132622-90-3

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 132622-88-9 (2S,4S)-4-Hydroxy-pyrrolidine-2-carboxylic acid benzyl ester 
• 100-39-0 benzyl bromide 
• 87691-27-8 N-tert-butoxycarbonyl-L-cis-4-hydroxyproline 
• 18610-59-8 trans-L-hydroxy-proline 
• 87250-97-3 tert-butyl 3-oxo-2-oxa-5-azabicyclo[2.2.1]heptane-5-carboxylate 
• 13726-69-7 (2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid 
• 51-35-4 4R-4-hydroxyproline 
• 1738-76-7 glycine benzyl ester p-toluenesulfonic acid salt 
• 618-27-9 hydroxy L-proline 

Downstream Products

• 587887-98-7 2-benzyl 1-(tert-butyl) (2S,4R)-4-fluoropyrrolidine-1,2-dicarboxylate 
• 958879-76-0 N-tert-butyloxycarbonyl-(2S,4R)-4-thioacetyl-proline benzyl ester 
• 870992-70-4 N-tert-butoxycarbonyl-(2S,4R)-4-fluoroprolylglycine benzyl ester 
• 870992-74-8 N-9-fluorenylmethoxycarbonyl-(2S,3S)-3-fluoroprolyl-(2S,4R)-4-fluoroprolylglycine benzyl ester 
• 870992-72-6 N-9-fluorenylmethoxycarbonyl-(2S,4S)-4-fluoroprolyl-(2S,4R)-4-fluoroprolylglycine benzyl ester 
• 203866-14-2 (2S,4R)-1-[(tert-butoxy)carbonyl]-4-fluoropyrrolidine-2-carboxylic acid 
• 1190617-94-7 N-tert-butoxycarbonyl-(2S,4S)-4-methoxyproline benzyl ester 
• 958879-77-1 N-tert-butyloxycarbonyl-(2S,4R)-4-thioproline 
• 176306-18-6 [R-(R*,S*)]-4-[(Triphenylmethyl)thio]-1,2-pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester 
• 185304-16-9 (2S,4S)-4-(Toluene-4-sulfonyloxy)-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester 

Relevant academic research and scientific papers

PI3K INHIBITORS AND USES THEREOF

The development of a new, targeted drug delivery paradigm coupled to improved PI3K inhibitors (e.g., PI3Kα inhibitors) represents a significant advance in cancer therapy. Provided herein are compounds, such as compounds of Formula (I) and (II), and pharmaceutically acceptable salts, hydrates, solvates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The compounds provided herein are PI3K (e.g., PI3Kα) inhibitors and are therefore useful for the treatment and/or prevention of various diseases (e.g., proliferative diseases such as cancer). Also provided herein are nanoparticles and nanogels (e.g., P-selectin targeting nanoparticles) comprising PI3K inhibitors, such a compound described herein. In certain embodiments, a nanoparticle or nanogel described herein encapsulates a compound described herein for targeting delivery to cancer cells or tumors.

NOVEL ANTIBACTERIAL CELL-PENETRATING PEPTIDES

The present disclosure relates to novel antibacterial cell-penetrating peptides and derivatives, and methods to make and use the novel antibacterial cell-penetrating peptides and derivatives. The novel antibacterial cell-penetrating peptides of the present invention with shorter linker between a pyrrolidine ring and a guanidine group provide unexpectedly higher potency against a broader scope of bacterial.

Hepatitis C Virus Inhibitors

The present disclosure is generally directed to antiviral compounds, and more specifically directed to combinations of compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such combinations, and methods for inhibiting the function of the NS5A protein.

COMBINATIONS OF HEPATITIS C VIRUS INHIBITORS

The present disclosure is generally directed to antiviral compounds, and more specifically directed to combinations of compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such combinations, and methods for inhibiting the function of the NS5A protein.

FAP-ACTIVATED THERAPEUTIC AGENTS, AND USES RELATED THERETO

Disclosed are prodrugs of cytotoxic anthracyclines (such as doxorubicin) and other therapeutic agents that are selectively cleaved and activated by fibroblast activating protein (FAP). The prodrugs are useful for targeted delivery of cytotoxic and other agents to FAP- expressing tissues, including cancer (e.g., solid tumors). Also provided are pharmaceutical compounds comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation, e.g., cancer, fibrosis, and inflammation.

A short diastereoselective synthesis of cis-(2S,4S) and cis-(2R,4R)-4-hydroxyprolines

A concise synthesis of (2R,4R)-4-hydroxyproline (1) and (2S,4S)-4-hydroxyproline (2) has been developed in enantiomerically pure form from commercially available starting materials with excellent diastereoselectivity. The tightly bound chelation controlled transition state formed during the 5-exo-tet ring closure reaction is assumed to be the origin of high diastereoselectivity.

Dual kinetically controlled native chemical ligation using a combination of sulfanylproline and sulfanylethylanilide peptide

Dual kinetically controlled native chemical ligation using a newly developed sulfanylproline-mediated reaction in combination with an N-sulfanylethylanilide peptide was successfully applied to a previously unreported sequential coupling of peptide fragments added simultaneously to the reaction.

Stereoelectronic and steric effects in the collagen triple helix: Toward a code for strand association

Collagen is the most abundant protein in animals. The protein consists of a helix of three strands, each with sequence X-Y-Gly. Natural collagen is most stable when X is (2S)-proline (Pro) and Y is (2S,4R)-4-hydroxyproline (4R-Hyp). We had shown previously that triple helices in which X is (2S,4S)-4- fluoroproline (4S-Flp) or Y is (2S,4R)-4-fluoroproline (4R-Flp) display hyperstability. This hyperstability arises from stereoelectronic effects that preorganize the main-chain dihedral angles in the conformation found in the triple helix. Here, we report the synthesis of strands containing both 4S-Flp in the X-position and 4R-Flp in the Y-position. We find that these strands do not form a stable triple helix, presumably because of an unfavorable steric interaction between fluoro groups on adjacent strands. Density functional theory calculations indicate that (2S,3S)-3-fluoroproline (3S-Flp), like 4S-Flp, should preorganize the main chain properly for triple-helix formation but without a steric conflict. Synthetic strands containing 3S-Flp in the X-position and 4R-Flp in the Y-position do form a triple helix. This helix is, however, less stable than one with Pro in the X-position, presumably because of an unfavorable inductive effect that diminishes the strength of the interstrand 3S-FlpC=O...H-NGly hydrogen bond. Thus, other forces can counter the benefits derived from the proper preorganization. Although (Pro-Pro-Gly) 7 and (4S-Flp-4R-Flp-Gly)7 do not form stable homotrimeric helices, mixtures of these two peptides form stable heterotrimeric helices containing one (Pro-Pro-Gly)7 strand and two (4S-Flp-4R-Flp-Gly) 7 strands. This stoichiometry can be understood by considering the cross sections of the two possible heterotrimeric helices. This unexpected finding portends the development of a "code" for the self-assembly of determinate triple helices from two or three strands.

NOVEL PEPTIDES AS NS3-SERINE PROTEASE INHIBITORS OF HEPATITIS C VIRUS

The present invention discloses novel peptide compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such peptides as well as methods of using them to treat disorders associated with the HCV protease.

Conformationally Restricted Arginine Analogues

We report the practical synthesis and structural characterization of a set of conformationally constrained protected arginine analogues.These enantiomerically pure analogues have the general structure 1 and are prepared in seven to eight steps from the co