- ALPHA-5 BETA-1 INHIBITORS
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The disclosure provides, inter alia, alpha-5 beta-1 inhibitors, pharmaceutical compositions comprising alpha-5 beta-1 inhibitors, methods for treating diseases using alpha-5 beta-1 inhibitors, and processes for making alpha-5 beta-1 inhibitors.
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Paragraph 0323; 0325-0328
(2021/06/11)
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- Functional Disruption of the Cancer-Relevant Interaction between Survivin and Histone H3 with a Guanidiniocarbonyl Pyrrole Ligand
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The protein Survivin is highly upregulated in most cancers and considered to be a key player in carcinogenesis. We explored a supramolecular approach to address Survivin as a drug target by inhibiting the protein–protein interaction of Survivin and its fu
- Aschmann, Dennis,Bayer, Peter,Beuck, Christine,Ehlers, Martin,Giese, Michael,Killa, Matthias,Knauer, Shirley K.,Meiners, Annika,Mertel, Marcel,Schmuck, Carsten,Vallet, Cecilia
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p. 5567 - 5571
(2020/02/04)
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- Design and synthesis of Fmoc-SPPS-ready iodoarene amino acid pre-catalysts and their reactivity in the catalytic oxytosylation of ketones
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A small suite of iodo-aryl amide containing amino acids were synthesized and assessed as catalysts for the hypervalent iodine(III) mediated α-oxytosylation of ketones. The efficiency of each catalyst was determined by comparing the relative rates of catalysis in the direct α-oxytosylation of propiophenone. In addition, these catalysts can be easily converted to congeners that are suitable for Fmoc-solid phase peptide synthesis for facile incorporation into a chiral peptide framework. This work facilitates the broader goal of our program to develop peptide-based enantioselective catalysts for hypervalent iodine chemistry.
- Brummel, Beau R.,Giambalvo, Lauren N.,Gross, Kristopher G.,Kobra, Khadijatul,Lex, Timothy R.,McMillen, Colin D.,Panda, Soham,Pennington, William T.,Swasy, Maria I.,Whitehead, Daniel C.
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supporting information
(2020/02/22)
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- TRICYCLIC COMPOUNDS
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The present invention provides a compound of formula I or a pharmaceutically acceptable salt thereof; and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
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Paragraph 0610; 0611; 0612
(2014/06/25)
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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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p. 1543 - 1550
(2011/10/08)
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- Novel inhibitors of the αvβ3 integrin-lead identification strategy
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A novel approach to inhibition of the αvβ3 integrin is described, which uses compounds designed to generate nM potency without using the arginine binding site.
- Elliot, David,Henshaw, Eleanor,MacFaul, Philip A.,Morley, Andrew D.,Newham, Peter,Oldham, Keith,Page, Ken,Rankine, Neil,Sharpe, Paul,Ting, Attilla,Wood, Christine M.
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scheme or table
p. 4832 - 4835
(2010/04/29)
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- 2-Piperazinecarboxamides as potent and selective melanocortin subtype-4 receptor agonists
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We report the discovery and optimization of substituted 2-piperazinecarboxamides as potent and selective agonists of the melanocortin subtype-4 receptor. The 5- and 6-alkylated piperazine compounds exhibit low bioactivation potential as measured by covale
- Palucki, Brenda L.,Park, Min K.,Nargund, Ravi P.,Tang, Rui,MacNeil, Tanya,Weinberg, David H.,Vongs, Aurawan,Rosenblum, Charles I.,Doss, George A.,Miller, Randall R.,Stearns, Ralph A.,Peng, Qianping,Tamvakopoulos, Constantin,Van Der Ploeg, Lex H. T.,Patchett, Arthur A.
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p. 1993 - 1996
(2007/10/03)
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- Inhibitors of farnesyl-protein transferase
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The present invention comprises analogs of the CAAX motif of the protein Ras that is modified by farnesylation in vivo. These CAAX analogs inhibit farnesyl-protein transferase. Furthermore, these CAAX analogues differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.
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- Inhibitors of farnesyl-protein transferase
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The present invention comprises analogs of the CA1 A2 X motif of the protein Ras that is modified by farnesylation in vivo. These CA1 A2 X analogs inhibit the farnesyl-protein transferase and the farnesylation of certain proteins. Furthermore, these CA1 A2 X analogs differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. The compounds of the instant invention also incorporate a cyclic amine moiety in the A2 position of the motif. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.
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- INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
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The present invention comprises analogs of the CAAX motif of the protein Ras that is modified by farnesylation in vivo. These CAAX analogs inhibit farnesyl-protein transferase. Furthermore, these CAAX analogues differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid antoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.
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- Nonpeptide glycoprotein IIb/IIIa inhibitors. 13. Design and synthesis of an orally active pyrazolopiperazinone nonpeptide fibrinogen receptor antagonist
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The synthesis and antiplatelet activity of a series of pyrazolopiperazinone nonpeptide fibrinogen receptor antagonists is reported. The sulfonamide analog 6 (L-734,115), significantly inhibited ex vivo platelet aggregation 24 h after oral administration at doses of 1.0 and 2.0 mg/kg to dogs and rhesus monkeys, respectively.
- Askew,McIntyre,Hunt,Claremon,Baldwin,Anderson,Gould,Lynch,Chang,Cook,Lynch,Holahan,Sitko,Stranieri
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p. 1531 - 1536
(2007/10/03)
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- 127. C-glycoside analogues of N4-(2-Acetamido-2-deoxy-β-D-glucopyranosyl)-L-asparagine: synthesis and conformational analysis of a cyclic C-glycopeptide
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The synthesis of C-glycosidic analogues 15-22 of N4-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-L-asparagine (ASn(N4GlcNAc)) possessing a reversed amide bond as an isosteric replacement of the N-glycosidic linkage is presented. The peptide cyclo(-D-Pro-Phe-Ala-CGaa-Phe-Phe-) (CGaa = C-glycosylated amino acid; 24) was prepared to demonstrate that 3-[(3-acetamido-2,6-anhydro-4,5,7-tri-O-benzyl-3-deoxy-β-D-glycero-D- guloheptonoyl)amino]-2-[(9H-fluoren-9-yloxycarbonyl)amino]propanoic acid (22) can be used in solid-phase peptide synthesis. The conformation of 24 was determined by NMR and molecular-dynamics (MD) techniques. Evidence is provided that the CGaa side chain interacts with the peptide backbone. The different C-glycosylated amino acids 15-21 were prepared by coupling 3-acetamido-2,6-anhydro-4,5,7-tri-O-benzyl-3-deoxy-β-D-glycero-D-gulo- heptonic acid (4) with diamino-acid derivatives 8-14 in 83-96% yield. The synthesis of 4 was performed from 2-(acetamido-3,4,6-tri-O-benzyl-2-deoxy-β-D-glucopyranosyl)tributylstannane (2) by treatment with BuLi and CO2 in 83% yield. Similarly, propyl isocyanat yielded the glycoheptonamide 7 in 52% from 2. Compound 2 was obtained from 2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-D-glucopyranose (1) by chlorination and addition of tributyltinlithium in 74% yield. A procedure for a multigram-scale synthesis of 1 is given.
- Hoffmann, Matthias,Burkhart, Fred,Hessler, Gerhard,Kessler, Horst
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p. 1519 - 1532
(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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- 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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