Binding and uptake studies with [3H]CP-93, 129, a radiolabeled selective 5-HT1B receptor ligand

3-(1,2,5,6-Tetrahydro-4-pyridyl)-5-pyrrolo[3,2-b]pyridone, CP-93, 129, is a selective agonist ligand for 5-HT_1B receptors. High affinity binding sites of [³H]CP-93, 129 were found in rat whole brain membranes, which showed K_D and B_max values similar to those for 5-HT_1B sites labeled by [³H]5-HT. Uptake of [³H]CP-93, 129 in crude rat synaptosomes was also observed, which was potently inhibited by 5-HT uptake blockers and 5-HT but not by desipramine (NE uptake blocker) or tametraline (NE and DA uptake blocker). Because of this sensitivity to 5-HT uptake inhibitors and the structural similarity of CP-93, 129 to serotonin, [³H]CP-93, 129 uptake probably occurred in 5-HT neurons.     

Biochemical and behavioral studies of the 5-HT1B receptor agonist,CP-94,253

CP-94,253, 3-(1,2,5,6-tetrahydro-4-pyridyl)-5-propoxypyrrolo[3,2-b]pyridine, a new serotonergic ligand, was found to exhibit significantly greater binding affinity at 5-HT_1B receptors than at 5-HT_1A or 5-HT_1C receptors. Saturation studies showed CP-94,253 to be a competitive inhibitor of [¹²⁵l]iodocyanopindolol binding to 5-HT_1B sites. Its competition curve with this radioligand was shifted to the right (decreased affinity) in the presence of Gpp(NH)p, indicating an agonist function for CP-94,253. Oral administration of CP-94,253 to rats caused inhibition of food intake, decrease in body weight gain, and hyperlocomotion, effects apparently elicited via activation of 5-HT_1B receptors. © 1992 Wiley-Liss, Inc.     

High-affinity [H]6-nitroquipazine binding sites in rat brain

6-Nitroquipazine is a very potent and selective inhibitor of neuronal 5-hydroxytryptamine (5-HT; serotonin) uptake. We have characterized the specific binding of [³H]6-nitroquipazine to rat brain membranes at 22°C. The present results indicate the presence of a single saturable high-affinity binding component for [³H]6-nitroquipazine. Scatchard analysis revealed an apparent equilibrium dissociation constant (K_d) of 93.0 ± 2.23 pM, and a maximal number of binding sites (B_max) of 831.7 ± 18.7 fmol/mg protein (mean ± S.D., n = 4). The kinetically derived dissociation constant was 74.5 pM. [³H]6-Nitroquipazine binding was inhibited selectively by 5-Ht uptake inhibitors, and a good correlation was demonstrated between the potency of various drugs to inhibit [³H]6-nitroquipazine binding and [³H]5-HT uptake. The highest densities of [³H]6-nitroquipazine binding were obtained in the hypothalamus and midbrain, intermediate binding was observed in the striatum, hippocampus, medulla oblongata and cortex, and the lowest binding was observed in the cerebellum. Lesioning of 5-HT neurons with p-chloroamphetamine resulted in a 72% reduction in [³H]6-nitroquipazine binding compared to controls. These results indicate that the binding site specifically labelled by [³H]6-nitroquipazine is associated with the neuronal 5-HT transporter complex. [³H]6-Nitroquipazine is an excellent radioligand for the study of the 5-HT uptake system.     

Selective visualization of rat brain 5-HT2A receptors by autoradiography with [3H]MDL 100,907

The recently developed 5-HT_2A receptor selective antagonist [³H]MDL100,907 ((+/–)2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol]) has been characterized as a radioligand for the autoradiographic visualization of these receptors. [³H]MDL100,907 binding to rat brain tissue sections was saturable, had sub-nanomolar affinity (Kd=0.2–0.3nM), and presented a pharmacological profile consistent with its binding to 5-HT_2A receptors (rank order of affinity for [³H]MDL100,907-labelled receptors: MDL100,907 > spiperone > ketanserin > mesulergine). The distribution of receptors labelled by [³H]MDL100,907 was compared to the autoradiographical patterns obtained with [³H]Ketanserin, [³H]Mesulergine, and [³H]RP62203 (N-[3-[4-(4-fluorophenyl)-piperazin-1-y1]propyl]-1,8-naphtalenesultam) and to the distribution of 5-HT_2A receptor mRNA as determined by in situ hybridization. As opposed to the other radioligands, [³H]MDL100,907 labelled a single population of sites (5-HT_2A receptors) and presented extremely low levels of non-specific binding. The close similarity of the distributions of [³H]MDL100,907-labelled receptors and 5-HT_2A mRNA further supports the selectivity of this radioligand for 5-HT_2A receptors and suggests a predominant somatodendritic localization of these receptors. The present results point to [³H]MDL100,907 as the ligand of choice for the autoradiographic visualization of 5-HT_2A receptors. Received: 7 April / Accepted: 18 May 1997     

Autoradiographic study on the pharmacological characteristics of [H]3-OH-PCP binding sites in rat brain

The pharmacological characteristics and the regional distribution of [³H]3-OH-PCP (1-[1(3-hydroxyphenyl)-cyclohexyl]piperidine) binding were investigated in rat brain by quantitative autoradiography. Kinetic analysis of [³H]3-OH-PCP binding revealed fast and slow components, in the association and dissociation studies. The regional distribution of binding closely corresponded to those of binding sites labeled by [³H]N-[1-(2-thienyl)-cyclohexyl]3,4-piperidine (TCP) and [³H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK 801). High densities of [³H]3-OH-PCP binding sites were found in the stratum radiatum and oriens of field CA1 in the hippocampus and in the outer layers of cerebral cortices. In contrast, low levels of binding were seen in the brain stem and the granular cell layer of the cerebellum. [³H]3-OH-PCP binding was strongly inhibited by MK 801 and 3-OH-PCP, while the potency of (+)-SKF 10047 in inhibiting [³H]3-OH-PCP binding was less in the cerebral cortex and hippocampus. The antagonists for the glutamate, glycine and polyamine recognition sites at the NMDA/PCP receptor complex displaced [³H]3-OH-PCP binding sites with a potency similar to that of [³H]MK 801. These findings suggest that the [³H]3-OH-PCP binding site is similar or identical to the PCP binding site labeled by [³H]TCP and [³H]MK 801.     

The 5-HT3 receptor ligand, [3H]BRL 43694, binds to presynaptic sites in the nucleus tractus solitarius of the rat

This study has employed receptor autoradiography to localise the distribution of binding sites for the 5-HT₃ receptor ligand [³H]BRL 43694 in sections of the brain of the rat (using a concentration of 10 nM [³H]BRL 43694 with 100 μM GR38032F to define non-specific binding). The highest density of binding sites for [³H]BRL 43694 was observed in the nucleus tractus solitarius and amounted to 652 fmol/mg tissue. The binding of [³H]BRL 43694 was also examined in sections prepared 10 days after unilateral nodose ganglionectomy, in an attempt to determine the neuronal location of these binding sites. Denervation reduced the binding of [³H]BRL 43694 by around 50% in the ipsilateral side of the nucleus tractus solitarius, relative to the contralateral side. This would indicate that the 5-HT₂ binding sites may have a presynaptic location on vagal afferent terminals.     

Binding studies with [3H]cis-methyldioxolane in different tissues

Summary Special conditions - tricine buffer containing Ca²⁺ and Mg²⁺, 22°C (TCM) — allow to label a much higher proportion of muscarinic receptors by [³H]cis-methyldioxolane (CD) than hitherto described (Vickroy et al. 1984 a). Taking the maximum number of binding sites, B _max, of [³H]QNB as 100%, B _max of [³H]CD amounts to 83% in the rat heart instead of the reported 17%, 33% in the cerebral cortex instead of 6%, 20% in hippocampus and 55% in pons/medulla. In the salivary glands specific binding was negligible. The affinities of a number of muscarinic agonists and antagonists to [³H]CD and [³H]QNB binding sites in different tissues of the rat are compared. Apparent affinities of agonists are much higher in the [³H]CD system, affinities of antagonists are slightly higher in the [³H]QNB system. In both assay systems receptors of heart and pons/ medulla membranes seem to have similar drug specificity. They differ somewhat from those in the cortex. Receptors in the salivary glands, however, seem to be completely different from those in the other three tissues. In the heart [³H]CD binding can be abolished almost completely by GppNHp. In the cortex about half of the [³H]CD binding is susceptible to GppNHp. The reduction of binding in the cortex is due to a change in B _max and not in the dissociation constant K _D. Competition of unlabelled pirenzepine with [³H]CD: In heart and pons/medulla only low affinity sites for pirenzepine (M₂-receptors) are labelled by [³H]CD. In regions rich in M₁ receptors like hippocampus (80% M₁ receptors) or cortex (65–70% M₁ receptors) the proportion of M₁ receptors labelled by [³H]CD is smaller than expected considering the concentration of M₁ receptors present in these tissues. Thus [³H]CD, under the conditions described in this paper, seems to label preferentially but not exclusively M₂ receptors in their agonist high affinity form. Send offprint requests to A. Closse at the above address     

Involvement of 5-HT1A and 5-HT1B receptors for citalopram-induced hypothermia in the rat

OBJECTIVES: To examine the role of 5-HT1A and 5-HT1B receptors for citalopram-induced hypothermia in the rat. METHODS: Core temperature measurements were performed in adult male Wistar rats (305-340 g) using a computer-assisted recording instrument. The temperature readings were automated and gave a printout when the core temperature had stabilised at +/- 0.1 degree C for 10 s. RESULTS: Citalopram (6.25-100.0 mumol/kg) produced a dose-dependent hypothermia. The effect was maximal within 60 min after administration, and had waned off at 120 min. The 5-HT1B receptor agonist anpirtoline (0.25-4.0 mumol/kg) produced a dose-dependent decrease in core temperature. The citalopram-induced hypothermia (25 mumol/kg) was antagonised by pretreatment with either of the 5-HT1A and the 5-HT1B receptor antagonists, WAY-100,635 (0.04 mumol/kg) and NAS-181 (1.0 mumol/kg), respectively, or by the two drugs in combination. Subchronic treatment with the SSRI zimeldine (100 mumol/kg once daily for 2 weeks) resulted in tolerance to the hypothermic effect of citalopram (100 mumol/kg). CONCLUSIONS: The hypothermia produced by acute administration of the SSRI citalopram is mediated via activation of 5-HT1A, as well as 5-HT1B receptors, and this effect is subject to the development of tolerance.     

5-HT1B receptors modulate release of [3H]dopamine from rat striatal synaptosomes

The effect of the selective r5-HT_1B agonist 3-(1,2,5,6-tetrahydro)-4-pyridil-5-pyrrolo [3,2-b] pyril-5-one (CP93,129) on the K⁺-evoked overflow of [³H]dopamine was studied in rat striatal synaptosomes loaded with [³H]dopamine. The aim of the study was to investigate the participation of 5-HT_1B receptors in the serotonergic modulation of striatal dopaminergic transmission. The Ca²⁺-dependent, tetrodotoxin-resistant K⁺-evoked overflow of [³H]dopamine was inhibited by CP93,129 (0.01–100 μM) in a concentration-dependent manner (IC₅₀=1.8 μM; maximal inhibition by 35.5% of control). [±]8-OH-DPAT, a 5-HT_1A receptor agonist, [+/–]DOI, a 5-HT₂ receptor agonist, and 2-methyl-5-hydroxytryptamine, a 5-HT₃ receptor agonist, at concentrations ranging from 0.01 μM to 100 μM did not show any significant effect. Neither ketanserin (1 μM and 5 μM), a selective 5-HT₂/5-HT_1D receptor antagonist, nor ondansetron (1 μM), a 5-HT₃ receptor antagonist, changed the inhibitory effect of CP93,129. SB224289, GR55562, GR127935, isamoltane and metergoline, selective and non-selective 5-HT_1B receptor antagonists, in contrast, used at a concentration of 1 μM, antagonized the inhibitory effect of CP93,129 (3 μM and 10 μM). SB224289, a selective 5-HT_1B receptor antagonist, inhibited the effect of CP93,129 in a concentration-dependent manner; the calculated K _i value was 1.8 nM. Our results indicate that in rat striatal axon terminals the K⁺-evoked release of dopamine is regulated by the presynaptic 5-HT_1B heteroreceptors. Received: 7 September 1998 / Accepted: 2 November 1998     

Distribution and characterization of the [H]granisetron-labelled 5-HT3 receptor in the human forebrain

The present study has demonstrated the distribution of [³H]granisetron-labelled 5-HT₃ receptors in the human forebrain with relatively high levels of this receptor in homogenates of hippocampus, caudate nucleus, putamen, nucleus accumbens and amygdala. Lower levels of 5-HT₃ receptors were found in other brain regions and the cervical vagus nerve. Pharmacological characterization of the labelled 5-HT₃ receptor in human putamen homogenates identified a relatively low affinity for d-tubocurarine compared to the 5-HT₃ receptor in NG108-15 neuroblastoma-glioma cell homogenates. In contrast, the affinities of 19 other 5-HT₃ receptor ligands were not significantly different for the [³H]granisetron-labelled receptor in these two preparations. Such findings indicate that the human putamen 5-HT₃ receptor displays a unique pharmacology which may have significance given the reported clinical potential of compounds active at this receptor when assessed in animal models of disease.     

[3H]sumatriptan labels both 5-HT1D and 5-HT1F receptor binding sites in the guinea pig brain: an autoradiographic study

We have used in vitro autoradiography to visualize [³H]sumatriptan binding sites in sections of guinea-pig and rat brain. In saturation studies, this ligand recognized a single saturable population of high affinity binding sites in all regions examined (pK_D = 8.3–9.3). While 5-HT and the sumatriptan derivative CP-122,288 (5-methyl-aminosulfonylmethyl-3-(N-methylpyrrolidin-2R-yl-methyl)-1H-indole) competed for [³H]sumatriptan binding sites with a high affinity and monophasic profile, displacement experiments with 5-carboxamidotryptamine revealed the existence of 2 classes of binding sites. The high affinity component (pKD = 9.2–9.9) probably corresponded to 5-HT_1B (rat) or 5-HT_1D (guinea-pig) receptors. The intermediate affinity (pK_D = 5.7–7.3) of the other component, taken together with their high affinity for [³H]sumatriptan, was similar to that of the cloned 5-HT_1F receptor. The regional distribution of the 5-HT_1B/1D [³H]sumatriptan binding sites was in agreement with previously published studies (striatonigral system, hypothalamus, central gray, superficial layer of the superior colliculus) and corresponded to the pattern of serotonin-5-O-carboxymethyl-glycyl [¹²⁵I]tyrosinamide labeling in consecutive sections. [³H]sumatriptan binding sites with a low affinity for 5-CT predominated in the intermediate neocortical layers, the claustrum (in the guinea-pig only), the mammillary nuclei, most of the thalamic nuclei and the principal oculomotor nucleus (in the guinea-pig only). This distribution is very similar to that of 5-HT_1F mRNA, indicating further the identity of these sites with 5-HT_1F receptors. Very high densities of 5-HT_1F sites were also found in the rat parafascicular nucleus.Some regions, such as the caudate/nucleus, the lateral geniculate nuclei and the spinal trigeminal nucleus appeared to contain both 5-HT_1B/1D and 5-HT_1F binding sites. Ketanserin had a low affinity for [³H]sumatriptan binding sites in all guinea-pig brain regions, compatible with the presence of the 5-HT_1D\ subtype. An exception was the substantia nigra, where a significant proportion of sites displayed an intermediate affinity for this compound, suggesting the presence of 5-HT_1D receptors. [³H]5-HT labeled 5-HT_1F sites in the claustrum and intermediate cortical layers in the guinea-pig. However these data show that [³H]sumatriptan, in the presence of 10 nM 5-carboxamidotryptamine, is a more suitable radioligand to study the distribution of 5-HT_1F binding sites.     

Angiotensin AT1 and AT2 receptor antagonists modulate nicotine-evoked [H]dopamine and [H]norepinephrine release

Tobacco smoking is the leading preventable cause of death in the United States. A major negative health consequence of chronic smoking is hypertension. Untoward addictive and cardiovascular sequelae associated with chronic smoking are mediated by nicotine-induced activation of nicotinic receptors (nAChRs) within striatal dopaminergic and hypothalamic noradrenergic systems. Hypertension involves both brain and peripheral angiotensin systems. Activation of angiotensin type-1 receptors (AT1) release dopamine and norepinephrine. The current study determined the role of AT1 and angiotensin type-2 (AT2) receptors in mediating nicotine-evoked dopamine and norepinephrine release from striatal and hypothalamic slices, respectively. The potential involvement of nAChRs in mediating effects of AT1 antagonist losartan and AT2 antagonist, 1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid (PD123319) was evaluated by determining their affinities for α4β2* and α7* nAChRs using [³H]nicotine and [³H]methyllycaconitine binding assays, respectively. Results show that losartan concentration-dependently inhibited nicotine-evoked [³H]dopamine and [³H]norepinephrine release (IC₅₀: 3.9 ± 1.2 and 2.2 ± 0.7 μM; I_max: 82 ± 3 and 89 ± 6%, respectively). In contrast, PD123319 did not alter nicotine-evoked norepinephrine release, and potentiated nicotine-evoked dopamine release. These results indicate that AT1 receptors modulate nicotine-evoked striatal dopamine and hypothalamic norepinephrine release. Furthermore, AT1 receptor activation appears to be counteracted by AT2 receptor activation in striatum. Losartan and PD123319 did not inhibit [³H]nicotine or [³H]methyllycaconitine binding, indicating that these AT1 and AT2 antagonists do not interact with the agonist recognition sites on α4β2* and α7* nAChRs to mediate these effects of nicotine. Thus, angiotensin receptors contribute to the effects of nicotine on dopamine and norepinephrine release in brain regions involved in nicotine reward and hypertension.     

咪苯嗪酮对花生四烯酸诱导的大鼠脑血栓形成的影响

花生四烯酸(AA)0.25～1 mg·kg~(-1)经颈内动脉注射能诱发大鼠同侧大脑半球脑内血栓形成,明显增加伊文思蓝通过血脑屏障渗入脑实质的量,峰值为205±s 50 mg·kg~1脑组织,相应对照组为10±s 5mg·kg~1,咪苯嗪酮0.25～0.5mg·kg~1 iv能对抗AA引起的大鼠脑血栓形成,显著降低脑实质内伊文思蓝的含量,作用呈剂量依赖性,且强于哒唑氧苯     

Autoradiographic localisation of D3-dopamine receptors in the human brain using the selective D3-dopamine receptor agonist (+)-[3H]PD 128907

The selective D₃-dopamine receptor agonist 4aR,10bR-(+)-trans-3,4,4a,10b-tetrahydro-4-[N-propyl-2,3-³H]-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol ([³H]PD 128907) was used to visualise D₃-dopamine receptors in whole hemisphere cryosections from post-mortem human brain. [³H]PD 128907 has an 18- to 40-fold selectivity for D₃- over D₂-dopamine receptors as compared to a 7- to 24-fold selectivity of the more commonly used ligand [³H]7-OH-DPAT. [³H]PD 128907 accumulated markedly in the nucleus accumbens and in the ventral parts of caudate nucleus and putamen, with a slightly heterogeneous (patch-matrix like) distribution. The binding in the lateral parts of caudate nucleus and putamen was much less dense. No binding was obtained in any other regions. A very high proportion of [³H]PD 128907 was specifically bound, as judged from the low binding remaining in the presence of the D₂/D₃-dopamine receptor antagonist raclopride. This gives the ligand a potential for the detection of low density D₃-dopamine receptors in the human brain. The binding obtained with [³H]PD 128907 was qualitatively similar to that using [³H]7-OH-DPAT in the presence of GTP. However, [³H]7-OH-DPAT labelled, in contrast to [³H]PD 128907, also D₃-dopamine receptors in neocortex. The new compound [³H]PD 128907 appears to be a suitable radioligand for autoradiographic examination of the D₃-dopamine receptor localisation in the human brain, and should also be useful for pharmacological studies of this receptor subtype. Received: 20 November 1995/Final version: 2 May 1996     

(R)-3-氨基-2,3,4,5-四氢-1H-[1]-2-氧代苯并氮杂(艹卓)的合成

3,4-二氢-2H-萘-1-酮与盐酸羟胺反应后,在PPA中经Beckmann重排、碘代得到3-碘代-2,3,4,5-四氢-1H-[1]-2-氧代苯并氮杂(5),5经氨解、D-焦谷氨酸拆分、浓氨水处理后催化氢化还原,得到(R)-3-氨基-2,3,4,5-四氢-1H[1]-2-氧代苯并氮杂(艹卓),总收率约44%,纯度98%,ee值99.5%.     

Studies on the binding of [3H]flumazenil and [3H]sarmazenil in post-mortem human brain

Two benzodiazepine analogues, [³H]flumazenil and [³H]sarmazenil, were used to study the GABA_A/benzodiazepine receptor complex in human post-mortem brain using in vitro receptor assays on homogenates and whole hemisphere autoradiography. Both radioligands bound in a saturable manner to single binding sites in the tissue preparations from any brain region. The highest levels of binding were found in the cortical regions and in cortex cerebelli. Both [³H]flumazenil and [³H]sarmazenil were excellent radioligands for autoradiography with high binding in cerebral and cerebellar cortex with no or very low binding in areas with white matter. The addition of a high concentration of flumazenil or clonazepam did not inhibit the binding of [³H]sarmazenil to granule cells in the cerebellum while the binding of [³H]flumazenil was abolished completely in all regions. The results show that with the two different radioligands, one an antagonist and one a partial inverse agonist, the binding pattern to GABA_A/benzodiazepine receptor complex is approximately similar in most brain regions. The additional binding seen in the cerebellum with [³H]sarmazenil is suggested to be due to binding to an α₆-containing complex.     

1-(5-硝基吲哚-2-羰基)-4-[3-(1-甲基乙胺基)-2-吡啶基]哌嗪的制备

地拉韦定(delavirdine)是由美国Pharmacia&Upjohn公司研制的非核苷HIV-1逆转录酶抑制剂(NNRTIs),临床与其它抗HIV药联合使用,用于治疗获得性免疫缺陷综合征[1].1-(5-硝基吲哚-2-羰基)-4-[3-(1-甲基乙胺基)-2-吡啶基]哌嗪(1)是其重要中间体.文献[2-4]以5-硝基吲哚-2-羧酸(2)和1-[3-(1-甲基乙胺基)-2-吡啶基]哌嗪(3)为原料,在1-(3-二甲胺基丙基)-3-乙基碳二亚胺(EDC)作用下缩合制得.EDC价昂,后处理用氯仿作提取溶剂,且需通过柱色谱纯化,不适于规模化生产.     

[3H]MDL 100,907: a novel selective 5-HT2A receptor ligand

In studies using standard radioligands, unlabeled MDL 100,907 (R-(+)--(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol) has been shown to have a high degree of selectivity for the 5-HT_2A receptor. The present study was undertaken to investigate the receptor binding characteristics of [³H]MDL 100,907 in rat cortical homogenates. [³H]MDL 100,907 was found to reach equilibrium at 37°C after 15 min. Saturation experiments indicated binding to a single site with a K_D of 0.56 nM, Hill slope of 1.15, and a B_max of 512 fmol/mg protein. In parallel experiments with the standard 5-HT_2A receptor radioligand, [³H]ketanserin, with prazosin added to block ₁ receptors, a similar Hill slope and B_max was noted but a two-fold higher K_D was found. In competition binding studies using 0.5 nM [³H]MDL 100,907, some 19 standard ligands to various receptors including the 5HT_1A, D₂, ₁, and receptors resulted in estimated K_I values that were consistent with [³H]MDL 100,907 selectively binding to the 5-HT_2A receptor. A comparison of the K_I values for 17 standard 5-HT_2A receptor agonists and antagonists displacing [³H]MDL 100,907 versus [³H]ketanserin resulted in a highly significant linear correlation (R² = 0.96, P<0.001). Taken together these results suggest that [³H]MDL 100,907 is binding to the 5-HT_2A receptor with a sub-nanomolar affinity without the use of secondary blocking agents.     

1,3-二甲基-6-[2-(对甲苯磺酰氧基)乙基氨基]尿嘧啶的合成

目的:合成盐酸尼非卡兰中间体1,3-二甲基-6-[2-(对甲苯磺酰氧基)乙基氨基]尿嘧啶.方法:以二甲基脲和氰乙酸为原料经3步反应合成目标产物.结果:以氰乙酸计,总收率44.4%.目标产物的光谱数据与文献报道一致.结论:新的合成方法所用原料价廉易得,适合生产.     

Synthesis of (+)-(3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9-[5,6,7,8,12,13-U-14C]carbazolepropanoic acid, [14C]BAY u 3405

The title compound [¹⁴C]BAY u 3405 ( 1 ) was synthesized as part of 8-step sequence. Starting from [U-¹⁴C]aniline hydrogensulfate the final product 1 was obtained with a specific activity of 741 MBq/mmol (20 mCi/mmol) and a radiochemical purity of > 98% in an overall yield of 6 and 10% depending on the method.