DM 《The Journal of biological chemistry》2005,280(8):6915-6922
Co-signaling events between integrins and cell surface proteoglycans play a critical role in the organization of the cytoskeleton and adhesion forces of cells. These processes, which appear to be responsible for maintaining intraocular pressure in the human eye, involve a novel cooperative co-signaling pathway between alpha5beta1 and alpha4beta1 integrins and are independent of heparan sulfate proteoglycans. Human trabecular meshwork cells isolated from the eye were plated on type III 7-10 repeats of fibronectin (alpha5beta1 ligand) in the absence or presence of the heparin (Hep) II domain of fibronectin. In the absence of the Hep II domain, cells had a bipolar morphology with few focal adhesions and stress fibers. The addition of the Hep II domain increased cell spreading and the numbers of focal adhesions and stress fibers. Cell spreading and stress fiber formation were not mediated by heparan sulfate proteoglycans because treatment with chlorate, heparinase, or soluble heparin did not prevent Hep II domain-mediated cell spreading. Cell spreading and stress fiber formation were mediated by alpha4beta1 integrin because soluble anti-alpha4 integrin antibodies inhibited Hep II domain-mediated cell spreading and soluble vascular cell adhesion molecule-1 (alpha4beta1 ligand)-induced cell spreading. This is the first demonstration of the Hep II domain mediating cell spreading and stress fiber formation through alpha4beta1 integrin. This novel pathway demonstrates a cooperative, rather than antagonistic, role between alpha5beta1 and alpha4beta1 integrins and suggests that interactions between the Hep II domain and alpha4beta1 integrin could modulate the strength of cytoskeleton-mediated processes in the trabecular meshwork of the human eye. 相似文献
18.
Bhondwe RS Kang DW Kim MS Kim HS Park SG Son K Choi S Kuhs KA Pavlyukovets VA Pearce LV Blumberg PM Lee J 《Bioorganic & medicinal chemistry letters》2012,22(11):3656-3660
The structure-activity relationships of N-(3-acyloxy-2-benzylpropyl)-N'-4-[(methylsulfonylamino)benzyl] thioureas, which represent simplified RTX-based vanilloids, were investigated by varying the distances between the four principal pharmacophores and assessing binding and antagonistic activity on rTRPV1. The analysis indicated that a 3-pivaloyloxy-2-benzylpropyl C-region conferred the best potency in binding affinity and antagonism. The molecular modeling of this best template with the tetrameric homology model of rTRPV1 was performed to identify its binding interactions with the receptor. 相似文献
19.
Bojarski AJ Paluchowska MH Duszyńska B Kłodzińska A Tatarczyńska E Chojnacka-Wójcik E 《Bioorganic & medicinal chemistry》2005,13(6):2293-2303
Starting with the structure of potent 5-HT(1A) ligands, that is, MM77 [1-(2-methoxyphenyl)-4-(4-succinimidobutyl)piperazine, 4] and its constrained version 5 (MP349), previously obtained in our laboratory, a series of their direct analogues with differently substituted aromatic ring (R=H, m-Cl, m-CF(3), m-OCH(3), p-OCH(3)) were synthesized. The flexible and the corresponding 1e,4e-disubstituted cyclohexane derivatives were designed in order to investigate the influence of rigidification on 5-HT(1A) affinity, selectivity for 5-HT(2A), 5-HT(7), D(1), and D(2) binding sites and functional profile at pre- and postsynaptic 5-HT(1A) receptors. The new compounds 19-25 were found to be highly active 5-HT(1A) receptor ligands (K(i)=4-44 nM) whereas their affinity for other receptors was: either significantly decreased after rigidification (5-HT(7)), or controlled by substituents in the aromatic ring (alpha(1)), or influenced by both those structural modifications (5-HT(2A)), or very low (D(2), K(i)=5.3-31 microM). Since a distinct disfavor towards rigid compounds was observed for 5-HT(7) receptors only, it seems that the bioactive conformation of chain derivatives at those sites should differ from the extended one. Several in vivo models were used to asses functional activity of 19-25 at pre- (hypothermia in mice) and postsynaptic 5-HT(1A) receptors (lower lip retraction in rats and serotonin syndrome in reserpinized rats). Unlike the parent antagonists 4 and 5, all the new derivatives tested were classified as partial agonists with different potency, however, similar effects were observed within pairs (flexible and rigid) of the analogues. The obtained results indicated that substitution in the aromatic ring, but not spacer rigidification, controls the 5-HT(1A) functional activity of the investigated compounds. Moreover, an o-methoxy substituent in the structure of 5 seems to be necessary for its full antagonistic properties. Of all the new compounds studied, trans-4-(4-succinimidocyclohexyl)-1-(3-trifluoromethylphenyl)piperazine 24 was the most potent 5-HT(1A) receptor ligand in vitro (K(i)=4 nM) and in vivo, with at least 100-fold selectivity for the other receptors tested. 相似文献
20.
Bhanubhai N. Suhagia Mahesh T. Chhabria Ashlesha G. Makwana 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):681-691
A series of N1-(substituted)aryl-5,7-dimethyl-2-(substituted)pyrido(2,3-d)pyrimidin-4(3H)-one was designed on the basis of the triangular pharmacophoric requirement of histamine H1-receptor antagonists. The designed series was synthesized by cyclo-condensation of monoaryl thiourea with ethyl cyanoacetate in the presence of dry HCl gas to give N1-(substituted aryl)-2-mercaptopyrimidine-4(3H)-one, which on cyclo-condensation with acetylacetone gave the pyridopyrimidinone. Further methylation of the mercapto group at C-2 with methyl iodide followed by nucleophilic displacement of the methylmercapto group by various amines gave the targeted compounds. All the synthesized compounds were screened for histamine H1-receptor antagonistic activity by the in vitro method of inhibition of the isotonic contraction induced by histamine on isolated guinea pig ileum using cetirizine as a standard drug. All the compounds exhibited potent histamine H1-receptor antagonistic activity with pA2 values from 7.30– 9.75 (cetirizine, pA2 value 9.40). The potent compounds were screened for their in vivo antihistaminic activity by protection of animal from asphyxic shock. The sedative potential of potent compounds was checked on albino mice by photoactometer and they had comparative sedative potential to the standard drug cetirizine. None of the compound exhibited anticholinergic activity in the in vitro rat ileum model. 相似文献