253177-06-9

Upstream product

• 71962-74-8 Ethyl nipecotate 
• 116574-71-1 (±)-tert-butyl 3-(hydroxymethyl)piperidine-1-carboxylate 
• 253177-04-7 3-[1-(tert-butyl-dimethyl-silanyl)-2-carboxy-4-oxo-azetidin-3-ylmethyl]-piperidine-1-carboxylic acid tert-butyl ester 
• 253177-03-6 3-iodomethylpiperidine-1-carboxylic acid tert-butyl ester 
• 100-39-0 benzyl bromide 
• 253177-05-8 3-((2S,3R)-2-Carboxy-4-oxo-azetidin-3-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester 

Downstream Products

• 163343-71-3 (S)-ethyl nipecotate (S,S)-hydrogen tartrate 
• 163343-71-3 (R)-piperidine-3-carboxylic acid ethyl ester*l-tartaric acid 
• 479622-31-6 (2S,3R)-3-(1-{Benzyloxycarbonylamino-[(E)-benzyloxycarbonylimino]-methyl}-piperidin-3-ylmethyl)-1-[4-(6-cyclohexyl-hexanoyl)-piperazine-1-carbonyl]-4-oxo-azetidine-2-carboxylic acid benzyl ester 
• 253177-42-3 (2S,3R)-3-(1-{Benzyloxycarbonylamino-[(E)-benzyloxycarbonylimino]-methyl}-piperidin-3-ylmethyl)-4-oxo-1-[4-(6-phenyl-hexanoyl)-piperazine-1-carbonyl]-azetidine-2-carboxylic acid benzyl ester 
• 479622-32-7 (2S,3R)-3-(1-{Benzyloxycarbonylamino-[(E)-benzyloxycarbonylimino]-methyl}-piperidin-3-ylmethyl)-4-oxo-1-[4-(4-phenyl-butylcarbamoyl)-piperazine-1-carbonyl]-azetidine-2-carboxylic acid benzyl ester 
• 384830-31-3 (2S,3R)-3-(1-{Benzyloxycarbonylamino-[(E)-benzyloxycarbonylimino]-methyl}-piperidin-3-ylmethyl)-4-oxo-1-[4-(6-pyridin-2-yl-hexanoyl)-piperazine-1-carbonyl]-azetidine-2-carboxylic acid benzyl ester 
• 384830-26-6 4-[(2S,3R)-2-Benzyloxycarbonyl-3-(1-{benzyloxycarbonylamino-[(E)-benzyloxycarbonylimino]-methyl}-piperidin-3-ylmethyl)-4-oxo-azetidine-1-carbonyl]-piperazine-1-carboxylic acid 3-phenoxy-propyl ester 
• 253177-10-5 4-[(2S,3R)-2-Benzyloxycarbonyl-3-(1-{benzyloxycarbonylamino-[(E)-benzyloxycarbonylimino]-methyl}-piperidin-3-ylmethyl)-4-oxo-azetidine-1-carbonyl]-piperazine-1-carboxylic acid 1-isopropyl-2-methyl-propyl ester 
• 384830-18-6 (2S,3R)-3-(1-{Benzyloxycarbonylamino-[(E)-benzyloxycarbonylimino]-methyl}-piperidin-3-ylmethyl)-4-oxo-azetidine-2-carboxylic acid benzyl ester 
• 253177-07-0 4-[(2S,3R)-2-Benzyloxycarbonyl-3-(1-tert-butoxycarbonyl-piperidin-3-ylmethyl)-4-oxo-azetidine-1-carbonyl]-piperazine-1-carboxylic acid 1-isopropyl-2-methyl-propyl ester 

Relevant academic research and scientific papers

Synthesis of potent and highly selective nonguanidine azetidinone inhibitors of human tryptase

Azetidinones such as BMS-363131 (2) and BMS-363130 (3), which contain a guanidine group in the C-3 side chain were previously shown to be very potent inhibitors of human tryptase with high selectivity versus other serine proteases, including trypsin. In this letter, we describe the discovery of a number of potent azetidinone tryptase inhibitors in which the guanidine moiety at the ring C-3 position is replaced with primary or secondary amine or aminopyridine functionality. In particular, BMS-354326 (4) is a highly potent tryptase inhibitor (IC50=1.8nM), which has excellent selectivity against trypsin and most other related serine proteases.

Synthesis of potent and highly selective inhibitors of human tryptase

The serine protease tryptase has been implicated in allergic and inflammatory diseases and associated with asthma. The synthesis and SAR of a series of N1-activated-4-carboxy azetidinones are described, resulting in identification of BMS-363131 (2) as a potent inhibitor of human tryptase (IC503000-fold) for tryptase versus related serine proteases including trypsin.

Beta lactam compounds and their use as inhibitors of tryptase

Compounds of the formulas: are disclosed. These compounds inhibit tryptase as well as other enzyme systems or are selective tryptase inhibitors and are useful as antiinflammatory agents particularly in the treatment of chronic asthma.