- Design, synthesis and anticancer mechanistic studies of linked azoles
-
Herein we report the synthesis and biological activity evaluation of 2,4 linked azole-containing molecules. A total of 13 linked thiazole- and oxazole-containing compounds were synthesized in good yields. Cytotoxicity evaluation of those compounds showed
- Islam, Md. Amirul,Zhang, Yuqi,Wang, Yao,McAlpine, Shelli R.
-
p. 300 - 305
(2015/03/30)
-
- Synthesis of macrocycles that inhibit protein synthesis: Stereochemistry and structural based studies on sanguinamide B derivatives
-
We report the synthesis of seven new sanguinamide B (SanB) analogues. Substitution of amino acids along the backbone of SanB and testing in HCT-116 colon cancer cell lines identified new biologically active SanB derivatives. These compounds establish a st
- Pietkiewicz, Adrian L.,Wahyudi, Hendra,McConnell, Jeanette R.,McAlpine, Shelli R.
-
p. 6979 - 6982
(2015/02/05)
-
- Mechanistic studies of sanguinamide B derivatives: A unique inhibitor of eukaryotic ribosomes
-
Described are mechanistic studies of two Sanguinamide B (San B) derivatives. These compounds were identified as eukaryotic ribosomal inhibitors. Two biotinylated San B derivatives were synthesized and used to capture protein targets in a pull-down assay.
- Tantisantisom, Worawan,Ramsey, Deborah M.,McAlpine, Shelli R.
-
supporting information
p. 4638 - 4641
(2013/10/08)
-
- Discovery of a new class of glucosylceramide synthase inhibitors
-
A novel series of potent inhibitors of glucosylceramide synthase are described. The optimization of biochemical and cellular potency as well as ADME properties led to compound 23c. Broad tissue distribution was obtained following oral administration to mice. Thus 23c could be another useful tool compound for studying the effects of GCS inhibition in vitro and in vivo.
- Koltun, Elena,Richards, Steven,Chan, Vicky,Nachtigall, Jason,Du, Hongwang,Noson, Kevin,Galan, Adam,Aay, Naing,Hanel, Art,Harrison, Amanda,Zhang, Jeff,Won, Kwang-Ai,Tam, Danny,Qian, Fawn,Wang, Tao,Finn, Patricia,Ogilvie, Kathleen,Rosen, Jon,Mohan, Raju,Larson, Christopher,Lamb, Peter,Nuss, John,Kearney, Patrick
-
scheme or table
p. 6773 - 6777
(2011/12/05)
-
- Synthesis of new oxathiazinane dioxides and their in vitro cancer cell growth inhibitory activity
-
New oxathiazinane dioxides derived from d- and l-serine have been tested for their in vitro cell growth inhibitory activity toward SKBR3 breast cancer cells. Compound (R)-24 (R′ = BrCH2C6H 4-C6H4CH2) showed a cytotoxicity with IC50 ≈ 10 μM.
- Borcard, Fran?oise,Baud, Matthias,Bello, Claudia,Dal Bello, Giovanna,Grossi, Francesco,Pronzato, Paolo,Cea, Michele,Nencioni, Alessio,Vogel, Pierre
-
supporting information; experimental part
p. 5353 - 5356
(2010/11/04)
-
- A class of novel Schiff's bases: Synthesis, therapeutic action for chronic pain, anti-inflammation and 3D QSAR analysis
-
To discover analgesics for treating chronic pain 17 novel Schiff's bases, N,N′-(Z-allylidene-1,3-diyl)bisamino acid methyl esters were prepared from 1,1,3,3,-tetramethoxypropane and amino acid methyl esters. On tail-flick mouse model 20 μmol/kg of these Schiff's bases were orally administered, the analgesic action started 30 min after administration, reached the maximum 120 min after administration, and at 180 min this action was still observed. On a xylene-induced ear edema mouse model 20 μmol/kg of these Schiff's bases exhibited desirable anti-inflammation. Thus the present Schiff's bases are able to treat chronic pain from inflammation. The effect of the side chains of the amino acid residues of these Schiff's bases on the analgesic activity was explained with 3D QSAR.
- Zhou, Yinjian,Zhao, Ming,Wu, Yingting,Li, Chunyu,Wu, Jianhui,Zheng, Meiqing,Peng, Li,Peng, Shiqi
-
experimental part
p. 2165 - 2172
(2010/05/18)
-
- NOVEL DIHYDROXYPYRROLIDINE DERIVATIVES AS ANTI-CANCER AGENTS
-
The present invention provides new dihydroxypyrrolidine derivatives for use as medicaments. The compounds are useful in the treatment in cancer, in particular non-solid neoplasms.
- -
-
Page/Page column 21-22
(2009/10/22)
-
- Efficient three-step sequence for the deamination of α-aminoesters. Application to the synthesis of CysLT1 antagonists
-
A practical and efficient three-step sequence for the deamination of α-aminoesters is reported. This method is based on the NaBH4-mediated selective reduction of α-diazoesters to α-hydrazonoesters and has been successfully applied to the deamin
- González, Alfredo,Pérez, Daniel,Puig, Carles,Ryder, Hamish,Sanahuja, Jordi,Solé, Laia,Bach, Jordi
-
supporting information; experimental part
p. 2750 - 2753
(2009/09/25)
-
- A microwave enhanced cross-metathesis approach to peptidomimetics
-
Functionalization of amino acid C- and N-termini with appropriate olefinic moieties allows for the generation of a peptidomimetic via a stereoselective cross-metathesis. This journal is The Royal Society of Chemistry.
- Morris, Thomas,Sandham, David,Caddick, Stephen
-
p. 1025 - 1027
(2008/01/01)
-
- PIPERAZINE UREA DERIVATIVES FOR THE TREATMENT OF ENDOMETRIOSIS
-
Use of a compound of the following formula (Ia) for the production of a medicament for the treatment of endometriosis in human wherein the treatment comprises administering to a human female in need of such treatment a therapeutically effective amount of said compound.
- -
-
Page/Page column 92
(2008/06/13)
-
- 2-QUINOXALINONE DERIVATIVES AS BRADYKININ ANTAGONISTS AND NOVEL COMPOUNDS
-
2-Quinoxalinone derivatives are bradykinin B1 antagonists or inverse agonists useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.
- -
-
Page/Page column 16
(2010/02/10)
-
- NOVEL QUINOXALINONE DERIVATIVES AS BRADYKININ B1 ANTAGONISTS
-
2-Quinoxalinone derivatives are bradykinin B1 antagonists or inverse agonists useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.
- -
-
Page/Page column 29
(2010/02/07)
-
- A biomimetic route to the peptide alkaloid anachelin
-
A postulated biogenesis forms the basis for a synthetic route to the natural product anachelin H (1). Key steps include a tellurium-mediated, oxidative aza annulation and a Claisen condensation under mild conditions. Experiments with a model substrate ind
- Gademann, Karl,Bethuel, Yann
-
p. 3327 - 3329
(2007/10/03)
-
- Growth hormone secretagogues
-
What is disclosed are growth hormone secretagogues, and their uses, of the formula wherein R1 is C6H5CH2OCH2—, C6H5(CH2)3— or indol-3-ylmethyl; Y is pyrrolidin-1-yl, 4-C1-C6alkylpiperidin-1-yl or NR2R2; R2 are each independently a C1to C6alkyl; R3 is 2-napthyl or phenyl para-substituted by W; W is H, F, CF3, C1-C6alkoxy or phenyl; and R4 is H or CH3, or a pharmaceutically acceptable salt or solvate thereof.
- -
-
Page column 9; 24
(2010/02/09)
-
- Combinations of β3 agonists and growth hormone secretagogues
-
This invention is directed to pharmaceutical compositions comprising β3adrenergic agonists including (4-(2-(2-(6-aminopyridin-3-yl)-2(R)-hydroxyethylamino)ethoxy)phenyl)acetic acid and growth hormone or growth hormone secretagogues, prodrugs thereof or pharmaceutically acceptable salts of said compounds or said prodrugs. The invention is also directed to methods of using those compositions in the treatment of obesity, diabetes, hypertension and frailty in animals and particularly in humans.
- -
-
Page column 96
(2008/06/13)
-
- Treatment of insulin resistance with growth hormone secretagogues
-
This invention is directed to methods of treating insulin resistance in a mammal which comprise administering an effective amount of a compound of formula I, where the variables are defined in the specification, or the stereoisomeric mixtures, diastereomerically enriched, diastereomerically pure, enantiomerically enriched or enantiomerically pure isomers, or the pharmaceutically acceptable salts and prodrugs thereof to said mammal. The compounds of formula I are growth hormone secretagogues and as such are useful for increasing the level of endogenous growth hormone. In another aspect this invention provides certain intermediates which are useful in the synthesis of the foregoing compounds and certain processes useful for the synthesis of said intermediates and the compounds of formula I. This invention is further directed to methods comprising administering to a human or other animal a combination of a functional somatostatin antagonist such as an alpha-2 adrenergic agonist and a compound of formula I.
- -
-
-
- Piperazine derivatives and their use as anti-inflammatory agents
-
This invention is directed to acyl piperazine derivatives which are useful as anti-inflammatory agents. This invention is also directed to pharmaceutical compositions containing the compounds of the invention, and methods of using the compounds to treat inflammatory disorders in humans.
- -
-
Page 47 - 48
(2008/06/13)
-
- PIPERAZINE DERIVATIVES AND THEIR USE AS ANTI-INFLAMMATORY AGENTS
-
This invention is directed to acyl piperazine derivatives of formula (Ia): wherein R 1a, R 2, R 3, R 4, R 5and R 6 are defined herein, which are useful as anti-inflammatory agents. This invention is also directed to other acyl piperazine derivatives, pharmaceutical compositions containing the compounds of the invention, and methods of using the compounds to treat inflammatory disorders in humans.
- -
-
-
- Stereospecific Synthesis of α-Deuteriated α-Amino Acids: Regiospecific Deuteriation of Chiral 3-Isopropyl-2,5-dimethoxy-3,6-dihydropyrazines
-
Base-catalysed deuteriation of (3R)- or (3S)-3-isopropyl-2,5-dimethoxy-3,6-dihydropyrazines in refluxing CH3O2H-2H2O gives the -isotopomer in excellent yields without disturbing the stereogenic centre at C-3.These compounds provide convenient and efficient access to a range of (R)- and (S)-α-deuteriated α-amino acids, including serine, aspartic acid, allylglycine and phenylalanine, via alkylation of the butyllithium generated C-6 anion.
- Rose, Janet E.,Leeson, Paul D.,Gani, David
-
p. 157 - 166
(2007/10/02)
-
- Synthesis of the (α,α-difluoroalkyl)phosphonate analogue of phosphoserine
-
The synthesis of the (α,α-difluoroalkyl)phosphonate analogue of L- phosphoserine, 5, in a form appropriate for solid phase peptide synthesis, is reported. Two independent routes are described, starting from L-serine or (R)-isopropylideneglycerol. In each case, PCF2-C bond formation is achieved by triflate displacement with diethyl lithiodifluoromethylphosphonate.
- Berkowitz, David B.,Shen, Quanrong,Maeng, Jun-Ho
-
p. 6445 - 6448
(2007/10/02)
-
- Chemoselective deprotection of benzyl esters in the presence of benzyl ethers, benzyloxymethyl ethers and N-benzyl groups by catalytic transfer hydrogenation
-
-COOBn, -PO(OH)OBn, -O-CBz and N-CBz groups are efficiently and chemoselectively deprotected in the presence of Bn and BOM ethers and N-Bn groups by hydrogenolysis under catalytic transfer hydrogenation using 10% palladium on carbon as the catalyst and cyclohexadiene as the hydrogen donor.
- Bajwa
-
p. 2299 - 2302
(2007/10/02)
-
- ENANTIOSELECTIVE SYNTHESIS OF NON-PROTEINOGENIC AMINO ACIDS VIA METALLATED BIS-LACTIM ETHERS OF 2,5-DIKETOPIPERAZINES
-
Bis-lactim ethers 1 of 2,5-diketopiperazines contain a chiral inducing center, an acidic CH-bond and two sites susceptible to hydrolysis.They react with BuLi to give Li compounds of type 4, 15, 29 or 32, which possess a prochiral C atom.They readily add electrophiles (such as alkylating agents or carbonyl compounds) with unusually high diastereoface differentiation.In many cases the d.e-value (d.e. = diastereomeric excess = asymmetric induction) of the adduct exceeds 95percent.On hydrolysis the adducts are cleaved liberating the chiral auxiliary (used to build up the bis-lactim ether 1) and the target molecules, the optically active amino acid methyl esters of type 8, 19, 25 or 36.The two amino acid esters are separable either by fractional distillation or (eventually after further hydrolysis to amino acids) by chromatography.Transition state models are discussed that could explain the exceptionally high asymmetric induction and the predictability of the induced configuration.
- Schoellkopf, Ulrich
-
p. 2085 - 2092
(2007/10/02)
-