- Sulfate Encapsulation in Supramolecular Structures from L -Asparagine-Derived 2,5-Diketopiperazine Scaffolds: Anion Binding
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We report a new sulfate receptor, anchored onto 2,5-diketopiperazine units, which results in the formation of two types of supramolecules; one in which the sulfate ion guest fits snugly into extended cavities and the other in which the guest is sandwiched between layers. In each case, the anion is held by six hydrogen bonds from the host. 1H NMR spectroscopic solution studies enabled the construction of Job plots, and calculation of stoichiometry and association constants. These findings are of possible significance in drug design and for construction of combinatorial libraries.
- Naini, Santhosh Reddy,Lalancette, Roger A.,Gorlova, Olga,Ramakrishna, Kallaganti V. S.,Yadav, Jhillu Singh,Ranganathan, Subramania
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p. 7015 - 7022
(2016/02/19)
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- Highly enantioselective synthesis of orthogonally protected (2S)-2,3-diaminopropanoates through catalytic phase-transfer aza-Henry reaction
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The syntheses of enantiomer-enriched orthogonally protected different (2S)-2,3-diaminopropanoates and unnatural furyl-substituted (tert-butoxy) carbonyl (Boc) as well as (benzyloxy)carbonyl (Cbz) protected amino acid esters are accomplished by means of an
- Kumaraswamy, Gullapalli,Pitchaiah, Arigala
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experimental part
p. 1543 - 1550
(2011/10/08)
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- ETHER DERIVATIVE
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The present invention relates to an ether derivative represented by the formula (I), a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof wherein each symbol is as defined in the description, and an ether derivative represented by the formula (III), a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof wherein each symbol is as defined in the description; a pharmaceutical composition containing the ether derivative; and a package containing the pharmaceutical composition and a description of use thereof. A pharmaceutical composition of the present invention, which contains this compound of the present invention has a superior anti-inflammatory and analgesic activity and is useful as various pharmaceutical agents such as an anti-inflammatory agent, an analgesic, a therapeutic agent for inflammatory bowel disease, a therapeutic agent for pollakiuria and/or incontinentia, a therapeutic agent for asthma and the like.
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Page/Page column 35
(2008/06/13)
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- ACRYLAMIDE DERIVATIVES AS VLA-1 INTEGRIN ANTAGONISTS AND USES THEREOF
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Compounds that are VLA-1 integrin antagonists are disclosed. Also disclosed are compositions containing such compounds, and methods of using such compounds in treating diseases mediated, at least in part, by the VLA-1 integrin.
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Page/Page column 294-295
(2010/02/10)
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- MODULATORS OF CELLULAR ADHESION
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The present invention provides compounds having formula (I): and pharmaceutically acceptable derivatives thereof, wherein R1-R4, n, p, A, B, D, E, L and AR1 are as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof for the treatment of disorders mediated by the CD11/CD18 family of cellular adhesion molecules (e.g., LFA-1).
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Page/Page column 134
(2010/02/11)
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- NOVEL ETHYLENEDIAMINE DERIVATIVES
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A compound represented by the following formula (1):Q-Q-T-N(R)-Q-N(R)-T-Q [wherein, R1 and R2 are hydrogen atoms or the like; Q1 is a saturated or unsaturated, 5- or 6- membered cyclic hydrocarbon group which may have a substituent, or the like; Q2 is a single bond or the like; Q3 represents the following group: -C(R3a)(R4a)-{C(R3b)(R4b)}m1-{C(R3c)(R4c)}m2-{C(R3d)(R4d)}m3-{C(R3e)(R4e)}m4-C(R3f)(R4f)- (in which, R3a to R4e represent hydrogen or the like); T0 represents a carbonyl group or the like; and T1 represents -COCONR- or the like]; or salt thereof, solvate thereof, or N-oxide thereof. The compound is useful as a preventive and/or therapeutic agent for cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.
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Page/Page column 222-223
(2010/02/14)
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- Anthranilic acid derivatives as inhibitors of the cGMP-phosphodiesterase
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Compounds of formula (I) STR1where R 1 is hydrogen; R 2 is nitro, cyano or halo(lower)alkyl; R 3 is phenyl substituted with one or more substituents selected from halogen, cyano and lower alkoxy; A is a lower alkylene group; R 4 is a group CR 6 R 7 R 8 wherein R 6 and R 7 form, together with the carbon atom to which they are attached a cycloalkyl group optionally substituted with hydroxy, lower alkoxy or a lower alkanoylamino; and R 8 is hydrogen; its prodrug and a salt thereof.
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- Non-peptide GPIIb/IIIa inhibitors. 20. Centrally constrained thienothiophene α-sulfonamides are potent, long acting in vivo inhibitors of platelet aggregation
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The synthesis and pharmacology of 4, a potent thienothiophene non- peptide fibrinogen receptor antagonist, are reported. Compound 4 inhibited the aggregation of human gel-filtered platelets with an IC50 of 8 nM and demonstrated an 8-fold improvement in affinity for isolated GPIIb/IIIa receptors over analogues possessing an isoindolinone backbone. Flow cytometry studies revealed that the binding of 4 to resting platelets is a diffusion- controlled process (k(on) = 3.3 x 106 M-1 s-1) and that 4 binds to dog and human platelets with comparable affinity (K(d) = 0.04 and 0.07 nM, respectively). Ex vivo platelet aggregation in dogs was completely inhibited by an iv dose of 5 mg/kg, and an oral dose of 50-90 mg/kg followed by low daily doses of 10 mg/kg was sufficient to maintain ~80% inhibition of ex vivo platelet aggregation over several days. Inhibition of ADP-induced platelet aggregation in anesthetized dogs at 77 ± 7% resulted in a moderate 2.5-fold increase in bleeding time, while complete inhibition (100%) resulted in an approximately 10-min bleeding time. Additional doses were required to increase the bleeding time to the maximum time allowed in the protocol (15 min), thus indicating a potentially useful and safe separation of efficacy and bleeding time.
- Egbertson, Melissa S.,Cook, Jacquelynn J.,Bednar, Bohumil,Prugh, John D.,Bednar, Rodney A.,Gaul, Stanley L.,Gould, Robert J.,Hartman, George D.,Homnick, Carl F.,Holahan, Marie A.,Libby, Laura A.,Lynch Jr., Joseph J.,Lynch, Robert J.,Sitko, Gary R.,Stranieri, Maria T.,Vassallo, Laura M.
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p. 2409 - 2421
(2007/10/03)
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- Tripeptide aldehyde inhibitors of human rhinovirus 3C protease: Design, synthesis, biological evaluation, and cocrystal structure solution of P1 glutamine isosteric replacements
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The investigation of tripeptide aldehydes as reversible covalent inhibitors of human rhinovirus (HRV) 3C protease (3CP) is reported. Molecular models based on the apo crystal structure of HRV-14 3CP and other trypsin- like serine proteases were constructe
- Webber, Stephen E.,Okano, Koji,Little, Thomas L.,Reich, Siegfried H.,Xin, Yue,Fuhrman, Sheila A.,Matthews, David A.,Love, Robert A.,Hendrickson, Thomas F.,Patick, Amy K.,Meador III, James W.,Ferre, Rose Ann,Brown, Edward L.,Ford, Clifford E.,Binford, Susan L.,Worland, Stephen T.
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p. 2786 - 2805
(2007/10/03)
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- 2,3-diaminopropionic acid derivative
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The present invention relates to a 2,3-diaminopropionic acid derivative of the formula (1): STR1 or a pharmaceutically acceptable salt thereof. The compounds of the present invention are useful as a platelet aggregation inhibitor, a cancer metastasis inhibitor, a wound healing agent or a bone resorption inhibitor.
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- Design, synthesis, and in vitro activities of benzamide-core glycoprotein IIb/IIIa antagonists: 2,3-Diaminopropionic acid derivatives as surrogates of aspartic acid
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In an effort to discover novel nonpeptide glycoprotein IIb/IIIa (GPIIb/IIa, α(IIb)/β3) inhibitors, we investigated RGD mimetics featuring a 3-substituted benzoic acid as the core, benzamidine as the basic moiety, and a series of β- and α-substituted β-alanine derivatives as aspartic acid surrogates. It was found that the use of β-methyl β-alanine slightly improved the anti-aggregant potency in human platelet-rich plasma over the unsubstituted β-alanine compound, while β-substitution with a trifluoromethyl group resulted in considerable loss in activity. Significant enhancement (up to 100-fold) in potency was obtained when the β-alanine was replaced with N2-substituted L-2,3-diaminopropionic acid derivatives. Among the three types of α-substituents (carbamate, amide, and sulfonamide) investigated, no apparent preference was observed with respect to in vitro potency. However, alkyl groups were more favorable than arylalkyl groups (Cbz) in the carbamate analogues. We also investigated piperidine, piperazine, and N-formamidinopiperidine as replacements for the benzamidine moiety. The former two replacements led to a drop in potency while the latter replacement resulted in maintenance of activity as compared with the corresponding benzamidine analogue.
- Xue, Chu-Biao,Roderick, John,Jackson, Sharon,Rafalski, Maria,Rockwell, Arlene,Mousa, Shaker,Olson, Richard E.,DeGrado, William F.
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p. 693 - 705
(2007/10/03)
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- Non-peptide glycoprotein IIb/IIIa inhibitors. 9. Centrally constrained alpha-sulfonamides are useful tools for exploring platelet receptor function
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Two fluorescent, centrally constrained fibrinogen receptor antagonists were prepared to probe ligand receptor interactions.
- Egbertson,Bednar,Bednar,Hartman,Gould,Lynch,Vassallo,Young
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p. 1415 - 1420
(2007/10/03)
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- Design, synthesis and in vitro activities of a series benzimidazole/benzoxazole glycoprotein IIb/IIIa inhibitors
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A potent centrally constrained series of benzimidazole and benzoxazole glycoprotein IIb/IIIa inhibitors has been discovered based on the solution conformation of a cyclic RGD-containing peptide, DMP 728. The high potency of this series of compounds in the inhibition of platelet aggregation requires a benzamidine as the basic moiety and an α-carbamate or sulfonamide substituted β-alanine as the acidic moiety.
- Xue,Rafalski,Roderick,Eyermann,Mousa,Olson,DeGrado
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p. 339 - 344
(2007/10/03)
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- Fibrinogen receptor antagonists
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Fibrinogen receptor antagonists having the formula STR1 for example STR2
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- Fibrinogen receptor antagonists
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Fibrinogen receptor antagonists of the formula: STR1 are disclosed for use in inhibiting the aggregation of blood platelets. wherein G is: STR2
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- A selective protection of 2,3-diaminopropionic acid
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A two step selective protection of 2,3-diaminopropionic acid yields the useful diaminopropionic acid methyl ester 3a. Further manipulation yields 2(S)-(N-benzyloxycarbonylamino)-3-aminopropionic acid methyl ester hydrochloride 5 in >99.9%ee.
- Egbertson,Homnick,Hartman
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p. 703 - 709
(2007/10/02)
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- TOTAL SYNTHESIS OF GALANTIN I. REVISION OF THE ORIGINAL STRUCTURE
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The proposed structure of galantin I, isolated as a mixture of homologs (1a/1b = 9/1), was shown to be incorrect by total synthesis and was revised twice to finally give 5a and 5c, respectively, by total synthesis.
- Sakai, Naomi,Ohfune, Yasufumi
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p. 3183 - 3186
(2007/10/02)
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- A Convenient Differential Protection Strategy for Functional Group Manipulation of Aspartic and Glutamic Acids
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Procedures are provided for selective protection of the α-carboxyl groups of aspartic and glutamic acids via the 5-oxazolidinones 2.A convenient synthesis of a differentially protected derivative of (S)-2,3-diaminopropanoic acid, 3, is described, along wi
- Scholtz, John M.,Bartlett, Paul A.
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p. 542 - 544
(2007/10/02)
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