Discovery and structure-activity relationships of novel selective norepinephrine and dual serotonin/norepinephrine reuptake inhibitors.

abstract：:A new class of kappa-opioid receptor agonists is described. The design of these agents was based upon energy minimization and structural overlay studies of the generic azepin-2-one structure 3 with the crystal structure of arylacetamide kappa agonist 1, ICI 199441. The most active compound identified was ligand 4a (K(...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tuthill PA,Seida PR,Barker W,Cassel JA,Belanger S,DeHaven RN,Koblish M,Gottshall SL,Little PJ,DeHaven-Hudkins DL,Dolle RE

更新日期：2004-11-15 00:00:00

abstract：:Antagonists of the integrin receptor alpha(v)beta(3) are expected to have utility in the treatment of osteoporosis through inhibition of bone resorption. A series of potent, chain-shortened, pyrrolidinone-containing alpha(v)beta(3) receptor antagonists is described. Two sets of diasteromeric pairs of high-affinity ant...

journal_title：Bioorganic & medicinal chemistry letters

authors： Perkins JJ,Duong LT,Fernandez-Metzler C,Hartman GD,Kimmel DB,Leu CT,Lynch JJ,Prueksaritanont T,Rodan GA,Rodan SB,Duggan ME,Meissner RS

更新日期：2003-12-15 00:00:00

abstract：:The reaction between methanethiosulfonate reagents and cysteine mutants of subtilisin is quantitative and can be used to prepare chemically modified mutant enzymes (CMMs) with novel properties. The virtually unrestricted structural variations possible for CMMs presents a preparative and screening challenge. To address...

journal_title：Bioorganic & medicinal chemistry letters

authors： Plettner E,Khumtaveeporn K,Shang X,Jones JB

更新日期：1998-09-08 00:00:00

abstract：:Analogues of the naturally occurring cyclic hydroxamate dealanylalahopcin, which is an inhibitor of procollagen prolyl-4-hydroxylase, were synthesised and shown to be inhibitors of the human hypoxia-inducible factor prolyl hydroxylases. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schlemminger I,Mole DR,McNeill LA,Dhanda A,Hewitson KS,Tian YM,Ratcliffe PJ,Pugh CW,Schofield CJ

更新日期：2003-04-17 00:00:00

abstract：:A three-dimensional pharmacophore model has been generated for HIV-1 integrase (HIV-1 IN) from known inhibitors. A dataset consisting of 26 inhibitors was selected on the basis of the information content of the structures and activity data as required by the catalyst/HypoGen program. Our model was able to predict the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mustata GI,Brigo A,Briggs JM

更新日期：2004-03-22 00:00:00

abstract：:Double-stranded RNA has become a ubiquitous tool for inhibition of gene expression in the laboratory. If similar success could be achieved in vivo, duplex RNA might provide a new class of therapeutics capable of treating a broad spectrum of disease. Chemists and biologists developing duplex RNA as a drug have made pro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Watts JK,Corey DR

更新日期：2010-06-01 00:00:00

abstract：:A series of competitive, reversible cathepsin S (CatS) inhibitors was investigated. An earlier disclosure detailed the discovery of the 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety as an effective replacement for the 4-arylpiperazin-1-yl group found in our screening hit. Continued investigation into replacement...

journal_title：Bioorganic & medicinal chemistry letters

authors： Grice CA,Tays K,Khatuya H,Gustin DJ,Butler CR,Wei J,Sehon CA,Sun S,Gu Y,Jiang W,Thurmond RL,Karlsson L,Edwards JP

更新日期：2006-04-15 00:00:00

abstract：:We disclose a novel series of insulin-like growth factor-1 receptor kinase inhibitors based on the 3-(pyrimidin-4-yl)-imidazo[1,2-a]pyridine scaffold. The influence on the inhibitory activity of substitution on the imidazopyridine and at the C5 position of the pyrimidine is discussed. In the course of this optimizatio...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ducray R,Simpson I,Jung FH,Nissink JW,Kenny PW,Fitzek M,Walker GE,Ward LT,Hudson K

更新日期：2011-08-15 00:00:00

abstract：:A series of N-7-methyl-imidazolopyrimidine inhibitors of the mTOR kinase have been designed and prepared, based on the hypothesis that the N-7-methyl substituent on imidazolopyrimidine would impart selectivity for mTOR over the related PI3Kα and δ kinases. The corresponding N-Me substituted pyrrolo[3,2-d]pyrimidines a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee W,Ortwine DF,Bergeron P,Lau K,Lin L,Malek S,Nonomiya J,Pei Z,Robarge KD,Schmidt S,Sideris S,Lyssikatos JP

更新日期：2013-09-15 00:00:00

abstract：:5-Hydroxyalkyl-4-phenylpyridines have been identified as a novel class of glucagon antagonists with potential utility for the treatment of diabetes. A lead structure with moderate activity was discovered through a high throughput screening assay. Structure-activity relationships led to the discovery of a potent antago...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ladouceur GH,Cook JH,Doherty EM,Schoen WR,MacDougall ML,Livingston JN

更新日期：2002-02-11 00:00:00

abstract：:Series of benzyl-phenoxybenzyl amino-phenyl acid derivatives (8a-q) are reported as non-steroidal GR antagonist. Compound 8g showed excellent h-GR binding and potent antagonistic activity (in vitro). The lead compound 8g exhibited significant oral antidiabetic and antihyperlipidemic effects (in vivo), along with liver...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shah K,Patel D,Jadav P,Sheikh M,Sairam KV,Joharapurkar A,Jain MR,Bahekar R

更新日期：2012-09-15 00:00:00

abstract：:A series of lobelane and GZ-793A analogues that incorporate aromatic 4-hydroxy and 4-(2-fluoroethoxy) substituents were synthesized and evaluated for inhibition of [(3)H]dopamine (DA) uptake at the vesicular monoamine transporter-2 (VMAT2) and the dopamine transporter (DAT), and [(3)H]serotonin uptake at the serotonin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Joolakanti SR,Nickell JR,Janganati V,Zheng G,Dwoskin LP,Crooks PA

更新日期：2016-05-15 00:00:00

abstract：:A facile method for the construction of double bond between 3-ylidene oxindoles and α-azido ketones has been successfully accomplished with a mild base. This method features azido reduction with concomitant double bond formation to provide the new class of bioactive enamino-2-oxindoles. These new compounds were screen...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumar NP,Vanjari Y,Thatikonda S,Pooladanda V,Sharma P,Sridhar B,Godugu C,Kamal A,Shankaraiah N

更新日期：2018-12-01 00:00:00

abstract：:Pyrimidine analogs of antimycobacterial purines have been synthesized and their biological activities evaluated. Several 5-formamidopyrimidines exhibited profound activity against Mycobacterium tuberculosis in vitro (IC(90)< or =1.5 microg/mL), and they were essentially inactive against other bacteria. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Braendvang M,Charnock C,Gundersen LL

更新日期：2009-06-15 00:00:00

abstract：:Eight peptoids have been synthesized as peptidomimetics of the cytostatic Dolastatin 15, a depsipeptide isolated from the Indian sea hare Dolabella auricularia. The compounds have been tested against several human cancer cell lines and did not show any cytostatic properties. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schmitt J,Bernd M,Kutscher B,Kessler H

更新日期：1998-02-17 00:00:00

abstract：:The α7-nicotinic acetylcholine receptor (α7-nAChR) subtype, is found to have a connection with the pathogenesis of a variety of psychiatric and neurological disorders. Herein, we report the development of radioiodinated 9-fluorenone derivatives as single-photon emission computed tomography (SPECT) imaging tracers for ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gao H,Wang S,Qi Y,He G,Qiang B,Wang S,Zhang H

更新日期：2019-12-01 00:00:00

abstract：:Naphthalimide-derived azoles as a new type of antimicrobial agents were synthesized and evaluated for their efficiency in vitro against eight bacteria and two fungi by two fold serial dilution technique. Most title compounds exhibited good antimicrobial potency with low MIC values ranging from 1 to 16μg/mL. Notably, s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang YY,Zhou CH

更新日期：2011-07-15 00:00:00

abstract：:We report the preliminary results of the synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a number of phenyl alkyl imidazole-based compounds as inhibitors of the two components of 17alpha-hydroxylase/17,20-lyase (P450(17alpha)), that is, 17alpha-hydroxylase (17alpha-OHase) and 17,20-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patel CH,Dhanani S,Owen CP,Ahmed S

更新日期：2006-09-15 00:00:00

abstract：:A series of MT-II related cyclic peptides, based on potent but non-selective hMC4R agonist (Penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2)) was prepared in which His(6) residue was systematically substituted. Two of the most interesting peptides identified in this study are Penta-c[Asp-5-ClAtc-DPhe-Arg-Trp-Lys]-N...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cheung AW,Danho W,Swistok J,Qi L,Kurylko G,Rowan K,Yeon M,Franco L,Chu XJ,Chen L,Yagaloff K

更新日期：2003-04-07 00:00:00

abstract：:A novel series of 4-arylphthalazin-1(2H)-one linked to arylpiperidines were synthesized and evaluated as MCH-R1 antagonists. The results of an extensive SAR study probing the effects of substituents on the 4-arylphthalazin-1(2H)-one C-4 aryl group led to the identification of the 4-(3,4-difluorophenyl) derivative as a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lim CJ,Kim SH,Lee BH,Oh KS,Yi KY

更新日期：2012-01-01 00:00:00

abstract：:A series of 1-indazol-3-(1-phenylpyrazol-5-yl)methyl ureas were investigated as hTRPV1 antagonists. The structure-activity relationship study was conducted systematically for both the indazole A-region and the 3-trifluoromethyl/t-butyl pyrazole C-region to optimize the antagonism toward the activation by capsaicin. Am...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kang JM,Kwon SO,Ann J,Blumberg PM,Ha H,Yoo YD,Frank-Foltyn R,Lesch B,Bahrenberg G,Stockhausen H,Christoph T,Lee J

更新日期：2020-12-01 00:00:00

abstract：:Novel derivatives of the D-glucosidase inhibitor 2,5-dideoxy-2,5-imino-D-mannitol bearing lipophilic aliphatic or aromatic amides attached to C-1 have been found to inhibit beta-glucosidase from Agrobacterium sp. in the nanomolar range. One of them, a coumarin derivative, ranks amongst the most active compounds in the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wrodnigg TM,Withers SG,Stütz AE

更新日期：2001-04-23 00:00:00

abstract：:A series of new 9-O-substituted berberine derivatives (4a-j) as telomeric quadruplex ligands was synthesized and evaluated. The results from biophysical and biochemical assay indicated that introducing of positive charged aza-aromatic terminal group into the side chain of 9-position of berberine significantly improved...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ma Y,Ou TM,Tan JH,Hou JQ,Huang SL,Gu LQ,Huang ZS

更新日期：2009-07-01 00:00:00

abstract：:6-(4H-Selenolo[3,2-b]pyrrolyl)-L-alanine 1, 4-(6H-selenolo[2,3-b]pyrrolyl)-L-alanine 2, and 6-(4H-furo[3,2-b]pyrrolyl)-L-alanine 3 have been synthesized via reactions of selenolo[3,2-b]pyrrole, selenolo[2,3-b]pyrrole, and furo[3,2-b]pyrrole, respectively, with L-serine. The reactions are catalyzed by Salmonella typhim...

journal_title：Bioorganic & medicinal chemistry letters

authors： Welch M,Phillips RS

更新日期：1999-03-08 00:00:00

abstract：:We re-examined the accessory site of the 4,5-epoxymorphinan skeleton by camdas conformational analysis in an effort to deign novel delta opioid receptor antagonists. We synthesized three novel compounds (SN-11, 23 and 28) with a 10-methylene bridge and without a 4,5-epoxy ring. Among them, compounds SN-23 (17-isobutyl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nagase H,Osa Y,Nemoto T,Fujii H,Imai M,Nakamura T,Kanemasa T,Kato A,Gouda H,Hirono S

更新日期：2009-05-15 00:00:00

abstract：:A novel class of 2,3-diaminopyridine bradykinin B1 receptor antagonists is disclosed. Structure-activity relationship studies (SARs) that led to compounds with significantly improved potency and pharmacokinetic properties relative to the lead compound are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Feng DM,Wai JM,Kuduk SD,Ng C,Murphy KL,Ransom RW,Reiss D,Chang RS,Harrell CM,MacNeil T,Tang C,Prueksaritanont T,Freidinger RM,Pettibone DJ,Bock MG

更新日期：2005-05-02 00:00:00

abstract：:A series of N1-activated C4-carboxy azetidinones was prepared and tested as inhibitors of human tryptase. The key stereochemical and functional features required for potency, serine protease specificity and aqueous stability were determined. From these studies compound 2, BMS-262084, was identified as a potent and sel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sutton JC,Bolton SA,Hartl KS,Huang MH,Jacobs G,Meng W,Ogletree ML,Pi Z,Schumacher WA,Seiler SM,Slusarchyk WA,Treuner U,Zahler R,Zhao G,Bisacchi GS

更新日期：2002-11-04 00:00:00

abstract：:In order to exploit cyclophilin as a potential target for neurological drug design, we demonstrate in this presentation that several nonimmunosuppressant analogues of cyclosporin A, modified at the various positions in the 'effector' domain, are equipotent nerve growth agents compared to cyclosporin A. Our results sug...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wei L,Steiner JP,Hamilton GS,Wu YQ

更新日期：2004-09-06 00:00:00

abstract：:The design and synthesis of a series of C28 amine-based betulinic acid derivatives as HIV-1 maturation inhibitors is described. This series represents a continuation of efforts following on from previous studies of C-3 benzoic acid-substituted betulinic acid derivatives as HIV-1 maturation inhibitors (MIs) that were e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen Y,Sit SY,Chen J,Swidorski JJ,Liu Z,Sin N,Venables BL,Parker DD,Nowicka-Sans B,Lin Z,Li Z,Terry BJ,Protack T,Rahematpura S,Hanumegowda U,Jenkins S,Krystal M,Dicker ID,Meanwell NA,Regueiro-Ren A

更新日期：2018-05-15 00:00:00

abstract：:We report the discovery of N-((benzo[d][1,3]dioxol-5-yl)methyl)-6-phenylthieno[3,2-d]pyrimidin-4-amine (2a) as an apoptosis inducer using our proprietary cell- and caspase-based ASAP HTS assay, and SAR study of HTS hit 2a which led to the discovery of 4-anilino-N-methylthieno[3,2-d]pyrimidines and 4-anilino-N-methylth...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kemnitzer W,Sirisoma N,May C,Tseng B,Drewe J,Cai SX

更新日期：2009-07-01 00:00:00