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We show that the behavior of a polymorphic transformation under high shear can be predicted up to pilot scales on the basis of laboratory experiments. Solubility measurements indicate that the tran...

Puerariae Radix is a commonly used Chinese herbal medicine derived from the dried root of the legume plant, which contains a series of isoflavones as its chief pharmacologically active constituents. Using 7 pueraria constituents as marker substances, a high performance liquid chromatography (HPLC) and a capillary electrophoresis (CE) method were developed to assay the quality of Puerariae Radix within 65 and 50 min, respectively. Extracted samples were analyzed with a Cosmosil 5C18-MS column and eluted with a mixture of potassium dihydrogenphosphate (30 mM, adjusted to pH 3.0 with phosphoric acid) and aqueous acetonitrile solution, or an uncoated capillary (75μm I.D.) and carried with an aqueous solution containing 10 mM sodium dihydrogenphosphate and 40 mM sodium dodecyl sulphate. The relative standard deviation of the marker substances, on the basis of peak-area ratios for 6 replicate injections, was 0.50~0.97% (intraday) and 0.48~0.97% (interday) for HPLC, and 0.88~1.25% (intraday) and 0.85~1.38% (interday) for CE. Both methods yielded accurate results differing by only 5% when applied to the analysis of practical samples of Puerariae Radix.

p-Aminobenzoates (PABA) and benzophenones in cosmetic products absorb UV radiation. We have developed two simple methods to simultaneously determine whether cosmetic products contain any of eight sunscreen compounds. The first method used high-performance liquid chromatography (HPLC) and a Cosmosil 5C18-MS column with an isocratic system consisting of acetonitrile-H2O solution (60/40, v/v) acidified by 0.1% phosphoric acid (v/v); the analysis was monitored by absorbance at 254 nm with a constant flow-rate 0.8 mL/min. This method could easily determine the presence of these compounds in non-pretreated sunscreen products in 30 min. The second method employed capillary electrophoresis (CE) in buffer solution (pH 10.0) containing 20 mM borate; the same analysis was made within 10 min. Reproducibility (relative standard deviation) of the proposed methods, on the basis of the peak-area ratios in six replicate injections, was good with only a slight deviation of 0.31-0.75% (for HPLC system) and 1.65-3.55% (for CE system). The detection limit (S/N=3) of the individual marker substances varied from 0.08 to 0.87 μg/mL (for HPLC system) and 0.23 to 1.86 μg/mL (for CE system). Although the HPLC method was superior to the CE method in both reproducibility and resolution, it required longer retention time. The HPLC and CE methods developed were both successfully applied to the assay of 8 UV-absorbing agents in 11 commercial sun protection products.

The mechanistic understanding of three key active pharmaceutical ingredient (API) drying elements: drying kinetics, physical property control, and stability control, is critical for downstream formulation development and manufacture. The objective of this study was to collect drying kinetic data through the use of a laboratory integrated sorption chamber to elucidate the drying mechanism and thereby establish a drying model. In addition, the collection of drying kinetic data would provide a greater understanding of the solvent to API ratio as well as the API stability to help develop a large-scale drying protocol. The study material is an ethanol solvate (ethanolate) of the API. There is no fundamental crystal structure change upon drying of the solvate in the temperature range from 50 to 90 °C, and the drying kinetic data show that the molar ratio of ethanol to API is 1:1. This is confirmed by X-ray crystallography. An analysis of the drying kinetics showed that the diffusion of ethanol through the cryst...

The protective effect of an aqueous Pericarpium Granati extract (APG) against carrageenan-induced inflammatory damage in mice was investigated. The results showed that APG displayed radical scavenging, reducing activity, and liposome protection activity in acellular systems. The implementation of an HPLC helped identify polyphenolic components including epicatechin (11.9 mg/g), gallic acid (3.9 mg/g), ellagic acid (2.4 mg/g), ferulic acid (1.0 mg/g), quercetin (0.7 mg/g), and kaempferol (0.5 mg/g). APG administration in the range of 0.25–1.0 g/kg showed a concentration dependent inhibition on inflammatory response in carrageenan induced mice. The anti-inflammatory effects of APG could be related to the suppression of tissue nitric oxide and tumor necrosis factor-α, and associated with the reduction of lipid peroxidation and an increase in antioxidant enzyme activities including catalase, superoxide dismutase, and glutathione peroxidase in vivo. The results showed that APG might serve as a natural source of anti-inflammatory and antioxidative compounds in vivo.

In this study, the effects of a water extract of Flos Inulae (WFI) on antioxidant, antimutation and antityrosinase were investigated. The results showed that WFI inhibited the mutagenicity of 2-aminoanthracene (2-AA), an indirect mutagen; and 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen toward Salmonella typhimurium TA 98 and TA 100. In addition, WFI, in the range of 0.2–0.6 mg/ml, showed radical scavenging, reducing activities and chelating activity as well as decreased lipid oxidative damage. Meanwhile, WFI also inhibited tyrosinase activity and NO generation in lipopolysaccharide (LPS) stimulated macrophages. High performance liquid chromatography analysis suggests that the major phenolic constituents in WFI are chlorogenic acid, rutin, quercetin, luteolin and kaempferol. These bioactive components may contribute to the protective effects of WFI. The obtained data suggests that Flos Inulae can be applied to antimutation, antityrosinase and anti-inflammation.

Dichondra repens (DR) is the main constituent in herbal beverages and consumed daily as a nutrition supplement for the liver in Taiwan. This study investigated the antioxidant and anti-inflammatory effects of D. repens ethanol extract (EDR) and its reference compounds ex vivo and in vivo . Fingerprint chromatograms (from HPLC) indicated that EDR contained vanillin, umbelliferone and scopoletin. EDR was evaluated for its antioxidant effects and LPS-induced NO production in RAW 264.7 cells. EDR decreased the LPS-induced NO production and expressions of iNOS and COX-2 in RAW 264.7 cells. In vivo anti-inflammatory activities of EDR were assessed in mouse paw oedema, induced by λ-carrageenan (Carr). We investigate the antioxidant mechanism of EDR via studies of the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the liver and the levels of malondialdehyde (MDA) and nitrite oxide (NO) in the oedematous paw. Serum NO and TNF-α were also measured. EDR exerts anti-inflammatory effects by suppressing TNF-α, NO, and might be related to the decrement of the level of MDA in the oedema paw via increasing the activities of CAT, SOD and GPx in the liver. The results show that EDR might be a natural antioxidant and anti-inflammatory agent.

The antioxidant and antityrosinase activities of the water extract ofFlemingia macrophyllaroot (WEFM) were investigated. The results showed that WEFM exhibited radical scavenging and reducing activities, as well as ferrous ion chelating property. In addition, WEFM also protected phospholipids against oxidation, indicating that WEFM could protect biomolecules from oxidative damage. Meanwhile, in the range of 50–100 μg/mL, the tyrosinase inhibitory activity of WEFM increased with an increase in sample concentration and was superior to that of the water extract ofGlycine tomentellaroot (WEGT). A high performance liquid chromatography analysis was used to determine the phenolic components, revealing that daidzin, daidzein, genistin, and genistein were present in WEFM and WEGT. Acting as an antioxidant and a tyrosinase inhibitor, these bioactive constituents could contribute to the protective effects of WEFM. Overall, the results showed that WEFM might serve as a natural antioxidant and tyrosinase inhibitor.

The effect of aqueous extracts of green asparagus (AGA) on antioxidation and tyrosinase inhibition in acellular and cellular systems was investigated. The results showed that AGA inhibited tyrosinase with an IC 50 value of 1.21 mg/ml in a mixed-type inhibition. In the range of 0.05–1 mg/ml, the inhibitory effect on tyrosinase activity in B16 cells increased with increasing concentration of AGA. Meanwhile, the levels of glutathione in B16 cells were elevated by AGA in comparison to the control. In addition, AGA, in the range of 0.1–0.5 mg/ml, also exhibited radical scavenging, chelating activities and protected liposome against oxidative damage. The high performance liquid chromatography analysis indicated that polyphenolic components such as rutin, quercetin, kaempferol, and isorhamnetin were present in the AGA. This study suggested that AGA could play an important role in the regulation of tyrosinase activity and seem to be a natural inhibitor of browning reaction.

In this study, the effects of four molasses related products including cane molasses (CM), carob molasses (CAM), grape molasses (GM), and sorghum molasses (SM) on the antimutation and nitric oxide (NO) production were examined. The results showed that the four molasses products, particularly CAM, inhibited the mutagenicity of 2-aminoanthracene (2-AA), an indirect mutagen; and 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen in Salmonella typhimurium TA98 and TA100. In addition, CAM also showed a higher ABTS radical inhibition, reducing activity, and decreasing lipid oxidative damage more than the others kinds of molasses. In the range of 0–0.8 mg/ml, the inhibitory effect of all molasses products on NO generation in lipopolysaccharide (LPS) stimulated macrophages increased with increasing concentrations, and CAM showed the best inhibition of NO production. These data suggested that the four molasses related products display their biological activities in terms of antioxidation, antimutation, and anti-inflammation.

Ethnopharmacological relevance Xanthii seeds commonly called Cang-Erzi were used as a traditional Chinese medicine for treating sinusitis, headache due to rheumatism and skin pruritus. Aim of the study In order to evaluate the actions of this plant, studies were performed on antioxidant, antinociceptive, and anti-inflammatory activities. Materials and methods The aqueous extract of Xanthii Fructus (AXF) was evaluated in mice for anti-inflammatory activity using carrageenan-induced hind paw edema model. The antinociceptive activity of AXF was evaluated by writhing and formalin tests. Antioxidant properties were assayed in terms of antioxidant activity by scavenging abilities on 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid (ABTS), reducing activity and liposome protection. In addition, the total phenolic content was determined with spectrophotometric method. Results AXF exhibited significant radical scavenging and reducing activity. And oral treatment with AXF elicited inhibitory activity on acetic acid effect and reduced the formalin effect at the late-phase. In the anti-inflammatory test, AXF inhibited the development of paw edema induced by λ-carrageenan (Carr). AXF decreased the paw edema at the fifth hour after Carr administration, and increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the liver tissue and decreased the malondialdehyde (MDA) level in the edema paw. AXF decreased the level of serum nitric oxide (NO) and tumor necrosis factor (TNF)-α after Carr injection and AXF decreased the levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in paw edema at the fifth hour. Conclusions AXF shows antioxidant, antinociceptive, and anti-inflammatory activities, supporting the folkloric usage of the plant to treat various inflammatory diseases.

In this study, the effects of a water extract of sugarcane leaves (WSL) on antimutation and nitric oxide (NO) production were investigated. The results showed that WSL inhibited the mutagenicity of benzo[a]pyrene (BP), an indirect mutagen; and N-methyl-N′-nitrosoguanidine (MNNG), a direct mutagen toward Salmonella typhimurium TA 98 and TA 100. In addition, WSL, in the range of 0–0.4 mg/ml, showed superoxide inhibiting, NO scavenging, and reducing activity, as well as decreased lipid oxidative damage. In the range of 0–1 mg/ml, the inhibitory effect of WSL on NO generation in lipopolysaccharide (LPS) stimulated macrophages increased with increasing concentrations. A high performance liquid chromatography analysis revealed that the polyphenolic constituents, such as caffeic acid, ferulic acid, apigenin, and vitexin were present in WSL. These data suggested that WSL exhibiting biological activities could contribute to antimutation, anti-inflammation as well as antioxidation.

Aims of the study Cardiospermum halicacabum (CH) has been used in Chinese medicine for a long time. However, its fingerprint chromatogram, antioxidant, anti-inflammatory effects and mechanism are still needed to be explored. Therefore, the aims of this study investigated the antioxidant and anti-inflammatory effects of CH extracts and its reference compounds ex vivo and in vivo. Materials and methods In HPLC analysis, the fingerprint chromatogram of ethanolic extract of CH (ECH) was established. The effects of ACH (aqueous extract of CH) and ECH extracts were assessed for the antioxidant and LPS-induced NO production in RAW264.7 cells. In vivo anti-inflammatory activities of ECH were evaluated in mouse paw edema induced by λ-carrageenan (Carr). We investigate the anti-inflammatory mechanism of ECH via studies of the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the liver and the levels of malondialdehyde (MDA) and nitrite oxide (NO) in the edema paw. Serum NO and TNF-α were also measured. Results ECH had better antioxidant activity than that of ACH. In the anti-inflammatory test, ECH inhibited the development of paw edema induced by Carr and increased the activities of CAT, SOD and GPx in the liver tissue. ECH also decreased the level of NO in edematous paw tissue and in serum level, and diminished the level of serum TNF-α at the fifth hour after Carr injection. Conclusions ECH exerts anti-inflammatory effects by suppressing TNF-α and NO. The anti-inflammatory mechanism of ECH might be related to the decrement of the level of MDA in the edema paw via increasing the activities of CAT, SOD and GPx in the liver. The results showed that ECH might serve as a natural antioxidant and anti-inflammatory agent.

This study investigated the analgesic and anti-inflammatory effects of an ethanol extract of Dunaliella salina Teod. (Chlorophyceae) (EDS) in Imprint- ing Control Region mice. Standard all-trans-b-carotene and the amount of all-trans-b-carotene in an EDS were analyzed by high-performance liquid chromatography (HPLC). In HPLC analysis, the fingerprint chromatogram of EDS was established. Both all-trans-b-carotene and EDS showed similar peaks at the retention time of 24 min. This implied that EDS contained the active ingredient all-trans-b-carotene. Treatment of animals with EDS significantly inhibited the numbers of acetic acid-induced writhing responses at doses of 0.5 g/kg (P < 0.01)

The inhibitory effects of a water extract of sweet potato leaves (WSPL) on nitric oxide (NO) production and protein tyrosine residue nitration were investigated. The results showed that WSPL inhibited NO production in a concentration-dependent manner. In the range of 0–1.0 mg/ml, the inhibitory effect on NO generation in macrophages increased with increasing concentration of WSPL. Meanwhile, the protein tyrosine residue nitration in mouse heart homogenates was inhibited by 1 mg/ml WSPL. In addition, WSPL, in the range of 0–0.4 mg/ml, also exhibited radical scavenging, reducing and chelating activities and protected liposomes against oxidative damage. A high performance liquid chromatography analysis revealed that phenolic acids and flavonols such as chlorogenic acid, caffeic acid, and quercetin were present in the WSPL, which could contribute to the protective effect against oxidative damage. Thus, WSPL might be useful in preventing protein nitration and oxidative stress.

A reliable and reproducible high performance liquid chromatography method with coulometric detection was developed and validated for the quantitative determination of trace-levels of hydrogen peroxide in crospovidone, a pharmaceutical excipient, and a capsule pharmaceutical product. The method conditions included: a reproducible extraction procedure to provide a concentrated extract, aqueous extraction solvent; a simple HPLC mobile phase (aqueous 50 mM ammonium acetate) compatible with the coulometric detection; a reserve-phase HPLC column that did not collapse under 100% aqueous mobile phase conditions providing sufficient retention and separation of hydrogen peroxide from interferences; and a coulometric detector with a multi-electrode array providing sensitive and selective detection. The method validation results, including those for specificity, linearity, accuracy, precision, and recovery, were acceptable for the determination of trace levels of hydrogen peroxide. The method was shown to be linear over the range of 0.6-4.5 ppm (microg/g) and 6-90 ppm (microg/g) for the pharmaceutical product and crospovidone, respectively. The described method was applied to the determination of trace levels of hydrogen peroxide in different batches of crospovidone and the corresponding pharmaceutical product batches manufactured from these batches of this excipient.

Substituted biphenyl I (BMS-207940), a selective antagonist of the endothelin A (ETA) receptor, has been proposed for the treatment of congestive heart failure. The structure of I possesses a stereogenic axis due to the hindered rotation about the biphenyl bond in the presence of its large ortho-substituents. As a result, I exhibits atropisomerism in which two nonplanar, axially enantiomers exist, which will be generically referred to as isomers A and B. Within the pharmaceutical industry, both from a scientific and regulatory point of view, characterization of enantiomeric drugs has become an important step in the development process. To investigate the configurational stability of I atropisomers, normal phase enantiomeric LC with tandem UV and laser polarimetric detection was used under pseudo-physiological conditions: first in a simple aqueous medium at 37 degrees C, and then in human serum at 37 degrees C. Kinetic studies indicated that the half-life of I enantiomerization in an aqueous medium at 37 degrees C was ca. 15 h. Enantiomerization of I atropisomers was greatly accelerated in the presence of human serum and human serum albumin, and the rate of enantiomerization depended on the concentration of I. The sera-concentration-dependent enantiomerization behavior of I strongly suggests a restricted site-specific substrate/I interaction mechanism. It was therefore demonstrated that atropisomeric interconversion studies for the compound studied required consideration of temperature, presence of plasma proteins, and drug concentration to account for the kinetic data.

A formal total synthesis of the iridoid monoterpene (′) -dimethyl secologanoside (6) is described. The Norrish 1 type fragmentation ofbicyclo[2.2.1]heptannone 9 is the key step.

This study investigated the inhibitory effects of aqueous extracts from Miracle Fruit leaves (AML) on mutation and oxidative damage. The results showed that AML in the range of 1–5 mg/plate inhibited the mutagenicity of 2-aminoanthracene (2-AA), an indirect mutagen, and 4-nitroquinoline- N -oxide (4-NQO), a direct mutagen toward Salmonella typhimurium TA 98 and TA 100. On the other hand, AML in the range of 0.05–0.2 mg/ml showed radical scavenging, reducing activities, liposome protection as well as decreased tert -butyl hydroperoxide ( t -BHP) induced oxidative cytotoxicity in HepG2 cells. High performance liquid chromatography (HPLC) analysis suggested that the active phenolic constituents in AML are p -hydroxybenzoic acid, vanillic acid, syringic acid, trans - p -coumaric acid and veratric acid. These active phenolic components may contribute to the biological protection effects of AML in different models. The data suggest that AML exhibiting biological activities can be applied to antimutation as well as anti-oxidative damage.

This study examined the antioxidant and anti-inflammatory activities of the water extract of longan pericarp (WLP). The results showed that WLP exhibited radical scavenging, reducing activity and liposome protection activity. In addition, WLP also inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophages. Further, administration of WLP, in the range of 100–400 mg/kg, showed a concentration-dependent inhibition on paw edema development following carrageenan (Carr) treatment in mice. The anti-inflammatory effects of WLP may be related to NO and tumor necrosis factor (TNF-α) suppression and associated with the increase in the activities of antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. Overall, the results showed that WLP might serve as a natural antioxidant and inflammatory inhibitor.

This study investigated the antioxidative and anti-inflammatory activities of aqueous extracts of Schizonepeta tenuifolia Briq. (STE). The results showed that STE displayed radical scavenging and reducing activity, as well as liposome protection activity. In addition, the implementation of an HPLC with a photodiode array detector helped to identify polyphenolic components including hesperidin, luteolin, and diosmetin. STE administration in the range of 125-500 mg/kg showed concentration dependent inhibition on carrageenan induced inflammatory response in mice. The anti-inflammatory effects of STE could be related to tissue NO and tumor necrosis factor a (TNF-α) suppression, and associated with the reduction of lipid peroxidation and an increase in antioxidant enzyme activities including catalase, superoxide dismutase, and glutathione peroxidase in vivo. Overall, the results showed that STE might serve as a natural inhibitor of oxidation and inflammation.

This study investigated the protective effect of the aqueous extract of Flemingia macrophylla (AFM) against hepatic injury induced by CCl4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected as biomarkers in the blood to indicate hepatic injury. Product of lipid peroxidation (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH) contents were evaluated for oxidative stress in hepatic injury. Moreover, histopathological observation was assayed for the degree of hepatic injury. After oral administration of AFM, 0.5 g/kg and 1.0 g/kg doses significantly decreased ALT and AST, attenuated the histopathology of hepatic injury, ameliorated oxidative stress in hepatic tissue, and increased the activities of CAT, SOD and GSH-Px. The hepatoprotective effect of daidzein and genistein were consistent to that of AFM. This study demonstrated for the first time that AFM has hepatoprotective effect on acute liver injuries induced by CCl4, and the results suggested that the effect of AFM against CCl4-induced liver damage was related to antioxidant properties.

The antioxidant and antityrosinase activities of the ethanolic extract of mulberry twigs (EEMT) were investigated. The results showed that EEMT exhibited radical scavenging and reducing activity, as well as ferrous ion-chelating activity. In addition, EEMT also protected phospholipids against free radicals, indicating that EEMT could protect biomolecules from oxidative damage. Meanwhile, in the range of 0-60 μg/ml, the tyrosinase inhibitory activity of EEMT increased with increase in sample concentration, and was superior to that of the ethanolic extract of mulberry root bark (EEMR). High-performance liquid chromatography (HPLC) analysis was employed to determine the phenolic components, revealing that maclurin, rutin, isoquercitrin, resveratrol, and morin were present in EEMT. Acting as an antioxidant and a tyrosinase inhibitor, these bioactive constituents could contribute to the protective effects of EEMT. Overall, the results showed that EEMT might serve as a natural antioxidant and tyrosinase inhibitor.

Aims of the study This study investigated the analgesic and anti-inflammatory effects of a water extract of Trachelospermum jasminoides (WET) in ICR mice. Materials and methods In HPLC analysis, the fingerprint chromatogram of WET was established. Acetic acid-induced writhing response and formalin-induced pain were examined the analgesics effects of WET. WET on λ-Carrageenan(carr)-induced paw edema was performed. We investigate the anti-inflammatory mechanism of WET via studies of the activities of glutathione peroxidase (GPx), glutathione reductase (GRx) in the liver and the levels of malondialdehyde (MDA) and nitrite oxide (NO) in the edema paw. Serum NO and TNF-α were also measured. Results The fingerprint chromatogram of WET was established through HPLC analysis, and implies that WET contains the active ingredient gallic acid, chlorgenic acid, caffeic acid, taxifolin, isoquercitrin and quercetin. WET significantly inhibited the numbers of acetic acid-induced writhing responses and the formalin-induced pain in the late phase. In the anti-inflammatory test, WET inhibited the development of paw edema induced by carr. WET decreased the paw edema at the third, fourth and fifth hour after carr administration, and increased the activities of SOD, GPx and GRx in the liver tissue and decreased the MDA level in the edema paw at the third hour after carr injection. WET decreased the level of NO in edematous paw tissue and in serum level, and diminished the level of serum TNF-α at the fifth hour after carr injection. Conclusions These results demonstrated that WET is an effective anti-inflammatory agent in carr-induced inflammation. WET probably exerts anti-inflammatory effects by suppressing TNF-α and NO. The anti-inflammatory mechanism of WET might be related to the decrease in the level of MDA in the edema paw via increasing the activities of SOD, GPx and GRx in the liver.

The reaction of a variety of methyl esters with dimethylsulfoxonium methylide at 0-25 degrees C affords the chain-extended beta-keto dimethylsulfoxonium ylides. Subsequent treatment with hydrogen chloride in THF proceeds with loss of DMSO to afford the corresponding alpha-chloroketones. This sequence has been utilized to convert the methyl esters of CBZ-protected alanine and valine to the anti N-protected alpha-amino epoxides, which are important pharmaceutical intermediates. When the same protocol is applied to BOC-protected phenylalanine methyl ester, epimerization occurs so that the use of a more reactive aryl ester is required. This chemistry provides a practical route to alpha-chloroketones that avoids the use of toxic and explosive diazomethane.

A series of N1-activated C4-carboxy azetidinones was prepared and tested as inhibitors of human tryptase. The key stereochemical and functional features required for potency, serine protease specificity and aqueous stability were determined. From these studies compound 2, BMS-262084, was identified as a potent and selective tryptase inhibitor which, when dosed intratracheally in ovalbumin-sensitized guinea pigs, reduced allergen-induced bronchoconstriction and inflammatory cell infiltration into the lung.

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 (IC(50)1.7 nM) with high selectivity (3000-fold) for tryptase versus related serine proteases including trypsin.