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Driven by the ever shrinking feature size in the chip design and the complexity of the heuristic subresolution assist feature (SRAF) placement rules, more wafer data for calibration and more effort on the part of design engineers are necessary for each process node. The main purpose of placing assist features around the main feature is to improve the through focus robustness on the target edge of the main feature. Therefore, it is desirable to study the effect of assist feature placement on the main feature in terms of the focus sensitivity with a quick and accurate method. In this paper, an innovative way of calculating the signal dependence on the locations of the SRAF placed in the isoline pattern is proposed. The results indicated that the optimal location for the assist feature placement to increase the depth of focus is about 380nm from the isoline center and is independent of the isoline structure for an annular illumination system. The results are verified by using independent tools and measured b...

Isofocal patterns produce the most ideal manufacturing conditions on a reticle, however, most semiconductor designs contain few isofocal features. A new way of looking at defocus conditions based on the change in intensity with respect to nominal focus [L. S. Melvin III et al., J. Vac. Sci. Technol. B 23, 2631 (2005)]—referred to as IΔ—can be used to resize the target pattern to isofocal dimensions. The pattern is quantitatively analyzed using IΔ to find modified pattern shapes that give isofocal target patterns for optical proximity correction and/or resolution enhancement techniques. The target pattern is then made isofocal by resizing the pattern to the modified shape prior to the use of optical proximity correction and/or resolution enhancement techniques. Results of this concept demonstrate excellent improvement in the feature robustness of different features at various defocus conditions. The proposed isofocal targeting method can be applied to layers where trade-offs between pattern shape and final...

As semiconductor manufacturing moves to smaller geometries, the existing methodologies for verifying the manufacturability of a design are increasingly cumbersome. Current practice is to use geometric “design rules”—such as minimum spacing and width constraints—to identify design configurations that are not manufacturable or likely to reduce yield. One manufacturing property that is particularly difficult to capture accurately with geometric rules is the robustness of the layout configuration with respect to variation through the lithographic process window. The nonlinear characteristics of optical partial coherence effects, particularly strong in modern exposure systems with off-axis illumination, are currently incorporated into the design rules through an exhaustive empirical process. The resulting design rules can be overly conservative to insure complete problem pattern capture, and this may result in unnecessary restrictions on the design that reduce the layout density or interfere with circuit perfo...

Novel, synthetic cannabimimetics and delta 9-tetrahydrocannabinol were found to enhance the binding of [3H]flunitrazepam to mouse brain in vivo. This property, suggestive of facilitation of binding to benzodiazepine receptors, is consistent with the potentiation of the anticonvulsant activity of diazepam against pentylenetetrazol by these compounds. The relative potencies of delta 9-tetrahydrocannabinol and the new cannabimimetics for enhancing [3H]flunitrazepam binding in vivo could also be correlated with their relative analgesic efficacies. Similar pharmacological stereospecificity was displayed for both binding enhancement and analgesic effects. The following order of decreasing potency was observed: N-methyllevonantradol and (-)-CP-55,244 greater than levonantradol, canbisol, CP-42,096 and (-)-CP-55,940 greater than 9-beta-normethyl-9-beta-hydroxyhexahydrocannabinol, nabilone and CP-47,497 greater than delta 9-tetrahydrocannabinol. Dextronantradol, (+)-CP-55,940 and (+)-CP-55,244 were considerably less active than the respective (-)-enantiomers; cannabidiol was inactive. Extensive investigation of structure versus activity led to N-methyllevonantradol and the 3-(2-hydroxyphenyl)cyclohexanols derivative, (-)-CP-55,244, which are approximately 1000-fold more potent than delta 9-tetrahydrocannabinol.

Based on the hypothesis that analgetic activity is a dissociable feature of the cannabinoid molecule, we examined modifications of the side chain, the phenolic moiety, and, most significantly, structures that lack the benzopyran functionality present in THC and (--)-9-nor-9 beta-hydroxyhexahydrocannabinol (HHC). A new grouping, the 1-methyl-4-phenylbutyloxy C-3 side chain, elaborates a unique lipopholic region. Replacement of the phenol substituent produced several derivatives which retain analgetic activity in the codeine potency range. Introduction of a weakly basic nitrogen at C-5 and deletion of the axial methyl group in the B ring, two structural changes forbidden by traditional cannabinoid SAR, resulted in a unique family of benzoquinolines with potent analgetic activity. The prototype of this series, levonantradol, exhibits potent and stereospecific analgetic and antiemetic activity.

The synthesis and analgesic testing of 3-[4-(1,1-dimethylheptyl)-2-hydroxyphenyl]cyclohexanol (1) are described. Prior (SAR) studies led us to conclude that the pyran ring of 9-nor-9 beta-hydroxyhexahydrocannabinol (HHC) was not necessary for the expression of biological activity in this series of cannabinoids. Analysis of models and the use of molecular mechanics calculations suggested that a simpler compound, such as 1, would possess the biological activity of HHC. Compound 1 was prepared in nine steps from [3-(benzyloxy)phenyl]acetonitrile (2). Biological testing in five models of pain shows that compound 1 and morphine are equally potent as analgesics and demonstrates that the pyran ring of HHC is not necessary for biological activity. Further simplification of 1 was pursued by the synthesis of 4-[4-(1,1-dimethylheptyl)-2-hydroxyphenyl]-2-pentanol (17), but this derivative exhibits significantly reduced analgesic activity.

Pentalenolactone, an antibiotic and antitumor agent which is a representative of the polycondensed cyclopentanoid natural products, requires the construction of a highly functionalized bicyclo[3.3.0]octyl system. Using the principle of transfer alkylation, a simple route to an acyclic precursor which involves anet y attack of a polyenolate allows the development of a [4+ 1] strategy to the basic ring system. Overall, an eight step route to an excellent precursor to pentalenolactone emerges. Using a further four step sequence, the fully elaborated ring system of pentalenolactone is created. In addition to the transfer alkylation strategy, a novel bromination utilizing liquid bromine as a solvent and a chemoselective unravelling of the resultant tribromide is reported.

While prototype cannabinoid analgetics such as levonantradol do not act at the opiate receptor, their opiate-like properties suggest a proximal site of action. Based on this reasoning we perceived a remarkable structural analogy between levonantradol and prostaglandin E2. We further postulated a three point receptor contact which enabled us to predict the minimum structural features for analgesia. In this report we describe a simple phenyl cyclohexanol ( 1 ) which was found to possess potent analgesia across a battery of analgetic assays and defines three key sites of receptor contact necessary for cannabinoid-like analgetic activity.

Publisher Summary This chapter discusses the pathogenic role for leukotrienes (LTs) in the lesser explored areas of disease. This perspective is limited to those LTs (5-HETE, LTB, LTC, LTD4, and LTE) that are synthesized from arachidonic acid (AA) via the 5-lipoxygenase (5-LO) pathway. In a study of 8 cluster headache patients, plasma levels of LTB4 have been found to be significantly elevated during an attack compared to the symptom-free periods. More recently, it has been reported that LTC 4 is detected in the plasma of migraine patients during the prodromal phase and in greater amounts during the beginning of the attack phase. Recent evidence strongly implicates LTs as significant factors in the pathophysiology of anaphylactic, endotoxic, and traumatic shock. In the presence of antihistamines, the selective 5-LOIs has been found to effectively block the ovalbumin-induced drop of coronary flow. Evidence, implicating the involvement of LTs in diseases of the kidney, has been discussed in the chapter. The most frequently mentioned renal disease suspected of being at least partly LT mediated is human glomerulonephritis. The upper gastrointestinal effects of LTs have been briefly described. Infusions of LTC 4 or LTD 4 significantly and dose-proportionally reduced gastric blood flow, gastric mucosal blood flow, gastric oxygen consumption, and acid output. The development of second generation 5-lipoxygenase inhibitors and antagonists of LTB 4 , LTC 4 , and LTD 4 , with extremely enhanced potency and selectivity, offers the promise of new insights into the contributions of leukotrienes to the pathophysiology of these diseases.

The high yield conversion of phenols into diethyl 2-hydroxyphenylphosphonates via base catalyzed rearrangement of diethyl phenyl phosphates has been achieved.