124994-66-7

Upstream product

• 100-39-0 benzyl bromide 
• 41088-86-2 L-2-(tert-butyloxycarbonylamino)-4-hydroxybutyric acid 
• 24424-99-5 di-tert-butyl dicarbonate 
• 1079307-01-9 (S)-benzyl 2-(tert-butoxycarbonylamino)-4-(methoxy(methyl)amino)-4-oxobutanoate 
• 34036-07-2 3,4 difluorobenzaldehyde 
• 40856-59-5 tert-butyl (3S)-2-oxotetrahydrofuran-3-ylcarbamate 
• 30925-18-9 2-tert-butoxycarbonylamino-succinic acid 1-benzyl ester 
• 105183-60-6 (S)-benzyl 2-((tert-butoxycarbonyl)amino)-4-hydroxybutanoate 

Downstream Products

• 156350-27-5 tert-butyl (2S,2'S,3'S,3S)-(3-benzyloxycarbonyl-3-tert-butoxycarbonylaminopropylamino)-3'-tert-butoxycarbonyl-2'-methoxymethoxypropyl-2-azetidinecarboxylate 
• 158534-32-8 (S)-benzyl-4-<(O-benzylhydroxy)amino>-2-<<(1,1-dimethylethoxy)carbonyl>amino>butanoate 
• 474766-44-4 (E)-(S)-2-tert-Butoxycarbonylamino-6-oxo-dec-4-enoic acid benzyl ester 
• 250291-82-8 (2S)-2-tert-butoxycarbonylamino-4-oxo-hexane-dioic acid 1-benzyl ester 6-ethyl ester 
• 682742-72-9 (2'S)-4-(2'-benzyloxycarbonyl-2'-tert-butoxycarbonylamino-ethyl)-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid di-tert-butyl ester 
• 250291-84-0 (2S)-2-tert-butoxycarbonylamino-4-oxo-hexane-dioic acid 1-benzyl ester 6-tert-butyl ester 
• 682742-71-8 (2'S)-4-(2'-benzyloxycarbonyl-2'-tert-butoxycarbonylamino-ethyl)-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester 
• 848785-45-5 (S)-1-((S)-3-Benzyloxycarbonyl-3-tert-butoxycarbonylamino-propyl)-azetidine-2-carboxylic acid 
• 848785-46-6 (S)-1-((S)-3-Amino-3-benzyloxycarbonyl-propyl)-azetidine-2-carboxylic acid 
• 848785-47-7 (S)-1-[(S)-3-Benzyloxycarbonyl-3-((S)-3-benzyloxycarbonyl-3-hydroxy-propylamino)-propyl]-azetidine-2-carboxylic acid 
• 860795-17-1 (S)-1-{(S)-3-Benzyloxycarbonyl-3-[(S)-3-benzyloxycarbonyl-3-(tetrahydro-pyran-2-yloxy)-propylamino]-propyl}-azetidine-2-carboxylic acid 
• 682742-81-0 (2'S)-4-(2'-amino-2'-benzyloxycarbonyl-ethyl)-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester 
• 682742-82-1 (2'S)-4-(2'-amino-2'-benzyloxycarbonyl-ethyl)-2,6-dimethyl-pyridine-3,5-dicarboxylic acid di-tert-butyl ester 
• 596828-16-9 (2'S)-4-(2'-tert-butoxycarbonylamino-2'-carboxyethyl)-2,6-dimethylpyridine-3,5-dicarboxylic acid di-tert-butyl ester 

Relevant academic research and scientific papers

NOVEL HISTONE METHYLTRANSFERASE INHIBITORS

The present invention relates to novel compounds of formula (I) as defined herein. The compounds are inhibitors of histone methyltransferases of the seven-beta-strand family, in particular of KMT9.

Macrocyclic Peptides that Selectively Inhibit the Mycobacterium tuberculosis Proteasome

Treatment of tuberculosis (TB) currently takes at least 6 months. Latent Mycobacterium tuberculosis (Mtb) is phenotypically tolerant to most anti-TB drugs. A key hypothesis is that drugs that kill nonreplicating (NR) Mtb may shorten treatment when used in combination with conventional drugs. The Mtb proteasome (Mtb20S) could be such a target because its pharmacological inhibition kills NR Mtb and its genetic deletion renders Mtb unable to persist in mice. Here, we report a series of macrocyclic peptides that potently and selectively target the Mtb20S over human proteasomes, including macrocycle 6. The cocrystal structure of macrocycle 6 with Mtb20S revealed structural bases for the species selectivity. Inhibition of 20S within Mtb by 6 dose dependently led to the accumulation of Pup-tagged GFP that is degradable but resistant to depupylation and death of nonreplicating Mtb under nitrosative stress. These results suggest that compounds of this class have the potential to develop as anti-TB therapeutics.

Esterase-sensitive prodrugs of a potent bisubstrate inhibitor of nicotinamide n-methyltransferase (Nnmt) display cellular activity

A recently discovered bisubstrate inhibitor of Nicotinamide N-methyltransferase (NNMT) was found to be highly potent in biochemical assays with a single digit nanomolar IC50 value but lacking in cellular activity. We, here, report a prodrug strategy designed to translate the observed potent biochemical inhibitory activity of this inhibitor into strong cellular activity. This prodrug strategy relies on the temporary protection of the amine and carboxylic acid moieties of the highly polar amino acid side chain present in the bisubstrate inhibitor. The modification of the carboxylic acid into a range of esters in the absence or presence of a trimethyl-lock (TML) amine protecting group yielded a range of candidate prodrugs. Based on the stability in an aqueous buffer, and the confirmed esterase-dependent conversion to the parent compound, the isopropyl ester was selected as the preferred acid prodrug. The isopropyl ester and isopropyl ester-TML prodrugs exhibit improved cell permeability, which also translates to significantly enhanced cellular activity as established using assays designed to measure the enzymatic activity of NNMT in live cells.

MACROCYCLIC COMPOUNDS AS PROTEASOME INHIBITORS

The compounds of the present invention are represented by the following compounds having Formula I and Formula (I'): where the substituents R1, R2, R2', R3, R4, R5, R', R", X, Y, and Z are as defined herein and where the substituents R1, R2, R3, R4, R5, R', R", X, Y, and Z are as defined herein. These compounds are used in the treatment of bacterial infections, parasite infections, fungal infections, cancer, immunologic disorders, autoimmune disorders, neurodegenerative diseases and disorders, inflammatory disorders, or muscular dystrophy or for providing immunosuppression for transplanted organs or tissues.

A practical route to long-chain non-natural α,ω-diamino acids

An efficient method for the synthesis of long-chain α,ω-diamino acids, starting from natural α-amino acids, has been developed. The long-chain skeleton has been generated through condensation between a protected aldehyde, derived from l-aspartic acid, and an ylide obtained from an ω-hydroxy-alkyl phosphonium salt. After conversion of the ω-hydroxy group into an amine, catalytic hydrogenation produced the N,N'-protected α,ω-diamino acid. The present route to α,ω-diamino acids allows the modulation of the chain length depending on the length of the ylide used for the Wittig olefination reaction.

AMINO- AND AMIDO-AMINOTETRALIN DERIVATIVES AND RELATED COMPOUNDS AS MU OPIOID RECEPTOR ANTAGONISTS

The invention provides amino- and amido-aminotetralin compounds of formula (I): wherein R1, R2, R3, R4, R5, R6, R7, and n are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are antagonists at the mu opioid receptor. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat conditions associated with mu opioid receptor activity, and processes and intermediates useful for preparing such compounds.

Synthesis of a serine-based neuraminic acid C-glycoside

Cell-surface carbohydrates are classified by the nature of their linkages to the protein as either N-linked or O-linked. O- and N-glycans are involved in a number of important biological functions. These activities can be lost on glycoprotein catabolism w

A novel dipeptide, N-γ-glutamyl boletine, and a cyclic iminium toxin from the mushroom Tylopilus sp. (Boletaceae)

N-γ-Glutamyl boletine and a toxin, 2-butyl-1-azacyclohexene iminium salt, were isolated from the mushroom Tylopilus sp. (Boltaceae). The absolute stereostructure of N-γ-glutamyl boletine was clarified based on spectroscopic analysis, acidic hydrolysis and total synthesis. N-γ-Glutamyl boletine exhibited moderate antibacterial activity. 2-Butyl-1-azacyclohexene iminium salt exhibited moderate acute toxicity against ddY mice. We proposed feasible biosynthetic pathway of piperidine alkaloids that the cyclic iminium compound might be biosynthesized from boletine, a new amino acid containing an δ-amino ketone moiety.

Fibrinogen receptor antagonists

Fibrinogen receptor antagonists having the structure, for example, of STR1 for example STR2

Total syntheses of phytosiderophores, 3-epi-hydroxymugineic acid, distichonic acid A, and 2'-hydroxynicotianamine

First total syntheses of unique phytosiderophores, 3-epi-hydroxymugineic acid (2), distichonic acid A (3), and 2'-hydroxynicotianamine (5), have been efficiently achieved from the same intermediates used for the synthesis of mugineic acid (1), the typical phytosiderophore.