Bioorganic & Medicinal Chemistry Letters

Article	Citations
Design, synthesis and biological evaluation of alginate oligosaccharide derivatives	156
Design, synthesis and biological evaluation of tanshinone IIA derivatives as NLRP3 inflammasome inhibitors	80
Amyloidogenic immunoglobulin light chain kinetic stabilizers comprising a simple urea linker module reveal a novel binding sub-site	80
Revisiting the dipeptidyl carboxypeptidase inhibitor captopril as a source of pan anti-trypanosomatid agents	59
Novel carbohydrate-based sulfonamide derivatives as selective carbonic anhydrase II inhibitors: Synthesis, biological and molecular docking analysis	55
Editorial Board	47
Synthesis and biological evaluation of novel 1,2,3,4-tetrahydro-β-carboline derivatives as potential antibacterial agents	46
Synthesis and SAR of novel GPR39 agonists and positive allosteric modulators	43
Design of 99mTc-labeled zinc-chelating imaging probe for SPECT imaging of the pancreas	42
Discovery of structural diverse reversible BTK inhibitors utilized to develop a novel in vivo CD69 and CD86 PK/PD mouse model	40
Graphical Abstract TOC	38
Studies on in vitro modulatory effects to base excision repair enzymes induced by small molecule binding to Deaminated CAG repeat hairpin	35
Discovery of 3-amino-4-{(3S)-3-[(2-ethoxyethoxy)methyl]piperidin-1-yl}thieno[2,3-b]pyridine-2-carboxamide (DS96432529): A potent and orally active bone anabolic agent	33
Editorial Board	33
Editorial Board	32
Non-alkylator anti-glioblastoma agents induced cell cycle G2/M arrest and apoptosis: Design, in silico physicochemical and SAR studies of 2-aminoquinoline-3-carboxamides	32
New class of fused [3,2-b][1,2,4]triazolothiazoles for targeting glioma in vitro	31
Development of a highly potent and selective degrader of LRRK2	30
Phytochemical investigation of Asarum sieboldii var. seoulense and the phenotypic profiles of its constituents against a Parkinson’s Disease olfactory cell line	30
Synthesis and characterization of chiral 6-azaspiro[2.5]octanes as potent and selective antagonists of the M4 muscarinic acetylcholine receptor	29
Improved synthesis and anticancer activity of a potent neuronal nitric oxide synthase inhibitor	27
Design, synthesis, biological evaluation and molecular modeling of N-isobutyl-N-((2-(p-tolyloxymethyl)thiazol-4yl)methyl)benzo[d][1,3] dioxole-5-carboxamides as selective butyrylcholinesterase inhibit	27
Design and evaluation of anaplastic lymphoma kinase degraders using a covalent fumarate handle	26
Contents continued	25
Discovery of quinuclidine modulators of cellular progranulin	25

Discovery of TNG-6132, a potent, selective, and orally bioavailable USP1 inhibitor	25
Armeniaspirol analogues disrupt the electrical potential (ΔΨ) of the proton motive force	24
SARS-CoV-2 papain-like protease (PLpro) inhibitory and antiviral activity of small molecule derivatives for drug leads	23
A PSMA-targeted doxorubicin small-molecule drug conjugate	23
Design, synthesis and characterizations of prodrugs of brexanolone	23
Discovery of DS-1093a: An oral hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of renal anemia	22
Design and structural optimization of thiadiazole derivatives with potent GLS1 inhibitory activity	22
Pyrazolo-1-carbothioamides as EGR-1–DNA binding disruptors	22
Neuropilin 1-targeted near-infrared fluorescence probes for tumor diagnosis	21
Enteroviral replication inhibition by N-Alkyl triazolopyrimidinone derivatives through a non-capsid binding mode	21
Epigallocatechin and epigallocatechin-3-gallate are not inhibitors of tyrosinase	21
Green synthesis and anti-biofilm activities of 3,5-disubstituted isoxazoline/isoxazole-linked secondary sulfonamide derivatives on Pseudomonas aeruginosa	20
A fluorescent molecular rotor for the selective detection of the hybrid-conformation 22AG G-Quadruplex	20
Contents continued	19
Contents continued	19
A simple yet multifaceted 90 years old, evergreen enzyme: Carbonic anhydrase, its inhibition and activation	19
New bis- and tetrakis-1,2,3-triazole derivatives: Synthesis, DNA cleavage, molecular docking, antimicrobial, antioxidant activity and acid dissociation constants	19
Editorial Board	19
Graphical abstract TOC	18
pH-responsive aggregates consisted of oligodeoxynucleotides bearing nitrophenol group that deliver drugs into acidic cells	18
Exploratory study of oxatomide derivatives with high P2X7 receptor inhibitory activity	18
Graphical abstract TOC	18
Photocrosslinking and capture for the analysis of carbohydrate-dependent interactions	17
Topoisomerase IIα inhibitory and antiproliferative activity of dihydroxylated 2,6-diphenyl-4-fluorophenylpyridines: Design, synthesis, and structure-activity relationships	17
Graphical abstract TOC	17
Identification and evaluation of 4-anilinoquin(az)olines as potent inhibitors of both dengue virus (DENV) and Venezuelan equine encephalitis virus (VEEV)	17
Graphical abstract TOC	17
Design, synthesis and biological evaluation of pteridine-7(8H)-one derivatives as potent and selective CDK4/6 inhibitors	17
Discovery of arylsulfonamides as a novel class of allosteric integrase inhibitors with antiviral activity	17
DDD-028: A potent, neuroprotective, non-opioid compound for the treatment of diabetic neuropathy	17
Graphical abstract TOC	17
Design, synthesis, and biological evaluation of 5ʹ-deoxy (N)-methanocarbanucleoside derivatives as A3 adenosine receptor ligands	17
Discovery and optimization of (2-naphthylthio)acetic acid derivative as selective Bfl-1 inhibitor	17
Pharmacokinetic analysis of 6-O-[18F]FEE for PET imaging of EGFR mutation	17
Optimisation of momelotinib with improved potency and efficacy as pan-JAK inhibitor	16
Rational design, synthesis and biological evaluation of novel HIV-1 protease inhibitors containing 2-phenylacetamide derivatives as P2 ligands with potent activity against DRV-Resistant HIV-1 variants	16
Retraction notice to “Preclinical metabolism of LB42908, a novel farnesyl transferase inhibitor, and its effects on the cytochrome P450 isozyme activities” [Bioorg. Med. Chem. Lett. 22(9) (2012) 3067–	16
Biocatalytic synthesis and evaluation of antioxidant and antibacterial activities of hydroxyequols	16
Design, synthesis and biological evaluation of novel cyano-cinnamate derivatives as mitochondrial pyruvate carrier inhibitors	16
α-Fluorination of tropane compounds and its impact on physicochemical and ADME properties	16
High-yield and high-purity amide bond formation using DMTMM PF6 for DNA-encoded libraries	16
Synthesis and pharmacological characterization of multiply substituted 2H-chromene derivatives as P2Y6 receptor antagonists	16
An overview of cyclopropenone derivatives as promising bioactive molecules	16
nTZDpa (non-thiazolidinedione PPARγ partial agonist) derivatives retain antimicrobial activity without improving renal toxicity	16
PEG-lipid-modified agonistic antibody against tumor necrosis factor receptor family elicits superior apoptosis-inducing activity against human carcinoma	16
Biological evaluation of newly synthesized α-benzil monoxime thiocarbohydrazide derivatives as an antimicrobial and anticancer agent: In vitro screening and ADMET predictions	16
Structure-activity relationship study of HIF-2α inhibitors with tricyclic scaffold	16
Design, synthesis and biological evaluation of novel procaine derivatives for intravenous anesthesia	16
Contents continued	16
Ultrasound-dependent RNAi using TatU1A-rose bengal conjugate	16

Design and activity evaluation of new EGFR tyrosine kinase inhibitors containing cyclic polyamines	16
A photoactivatable self-localizing ligand with improved photosensitivity for chemo-optogenetic control of protein localization in living cells	15
Design and synthesis of novel fluorene derivatives as inhibitors of pyruvate dehydrogenase kinase	15
Comparative analysis of p-terphenylquinone and seriniquinone derivatives as reactive oxygen species-modulating agents	15
Synthesis and evaluation of lipoic acid – donepezil hybrids for Alzheimer’s disease using a straightforward strategy	15
Synthesis and evaluation of potent novel inhibitors of human sulfide:quinone oxidoreductase	15
Design and discovery of C2-fluoroalkyl iminothiazine dioxides as BACE inhibitors	15
Novel pyridinium-type fullerene derivatives as multitargeting inhibitors of HIV-1 reverse transcriptase, HIV-1 protease, and HCV NS5B polymerase	15
Design, synthesis and properties of peptide inhibitors based on BRCA1856-871	15
Stereochemical inversion at a 1,4-cyclohexyl PROTAC linker fine-tunes conformation and binding affinity	15
Synthesis and evaluation of 3-hydroxyquinolin-2(1H)-one derivatives as inhibitors of tyrosinase	15
Editorial Board	14
SAR towards indoline and 3-azaindoline classes of IDO1 inhibitors	14
Synthesis of a tricyclic hexapeptide –via two consecutive ruthenium-catalyzed macrocyclization steps– with a constrained topology to mimic vancomycin's binding properties toward D-Ala-D-Ala dipeptide	14
Structure–activity relationship of 2-aminodibenzothiophene pharmacophore and the discovery of aminobenzothiophenes as potent inhibitors of Mycobacterium smegmatis	14
Graphical Abstract Continued	14
Editorial Board	14
Synthesis of dolutegravir derivatives modified by 1,2,3-triazole structure and their anti-inflammatory activity in LPS-induced BV2 cells	14
Design and synthesis of a series of OFF-ON near infrared fluorescent probes for nucleic acid in aqueous solution	14
6-Aryl-quinazolines as novel GABAB receptor positive allosteric modulators	14
Design, synthesis and biological evaluation of cajanonic acid A analogues as potent PPAR γ antagonists	14
Reinvestigation of clopidogrel bioactivation unveils new cytochrome P450-catalyzed thioester cleavage mechanism	14
Synthesis and biological evaluation of substituted amide derivatives of C4-ageratochromene dimer analog	14
Design, synthesis and biological evaluation of pyrimidine base hydroxamic acid derivatives as dual JMJD3 and HDAC inhibitors	14
Improving reactivity of naphthalimide-based GST probe by imparting TPP cation: Development and application for live cell imaging	14
Design, synthesis and activity evaluation of Hedgehog inhibitor Itraconazole derivatives in A549 cells	14
(E)-3-(3-([1,1′-Biphenyl]-4-yl)-1-phenyl-1H-pyrazol-4-yl)-1-phenylprop-2-en-1-ones inducing reactive oxygen species generation through glutathione depletion	14
Graphical abstract TOC	14
Editorial Board	14
Graphical abstract TOC	13
Contents continued	13
A unified “top-down” approach for the synthesis of diverse lead-like molecular scaffolds	13
Enzymatic reconstitution of salicylate formation in promysalin biosynthesis	13
Editorial Board	13
Neratinib derivative 7A induces apoptosis in colon cancer cells via the p53 pathway	13
Discovery of sinomenine/8-Bis(benzylthio)octanoic acid hybrids as potential anti-leukemia drug candidate via mitochondrial pathway	13
Discovery of novel N-(1-benzyl-1H-imidazol-2-yl)amide derivatives as melanocortin 1 receptor agonists	13
Graphical Abstract Contents Continued	13
Structure-activity relationship of dual inhibitors containing maleimide and imidazole motifs against glutaminyl cyclase and glycogen synthase kinase-3β	13
Graphical abstract TOC	13
Structure-activity relationship of dibenzylideneacetone analogs against the neglected disease pathogen, Trypanosoma brucei	12
Phenyl urea based adjuvants for β-lactam antibiotics against methicillin resistant Staphylococcus aureus	12
A dual aurora and lim kinase inhibitor reduces glioblastoma proliferation and invasion	12
Design, synthesis and biological evaluation of novel cationic liposomes loaded with melphalan for the treatment of cancer	12
Rationalizing the binding and α subtype selectivity of synthesized imidazodiazepines and benzodiazepines at GABAA receptors by using molecular docking studies	12
Antibacterial activity of β-sitosterol isolated from the leaves of Odontonema strictum (Acanthaceae)	12
Design, synthesis, in silico studies, and antiproliferative evaluations of novel indolin-2-one derivatives containing 3-hydroxy-4-pyridinone fragment	12
Identification of potent and selective inhibitors of PKR via virtual screening and traditional design	12
Potent and selective carbonic anhydrase inhibition activities of pyrazolones bearing benzenesulfonamides	12
Synthesis of a new series of quinoline/pyridine indole-3-sulfonamide hybrids as selective carbonic anhydrase IX inhibitors	12
Graphical abstract TOC	12
Design, synthesis, and biological evaluation of polyphenol derivatives as DYRK1A inhibitors. The discovery of a potentially promising treatment for Multiple Sclerosis	12
Syntheses and antitumor activities of neorautenol and shinpterocarpin analogs	12
Discovery of triazenyl triazoles as Nav1.1 channel blockers for treatment of epilepsy	12
Direct-to-biology platform: From synthesis to biological evaluation of SHP2 allosteric inhibitors	12
Discovery of 3-acyl-2-anilino-1,4-dihydroquinolin-4-one derivatives as potential inhibitors of methicillin-resistant Staphylococcus aureus	11
Harnessing dual-mode RIPK1 ligands for cross-species anti-necroptosis inhibitor compounds	11
Graphical abstract TOC	11
Corrigendum to “Discovery of 4-aminopyrimidine analogs as highly potent dual P70S6K/Akt inhibitors” [Bioorgan. Med. Chem. Lett. 50 (2021) 128352]	11
Editorial Board	11
Graphical abstract TOC	11
Synthesis and evaluation of antimycobacterial activity of riboflavin derivatives	11
Methyl N-(tert-butoxycarbonyl)pyridine-2-carbimidothioate: A new reagent for the synthesis of N-phenylpyridinecarboxamidine (“arylimidamide”) DNA-minor groove binders from poorly nucleophilic amines	11
Graphical abstract TOC	11
Investigation of the site 2 pocket of Grp94 with KUNG65 benzamide derivatives	11
Contents continued	11
Design, synthesis and evaluation of clickable photoaffinity probes for nuclear lamins	11
Synthesis of mizoribine prodrugs and their in vivo evaluation as immunosuppressive agents	11
Development of novel GI-centric prostaglandin E2 receptor type 4 (EP4) agonist prodrugs as treatment for ulcerative colitis and other intestinal inflammatory diseases	11
A guanidinium group is an effective mimic of the tertiary carbocation formed by isopentenyl diphosphate isomerase	11
Graphical abstract TOC	11
Graphical abstract TOC	11
PSMA-targeted SMART molecules outfitted with SN38	11
Contents continued	11
Iodophenyl-conjugated closo-dodecaborate as a promising small boron molecule that binds to serum albumin and accumulates in tumor	10
A small molecule binding to TGGAA pentanucleotide repeats that cause spinocerebellar ataxia type 31	10
Hydrazinecarbonyl-thiazol-2-acetamides with pronounced apoptotic behavior: synthesis, in vitro/in vivo anti-proliferative activity and molecular modeling simulations	10
Synthesis and biological evaluation of biotinylated ZJ-101	10
Synthesis of esters and amides of 2-aryl-1-hydroxy-4-methyl-1H-imidazole-5-carboxylic acids and study of their antiviral activity against orthopoxviruses	10
Discovery of an ellipticine derivative as TLR3 inhibitor against influenza A virus and SARS-CoV-2	10

Photo-regulated PROTACs: A novel tool for temporal control of targeted protein degradation	10
Design, synthesis, and bioevaluation of SOS1 PROTACs derived from pyrido[2,3-d]pyrimidin-7-one-based SOS1 inhibitor	10
Synthesis, modeling, and biological evaluation of anti-tubulin indole-substituted furanones	10
Conversion of oxadiazolo[3,4-b]pyrazines to imidazo[4,5-b]pyrazines via a tandem reduction-cyclization sequence generates new mitochondrial uncouplers	10
Evaluation of an ester-linked immunosuppressive payload: A case study in understanding the stability and cleavability of ester-containing ADC linkers	10
Highly potent anti-inflammatory, analgesic and antioxidant activities of 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazine thiones	10
Permeation behavior of porphyrin derivatives with different functional group positions across cancer cell membranes	10
Novel drug discovery approaches for MMP-13 inhibitors in the treatment of osteoarthritis	10
Zinc-dependent deacetylases (HDACs) as potential targets for treating Alzheimer’s disease	10
A small-molecule pretargeting approach for PSMA-targeted conjugates	10
Further structural optimization and SAR study of sungsanpin derivatives as cell-invasion inhibitors	10
PES derivative PESA is a potent tool to globally profile cellular targets of PES	10
Discovery of a potent orally available pyrazolopyridone derivative as a novel selective bromodomain and extra-terminal domain (BET)-first bromodomain (BD1) inhibitor	10
Discovery of a proteolysis targeting chimera (PROTAC) as a potent regulator of FOXP3	10
Discovery of a potent and subtype-selective TYK2 degrader based on an allosteric TYK2 inhibitor	10
Designing a novel photoinduced electron transfer-based small-molecule fluorescent probe specific for CYP3A isozymes	10
New diarylpentanoids and chalcones as potential antimicrobial adjuvants	10
Activation of 8–17 DNAzyme with extra functional group at conserved residues is related to catalytic metal ion	9
Editorial Board	9
Thiamine analogues featuring amino-oxetanes as potent and selective inhibitors of pyruvate dehydrogenase	9
Editorial Board	9
Retraction notice to “Synthesis and bioevaluation of aryl-guanidino polyamine conjugates targeting the polyamine transporter” [Bioorg. Med. Chem. Lett. 20 (2010) 6421–6425]	9
Contents continued	9
Synthesis, in vitro cytotoxicity evaluation and mechanism of 5′ monosubstituted chalcone derivatives as antitumor agents	9
Design, synthesis, and biological evaluation of 2,4-diaminopyrimidine inhibitors of hematopoietic progenitor kinase 1	9
Imidazo[2,1-b]thiazole based indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor: Structure based design, synthesis, bio-evaluation and docking studies	9
Discovery of aryl aminothiazole γ-secretase modulators with novel effects on amyloid β-peptide production	9
Pyrimidine-2,4-dione targets STAT3 signaling pathway to induce cytotoxicity in hepatocellular carcinoma cells	9
Recent developments of benzimidazole based analogs as potential tubulin polymerization inhibitors: A critical review	9
Contents continued	9
Discovery of a DCAF11-dependent cyanoacrylamide-containing covalent degrader of BET-proteins	9
Synthesis of drimanyl indole fragments of drimentine alkaloids and their antibacterial activities	9
Discovery of IDO1 inhibitors containing a decahydroquinoline, decahydro-1,6-naphthyridine, or octahydro-1H-pyrrolo[3,2-c]pyridine scaffold	9
Graphical abstract TOC	9
Graphical abstract TOC	9
Graphical Abstract TOC	9
Cyano-Hydrol green derivatives: Expanding the 9-cyanopyronin-based resonance Raman vibrational palette	9
Graphical Abstract Contents Continued	9
Diamino variants of piperazine-based tissue transglutaminase inhibitors	9
Synthesis of proposed structure of ledebourin A	9
The structural modification and biological evaluation of tetrahydrothienopyridine derivatives as selective BChE inhibitors	9
Design, synthesis and antiproliferative activity of novel 2,4-diamino-5-methyleneaminopyrimidine derivatives as potential anticancer agents	9
Development of chromone-thiazolidine-2,4-dione Knoevenagel conjugates as apoptosis inducing agents	9
Graphical Abstract TOC	9
5-Fluoro-2′-deoxyuridine as an efficient 19F NMR reporter for G-quadruplex and i-motif structures	9
Graphical abstract TOC	9
Novel imidazo[1,5-a]quinoxaline derivatives: SAR, selectivity and modeling challenges en route to the identification of an α5-GABAA receptor NAM	9
Multigram-scale total synthesis of (±)-ambreinolide by a diastereoselective polyene cyclization	9
Discovery of BI-9787, a potent zwitterionic ketohexokinase inhibitor with oral bioavailability	9
Design, synthesis and biological evaluation of novel indole-piperazine derivatives as antibacterial agents	9
Synthesis and evaluation of catecholamine derivatives as amyloid-beta aggregation inhibitors	9
Synthesis and antitumor activity of a series of novel N-aryl-5-(2,2,2-trifluoroethoxy)-1,5-dihydro-2H-pyrrol-2-ones derivatives	9
An ascidian Polycarpa aurata-derived pan-inhibitor against coronaviruses targeting Mpro	9
Synthesis and properties of PNA containing a dicationic nucleobase based on N4-benzoylated cytosine	9
Design, synthesis, and biological evaluation of novel HDAC inhibitors with a 3-(benzazol-2-yl)quinoxaline framework	8
Discovery of the potent covalent inhibitor with an acrylate warhead for SARS-CoV-2 3CL protease	8
SAR study of niclosamide derivatives for neuroprotective function in SH-SY5Y neuroblastoma	8
Graphical abstract TOC	8
Exploration of inhibitors of the bacterial LexA repressor-protease	8
l-Hypaphorine and d-hypaphorine: Specific antiacetylcholinesterase activity in rat brain tissue	8
A FOXC2 inhibitor, MC-1-F2, as a therapeutic candidate for targeting EMT in castration-resistant prostate cancer	8
Identification of Plasmodium falciparum falcilysin inhibitors by a virtual screen	8
Retraction notice to “Corrigendum to “Preclinical metabolism of LB42908, a novel farnesyl transferase inhibitor, and its effects on the cytochrome P450 isozyme activities” [Bioorg. Med. Chem. Lett. 22	8
Graphical abstract TOC	8
Graphical Abstract Contents Continued	8
Discovery of L15 as a novel Vif PROTAC degrader with antiviral activity against HIV-1	8
Identification of (−)-Epigallocateshin gallate derivatives promoting innate immune activation via 2′,3′-cyclic GMP-AMP-stimulator of interferon genes pathway	8
Novel detection method for gallic acid: A water soluble boronic acid-based fluorescent sensor with double recognition sites	8
Graphical abstract TOC	8
Graphical abstract TOC	8
Design, synthesis and antitumor activity of novel 4-oxobutanamide derivatives	8
Editorial Board	8
Estimation of the lipophilicity of purine-2,6-dione-based TRPA1 antagonists and PDE4/7 inhibitors with analgesic activity	8
Editorial Board	8
Design, synthesis and evaluation of the Brigatinib analogues as potent inhibitors against tertiary EGFR mutants (EGFRdel19/T790M/C797S and EGFRL858R/T790M/C797S)	8
Synthesis and preliminary immunologic properties of di-/trisaccharide-conjugates related to Bacillus anthracis	8
Sensitive and reliable gastric ulcer related MicroRNA detection by bridge catalytic hairpin assembly (bCHA) mediated primer exchange reaction	8
Editorial Board	8
Discovery of EP300/CBP histone acetyltransferase inhibitors through scaffold hopping of 1,4-oxazepane ring	8
Discovery of cinnoline derivatives as potent PI3K inhibitors with antiproliferative activity	8
Expanded library of novel 2,3-pyrrolidinedione analogues exhibit anti-biofilm activity	8
The lipidation and glycosylation enabling bioactivity enhancement and structural change of antibacterial peptide G3	8
Inhibitors for metallo-β-lactamases from the B1 and B3 subgroups provide an avenue to combat a major mechanism of antibiotic resistance	8
Design, synthesis and biological evaluation of sulfonylurea derivatives as NLRP3 inflammasome inhibitors	8
Editorial Board	8
4-Oxooctahydroquinoline-1(2H)-carboxamides as hepatitis B virus (HBV) capsid core protein assembly modulators	8
Aiming to improve binding of porphyrin diphenyl guanidinium conjugates to guanine-quadruplexes: When size matters	8
Discovery of acyl ureas as highly selective small molecule CSF1R kinase inhibitors	8
Design, synthesis, and activity evaluation of Asiatic acid derivatives as Survivin inhibitors	8
Synthesis, antiproliferative activity, and biological profiling of C-19 trityl and silyl ether andrographolide analogs in colon cancer and breast cancer cells	8
Design and synthesis of novel orexin 2 receptor agonists based on naphthalene skeleton	8
Editorial Board	8
Fragment-based discovery of novel phenyltriazolyl derivatives as allosteric type-I1/2 ALK inhibitors with promising antitumor effects	8
The association between oxidized low-density lipoprotein and cancer: An emerging targeted therapeutic approach?	8
Synthesis and biological evaluation of novel 18F-labeled 2,4-diaminopyrimidine derivatives for detection of ghrelin receptor in the brain	8