CN105753811A - Dopamine D4 receptor ligand and preparation method thereof - Google Patents
Dopamine D4 receptor ligand and preparation method thereof Download PDFInfo
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- CN105753811A CN105753811A CN201610199686.0A CN201610199686A CN105753811A CN 105753811 A CN105753811 A CN 105753811A CN 201610199686 A CN201610199686 A CN 201610199686A CN 105753811 A CN105753811 A CN 105753811A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
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Abstract
The invention discloses a dopamine D4 receptor ligand and a preparation method thereof.The dopamine D4 receptor ligand is a 2-(3-(4-(4- substituted-benzyl) piperazine-1-base) propyl group) benzothiazole type compound, and the structural formula is as shown in formula (I).The preparation method includes the steps that 2-(3-three methyl chlorine) benzothiazole and N-piperazinecarboxaldehyde are dissolved in anhydrous solvent, a reducing agent is added, stirring is conducted at the room temperature, ice water is added, extraction is conducted with organic solvent, separation and purification are conducted, and the 2-(3-(4-(4- substituted-benzyl) piperazine-1-base) propyl group) benzothiazole is obtained; the 2-(3-(4-(4- substituted-benzyl) piperazine-1-base) propyl group) benzothiazole reacts with H2SO4 and is then cooled to the room temperature, alkali is added for neutralization, an alkalinity mixture is obtained, extraction is conducted with organic solvent, separation and purification are conducted, and the 2-(3-(4-(4- substituted-benzyl) piperazine-1-base) propyl group) benzothiazole is obtained; the 2-(3-(4-(4- substituted-benzyl) piperazine-1-base) propyl group) benzothiazole is dissolved in organic alcohol solvent, 4-substituted benzaldehyde, acetic acid and the reducing agent are added, stirring is conducted at the room temperature, the mixture is extracted with organic solvent and water, an organic layer is subjected to drying, pressure reduction and concentration, and a product is obtained after a coarse product is separated.
Description
Technical field
The invention belongs to a class dopamine D4Receptor-ligand, is specifically related to a kind of dopamine D4Receptor-ligand
2-(3-(4-(4-substituted benzyl) piperazine-1-base) propyl group) benzothiazole compound and preparation method thereof.
Background technology
Dopamine plays a significant role, although dopamine neuron is relatively in brain in many physiology courses
Few, but for such as remembering, learn, cognitive, motor behavior and drug habit, schizophrenia, handkerchief golden
For many brain physiological activities regulated by dopamine receptor such as gloomy disease and disease, its importance is extensively recognized
Know.Therefore, there are many drug targeting dopamine receptors.Based on pharmacological characteristic, design feature and to cAMP
Impact different, dopamine receptor can be divided into D1-sample and D2The big type of-sample acceptor two.D1-sample acceptor bag
Include D1Acceptor, D5Acceptor;D2-sample acceptor can be divided into again D2Acceptor, D3Acceptor, D4Three kinds of hypotypes of acceptor.
Dopamine D4Acceptor belongs to the acceptor of G-protein coupling class, is made up of 387 amino acid, and its peptide chain is crossed over
Cell membrane seven times, the aminoterminal (N end) of peptide chain is in extracellular, and c-terminus (C end) is intracellular.D4
Acceptor and D2Acceptor belongs to the 11st chromosome together, on 11P15 position.D4Acceptor and D2Acceptor, D3It is subject to
Body is respectively provided with the homology of 41% and 39%.Dopamine D4By physical efficiency and Gi/oAlbumen effect, suppresses gland
Purine cyclase, in early days research disclose dopamine receptor spirit, sacred disease treatment in play important work
With.
Dopamine D4Receptor-ligand include N-heteroaromatic compounds, 7-Azaindoles, phenylpiperazine class,
Chromene [3,4-c] pyridine-5-ketone etc., according to they differences to receptor acting, can be divided into activator and
Antagonist.Dopamine D4Receptor stimulating agent is mainly used in attention deficit hyperactivity disorder, parkinsonism, mood
The treatment of the diseases such as obstacle, and antagonist is commonly used for antipsychotics.Clozapine is D4Receptor antagonist
In Typical Representative, it can effectively treat the various related symptoms that schizophreniac is showed, and
The outer pair of cone is caused to answer hardly.Atypical antipsychotic Clozapine is to D4Acceptor has certain parent
And property, only occupy the D of 30~60% during treatment concentration2Acceptor, can alleviate " intractable " patient's disease of 50%
Shape and seldom cause extrapyramidal system and neuroendocrine side effect, this result of study shows specific D4
Receptor-ligand may have preferable curative effect to schizophrenia.Recent study reports multiple dopamine
D4Receptor-ligand, but these aglucons fail owing to lacking selectivity or pharmacological property and do not reach requirement into
Enter Clinical practice.Due to existing D4The selectivity of receptor-ligand, compatibility or pharmacological property do not make us
Satisfied, therefore, people are exploring new D4Receptor-ligand.If D4Receptor antagonist can be controlled really
Treat schizophrenia, and don't produce the from outside symptom of cone, then, exploitation is with D4Acceptor is the spy of target
Specific ligand, it would be possible to provide effective, without EPS and nerve for schizoid treatment
The medicine of endocrine side effect.
Summary of the invention
An object of the present invention is the dopamine D providing a class potential4Receptor-ligand, this dopamine D4
Receptor-ligand is 2-(3-(4-(4-substituted benzyl) piperazine-1-base) propyl group) benzothiazole compound, its structural formula
As shown in formula (I):
The two of the purpose of the present invention are to provide above-mentioned dopamine D4The preparation method of receptor-ligand, the method
Comprise the steps:
(1) by 2-(3-chloropropyl) benzothiazole that mol ratio is 1.0:1.5~2.0 and N-formyl piperazine
It is dissolved in anhydrous solvent, adds reducing agent, add frozen water after stirring 20-30 hour under room temperature, after mixing
Extracting with organic solvent, organic layer anhydrous sodium sulfate obtains 2-(3-(4-through column chromatographic isolation and purification after being dried
Piperazine formaldehyde-1-base) propyl group) benzothiazole;
(2) 2-(3-(4-piperazine formaldehyde-1-base) propyl group) benzothiazole step (1) prepared and 3-10mol/L
H2SO4It is cooled to room temperature after reacting 10 hours at 60 DEG C-90 DEG C, adds in alkali and unnecessary acid, and shape
Becoming alkaline mixt, extract with organic solvent, organic layer anhydrous sodium sulfate is pure through column chromatography for separation after being dried
Change and obtain 2-(3-(4-piperazine-1-base) propyl group) benzothiazole;
(3) 2-(3-(4-piperazine-1-base) propyl group) benzothiazole that step (2) is prepared and 2-[4-piperazine-1-
Ylmethyl] pyrazolo [1,5-α] pyridine is dissolved in organic alcohol solvent, adds 4-substituted benzaldehyde, acetic acid, reduction
Agent, is stirred at room temperature 3-5 hour, extracts mixture with organic solvent and water, and organic layer is through anhydrous slufuric acid
Sodium is dried, and reduced pressure concentration, crude product obtains 2-(3-(4-(4-substituted benzyl) after Flash pillar layer separation
Piperazine-1-base) propyl group) benzothiazole.
Shown in its reaction equation such as formula (II):
Concrete, described in step (1)~(3), anhydrous solvent and organic solvent are dichloromethane, trichlorine
One in methane, acetonitrile, acetone, ethyl acetate and toluene;Described reducing agent is lithium aluminium hydride reduction, boron hydrogen
Change the one in sodium, triacetoxyborohydride and sodium cyanoborohydride;Described in step (2), alkali is hydrogen
One in sodium oxide molybdena, potassium hydroxide, ammonium hydroxide, barium hydroxide;Step (3) has described in reaction
Machine alcoholic solvent is the one in methyl alcohol, ethanol, n-butanol, octanol.
Concrete, in step (2), regulation mixture ph to 8.0-10.0.
The preparation method technique of the present invention is simple, without high temperature, high pressure, the particular/special requirement of sensitive agents, commonly
Consersion unit can complete, and purifying products uses the method such as solvent extraction, column chromatography, simple, product
Productivity and purity are higher.Dopamine D prepared by the inventive method4Receptor-ligand, is competed by extracorporeal receptor
Suppression Binding experiment, determines target compound to D2The compatibility of-sample acceptor and selectivity, measurement result
Showing, this compounds, to dopamine D4Acceptor has higher compatibility.
Detailed description of the invention
By embodiment, the relevant details of the present invention will be further described below, but embodiment does not limit
Protection scope of the present invention processed.
The synthesis of embodiment 1:2-(3-(4-(4-luorobenzyl) piperazine-1-base) propyl group) benzothiazole
(1) 2-(3-(4-piperazine formaldehyde-1-base) propyl group) benzothiazole
By 2-(3-chloropropyl) benzothiazole 0.50g (2.36mmol) and N-formyl piperazine 0.50g (3.80
Mmol) it is added in 10mL anhydrous methylene chloride, adds triacetoxyborohydride 1.00g (4.72mmol),
Add 20mL frozen water after stirring reaction 24h under room temperature, extract with dichloromethane (3 × 10mL), organic
Layer anhydrous sodium sulfate obtains 2-(3-(4-piperazine formaldehyde-1-base) propyl group) benzo through column chromatographic isolation and purification after being dried
Thiazole 0.42g, productivity: 61.7%.1H NMR(CDCl3, 500MHz) and δ: 7.91 (d, J=8.0Hz, 1H),
7.83 (s, 1H), 7.50 (d, J=8.0Hz, 1H), 7.40 (t, J=8.0Hz, 1H), 7.32 (t, J=8.0Hz, 1H),
3.60 (t, J=9.4Hz, 2H), 3.36 (m, J=6.8Hz, 2H), 3.16-3.20 (m, 4H), 2.70-2.75 (m
4H),2.26-2.32(m,2H);ESI MS m/z (%) 290.4 (M+1+,100);Elementary analysis, measured value
(calculated value), %:C62.11 (62.26), H6.69 (6.62), N14.49 (14.52).
(2) synthesis of 2-(3-(4-piperazine-1-base) propyl group) benzothiazole
2-(3-(4-piperazine formaldehyde-1-base) propyl group) benzothiazole (0.30g, 1.04mmol) is joined 5mol/L
H2SO4(10mL) in, after 80 DEG C of heating 10h, it is cooled to room temperature, adds 5mol/L NaOH and be adjusted to
PH=9.0, forms alkaline mixt, extracts with dichloromethane, organic layer filters after drying through anhydrous sodium sulfate,
Concentrate, use column chromatography and purify to obtain 2-(3-(4-piperazine-1-base) propyl group) benzothiazole 0.16g, productivity
59.0%).1H NMR(CDCl3, 500MHz) and δ: 7.90 (d, J=8.5Hz, 1H), 7.47 (d, J=8.5Hz,
1H), 7.42 (t, J=8.3Hz, 1H), 7.33 (t, J=8.8Hz, 1H), 3.66 (t, J=9.4Hz, 2H), 3.32 (m,
J=6.8Hz, 2H), 3.15-3.19 (m, 4H), 2.69-2.76 (m 4H), 2.25-2.33 (m, 2H);ESI MS
M/z (%) 262.4 (M+1+,100);Elementary analysis, measured value (calculated value), %:C64.18 (64.33), H
7.39(7.33),N16.15(16.08)。
(3) synthesis of 2-(3-(4-(4-luorobenzyl) piperazine-1-base) propyl group) benzothiazole
2-(3-(4-piperazine-1-base) propyl group) benzothiazole (0.10g, 0.38mmol) is dissolved in methyl alcohol (10mL)
In, add 4-fluorobenzaldehyde (60 μ L, 0.55mmol), acetic acid (80 μ L), sodium cyanoborohydride (0.050
G, 0.80mmol), stir 5 hours under room temperature, extract mixture with dichloromethane and water, organic layer is through nothing
Aqueous sodium persulfate is dried, reduced pressure concentration, and crude product obtains 2-(3-(4-(4-luorobenzyl) after Flash pillar layer separation
Piperazine-1-base) propyl group) benzothiazole 0.11g, productivity 77.8%.1H NMR(CDCl3, 500MHz) and δ:
7.95 (d, J=8.5Hz, 1H), 7.52 (d, J=8.5Hz, 1H), 7.44 (t, J=8.3Hz, 1H), 7.40 (q,
J=5.5Hz, 2H), 7.31 (t, J=8.8Hz, 1H), 7.19 (t, J=8.5Hz, 2H), 3.68 (t, J=9.4Hz, 2H),
3.29 (m, J=6.8Hz, 2H), 3.13-3.20 (m, 4H), 3.27 (s, 2H), 2.70-2.77 (m 4H),
2.22-2.30(m,2H);19F NMR(DMSO-d6, 470MHz) and δ :-116.32 (s) .ESI MS m/z (%)
370.5(M+1+,100);Elementary analysis, measured value (calculated value), %:C68.12 (68.26), H6.63 (6.55),
N11.49(11.37)。
The synthesis of embodiment 2:2-(3-(4-(4-hydroxybenzyl) piperazine-1-base) propyl group) benzothiazole
2-(3-(4-piperazine-1-base) propyl group) benzothiazole (0.10g, 0.38mmol) is dissolved in methyl alcohol (10mL)
In, add parahydroxyben-zaldehyde 70 μ L (0.65mmol), acetic acid (80 μ L), sodium cyanoborohydride (0.050
G, 0.80mmol), stir 5 hours under room temperature, extract mixture with dichloromethane and water, organic layer is through nothing
Aqueous sodium persulfate is dried, reduced pressure concentration, and crude product obtains 2-(3-(4-(4-hydroxyl benzyl after Flash pillar layer separation
Base) piperazine-1-base) propyl group) benzothiazole 0.12g, productivity 85.4%.1H NMR(CDCl3, 500MHz) and δ:
9.32 (s, 1H), 7.92 (d, J=7.5Hz, 1H), 7.50 (d, J=9.3Hz, 1H), 7.43 (t, J=6.2Hz, 1H),
7.40 (q, J=5.0Hz, 2H), 7.32 (t, J=6.5Hz, 1H), 7.20 (t, J=8.0Hz, 2H), 3.65 (t, J=9.4
Hz,2H),3.35(s,2H),3.26(s,2H),3.12-3.19(m,4H),2.72-2.77(m 4H),2.25-2.30
(m,2H);ESI MS m/z (%) 368.5 (M+1+,100);Elementary analysis, measured value (calculated value), %:
C68.51(68.63),H6.95(6.86),N11.49(11.43)。
The synthesis of embodiment 3:2-(3-(4-(4-methyl-benzyl) piperazine-1-base) propyl group) benzothiazole
2-(3-(4-piperazine-1-base) propyl group) benzothiazole (0.10g, 0.38mmol) is dissolved in methyl alcohol (10mL)
In, add p-tolyl aldehyde 70 μ L (0.59mmol), acetic acid (80 μ L), sodium cyanoborohydride (0.050g,
0.80mmol), stirring 5 hours under room temperature, extract mixture with dichloromethane and water, organic layer is through anhydrous
Sodium sulphate is dried, reduced pressure concentration, and crude product obtains 2-(3-(4-(4-methyl-benzyl) after Flash pillar layer separation
Piperazine-1-base) propyl group) benzothiazole 0.09g, productivity 64.3%.1H NMR(CDCl3, 500MHz) and δ:
7.93 (d, J=8.0Hz, 1H), 7.49 (d, J=8.0Hz, 1H), 7.45 (t, J=8.5Hz, 1H), 7.42 (q,
J=5.5Hz, 2H), 7.30 (t, J=8.2Hz, 1H), 7.18 (t, J=8.6Hz, 2H), 3.66 (t, J=8.0Hz, 2H),
3.32 (s, 2H), 3.25 (m, J=6.0Hz, 2H), 3.15-3.20 (m, 4H), 2.72-2.75 (m 4H), 2.32 (s,
3H),2.20-2.24(m,2H);ESI MS m/z (%) 366.5 (M+1+,100);Elementary analysis, measured value
(calculated value), %:C 72.15 (72.29), H 7.56 (7.44), N 11.58 (11.50).C21H24FN3S。
The synthesis of embodiment 4:2-(3-(4-(4-methoxy-benzyl) piperazine-1-base) propyl group) benzothiazole
2-(3-(4-piperazine-1-base) propyl group) benzothiazole (0.10g, 0.38mmol) is dissolved in methyl alcohol (10mL)
In, add P-methoxybenzal-dehyde 70 μ L (0.58mmol), acetic acid (80 μ L), sodium cyanoborohydride (0.050
G, 0.80mmol), stir 5 hours under room temperature, extract mixture with dichloromethane and water, organic layer is through nothing
Aqueous sodium persulfate is dried, reduced pressure concentration, and crude product obtains 2-(3-(4-(4-methoxyl group after Flash pillar layer separation
Benzyl) piperazine-1-base) propyl group) benzothiazole 0.08g, productivity 54.8%.1H NMR(CDCl3,500MHz)
δ: 7.93 (d, J=5.5Hz, 1H), 7.53 (d, J=7.0Hz, 1H), 7.44 (t, J=7.0Hz, 1H), 7.38 (q,
J=7.5Hz, 2H), 7.28 (t, J=8.0Hz, 1H), 7.16 (t, J=8.0Hz, 2H), 3.84 (s, 3H), 3.63 (t,
J=8.2Hz, 2H), 3.33 (s, 2H), 3.25 (m, J=6.6Hz, 2H), 3.14-3.18 (m, 4H), 2.70-2.75
(m 4H),2.25-2.32(m,2H);ESI MS m/z (%) 382.5 (M+1+,100);Elementary analysis, actual measurement
Value (calculated value), %:C69.38 (69.26), H7.02 (7.13), N11.58 (11.65).
Embodiment 5:2-(3-(4-(4-substituted benzyl) piperazine-1-base) propyl group) benzothiazole extracorporeal receptor binding analysis
Take 33, test tube (12 × 60mm), be divided into 3 groups: be total binding pipe (TB manage, 1 × 3), non-
Specific bond pipe (NSB manages, 1 × 3), sample cell (SB manages, 9 × 3).Every Guan Zhongjia [3H]Spiperone
(spiperone) (final concentration is 0.7nmol/L), adds cushioning liquid 100 μ L in total binding pipe,
The addition of non-specific binding pipe (+) (end is the denseest for-Butaclamol hydrochloride (butaclamol hydrochloride) 20 μ L
Spend 1 μM), sample cell adds 2-(3-(4-(4-substituted benzyl) piperazine being dissolved in DMF and water of series concentration
Piperazine-1-base) propyl group) (often pipe final concentration is respectively 1 × 10 to benzothiazole (aglucon)-11Mol/L, 1 × 10-10Mol/L,
1×10-9Mol/L, 1 × 10-8Mol/L, 1 × 10-7Mol/L, 1 × 10-6Mol/L, 1 × 10-5Mol/L, 1 × 10-4Mol/L,
1×10-3Mol/L), add various reagent and dopamine receptor by table 1, react cumulative volume 200 μ L.
Table 1. extracorporeal receptor competion experiment sample-adding table
In 30 DEG C of water-baths, hatch 1h, take out and be placed on ice face, pipe is often rapidly added 2mL 50mmol/L Tris
HCl cushioning liquid (4 DEG C) is to terminate reaction, and proceeds to suction funnel immediately through fibrous filter membrane filtration under diminished pressure,
After 2mL ice-cold buffer solution washing test tube, also through suction filtration, then with 5mL ice-cold buffer solution in three times
After washing filter membrane, take off filter membrane, put after 80 DEG C of drying boxes are dried 1h, filter membrane is put into scintillation solution cup,
Add scintillation solution 5mL, after standing, use liquid flashing counting determining umber of pulse.The data obtained presses unit point method warp
GraphPad Prism 4 matching obtains competition binding curve, and according to Cheng equation by IC50Obtain affine often
Number (Ki), the results are shown in Table 2.
Table 2 target compound is to D2The compatibility of-sample acceptor and selectivity
Extracorporeal receptor binding analysis shows 2-(3-(4-(4-substituted benzyl) piperazine-1-base) propyl group) benzothiazole pair
D4Receptor subtype has compatibility and selectivity, wherein with compound 2-(3-(4-(4-luorobenzyl) piperazine-1-base)
Propyl group) compatibility of benzothiazole (4A) is maximum.
Claims (4)
1. a dopamine D4Receptor-ligand, for 2-(3-(4-(4-substituted benzyl) piperazine-1-base) propyl group) benzo
Thiazole compound, shown in its structural formula such as formula (I):
2. a dopamine D as claimed in claim 14The preparation method of receptor-ligand, it is characterised in that
Comprise the steps:
(1) by 2-(3-chloropropyl) benzothiazole that mol ratio is 1.0:1.5~2.0 and N-formyl piperazine
It is dissolved in anhydrous solvent, adds reducing agent, add frozen water after stirring 20-30 hour under room temperature, after mixing
Extracting with organic solvent, organic layer anhydrous sodium sulfate obtains 2-(3-(4-through column chromatographic isolation and purification after being dried
Piperazine formaldehyde-1-base) propyl group) benzothiazole;
(2) 2-(3-(4-piperazine formaldehyde-1-base) propyl group) benzothiazole step (1) prepared and 3-10mol/L
H2SO4It is cooled to room temperature after reacting 10 hours at 60 DEG C-90 DEG C, adds in alkali and unnecessary acid, and shape
Becoming alkaline mixt, extract with organic solvent, organic layer anhydrous sodium sulfate is pure through column chromatography for separation after being dried
Change and obtain 2-(3-(4-piperazine-1-base) propyl group) benzothiazole;
(3) 2-(3-(4-piperazine-1-base) propyl group) benzothiazole that step (2) prepares is dissolved in Organic Alcohol molten
In agent, add 4-substituted benzaldehyde, acetic acid, reducing agent, be stirred at room temperature 3-5 hour, with organic molten
Agent and water extract mixture, and organic layer is dried through anhydrous sodium sulfate, and reduced pressure concentration, crude product is through Flash
2-(3-(4-(4-substituted benzyl) piperazine-1-base) propyl group) benzothiazole is obtained after pillar layer separation.
Dopamine D the most according to claim 24The preparation method of receptor-ligand, it is characterised in that:
Anhydrous solvent and organic solvent described in step (1)~(3) be dichloromethane, chloroform, acetonitrile,
One in acetone, ethyl acetate and toluene;Described reducing agent is lithium aluminium hydride reduction, sodium borohydride, triacetic acid
One in base sodium borohydride and sodium cyanoborohydride;Described in step (2), alkali is NaOH, hydrogen-oxygen
Change the one in potassium, ammonium hydroxide, barium hydroxide;Reacting described organic alcohol solvent in step (3) is first
One in alcohol, ethanol, n-butanol, octanol.
Dopamine D the most according to claim 24The preparation method of receptor-ligand, it is characterised in that:
In step (2), regulation mixture ph to 8.0-10.0.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6291463B1 (en) * | 1998-06-30 | 2001-09-18 | Neurogen Corporation | 1-(Benzothiazol-2-yl)-4-(1-phenylmethyl) piperazines: dopamine receptor subtype specific ligands |
CN1325397A (en) * | 1998-09-30 | 2001-12-05 | 纽罗根公司 | 2-piperazino alkylatnino benzoazole derivatives: dopamine receptor subtype sepcific ligands |
US20040063713A1 (en) * | 2002-05-29 | 2004-04-01 | Cowart Marlon D. | Fused bicyclic aromatic compounds that are useful in treating sexual dysfunction |
CN103110966A (en) * | 2013-03-14 | 2013-05-22 | 湖南工程学院 | Fluoride-18 marked dopamine D4 receptor developing agent and preparation method thereof |
-
2016
- 2016-03-31 CN CN201610199686.0A patent/CN105753811A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6291463B1 (en) * | 1998-06-30 | 2001-09-18 | Neurogen Corporation | 1-(Benzothiazol-2-yl)-4-(1-phenylmethyl) piperazines: dopamine receptor subtype specific ligands |
CN1325397A (en) * | 1998-09-30 | 2001-12-05 | 纽罗根公司 | 2-piperazino alkylatnino benzoazole derivatives: dopamine receptor subtype sepcific ligands |
US20040063713A1 (en) * | 2002-05-29 | 2004-04-01 | Cowart Marlon D. | Fused bicyclic aromatic compounds that are useful in treating sexual dysfunction |
CN103110966A (en) * | 2013-03-14 | 2013-05-22 | 湖南工程学院 | Fluoride-18 marked dopamine D4 receptor developing agent and preparation method thereof |
Non-Patent Citations (4)
Title |
---|
DINITHIA SAMPSON ET AL: "Identification of a new selective dopamine D4 receptor ligand", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
GU-CAI L ET AL: "Synthesis and in vitro evaluation of no-carrier-added 2-(3-(4-(4-[18F] fluorobenzyl) piperazin-1-yl) propyl) benzo [d] thiazole, a potential dopamine D4 receptor radioligand", 《RADIOCHIMICA ACTA》 * |
OLAF PRANTE ET AL: "Synthesis, Radiofluorination, and in vitro evaluation of Pyrazolo[1, 5-a]pyridine-Based Dopamine D4 Receptor Ligands: Discovery of an inverse Agonist Radioligand for PET", 《JOURNAL OF MEDICINAL CHEMISTRY》 * |
李谷才 等: "2-吲哚啉酮类化合物的合成及其体外活性研究", 《化学试剂》 * |
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