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FIELD OF THE INVENTION
The present invention relates to systems and methods for monitoring service on communications networks, and particularly to systems and methods that cause minimal disruption to the communications network traffic by using passive monitoring of network traffic data packets.
BACKGROUND OF THE INVENTION
Internet Service Providers (ISPs) are highly desirous of providing Internet Protocol (IP) services, such as Voice over IP (VoIP) and IPTV, to their customers. In order to provide these high value services, the ISP networks need to provide a high Quality of Service (QoS) even as their networks become more complex. There is, therefore, an increased demand for sophisticated monitoring tools that allow the ISPs to rapidly identify degradation in their networks performance and quickly isolate the root cause of any problems. Such tools are critical for ensuring QoS guarantees and for reducing service downtimes through timely resolution of network problems. These monitoring tools typically monitor network traffic parameters such as delay and packet loss using either active or passive measurements.
Active monitoring tools typically inject data packets into the network, or send data packets to applications, in order to obtain measurements of delays or losses.
Passive monitoring devices, in contrast, snoop on existing data-packets as they traverse the network lines as normal network traffic. Passive monitoring has the advantage that it does not increase the traffic in the network. This can be critical when a network interface or link becomes congested. During such times, injecting additional traffic into the network for active measurements may exacerbate the very problem that is being diagnosed. The disadvantages of passive measurements, however, include having less control over the measurement process as only existing network traffic is used and that the amount of data that needs to be collected can be enormous.
In order to control the costs of a passive monitoring infrastructure and the communication overhead between the monitors and the Network Operations Center (NOC), it is important to carefully select the locations at which passive monitoring probes are placed and the paths they are used to monitor. At the same time, it is important to ensure that the data collected by the monitoring probes is sufficient to provide a comprehensive and timely overview of the network's performance. In particular, it is important to provide enough passive monitoring locations that both a detection set of paths and a diagnostic set of paths can be monitored. A detection set of paths for passive monitoring of a communications network is the minimum set of paths that need to be monitored in order to detect that there is an anomaly somewhere in the network. A diagnostic set of paths is the minimum set of paths that need to be monitored in order to accurately locate and diagnose any anomaly that occurs anywhere in the network.
SUMMARY OF THE INVENTION
Briefly described, the invention provides a system and method for determining the optimal selection of paths for passively monitoring a communications network in order to detect and diagnose faults, and the optimal location for placing monitoring probes on the network to be able to monitor those paths.
In a preferred embodiment of the invention, a diagnostic set of paths, or a close approximation to it, is determined by ensuring that, for all pairs of links in the network, the diagnostic set of paths contains at least one path having only one member of that pair of links.
In a preferred embodiment of the invention, a detection set of paths that is a subset of the diagnostic set of paths is determined by ensuring that, for all the links in the communications network, there is at least one member of the detection subset of paths that contains that link.
During normal operation of the network, only the detection subset of paths needs to be monitored, reducing the amount of data that needs to be collected and reported to a network central control. Once an anomaly is detected, the system may switch to monitoring the full diagnostic set of paths so that the anomaly can be fully diagnosed.
The cost of deploying and operating the passive monitoring equipment is minimized by determining a probe location set of links in the communications network. This is the minimum set of links on which a probe needs to be placed in order to monitor the diagnostic set of paths. As the detection set of paths is a subset of the diagnostic set of paths, they will also be monitored by the probe place on the probe location set of links.
These and other features of the invention will be more fully understood by references to the following drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic representation of a simple service provider network.
FIG. 2A is a schematic representation of a first case of a node in a tree topology having an edge on which a probe can be placed to distinguish an undistinguished edge pair.
FIG. 2B is a schematic representation of a second case of a node in a tree topology having an edge on which a probe can be placed to distinguish an undistinguished edge pair.
FIG. 2C is a schematic representation of a third case of a node in a tree topology having an edge on which a probe can be placed to distinguish an undistinguished edge pair.
FIG. 2D is a schematic representation of a fourth case of a node in a tree topology having an edge on which a probe can be placed to distinguish an undistinguished edge pair.
DETAILED DESCRIPTION
The present invention provides low-cost, low impact solutions for communications network monitoring infrastructures. In such systems, link level anomalies, such as excessive loss or delay of data packets traversing the network, are inferred from path-level passive measurements, i.e., network faults are monitored by observing the normal traffic flowing across the network. Such monitoring may be performed by placing and operating sophisticated monitoring tools at all nodes in the networks. This simple approach, however, is very costly. In order to reduce the cost, the method of this invention determines the optimum location of data monitoring probes on the network in order to minimize the number of data monitoring probes needed while ensuring that any anomaly that occurs anywhere in the network can be fully diagnosed.
Communications networks may be modeled as directed graphs G (V, E) having vertices V and edges E. In such a model, a node v that is an element of V may represent a network router, a switch or a gateway, while the edges of the graph may represent communications links connecting the nodes. A directed communication from a node u to a node v may then be represented by <u, v> and the corresponding undirected physical link by {u, v}. As most modern networks are full-duplex networks, for every directed edge <u i , v i >εE, there is a directed edge <v i , u i >εE.
Many Wide Area Networks (WAN) provided by, for instance, Service Providers have a general mesh topology with multiple paths between nodes in order to provide redundant paths. In enterprise environments, however, networks such as Ethernet frames are generally deployed using tree topologies, as they are simpler to implement and are more cost effective.
All Internet Protocol (IP) packets in a typical Service Provider communications network originate and terminate at edge routers that interface with customer networks or other service provider networks, and are represented in a graph model of the network by edge nodes that are a subset of nodes from the set V. In an enterprise network, edge nodes may be client hosts or application servers such as web servers or mail servers. The IP traffic between a pair of nodes traverses the network through a sequence of nodes and links dictated by the network topology and routing protocol. For instance, in a Service Provider network, the communication path between a pair of edge nodes may either be a pre-configured Multiprotocol Label Switching (MPLS) or the shortest path between nodes computed used the Open Shortest Path First (OSPF). In a tree topology network the communication path between an edge node pair is unique and traces the edges of the spanning tree.
In the graph model of the network, the set of paths between edge nodes are denoted by the set P that has members p, and where each p that is an element of P is a sequence of directed links that the path traverses. For simplicity, we assume that routing is symmetric, i.e., for every path p, there is a path {tilde over (p)} that is an element of P in the opposite direction. However, the schemes discussed in this paper are applicable even if the routing paths are asymmetric. Because passive monitoring relies on observing IP packets traversing the network to detect anomalies, paths with no traffic are not typically included in the set P.
In most commercially available routers, data packets get delayed or lost primarily due to queuing at the transmitting or outbound interfaces. Thus, a loss or delay on a directed communication link <v i , v j > can usually be traced back to the outbound interface v i . Hence, a one-to-one correspondence between the link <v i , v j > and the outbound interface v i may be assumed for the purpose of anomaly detection.
A passive monitoring infrastructure consists of a set of passive monitoring devices placed at various points in the network where they passively analyze the traffic that passes by. Various devices are available to do the observing. Most commercial routers or switches, for instance, support port mirroring in which each incoming and outgoing packet from one port of the network switch can be copied to another port where the copy of the packet can be studied. There are also hardware devices known as network taps that hook directly into a network cable and send a copy of the traffic that passes through it to one or more other networked devices. A network tap placed on a link between two nodes can measure both forward and reverse traffic on the link and is effectively measuring the incoming and outgoing traffic on the ports at the endpoints of the link. The measurements made by port mirroring and network taps are, therefore, logically equivalent. Passive monitoring devices may include the port mirrors or network taps and any associated local processing device for storing and/or forwarding the information gathered.
FIG. 1 is a schematic representation of a simple service provider network 10 , having four passive monitoring devices 12 , five links 14 and twelve possible paths 16 that can be passively monitored if they contain data. For simplicity, FIG. 1 shows only two of the paths 16 . The paths 16 may be represented as <a, v 1 , v 2 , b>, <a, v 1 , v 2 , c>. <a, v 1 , v 2 , d>, <b, v 2 , v 1 , c>, <b, v 2 , d>, <a, v 1 , c> and their inverses. In providing a passive monitoring infrastructure for the service provider network 10 , an objective is to minimize costs by deploying as few passive monitoring devices 12 as possible that will allow the accurate detection and diagnosis of all single link anomalies. In doing this placement, the assumption is that a path reports an anomaly if and only if it contains a link with an anomaly, and that each network anomaly is caused by a single link.
The anomalies to be monitored include data packet losses and data packet delays. Excessive data packet losses may be detected by, for instance, using passive monitoring devices tap 1 and tap 2 to monitor the data packets traversing the network via the path p 1 represented by <a, v1, v2, b>. At regular intervals, e.g., 1, 10 or 30 seconds, both tap 1 and tap 2 send to a central Network Operations Center (NOC) the number of packets seen on path p 1 in the most recent time interval. If the difference between the packet counts by tap 1 and tap 2 exceeds a certain pre-specified threshold even after accounting for packets still in transit along the path, then the NOC may conclude that an excessive amount of packets are being lost along some links of the path p. Alternately, the passive monitoring devices tap 1 and tap 2 may send samples of the observed packets on path p 1 to the NOC, and an inference of excessive losses on path p can be made if there is a large discrepancy in the samples from the two passive monitoring devices (also known as probes). Similarly, by associating timestamps with the data packets, it is possible to detect excessive delays along path p by keeping track at the NOC of the difference between packet timestamps averaged over an interval or for sample packets.
If an anomaly is reported on path p 1 , additional paths may be monitored in order to determine in which of the links <a, v1>,<v1, v2> or <v2, b> the anomaly has occurred. Assuming that a path reports an anomaly if and only if it contains a link with an anomaly and that the network anomaly is caused by a single link (representing an interface), it is possible to show that a set of monitored paths Q is sufficient to diagnose which is the anomalous link if, for every pair of links (e1, e2) in the set E of the graph G(V, E) representing the network, there is at least one monitored path in Q that contains exactly one of the two links.
Probe Placement
The probe placement problem solved by the method of this invention may be stated formally along the following lines. Given a directed graph, G=(V, E) and a set of paths P between edge nodes in V, let L represent the set of directed edge-pairs which cannot be distinguished by paths in P. Select the smallest number of undirected edges F on which to place probes so that every link pair in L is distinguished by some edge in F.
If each potential probe location edge F is represented by the subset LF of link pairs L that a probe on F will distinguish, then the problem becomes selecting the smallest number of subsets LF that contain all of L, i.e., the union of all selected subsets LF is L. The probe placement problem is, therefore, reduced to a classic Set Cover optimization problem.
Given a universe U and a collection of subsets S of U, a set cover is the sub-collection C of the subsets S whose union is U, i.e., a set cover is the sub-collection C that contains all the elements of U. Set Cover optimization comprises finding the smallest sub-collection C that is a set cover.
It is well-known that the Set Cover problem is Non-deterministic Polynomial-time (NP) complete, and the optimization version of set cover is NP hard.
It is also well-known that that the greedy algorithm is the best-possible polynomial time approximation algorithm for set cover under plausible complexity assumptions. The greedy algorithm for set cover chooses sets according to one rule: at each stage, choose the set which contains the largest number of uncovered elements.
For a mesh topology network, the minimum number of probe locations needed for passive monitoring of the network can, therefore, be found by the following greedy algorithm for optimal probe placement:
1. Represent the network as a directed graph G=(V, E);
2. Determine P, the set of paths between edge nodes in V;
3. Determine L, the set of directed edge-pairs which cannot be distinguished by paths in P;
4. Determine F, the set of undirected edges available to have probes placed on them;
5. Represent each member of F by the subset LF of link pairs L that a probe on F will distinguish;
6. Select F corresponding to the largest subset L F ; and
7. Repeat 2 to 6 with P now including all new paths made possible by selecting F until L=0.
For tree topology networks, an alternate algorithm can be used to find near optimal probe location. This more restricted problem can be shown to correspond to finding an optimal vertex cover. As vertex cover is known to be NP complete and, therefore, there is unlikely to be an efficient algorithm to solve it. A lazy placement algorithm embodiment of this invention can, however, be shown to be a 3-approximation of the optimal solution, i.e., if the algorithm of this invention produces placement of F probes, and the optimal solution is O probes, |F|≦3|O|.
The lazy placement algorithm proceeds bottom up in a tree topology and uses a lazy probe placement strategy, i.e., a link is only selected for placement if it distinguishes a link that cannot be distinguished further up in the tree.
TABLE 1
Lazy placement algorithm for solving the probe placement
problem in a tree topology network
Initially set the solution F(O) = { }, and the set of
undistinguished link pairs L(0) = L;
for i = 1 to |V| do
Given the set L(i − 1), make local decision for child
edges of n i ;
Add the selected edges to the solution F(i);
Remove the link pairs distinguished by F(i) from
L(i − 1) to get L(i);
end
In a preferred embodiment of the invention, the algorithm proceeds as follows:
Chose a root node;
Then proceed bottom up the tree, i.e., before processing any node, process all the node's children;
For each node, decide whether to select the child nodes for probe placement, where a child node for node n denotes the edges connecting a node n to its direct children, child(n)={c 1 , c 2 , . . . c m ). A probe on any edge in a tree topology can distinguish a directed link pair if and only if the two links are on either side of it. A child edge {n, c j } of n, therefore, can only distinguish an undistinguished link pair if one of the two directed links in the pair is in the subtree rooted at c j or on {n, c j } and the other is outside the subtree or on {n, c j }.
Furthermore, such a link pair is characterized as being a “ripe link”, i.e., a link pair that cannot be distinguished further up the tree if it satisfies one of the four cases illustrated in FIG. 2A , 2 B, 2 C or 2 D.
FIG. 2A shows the case in which one, upwardly directed link e 2 is either in the subtree rooted at the child node c j or is <c j n,> and the other upwardly directed link e 1 is on the edge connecting n to its parent.
FIG. 2B shows the case in which one, downwardly directed link e 2 is in the subtree rooted at the child node c j o and the other downwardly directed link e 1 is on the link <n, c j >.
FIG. 2C shows the case in which one, upwardly directed link e 2 is either in the subtree rooted at the child node c j or is <c j n,> and the other downwardly directed link e 1 is on the edge connecting n to another child.
FIG. 2D shows the case in which one, upwardly directed link e 1 is either in the subtree rooted at the child node c j or is <c j n,> and the other downwardly directed link e 2 is in a subtree of another child of n
In the cases represented by FIGS. 2A , 2 B and 2 C, the probe is placed on the child edge {n, c j }. In the case represented by 2 D the probe may be placed on either of the two child edges involved, {n, c j } or {n, c k }.
The lazy placement algorithm of table 1 ensures that at each step all the ripe pairs in L are distinguished. Each time an edge is added to F, the probe placement solution set, all the link pairs distinguished by it are removed from L.
If, from the remaining child edges of n, the subset of child edges which distinguish one or more undistinguished link pairs from L under the case of FIG. 2D can be represented by a set C and the set of those case of FIG. 2D link pairs from L can be represented by a set S. As each pair in S can be distinguished by two child edges, {n, c j } or {n, c k }, the problem of selecting the minimum subset of C such that all the link pairs in S are distinguished can be reduced to the Set Cover problem instance (S, C) with each element belonging to exactly two sets, which is the definition of a Vertex Cover. A Vertex Cover of an undirected graph G=(V,E) is a subset V′ of the vertices of the graph which contains at least one of the two endpoints of each edge.
The well known 2-approximation algorithm for Vertex Cover can be used to find a subset of C which distinguishes all the link pairs in S and add the subset to the solution F. The factor-2 approximation algorithm is to repeatedly take both endpoints of an edge into the vertex cover, then remove them from the graph. No better constant-factor approximation is known.
Path Selection for Anomaly Detection
The problem of path detection for anomaly detection can be stated formally as follows. Given a directed graph G=(V, E) and a set of paths P′ that can be monitored by passive probes, select the minimum subset of paths Q det such that every directed link in E belongs to at least one path in Q det . This may be termed the path cover problem.
In a mesh topology, a the path cover problem can be shown to be equivalent to the set cover problem. The greedy algorithm for set cover can, therefore, be used as a logarithmic approximation algorithm for selecting a minimum subset of paths to cover all the directed links. As described above, the greedy algorithm chooses sets according to one rule: at each stage, choose the set which contains the largest number of uncovered elements.
In a tree-topology network, a 2-approximation to the optimal path cover in the network is possible. The method consists of selecting a root, then, from each leaf node of the tree, selecting the path that comes closest to the root. Both directions of the path are then included in the solution set. If there are n leaf node vertices, clearly at least n paths are needed to completely cover all the directed links in the network. This is because each path can cover at most two directed links from those incident on the leaf nodes: the link directed from the leaf node at which the path starts to an inner node and the link directed from an inner node to the leaf node at which the path terminates. Thus at least n paths are required to cover the 2n directed links on n leaf nodes. Our solution has 2n paths and so is at least a 2-approximation. If a link is covered by a path, then from one of the leaf nodes serving as endpoints of the path, the link will be on the path from the leaf node to the root, so the link will be covered by the closest path to the root from that leaf node. Therefore, all the links in the tree will be covered by the selected paths. By including both the forward and reverse paths in the solution set, all the directed links will be covered.
Path Selection for Anomaly Diagnosis
A set of paths Q is sufficient to diagnose an anomalous link, if, for every pair of links (e 1 , e 2 ) in E, there is at least one path in Q that contains exactly one of the two links. Such a path is said to distinguish between the links e 1 and e 2 . Given a network defined as a directed graph G=(V, E) and a set of paths P′ that can be monitored by passive probes, path selection for anomaly diagnosis requires finding the minimum set of paths Q that distinguish all link pairs in E and is a subset of P′.
For mesh graph topologies, the anomaly diagnosis problem can be reduced to a set cover problem by reducing each link pair to an element and each path to the set of link pairs it distinguishes. As noted above, a path distinguishes all the links it contains from all the links it does not contain. In this reduction, p={e 1 , e 2 }εP, where e 1 , e 2 εE is reduced to the set {(e 1 , e j )|e j εE, e j {tilde over (ε)}p}∪{(e 2 , e j )|e j εE, e j {tilde over (ε)}p}. The greedy algorithm for set cover can then be used to give a logarithmic factor approximation algorithm to compute a subcollection of paths that distinguishes all the link pairs. In the greedy algorithm, sets are chosen according to one rule: at each stage, choose the set which contains the largest number of uncovered elements.
For tree topologies, there is a 12-approximation algorithm for solving the anomaly diagnosis problem. Given a tree T having n vertices, with the edges denoted by E and where P is the required set of paths, the algorithm proceeds by first obtaining a solution in each undirected edge of the tree. Once a diagnosis path set is obtained for an undirected tree network, each path in the solution can be replaced by the corresponding directed paths in both directions in order to differentiate any two directed links. A diagnosis path set should be at least a constant fraction of the number of vertices n in the tree network. Such a diagnosis path set whose size is a constant times n may be chosen as follows:
Let the optimal diagnosis path set be D o , a solution be DC and an undirected solution path set D.
First, find the undirected path cover using the 2-approximation algorithm detailed above. In this method a root is selected, then, from each leaf node of the tree, selecting the path that comes closest to the root. For the undirected case, any path cover size is at least n 1 /2, and the 2-approximation algorithm gives a path cover size of n 1 where n 1 are the leaf nodes of the tree. Call this undirected path cover set C and make D=C.
Second, for each edge e={u e , v e }, fix a path P e in the path cover that covers this edge. Also, denote by s e and t e the end points Of P e and let s e be the end closer to u e .
Thirdly, each edge e={u, v} divides the path P e into at most three segments (s e , u e ), (u e , v e ) and (v e , t e ). Among all the paths that pass through e and deviate from P e in the segment (s e , u e ), choose the one that deviates at a vertex closest to u e . Call this path P s,e . Similarly, choose P t,e . If no such path exists, or u e or v e are the endpoints, do not choose the corresponding path. Add the chosen paths to D.
The diagnostic path solution set DC can be shown to be a 12-approximation of the optimum solution D o .
Although the invention has been described in language specific to structural features and/or methodological acts, it is to be understood that the invention defined in the appended claims is not necessarily limited to the specific features or acts described. Rather, the specific features and acts are disclosed as exemplary forms of implementing the claimed invention. Modifications may readily be devised by those ordinarily skilled in the art without departing from the spirit or scope of the present invention. | A system and method for determining optimal selection of paths for passively monitoring a communications network. A diagnostic set of paths is determined by ensuring that, for all pairs of links in the network, the set contains one path having only one member of that pair. A detection subset of paths is determined by ensuring that, for all the links in the network, one member of the subset contains that link. Selecting a minimum detection and diagnostic set of paths minimizes the communication overhead imposed by monitoring. During normal operation, only the detection subset need be monitored. Once an anomaly is detected, the system may switch to monitoring the full diagnostic set. The cost of deploying and operating the passive monitoring equipment is minimized by determining the minimum set of links on which a probe needs to be placed in order to monitor the diagnostic set of paths. | 28,063 |
BACKGROUND INFORMATION
[0001] 1. Field
[0002] Embodiments of the disclosure relate generally to the field of packaging for pastry and baked goods and more particularly to a multidiametric case for a cupcake or similar good, the case having a relieved upper portion for clearance of frosting or topping, an aperture in the bottom allowing easy removal of the cupcake from the package and retaining elements within the case for closely contacting the cupcake for retention in the package until removal.
[0003] 2. Background
[0004] Cupcakes and similar baked goods and pastries are typically packaged in boxes containing multiple units. Baked goods such as cupcakes are quite fragile in nature and such packaging does not provide satisfactory protection for the baked goods, allowing individual cupcakes to move within the box creating distortion or damage to the soft cake and frosting. Retaining elements within the multiunit box have been previously employed as disclosed in U.S. Pat. No. 6,003,671 issued to McDonnough et al on Dec. 21, 1999. However extracting individual cupcakes is typically not easy or convenient and such packaging is not readily economically adaptable for individual cupcakes.
[0005] Individual packaging has been provided in the form of small boxes or paper wrapping which suffer many of the same issues as multiunit packaging. Certain single item packages such as that disclosed in US patent publication 2004/0251162 to McGinnis et al published on Dec. 16, 2004 have been provided, however, such packaging is overly complex and expensive to be cost effective for high quantity production and sale of baked goods.
[0006] It is therefore desirable to provide a cost effective packaging system for individual cupcakes or similar baked goods. It is additionally desirable that such a packaging system would allow easy removal of the cupcake without damage while retaining the cupcake safely within the package until removal is desired.
SUMMARY
[0007] Exemplary embodiments provide cupcake package employing a base element having a primary diameter for receiving a cupcake body and a relieving cylinder having a second diameter extending from the base element for clearance of a top contour of the cupcake. A bottom surface closes the base element and includes an aperture centrally located therein sized to accept insertion of a finger for removal of the cupcake. A cylindrical lid is closely received over the relieving cylinder to close the package. In one exemplary embodiment the base element is frustoconical.
[0008] In certain implementations, the base element further incorporates a restraint system for the cupcake. A first restraint system includes two sets of opposing apertures in the base element vertically displaced from and perpendicular to each other. A first dowel is received through the first set of apertures and extending through a cupcake body carried in the base element and a second dowel is received through the second set of apertures and extending through the cupcake body.
[0009] A second restraint system incorporates multiple pyramidal protuberances extending from an inner surface of the base element oriented with an extended point downward toward the bottom to engage the body of the cupcake.
[0010] A third restraint system uses one or more circular ridges extruded from an inner surface of the base element to engage the body of the cupcake.
[0011] The features, functions, and advantages that have been discussed can be achieved independently in various embodiments of the present invention or may be combined in yet other embodiments further details of which can be seen with reference to the following description and drawings
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] FIG. 1A is a bottom angle isometric view of a general embodiment of the cupcake package of the present invention;
[0013] FIG. 1B is a side view of the embodiment of FIG. 1A ;
[0014] FIG. 1C is a bottom view of the embodiment of FIG. 1A ;
[0015] FIG. 1D is a top angle isometric view of the embodiment of FIG. 1A with the closure lid removed;
[0016] FIG. 1E is a side section view of the embodiment of FIG. 1A with a cupcake inserted in the case;
[0017] FIG. 1F is the side section view of the case with the cupcake being removed;
[0018] FIG. 2A is a bottom angle isometric view of an embodiment of the cupcake package with a first restraint structure;
[0019] FIG. 2B is a top angle isometric view of the embodiment of FIG. 2A ;
[0020] FIG. 2C is a bottom view of the embodiment of FIG. 2A ;
[0021] FIG. 2D is a top view of the embodiment of FIG. 2A showing interior details of the embodiment;
[0022] FIG. 2E is a side section view of the embodiment of FIG. 2A ;
[0023] FIG. 3A is a top isometric view of an embodiment of the cupcake package with a second restraint structure;
[0024] FIG. 3B is a top view of the embodiment of FIG. 3A ;
[0025] FIG. 3C is a side section view of the embodiment of FIG. 3A ;
[0026] FIG. 4A is a top isometric view of an embodiment of the cupcake package with a third restraint structure; and,
[0027] FIG. 4B is a side section view of the embodiment of FIG. 4A .
DETAILED DESCRIPTION
[0028] The embodiments described herein disclose a cupcake package having a multidiametric case with multiple cylindrical elements or a combination of cylinders and conical frustrums to receive the cupcake and having a bottom with an aperture for urging the cupcake from the case with a consumer's finger, a lid for closing the case, and various restraint elements within the case to maintain the cupcake in the case until removed.
[0029] As shown in FIG. 1A-1E for an exemplary embodiment, a frustoconical base element 10 of the case with a first primary diameter 11 receives the body of the cupcake (as best seen in FIG. 1E ). The shape of the base element may be a conical frustrum as shown for use with a conventional cupcake or various depths and diameters of cylindrical elements or other rotated geometric shapes defined to closely receive the baked good. The inner surface 12 of the base element frictionally engages the sides of the cupcake to assist in retaining the cupcake in the package and prevent unwanted motion in the package during handling or transport. A cylindrical top element 14 expands from the base element 10 to a second diameter 15 to allow volumetric relief within the package for frosting or top contouring of the cupcake or other baked good to be contained in the case. Further, the larger diameter of the top element simplifies the insertion of the cupcake or baked good into the case.
[0030] A lid 16 having an inner diameter sized to be closely received over the cylindrical top element 14 provides a closure for the case to protect the cupcake or baked good after insertion into the case. For the embodiment shown a filleted external surface of the lid allows for easy grasping by the consumer for removal. In alternative embodiments, a smooth cylindrical external surface or a textured surface may be employed.
[0031] A bottom surface 18 of the base element 10 incorporates an aperture 20 which is sized to accommodate insertion of a fingertip. As best seen in FIG. 1F , after removing the lid, inserting a fingertip through aperture 20 and pressing upward against the bottom 22 of the cupcake urges the cupcake body 24 from the case allowing the consumer to easily remove the cupcake for consumption.
[0032] For the exemplary embodiments, injection molded polystyrene or similar material may be employed for the case and lid providing a very low cost, mass producible product. Alternative paper, cardboard or plastic materials may be employed in alternative embodiments using standard fabrication techniques known to those skilled in the art.
[0033] To further restrain the cupcake in the case, a restraint system is employed. As shown in FIGS. 2A-2E , a first exemplary restraint system for the embodiment shown incorporates apertures 30 in the base element through which wooden or plastic toothpicks or dowels 32 are inserted, piercing the body of the cupcake. The dowel ends extend through the apertures 30 on each side of the base element thereby restraining the cupcake within the case. For the embodiment shown, two perpendicular vertically offset sets of apertures and dowels are employed. In alternative embodiments, a single aperture set and dowel may be employed or additional sets for increased security. For removal of the cupcake, the dowels are extracted from the case and the cupcake is removed by inserting a finger into the aperture 20 in the bottom 18 to urge the cupcake out of the case.
[0034] A second exemplary restraint system is shown in FIGS. 3A-3C which employs pyramidal protuberances 34 extending from the inner surface 12 of the base element 10 . Orientation of the protuberances with point 36 extending downwardly toward the bottom 18 of the base element engages and restrains the body of the cupcake when the cupcake is placed into the case and urged toward the bottom. For the embodiment shown, four pyramidal protuberances 34 are shown. In alternative embodiments one or more protuberances may be employed as required to firmly secure the cupcake or other backed good in the case. For removal of the cupcake, inserting a finger into the aperture 20 in the bottom 18 and urging the cupcake upwards with sufficient force overcomes the friction created by the indentation of the pyramidal protuberances in the body of the cupcake allowing it to be removed from the case.
[0035] Ridges 38 extruded from the inner surface 12 of the base element 10 provide a third exemplary retention system for the embodiments disclosed as shown in FIGS. 4A and 4B . For the embodiment shown, the ridges extend around an entire circumference of the inner surface and two ridges are employed. In alternative embodiments ridges extending over a portion of the circumference or a single or additional multiples of ridges are employed. A substantially circular cross section of the ridges is employed which provides sufficient resistance against the body of the cupcake to retain the cupcake in the case. However, alternative cross sections such as triangular or rectangular may be employed in alternative embodiments. As with the pyramidal protrusions, removal of the cupcake is accomplished by inserting a finger into the aperture 20 in the bottom 18 and urging the cupcake upwards with sufficient force overcomes the friction created by the indentation of the circular ridges in the body of the cupcake allowing it to be removed from the case.
[0036] Having now described various embodiments of the invention in detail as required by the patent statutes, those skilled in the art will recognize modifications and substitutions to the specific embodiments disclosed herein. Such modifications are within the scope and intent of the present invention as defined in the following claims. | A cupcake package includes a base element having a primary diameter for receiving a cupcake body and a relieving cylinder having a second diameter extending from the base element for clearance of a top contour of the cupcake. A bottom surface closes the base element and includes an aperture centrally located therein sized to accept insertion of a finger for removal of the cupcake. A cylindrical lid is closely received over the relieving cylinder to close the package. | 11,558 |
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to magnetic separation generally and, more particularly, but not by way of limitation, to a novel apparatus that permits the automatic separation of magnetic components in a laboratory microplate.
[0003] 2. Background Art
[0004] In the field of biology, there are requirements for the separation of one constituent from another. Some of the more commonly used methods are centrifugation, filtration, and magnetic separation. Centrifugation uses centrifugal force to provide separation by elements of mass. Filtration provides separation by size. Magnetic separation uses a magnetic field to attract and hold magnetic particles, or magnetic beads, so that the supernate in which the suspended are disposed can be removed.
[0005] Magnetic beads are particularly useful in immunoassays. Constituents of interest may be coated on the surface of paramagnetic particles. Using an applied magnetic field, the beads may be congregated and retained from the surrounding liquid reagents of reactants. U.S. Pat. No. 5,779,907, issued Jul. 14, 1998, to Yu, and titled MAGENTIC MICROPLATE SEPARATOR, describes a means and method of providing magnetic separation. As described in the patent, a laboratory tray, or microplate, containing a number of vertical wells is placed on a fixture having a number of upstanding cylindrical magnets. The arrangement of wells and magnets is such that each magnet is disposed adjacent four of the wells. Thus, a 96-well plate requires a fixture that has 24 magnets. The magnetic components in the wells are attracted to the sides of the wells adjacent the magnets. The supernate in the wells can then be removed. The apparatus described by Yu is entirely satisfactory for manual use; however, it does not meet the need of processing the large numbers of samples that are required in the fields of genomic and drug discovery research. Automation is required for processing large numbers of samples.
[0006] Conventionally, in automated magnetic separation systems, a robotic arm moves the laboratory trays over a fixed plate of magnets. While this provides an improvement over the manual method, it requires an additional positioning of the laboratory tray.
[0007] Accordingly, it is a principal object of the present invention to provide an apparatus for magnetic separation that does not require a separate step of positioning of the laboratory plate.
[0008] It is a further object of the invention to provide such an apparatus that can be remotely and automatically controlled.
[0009] It is an additional object of the invention to provide such an apparatus that can be economically constructed using conventional techniques.
[0010] It is another object of the invention to provide such an apparatus that can be part of a robotic liquid handling system.
[0011] Other objects of the present invention, as well as particular features, elements, and advantages thereof, will be elucidated in, or be apparent from, the following description and the accompanying drawing figures.
SUMMARY OF THE INVENTION
[0012] The present invention achieves the above objects, among others, by providing, in a preferred embodiment, an apparatus for automated magnetic separation of materials in laboratory trays, comprising: a frame upon an upper surface of which a multiwell laboratory tray may be placed, a base plate on which is mounted a plurality of upstanding magnets disposed below said upper surface; and means to raise said base plate such as to insert said upstanding magnets into interwell spaces in said laboratory tray.
BRIEF DESCRIPTION OF THE DRAWING
[0013] Understanding of the present invention and the various aspects thereof will be facilitated by reference to the accompanying drawing figures, provided for purposes of illustration only and not intended to define the scope of the invention, on which:
[0014] [0014]FIG. 1 is an isometric view of a microplate positioned over a plate of magnets.
[0015] [0015]FIG. 2 is a side elevational view of the invention, partially in cross-section, with a plate of magnets in lowered position.
[0016] [0016]FIG. 3 is a side elevational view of the invention, partially in cross-section, with a plate of magnets in raised position, such that the magnets are disposed between the wells of the microplate.
[0017] [0017]FIG. 4 is a block/schematic view of a control system for the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0018] Reference should now be made to the drawing figures on which similar or identical elements are given consistent identifying numerals throughout the various figures thereof, and on which parenthetical references to figure numbers direct the reader to the view(s) on which the element(s) being described is (are) best seen, although the element(s) may be seen on other figures also.
[0019] [0019]FIG. 1 illustrates a microplate 10 having a plurality of vertical wells, as at 12 , positioned over a plate of magnets 14 having a plurality of upstanding cylindrical magnets, as at 16 Wells 12 and magnets 16 are arranged such that, when microplate 10 and plate of magnets 14 are brought together, each magnet 16 will be moved into one of a plurality of positions, as at 20 , in the microplate and, so disposed, each magnet will be adjacent four of the wells. Microplate 10 is shown as having 96 wells arranged in a 8×12 matrix and plate of magnets 14 consequently has 24 magnets. It will be understood, however, that the invention may be applied as well to other numbers of microplate wells. In this position, the magnetic flux surrounding each magnet 16 encompasses four adjacent wells 12 . Paramagnetic particles in wells 12 will be attracted by this field and will be drawn to the sidewalls of the wells, adjacent to each magnet 16 . The supernate can then be withdrawn from the wells by, for example, aspiration.
[0020] [0020]FIG. 2 illustrates an apparatus, constructed according to the present invention, and generally indicated by the reference numeral 50 . Apparatus 50 includes a frame 60 having a horizontal bottom plate 62 and a horizontal top plate 64 , the latter having a plurality of vertical holes defined therethrough, as at 66 . A plurality of upstanding vertical magnets, as at 70 , is fixedly attached to a horizontal, non-magnetic base plate 72 that includes four bearings 74 (only two shown) journaled on four vertical guide pins 76 (only two shown) extending between and fixedly attached to bottom plate 62 and top plate 64 . Thus arranged, base plate 72 may move vertically upwardly and downwardly in frame 60 . Base plate 72 is held in its down position against four stops 80 (only two shown) fixedly attached to bottom plate 62 by the action of four compression springs 82 (only two shown) disposed around guide pins 76 and compressed between the lower surface of top plate 64 and the upper surface of the base plate.
[0021] A flexible bladder 90 disposed between the upper surface of bottom plate 62 and the lower surface of base plate 72 provides the motive force to raise the base plate. Bladder 90 may be simply constructed from a bicycle inner tube that is clamped between two clamps 100 fixedly attached to bottom plate 62 . One of clamps 100 is fitted with an air line connection (not shown) to permit flow of pressurized air to the closed interior of bladder 90 .
[0022] As shown on FIG. 2, a microplate 110 having a plurality of vertical wells 1 12 has been placed on the upper surface of top plate 64 . Since base plate 72 is shown in its lowered position, magnets 70 are spaced below wells 112 .
[0023] [0023]FIG. 3 illustrates the elements of apparatus 50 described above (FIG. 2), with pressurized air having been introduced into bladder 90 . The inflation of bladder 90 causes base plate 72 to rise, that motion causing magnets 70 to extend through openings 66 and between wells 112 . As will be understood from inspection of FIG. 1 and the accompanying text, each of magnets 70 will be inserted adjacent four of wells 112 in microplate 110 . Supernate can now be removed from wells 112 by any suitable means such as by aspiration of the supernate.. Expansion of bladder 90 is limited by the confines of frame 60 . The upward force provided by the inflation of bladder 90 exceeds the downward forces being applied by compression springs 82 , permitted the elevation of base plate 72 . Venting of compressed air from bladder 90 will cause the bladder to collapse and base plate 72 to return to its lowered position (FIG. 2) by means of the downward force provided by compression springs 82 .
[0024] [0024]FIG. 4 illustrates a control system that may be used with apparatus 50 , the control system being generally indicated by the reference numeral 200 . Control system 200 includes a system controller 210 that may be a section of a controller used to control other features of a complete analysis system. Controller 210 is operatively connected to control a three-way solenoid valve 220 that permits compressed air from a compressed air source 222 to inflate bladder 90 to raise base plate 72 to its elevated position (FIG. 3) or to vent air from the bladder to cause the base plate to move to its lowered position (FIG. 2).
[0025] The present invention provides a simple and effective means of moving magnets into the interwell spacing of a microplate by remote means. In the case described, low air pressure applied to a bladder, lifts the magnets.
[0026] Using a remotely controlled method of actuating the magnets into the interwell spacing permits the inclusion of the device into a liquid handling robot. This permits completed automation of the entire liquid handling function. The first step in bioassays, using magnetic beads or particles, is to react the coated elements on the beads with other liquid reagents. This requires the beads to be in suspension to provide full exposure of the reacting elements. Normally, some means of agitation is incorporated, such as shaking or multiple aspirations dispensings.
[0027] Following the reaction step is the separation step. A magnetic field is applied, drawing the magnetic beads to the sidewalls of the containing well. This separates the beads from the liquid in the well, permitting the liquid to be withdrawn by an automated pipettor. This process may be repeated multiple times, depending on the assay protocol and how many different reagent reactions are required.
[0028] By the use of a remote means of controlling the insertion of the magnets, the action may by easily accommodated in liquid handling robotics control systems, such as supplied by Tomtec, Inc., of Hamden, Conn. An actuating signal is generated in the control system software This signal controls an electrically operated solenoid valve that applies controlled air pressure to the device operating the magnets. By being small and compact, the magnetic device can be located directly on the robot's operating deck. In other words, frame 60 (FIGS. 2 and 3) simply replaces what would have been a fixed nest, to hold the microplate being used for the test.
[0029] This simplicity eliminates the necessity of physically moving the microplate from the station where it receives the reagent, without magnetization, to a station with magnetization. The invention permits the system control to apply magnetization on demand where and when it is required.
[0030] In the embodiments of the present invention described above, it will be recognized that individual elements and/or features thereof are not necessarily limited to a particular embodiment but, where applicable, are interchangeable and can be used in any selected embodiment even though such may not be specifically shown.
[0031] Terms such as “upper”, “lower”, “inner”, “outer”, “inwardly”, “outwardly”, “vertical”, “horizontal”, and the like, when used herein, refer to the positions of the respective elements shown on the accompanying drawing figures and the present invention is not necessarily limited to such positions.
[0032] It will thus be seen that the objects set forth above, among those elucidated in, or made apparent from, the preceding description, are efficiently attained and, since certain changes may be made in the above construction without departing from the scope of the invention, it is intended that all matter contained in the above description or shown on the accompanying drawing figures shall be interpreted as illustrative only and not in a limiting sense.
[0033] It is also to be understood that the following claims are intended to cover all of the generic and specific features of the invention herein described and all statements of the scope of the invention which, as a matter of language, might be said to fall therebetween. | In a preferred embodiment, an apparatus for automated magnetic separation of materials in laboratory trays, including: a frame upon an upper surface of which a multiwell laboratory tray may be placed; a base plate on which is mounted a plurality of upstanding magnets disposed below the upper surface; and apparatus to raise the base plate such as to insert the upstanding magnets into interwell spaces in the laboratory tray. | 13,464 |
TECHNICAL FIELD
[0001] The invention relates to a broadcast communication system architecture and receiving terminals used within the system, and more particularly to a digital television (TV) network architecture and client terminals.
BACKGROUND
[0002] The conventional terrestrial digital TV transmission systems widely employ a single-frequency network architecture, namely, TV towers at different locations transmit the same signal at the same frequency simultaneously.
[0003] The disadvantage is that the number of the transmit towers and the transmit power are subject to certain constraints. For urban topography, there will be many shadow areas for indoor reception, and for rural topography, the coverage range will be limited in some extent. On the other hand, the conventional digital TV transmission system is for one-way broadcast. This one-way broadcast mode transmits a fixed number of video programs with limited bandwidth, without taking into account the specific service needs of users, e.g., two-way services such as video on-demand, information customization, games, etc.
SUMMARY
[0004] The invention intends to provide a digital TV network architecture and client terminal, to solve the inadequacy of the only existing broadcast approach, the incapability in integrating and sharing with other networks, and the improper allocation of broadcast and network resources.
[0005] According to the aforementioned purpose, a client terminal according to this invention is implemented, wherein the client terminal comprises: a first receiving module for connecting with a broadband communication network, and a second receiving module for connecting with a digital TV broadcast system, wherein the client terminal is operable to receive, via the second receiving module, an information index transmitted by the digital TV broadcast system, and to retrieve corresponding information content from the broadband communication network via the first receiving module based on the information index.
[0006] According to the above main features, the client terminal receives, via the second receiving module, the content transmitted by the digital TV broadcast system, and selectively stores and recommends the content according to a user's behavior habits.
[0007] According to the above main features, the client terminal is operable to directly retrieve information content from the broadband communication network via the first receiving module.
[0008] According to the above main features, the broadband communication network deploys an edge server that is close to the client terminal, wherein the client terminal connects to the broadband communication network via the edge server.
[0009] According to the above main features, the digital TV broadcast system coordinates with the broadband communication network by connecting to a content clustering server, wherein the content clustering server chooses popular content from a plurality of data sources and generates an information index, wherein the information index of the popular content is sent to the client terminal via the digital TV broadcast system and the second receiving module, such that the client terminal is operable to retrieve the corresponding popular content from the edge server via the first receiving module based on the information index of the popular content.
[0010] According to the above main features, the client terminal is connected to the digital TV broadcast system through a wireless digital broadcast channel.
[0011] According to the above main features, the client terminal selectively downloads some of the popular content from the edge server to the client terminal according to a user's behavior habits, and recommends the content to the user.
[0012] According to the aforementioned purpose, a digital TV broadcast system coordinated with a broadband communication network according to this invention is implemented, for providing information to a client terminal, wherein the broadband communication network comprises an edge server that is close to the client terminal, wherein a bidirectional information channel is provided between the client terminal and the edge server, a broadcast information channel is provided between the digital TV broadcast system and the edge server, and a broadcast information channel is provided between the digital TV broadcast system and the client terminal.
[0013] According to the above main features, the digital TV broadcast system coordinates with the broadband communication network by connecting to a content clustering server, wherein the content clustering server performs clustering analysis on multimedia content from a plurality of data sources based on the sources of the content, analysis and prediction of relevance between the content and users, and feedback information to the content including user's click response, to identify the multimedia content as popular content or normal content, so as to choose, classify and index the popular content.
[0014] According to the above main features, the content clustering server sends the popular content to the edge server through the information channel between the digital TV broadcast system and the edge server.
[0015] According to the above main features, the digital TV broadcast system sends the popular content or its index directly to the client terminal through the information channel between the digital TV broadcast system and the client terminal.
[0016] According to the above main features, the digital TV broadcast system sends the popular content or its index to the client terminal through the information channel between the digital TV broadcast system and the client terminal, wherein the client terminal retrieves the corresponding popular content from the edge server via the information channel between the client terminal and the edge server based on the index of the popular content.
[0017] According to the above main features, the content clustering server sends all the content to the broadband communication network, and the client terminal is connected to the broadband communication network via the information channel between the client terminal and the edge server.
[0018] According to the above main features, the information channel between the digital TV broadcast system and the edge server comprises a cable digital broadcast channel, a satellite digital broadcast channel, or a terrestrial digital broadcast channel.
[0019] According to the above main features, the information channel between the digital TV broadcast system and the client terminal comprises a wireless digital broadcast channel.
[0020] According to the above main features, the information channel between the digital TV broadcast system and the edge server and the information channel between the digital TV broadcast system and the client terminal are two logical channels on one physical channel.
[0021] According to the above main features, the information channel between the digital TV broadcast system and the edge server and the information channel between the digital TV broadcast system and the client terminal are two different physical channels.
[0022] According to the aforementioned purpose, an information transmission network according to the invention is implemented, for providing information to a client terminal, wherein the information transmission network comprises a broadband communication network and a digital TV broadcast system, wherein the broadband communication network comprises an edge server that is close to the client terminal, wherein a bidirectional information channel is provided between the client terminal and the edge server, a broadcast information channel is provided between the digital TV broadcast system and the edge server, and a broadcast information channel is provided between the digital TV broadcast system and the client terminal.
[0023] According to the above main features, the information transmission network further comprises a content clustering server connected to the broadband communication network and the digital TV broadcast system, wherein the content clustering server performs clustering analysis on multimedia content from a plurality of data sources based on the sources of the content, analysis and prediction of relevance between the content and users, and feedback information to the content including user's click response, to identify the multimedia content as popular content or normal content, so as to choose, classify and index the popular content.
[0024] According to the above main features, the content clustering server sends the popular content to the edge server through the information channel between the digital TV broadcast system and the edge server.
[0025] According to the above main features, the digital TV broadcast system sends the popular content or its index directly to the client terminal through the information channel between the digital TV broadcast system and the client terminal.
[0026] According to the above main features, the digital TV broadcast system sends the popular content or its index to the client terminal through the information channel between the digital TV broadcast system and the client terminal, wherein the client terminal retrieves the corresponding popular content from the edge server via the information channel between the client terminal and the edge server based on the index of the popular content.
[0027] According to the above main features, the content clustering server sends all the content to the broadband communication network, and the client terminal is connected to the broadband communication network via the information channel between the client terminal and the edge server.
[0028] According to the above main features, the information channel between the digital TV broadcast system and the edge server comprises a cable digital broadcast channel, a satellite digital broadcast channel, or a terrestrial digital broadcast channel.
[0029] According to the above main features, the information channel between the digital TV broadcast system and the client terminal comprises a wireless digital broadcast channel.
[0030] According to the above main features, the information channel between the digital TV broadcast system and the edge server and the information channel between the digital TV broadcast system and the client terminal are two logical channels on one physical channel.
[0031] According to the above main features, the information channel between the digital TV broadcast system and the edge server and the information channel between the digital TV broadcast system and the client terminal are two different physical channels.
[0032] According to the aforementioned purpose, a digital TV heterogeneous network architecture of the invention is implemented for providing digital TV content to a client terminal, wherein the digital TV heterogeneous network architecture comprises: a transmission control module, a broadcast TV network and a secondary network, wherein both the broadcast TV network and the secondary network are connected to the transmission control module, wherein the broadcast TV network is a unidirectional transmission network for sending the digital TV content to the client terminal directly, and the secondary network is a bidirectional network for transmitting the digital TV content to the client terminal and for transmitting control information between the client terminal and the transmission control module, wherein the transmission control module governs the digital TV content to be transmitted via the broadcast TV network and the secondary network.
[0033] According to the above main features, the broadcast TV network further comprises a multiplexing and distribution module connected to the transmission control module, for performing channel multiplexing and content distribution for the content output from the transmission control module; wherein the channel multiplexing means that a plurality pieces of content might occupy one frequency resource chronologically or a plurality pieces of content might occupy one time block at different frequency resources.
[0034] According to the above main features, the control information comprises a VOD request, a broadcast content retransmission request, or a direct video content request.
[0035] According to the above main features, the digital TV content comprises broadcast content as well as VOD content for the client terminal.
[0036] According to the above main features, the secondary network comprises a 3G, LTE, or WiFi network and the wired Internet, wherein the 3G, LTE, or WiFi network is used to connect the client terminal with the Internet, wherein the client terminal uploads control information or video content to the Internet via the 3G, LTE, or WiFi network. The Internet delivers feedback information, broadcast retransmission content or direct video content from the transmission control module to the client terminal via the 3G, LTE, or WiFi network; wherein the feedback information comprises acceptance, waiting, or timeout of a VOD request, acceptance, waiting, or timeout of a broadcast content retransmission request, or acceptance, waiting, or timeout of a direct content request.
[0037] According to the above main features, the client terminal further comprises a storage device, for storing the digital TV content transmitted to the client terminal from the broadcast TV network or the secondary network.
[0038] According to the above main features, the broadcast TV network architecture further comprises a content classification and preparation module connected to the transmission control module, for classifying acquired digital TV content and further creating an index label for each piece of multimedia content.
[0039] According to the above main features, the broadcast TV network architecture further comprises a content acquisition module connected to the content classification and preparation module, for acquiring digital TV content from various sources.
[0040] According to the above main features, the secondary network has a plurality of information transmission channels, and the client terminal comprises an evaluation unit for evaluating a channel condition in real-time based on return channels of the information transmission channels, so as to select an optimal information transmission channel.
[0041] According to the aforementioned purpose, a terrestrial digital TV network architecture according to this invention is implemented, wherein the terrestrial digital TV network architecture comprises: a TV tower base station and a client terminal; wherein a downlink at a first frequency and an uplink at a second frequency are employed between the TV tower base station and the client terminal.
[0042] According to the above main features, the downlink carries broadcast information transmitted to all users in a broadcast mode and proprietary information specific to individual users transmitted in a broadcast or directional transmission mode; and the uplink is accessed according to a time-frequency resource table specified individually and delivered on the downlink.
[0043] According to the above main features, an uplink signal is transmitted by the client terminal in a directional transmission mode; wherein the directional transmission mode is implemented by a directional antenna or through beamforming of an antenna array.
[0044] According to the above main features, a wireless repeater is also included, wherein the TV tower base station transmits a broadcast signal to the wireless repeater, which forwards the broadcast signal to the client terminal; wherein the client terminal transmits an uplink signal to the wireless repeater, which forwards the uplink signal to the TV tower base station.
[0045] According to the above main features, the wireless repeater comprises a pair of back-to-back wireless access points, one for receiving and the other for transmitting; the wireless repeater utilizes analog intra-frequency forwarding, analog inter-frequency forwarding, digital intra-frequency forwarding, or digital inter-frequency forwarding, or utilizes Bluetooth or Wifi forwarding.
[0046] According to the aforementioned purpose, a TV tower base station of this invention is implemented for transceiving signals with a client terminal, wherein: the TV tower base station comprises a receiving device and a transmitting device, wherein the transmitting device transmits information to the client terminal at a first frequency, and the receiving device receives information transmitted from the client terminal at a second frequency.
[0047] According to the above main features, the information transmitted by the transmitting device comprises broadcast information transmitted to all users in a broadcast mode, and proprietary information specific to individual users transmitted in a broadcast or directional transmission mode.
[0048] According to the above main features, the receiving device receives the information transmitted from the client terminal according to a time-frequency resource table for the client terminal.
[0049] According to the aforementioned purpose, a client terminal of this invention is implemented for transceiving signals with a TV tower base station, wherein: the client terminal comprises a receiving device and a transmitting device, wherein the receiving device receives information transmitted from the TV tower base station at a first frequency, and the transmitting device transmits information to the TV tower base station at a second frequency.
[0050] According to the above main features, the client terminal transmits information to the TV tower base station in a directional transmission mode, wherein the directional transmission mode is implemented by a directional antenna or through beamforming of an antenna array.
[0051] With the technical solutions of the invention, the integration of the broadcast network and other networks is provided, to support multiple network access modes for users, and to provide accurate, efficient, and high quality information services to users with best efforts. Moreover, such heterogeneous architectures utilize the WiFi/GPRS/3G, LTE and broadcast networks in a site-specific way to provide a collaborative coverage to solve the blind spots and shadows in the cities. In addition, the network architecture of the invention can support an uplink of broadcasting and also utilizes the different advantages of various networks in coverage range, transmission speed, mobility support, QoS support, setup cost, and targeting market, which are complementary to each other, thereby providing services with more variety, higher quality, and lower price for users.
BRIEF DESCRIPTION OF THE DRAWINGS
[0052] In this invention, like reference numerals refer to like parts throughout the drawings, in which:
[0053] FIG. 1 is a schematic diagram of an information transmission network combining a digital TV broadcast system and a broadband communication network according to a first embodiment of the invention;
[0054] FIG. 2 is a schematic block diagram of a Broadcast-to-Client channel and a Broadcast-to-Server channel in FIG. 1 ;
[0055] FIG. 3 is a schematic diagram of a digital TV heterogeneous network architecture according to a second embodiment;
[0056] FIG. 4 is a schematic diagram of a network architecture according to a third embodiment of the invention;
[0057] FIG. 5 is a schematic diagram of a network architecture according to a fourth embodiment of the invention.
DETAILED DESCRIPTION
[0058] The technical solutions of this invention will be further described below in connection with the figures and embodiments.
[0059] As seen from the prediction in the Background, the explosive increase in demands for video data services places a heavy burden on the broadband communication network; while the high homogenity of a large amounts of data services makes it possible for the digital TV broadcast system to assist the broadband communication network. Accordingly, the digital TV broadcast system and the broadband communication network of multimedia data are inevitably integrated and complement each other. Thus, this invention proposes a network architecture coordinated with the broadband communication network, and is particularly applicable in the digital TV broadcast system.
[0060] As shown in FIG. 1 , with a network architecture that coordinates the broadband communication network and the digital TV broadcast system, the information transmission network of this invention is operable for providing information to a client terminal, and mainly includes two sub-networks, the broadband communication network and the digital TV broadcast system. The broadband communication network includes a plurality of servers in the network. Particularly in this invention, a server close to the client terminal is referred as an edge server, wherein a bidirectional information channel is provided between the client terminal and the edge server, an information channel is provided between the digital TV broadcast system and the edge server, and an information channel is provided between the digital TV broadcast system and the client terminal.
[0061] The edge server is deployed at the backend of the digital TV broadcast system and the broadband communication network. The digital TV broadcast system is connected to the client terminal, forming a Broadcast-to-Client (BC) channel, the digital TV broadcast system is connected to the edge server, forming a Broadcast-to-Server (BS) channel, and the client terminal is connected to the edge server, forming a Server-to-Client (SC) channel.
[0062] Among the above three channels, the SC channel is a bidirectional channel, for interconnectivity between the client and the broadband communication network. The BC channel and the BS channel may be two logical channels on one physical channel, wherein the BC channel and the BS channel multiplexes the physical channel by time-division multiplexing or frequency-division multiplexing. In another aspect, the BC channel and the BS channel may simply be two different physical channels. Regardless the form of the BC channel and the BS channel, the BC channel and the BS channel are not limited to unidirectional channels. In other words, both the BC channel and the BS channel may include an uplink, wherein the uplink and downlink of the BC channel and the BS channel are differentiated by different frequency bands.
[0063] In consideration of the unidirectional or bidirectional characteristics of the BC channel, the BS channel and the SC channel, the BS channel may be a cable digital broadcast channel, or a satellite digital broadcast channel, or a terrestrial digital broadcast channel, the BC channel may be a wireless digital broadcast channel, and the SC channel may be a common wired network channel, or a Wifi channel, etc.
[0064] The multimedia data firstly undergoes content clustering. Accordingly, the information transmission network of this invention further comprises a content clustering server, which is connected to the broadband communication network and the digital TV broadcast system, and which is deployed at frontend of the digital TV broadcast system and the broadband communication network.
[0065] The content clustering server first analyzes popularity of various multimedia data based on the sources of the multimedia content, analysis and prediction of relevance between the content and users, and feedback information to the content including user's click response, and chooses the content that most people concern (i.e., popular content), such that the popular content is separated from normal content. Next, the popular content is further processed to extract key words of the multimedia data based on the popularity characteristics of the multimedia data, which may then be indexed by the key words, and all the indices are managed collectively on the content clustering server.
[0066] For each multimedia data label, the content clustering server needs to continuously update its popularity, so as to update the key words and the corresponding index. Accordingly, the popularity and index of multimedia data are dynamic parameters. For example, in a period of time, some multimedia content is concerned by many people, and the multimedia content becomes popular. After a time period, the concern for the multimedia content decreases, and then the content clustering server may modify the label of the multimedia content from popular to normal. Finally, the digital TV broadcast system assists the broadband communication network to deliver the popular content.
[0067] During the data delivery, the content clustering server groups the multimedia data into two clusters: one cluster for the popular content in all the multimedia data and its information index, the other cluster for content of all the multimedia data. The content clustering server delivers the two clusters through two different networks.
[0068] The first network is the digital TV broadcast system, for delivering the popular content and/or the information index of the content. The transmission on the digital TV broadcast system is carried through a BS channel and a BC channel. The BS channel transmits the popular content directly to the edge server close to the terminal, and the BC channel transmits the popular content and/or the information index of the content directly to the client terminal. Alternatively, the client terminal may retrieve the full information of the corresponding popular content from the edge server via the SC channel based on the information index of the popular content.
[0069] The secondary network is the broadband communication network, for delivering all the multimedia data and the information index thereof. The content clustering server delivers all the content and the information index thereof to the broadband communication network. The edge server is capable of both receiving the BS channel and accessing the broadband communication network. The client terminal connects to the broadband communication network via the SC channel, so as to retrieve the information index of all the multimedia data and the full content.
[0070] As a preferred embodiment of this invention, FIG. 2 illustrates the content clustering, BS channel and BC channel which constitute three essential parts of this invention. The BS channel may be a cable digital broadcast channel, a satellite digital broadcast channel, or a terrestrial digital broadcast channel, which is of high spectrum efficiency. A large amount of popular multimedia data can be delivered to the edge server directly via the BS channel. The BC channel merely employs wireless digital broadcasting, can be widely deployed, can accommodate different requirements of terminals, and benefits power saving in some extent.
[0071] Broadcasting is characterized in the point-to-plane information transmission. The delivery of the popular content through the digital TV broadcast system may offload a high traffic from the broadband communication network. The client terminal receives the broadcast popular content and its information index via the BC channel, may selectively store some popular content for recommendation according to user's behavior habits, and may also store the index information of the popular content. The user may select information based on the recommendation from the client terminal, the index information or other requirements. Although the user does not concern the source of the information, the three different access modes can ensure the user to obtain the required information more quickly and accurately. Based on the user's needs, the user may decide whether to browse the recommended content, whether to browse all the content of the index information, or whether to inquire about other information. If the user simply browses the content recommended by the terminal, the information may be found on the client terminal itself; if the user is interested in specific content of the index information, such information may be retrieved from the nearest edge server via the SC channel; or if the user want to query other content information, the Internet may be accessed via the edge server for information query and browsing.
[0072] The integration of the digital TV broadcast system with the broadband communication network is a trend in the next generation of network architecture. Such an architecture may leverage the characteristic of point-to-plane transmission of the digital TV broadcast system, separate and index the popular content by the content clustering server, and deliver the content that most people concern directly via the BC channel, thereby significantly reducing the traffic load on the broadband communication network. By analyzing the user's behaviors, the terminal may store and recommend the content that the user may concern. Meanwhile, the content may be delivered to the edge server via the BS channel, so as to reduce the access distance between the user and most content. Such a digital TV broadcast architecture provides multiple access modes for users, and is capable of providing accurate, efficient and high quality information services for users with best efforts. The digital TV broadcast system combined with the broadband communication network becomes the information highway in the new era, whereby a large amount of multimedia data may be delivered to the user quickly and accurately by broadcasting.
[0073] As the continuous development of digital TVs and the trends of diversity and interaction of networks, the integration and heterogeneity based on the coexistence of multiple network become a considerable trend of the future digital TV wireless signal communication development. The various networks have different advantages in coverage range, transmission speed, mobility support, QoS support, setup cost, and targeting market, and are complementary to each other. The network integration intends to utilize the complementary characteristics of the heterogeneous networks, so as to provide services with more variety, higher quality, and lower prices for users.
[0074] A terrestrial broadcast TV network architecture established with the concept of heterogeneous networks and having a return link and a collaborative coverage function is shown in FIG. 3 , and mainly comprises a content acquisition module, a content classification and preparation module, a transmission control module, a broadcast TV network, a secondary network, a client terminal and a storage device. The digital TV content of this invention comprises broadcast content as well as VOD content for the client terminal. In particular, as an alternative embodiment of this invention, the broadcast TV network is a broadcast network, the secondary network is a 3G, LTE or WiFi network. Alternatively, the secondary network may be an analog intra-frequency (on-channel) forwarding, digital intra-frequency (differential-channel) forwarding, or digital inter-frequency forwarding communication system, and this invention is not so limited. The connections and functions of these modules are illustrated individually below.
[0075] The content acquisition module is connected to the content classification and preparation module, and acquires resource information mainly by means of photography, audio recording, computer synthesis and so on, creates multimedia content from the resource information by post-processing such as editing, composing, clipping, rendering, etc., and sends the created media content a content classification and preparation module.
[0076] The content classification and preparation module has a receiving terminal connected to the content acquisition module, and a sending terminal connected to the transmission control module. The content classification and preparation module is primarily used to classify the resulting multimedia content, e.g., according to the characteristics of video source effects: distinguishing between real-time and non real-time services, distinguishing the definition (Ultra HD, HD, SD), distinguishing between the dimensions (3D, 2D); according to the categories of the video source content: distinguishing among sport, financial, political, social, educational, historical, variety, drama, film and TV, and so on. Based on the above, further subdivision may be performed. Finally, an index label is created for each video source, which is packaged separately in accordance with the stream format.
[0077] The transmission control module controls both the broadcast TV network and the secondary network to transmit content signals to the client terminal. In this invention, multiple broadcast TV networks and secondary networks may coexist, for example, multiple broadcast networks and multiple 3G or LTE networks, etc. may coexist, at least one or more or all of which has information transmissions being controlled by the transmission control module. The transmission control module communicates control signals and content signals with the client terminal via at least one or more or all of the secondary networks. However, for the broadcast TV network, such as the broadcast network, the transmission control module transmits only content signals. In this invention, the control information comprises a VOD request, a broadcast content retransmission request, or a direct video content request.
[0078] As a preferred embodiment of this invention, the broadcast TV network (the broadcast network) also includes a multiplexing and distribution module. The transmission control module provides broadcast multimedia content to the multiplexing and distribution module of the broadcast system. The broadcast multimedia content is service content being broadcast, including normal broadcast services on various channels and user's video on demand (VOD) service content on special channels. The multiplexing and distribution module performs channel multiplexing and matching, etc., for the broadcast content provided by the transmission control module (including normal video services, Ultra HD, 3D, special VOD services, etc.), which is then distributed to clients such as stationary TVs, mobile phones, mobile terminals by radio frequency signal broadcasting. The channel multiplexing herein means that a plurality pieces of content might occupy one frequency resource chronologically or a plurality pieces of content might occupy one time block on different frequency resources.
[0079] The secondary network of this invention has a plurality of information transmission channels, typically via a 3G, LTE or WiFi network, connected to the transmission control module. Alternatively, the secondary network may be divided into a frontend and a backend, wherein the frontend is the Internet, and the backend includes a 3G, LTE or WiFi network. The transmission control module has access to the frontend, i.e., the Internet, and the client terminal has access to the backend, i.e., access to a 3G, LTE or WiFi network, etc. The frontend Internet is connected to the backend 3G, LTE or WiFi network, to communicating multimedia services and control signals therebetween.
[0080] In this invention, the feedback information comprises acceptance, waiting, or timeout of a VOD request, acceptance, waiting, or timeout of a broadcast content retransmission request, or acceptance, waiting, or timeout of a direct content request. The client terminal may upload control information or video content to the Internet via the 3G, LTE, or WiFi network. The Internet may deliver feedback information, broadcast retransmission content or direct video content from the transmission control module to the client terminal via the 3G, LTE, or WiFi network.
[0081] The transmission control module provides multimedia content to the Internet module, and also exchanges control signaling with the Internet. The transmission control module receives control signaling sent from the Internet, including an on-demand (VOD) request, to control the on-demand content output from the transmission control module to the multiplexing and distribution module. After receiving a request from the Internet, the transmission control module will feedback its processing result to the Internet by control signaling, “acceptance” or “waiting”. If a predetermined latency expires, “no response” is returned, and then the user may resend the request.
[0082] This invention selects the 3G, LTE or WiFi network because 3G, LTE/WiFi base stations are densely deployed in urban regions, thus almost having a seamless coverage. In one aspect, these modules receive control signals from clients (stationary TVs, mobile terminals, etc) via radio frequency, including on-demand requests, direct content requests, and retransmission requests due to a broadcast content package loss, etc, and also (optionally) receive content uploaded from clients, and further upload the content to the Internet. In another aspect, these modules also receive feedback control signaling from the Internet, including a result feedback for the on-demand request (acceptance, waiting, or no response), a feedback for the direct content request (acceptance, waiting, or no response), and a feedback for a lost package retransmission request (acceptance, waiting, or no response), receive the content requested by the client provided from the Internet, and transmit the information received from the Internet module to the requesting client terminal via a radio frequency.
[0083] The client terminal has access to the 3G, LTE or WiFi network, and is equipped with a built-in storage device or connected to an external storage device, for storing information received from the broadcast network or the Internet. In another aspect, the client terminal includes an internal evaluation unit for evaluating a channel condition in real-time based on return channels of the information transmission channels of the secondary network, so as to select an optimal information transmission channel.
[0084] As another aspect of this invention, the above terrestrial broadcast TV network architecture has two primary control modes.
[0085] One control mode is that the secondary network assists the broadcast TV network to achieve collaborative coverage. In particular, the client terminal assesses the broadcast information received from the broadcast network in real-time to identify missing signals in the broadcast information, and sends a retransmission signal to the transmission control module via the 3G, LTE or WiFi network and then the Internet, whereby the transmission control module transmits the missing signals to the client terminal through the Internet and then the 3G, LTE or WiFi network.
[0086] Another control mode is that the secondary network controls the broadcast TV network or the secondary network itself. In particular, the client terminal sends an on-demand control signal to the transmission control module through the 3G, LTE or WiFi network and then the Internet, and the transmission control module transmits the on-demand content to the client terminal through the broadcast network, or again through the Internet and then the 3G, LTE or WiFi network.
[0087] The two control modes of this invention are illustrated below by embodiments.
[0088] In one aspect, the user receives and watches multimedia content through the broadcast network. When a packet loss occurs in the multimedia content received through the broadcast network due to channel environment deterioration, a retransmission request for the lost content (simply referred to lost packet retransmission request) might be sent to the transmission control module through the 3G, LTE or Wifi wireless network and then the Internet. Upon receiving the request, the transmission control module provides a retransmission of the lost content to the client terminal according to normal criteria (for example, the user request arriving first will be processed first), or prioritization criteria (for example, premium users and privileged users are prioritized). If the user request has to wait, the control signaling feedback to the user is waiting, if the user request can be processed directly, then the control signaling of acceptance is returned, or if the user has been waiting for more than a preset value, then the control signaling of “no response” is returned. This service achieves collaborative coverage of heterogeneous networks and the broadcast network, to overcome the deficiency of packet loss in coverage shadow of the broadcast network.
[0089] In another aspect, the user may send a video on-demand (VOD) request to the transmission control module through the 3G, LTE or Wifi wireless network and then the Internet, wherein after receiving the request, the transmission control module controls the on-demand content to be transmitted on the broadcast link, and transmits the on-demand content to the user through the broadcast network timely, so as to meet the on-demand needs of the client terminal. This functionality integrates the heterogeneous networks and the broadcast network, enabling bidirectional transmissions with the client end.
[0090] In addition, the client terminal may send a direct content request to the transmission control module through the 3G, LTE or Wifi wireless network and then through the Internet. This service intends to enable the client terminal to obtain content from the Internet resources directly. After receiving the request, the transmission control module provides a content service directly to the client terminal based on normal criteria (for example, the user request arriving first will be processed first), or prioritization criteria (for example, premium users and privileged users are prioritized). Similarly, the control signaling may be acceptance, waiting or no response.
[0091] When the client terminal selects the 3G, LTE or Wifi access mode, in accordance with the optimal channel criterion, the client terminal evaluates the channel condition in real-time based on the 3G, LTE or Wifi return channel to select an optimal interaction mode. If the client terminal is a mobile device and a network handover is required, it follows the optimal channel criteria for handover.
[0092] The terrestrial digital TV network architecture of the invention is primarily applicable to some regions with limited hardware environment, for example in rural areas, without too many obstacles and with a relatively simple channel environment. In this circumstance, the network architecture of the invention applies in two scenarios as following.
[0093] When the user is near the TV tower base station and has a Light-of-Sight transmission condition, a direct return uplink may be added on the basis of the broadcast link.
[0094] When the user is far from the TV tower base station, or there is no Light-of-Sight transmission between the user and the TV tower base station, a return uplink with repeaters may be added on the basis of the broadcast link.
[0095] The network architectures of the invention operable in the above two scenarios are illustrated below with two embodiments.
[0096] As shown in FIG. 4 , the network architecture of the invention mainly includes a TV tower base station (for example, a broadcast signal TV tower base station) and a client terminal, as well as an uplink and a downlink between the TV tower base station and the client terminal. When the user is near the TV tower base station and might be in a Light-of-Sight transmission condition, e.g., the user is located within 10 km from the broadcast TV tower base station, a direct return uplink may be added on the basis of broadcast link.
[0097] The downlink and uplink utilize a combination of TDD and FDD, wherein the downlink is on a different frequency band from the uplink. The downlink carries broadcast information transmitted to all users in a broadcast mode and proprietary information specific to individual users transmitted in a broadcast or directional transmission mode. The coverage of downlink information is improved by transmitting high rate signals through transmit diversity of the TV tower base station, which is suitable for immersive applications such as SHDTV, HDTV and 3DTV, as well as Rich Media applications. The uplink is accessed according to information in a time-frequency resource table specified individually and delivered on the downlink.
[0098] The uplink signal is transmitted by the client terminal in a directional transmission mode, which can be implemented by a directional antenna or through beamforming of an antenna array, thus achieving high system power efficiency, far transmission distance, and security. The modulation and demodulation for the uplink burst transmissions rely on the PSK modulation method with a relatively low peak-to-average power ratio to improve power efficiency. The uplink also employs a multi-rate Turbo convolutional coding technology, and utilizes the long preamble sequence readily to be captured. The MAC layer protocol for the uplink employs the DOCSIS protocol which has been applied in cable TVs, and employs the combined “contention and reservation” resource allocation method, wherein the contention method may be utilized for short data service like a VOD request, and the resource reservation method may be utilized for real-time video call, video interaction service, etc. The frame structure defines essential signaling frames: ranging frame and MAP frame. By division of time slots and subcarrier clusters, it is possible to support a plurality of multi-access modes, such as TDMA, OFDMA or SC-FDMA.
[0099] As shown in FIG. 5 , when the user is far from the TV tower base station, for example, when the user is about 10-35 km from the broadcast TV tower base station, there is typically no Light-of-Sight (LoS) path due to occlusion. On the basis of the first embodiment, the invention employs a network architecture with wireless repeaters to extend the coverage of downlink transmissions (there may be multiple wireless repeaters, without being limited to the single repeater mode as shown in FIG. 5 ). Typically, the wireless repeater includes a pair of back-to-back wireless access points (APs), one for receiving, and the other for transmitting.
[0100] In particular, the wireless repeater may use one or more of various wireless forwarding modes, such as analog intra-frequency forwarding, analog inter-frequency forwarding, digital intra-frequency forwarding, digital inter-frequency forwarding, or Bluetooth or Wifi forwarding, etc. The TV tower base station transmits a broadcast signal to the wireless repeater, which forwards the broadcast signal to the client terminal; the client terminal transmits an uplink signal to the wireless repeater, which forwards the uplink signal to the TV tower base station.
[0101] Also, when there is no Light-of-Sight transmission in the uplink transmission path, the return uplink with a wireless repeater as in FIG. 5 may be employed to enable the uplink transmission between the client terminal and the TV tower base station. Selecting the coding with a low constellation and a low bit rate can further improve the uplink coverage range, thereby enhancing the capability of direct return uplink.
[0102] As known from the above, the TV tower base station implementing this invention includes a receiving device (not shown) and a transmitting device (not shown), wherein the transmitting device transmits information to the client terminal at a first frequency in a broadcast mode, and the receiving device receives information transmitted from the client terminal at a second frequency. Moreover, the information transmitted from the transmitting device in the broadcast mode includes broadcast information transmitted to all users and proprietary information specific to individual users. The receiving device receives the information transmitted from the client terminal according to a time-frequency resource table for the client terminal.
[0103] Meanwhile, the client terminal implementing this invention also includes a receiving device (not shown) and a transmitting device (not shown), wherein the receiving device receives information sent by the TV tower base station in a broadcast mode at a first frequency, and the transmitting device transmits information to the TV tower base station at a second frequency. Moreover, the client terminal transmits information to the TV tower base station in a directional transmission mode, which can be implemented by a directional antenna or through beamforming of an antenna array.
[0104] Those skilled in the art shall appreciate that the specification above illustrates one or more of the numerous embodiments of this invention, rather than limiting thereof. Any equivalent modification, variations and equivalents to the above embodiments, that are consistent with the substantial spirit and scope of this invention, fall within the scope of the claims of this invention. | This invention discloses a digital TV broadcast system coordinated with a broadband communication network, an information transmission network in which the broadcast system is applied, a digital TV heterogeneous network architecture, and a client terminal used in each of the above network systems. The various broadcast system architectures of the invention adopt the design concept of heterogeneous network which integrates a broadcast network with other networks, for example, a communication network, the Internet and the like, to form a heterogeneous network architecture coordinating various networks. Meanwhile, the usage in bad conditions are taken into account, and a broadcast TV system which enables uplink transmission by using a broadcast link is designed. The terminal of the invention is a terminal applicable in these heterogeneous network architectures, is capable of receiving signals transmitted from various networks, and can enable flexible receiving and access modes with a series of control means. The network system and client terminal of the invention can achieve an optimized allocation of network resources, save spectrum resources, and enable optimized transmission and management of information resources. | 50,572 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to thiophenesulfonamides that have carbonic anhydrase inhibition activity and are useful as anti-glaucoma agents.
2. Background of the Art
Glaucoma is an ocular disorder associated with elevated intraocular pressures which are too high for normal function and may result in irreversible loss of visual function. If untreated, glaucoma may eventually lead to blindness. Ocular hypertension, i.e., the condition of elevated intraocular pressure without optic nerve head damage or characteristic glaucomatous visual field defects, is now believed by many ophthalmologists to represent the earliest phase of glaucoma.
Many of the drugs formerly used to treat glaucoma proved not entirely satisfactory. Indeed, few advances were made in the treatment of glaucoma since pilocarpine and physostigmine were introduced. Only recently have clinicians noted that many β-adrenergic blocking agents are effective in reducing intraocular pressure. While many of these agents are effective in reducing intraocular pressure, they also have other characteristics, e.g. membrane stabilizing activity, that are not acceptable for chronic ocular use. (S)-1-tert-Butylamino-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy]-2-propanol, a β-adrenergic blocking agent, was found to reduce intraocular pressure and to be devoid of many unwanted side effects associated with pilocarpine and, in addition, to possess advantages over many other β-adrenergic blocking agents, e.g., to be devoid of local anesthetic properties, to have a long duration of activity, and to display minimal tolerance.
Although pilocarpine, physostigmine and the β-adrenergic blocking agents mentioned above reduce intraocular pressure, none of these drugs manifests its action by inhibiting the enzyme carbonic anhydrase and, thereby, impeding the contribution to aqueous humor formation made by the carbonic anhydrase pathway.
Agents referred to as carbonic anhydrase inhibitors, block or impede this inflow pathway by inhibiting the enzyme, carbonic anhydrase. While such carbonic anhydrase inhibitors are now used to treat intraocular pressure by oral, intravenous or other systemic routes, they thereby have the distinct disadvantage of inhibiting carbonic anhydrase throughout the entire body. Such a gross disruption of a basic enzyme system is justified only during an acute attack of alarmingly elevated intraocular pressure, or when no other agent is effective.
Topically effective carbonic anhydrase inhibitors are reported in U.S. Pat. Nos. 4,386,098; 4,416,890; and 4,426,388. The compounds reported therein are 5 (and 6)-hydroxy-2-benzothiazolesulfonamides and acyl esters thereof.
Additionally, U.S. Pat. No. 4,544,667 discloses a series of benzofuran-2-sulfonamides, and U.S. Pat. Nos. 4,477,466; 4,486,444; 4,542,152; and 4,585,787 disclose 5-phenylsulfonylthiophene-2-sulfonamides and 5-benzoylthiophene-2-sulfonamides and alkanoyloxy derivatives thereof which are reported to be topically effective carbonic anhydrose inhibitors useful in the treatment of elevated intraocular pressure and glaucoma.
Finally, U.S. Pat. No. 4,914,111 reports that thiophene or furan-2-sulfonamides, having a 4-benzyl substituent are effective for the topical treatment of elevated intraocular pressure and glaucoma.
In view of the above, it is clear that a great deal of research has been carried out on the use of sulfonamides for the topical treatment of glaucoma. Furthermore, certain thiophenesulfonamides have been suggested for the topical treatment of glaucoma. However, the use of 3-thiophenesulfonamides has not been suggested for use in the topical treatment of glaucoma.
Therefore, it is one objective of this invention to provide 3-thiophenesulfonamides for the treatment of glaucoma.
It is another object of this invention to provide compounds having carbonic anhydrase inhibition activity.
Another object of this invention is to provide a method of inhibiting carbonic anhydrase activity to thereby treat glaucoma.
Other objects and advantages of the instant invention will become apparent from a careful reading of the specification below.
SUMMARY OF THE INVENTION
The present invention provides novel compounds having carbonic anhydrase inhibition activity and useful in the treatment of glaucoma. These compounds are represented by the structural formula: ##STR2## wherein R 1 and R 2 are independently (a) hydrogen; or
(b) OR 4 , wherein R 4 is hydrogen or C 1-7 alkyl or C 1-3 alkylcarbonyl or phenylcarbonyl or phenyl; or
(c) NR 5 R 6 , wherein R 5 and R 6 are independently hydrogen, or C 1-7 alkyl, or C 1-7 alkyl substituted with one or more halogen or OR 4 ; or
(d) --COR 7 , wherein R 7 is hydrogen, C 1-7 alkyl, or NR 5 R 6 ; or
(e) --SR 8 , wherein R 8 is hydrogen or C 1-7 alkyl, or C 1-7 alkyl substituted with one or more halogen, or OR 4 ; or
(f) C 1-7 alkyl, or C 1-7 alkyl substituted with one or more halogen, or OR 4 or NR 5 R 6 ; or
(g) R 1 and R 2 are together
(i) ═O, or
(ii) ═NOR 8 , or
(iii) ═S;
and R 3 is
(h) C 1-7 alkyl or C 1-7 substituted with one or more halogen, OR 4 or NR 5 R 6 ; or
(i) aryl, wherein said aryl comprises up to 10 carbon atoms and is an unsubstituted carbocyclic aryl or heterocyclic aryl, which may be selected from the group consisting of phenyl, thienyl, furyl, pyridyl, pyrryl, piperidyl, pyrrolidyl, morpholinyl, or said carbocyclic aryl or heterocyclic aryl is substituted with one or more halogen, or OR 4 , or NR 5 R 6 , or carboxylic acid or lower alkyl esters thereof, or carboxaldehyde or C 1-7 alkyl, or C 1-7 alkyl substituted with one or more halogen, or OR 4 , or NR 5 R 6 or carboxylic acid or lower alkyl esters thereof; or
(j) --COR 9 , wherein R 9 is R 7 or a carbocyclic or a heterocyclic radical, e.g. aryl, wherein said carbocyclic or a heterocyclic radical comprises up to 10 carbon atoms and may be selected from the group consisting of phenyl, cyclopentyl, cyclohexyl, thienyl, furyl, pyridyl, pyrryl, piperidyl, pyrrolidyl, morpholinyl or said carbocyclic aryl or heterocyclic aryl radical is substituted with one or more halogen, or OR 4 , or NR 5 R 6 , or C 1-7 or C 1-7 alkyl substituted with one or more halogen, OR 4 or NR 5 R 6 .
Preferably, in the novel compounds of the invention R 1 and R 2 , together, represent O; or at least one of R 1 or R 2 is hydrogen and the other is OH, OCOCH 3 , NOH, or H. (That is, the novel compounds of this invention may include an alpha carbonyl or hydroxy, or acetoxy, or hydroxyamino, etc. group at the 5 position on the thiophene ring.) R 3 preferably represents C 1 to C 6 alkyl or phenyl or phenyl substituted with one or more, more preferably one, hydroxy, methoxy, acetoxy, acetoxymethylene, carboxy, hydroxymethyl, formyl, N,N-dimethylaminomethyl fluoro, chloro or bromo radicals.
DETAILED DESCRIPTION OF THE INVENTION
The novel compounds of the invention may be prepared by the following general reaction scheme:
4-Bromo-2-thiophenecarboxaldehyde is reacted with R 3 Li or R 3 MgX, wherein X is a halogen, e.g., bromo or iodo, in tetrahydrofuran, or any other dipolar, aprotic solvent, e.g. diethylether, dioxane, etc., at a temperature of from about 0° C. to -78° C., to yield an alkoxide of the addition product. This intermediate is reacted with trimethylsilylchloride, at a temperature of from about 0° C. to -78° C., to provide a "protected" alcohol. The protected intermediate is consecutively reacted with n-Butyllithium in tetrahydrofuran at a temperature of about -100° C. to yield the 3-lithio compound. The lithio compound is reacted with SO 2 at a temperature of about -100° C. in THF, or other aprotic solvent, to yield the lithio sulfinate. The lithium sulfinate is reacted with N-chloro succinimide (NCS) at ambient temperatures in dichloromethane to yield the sulfonyl chloride. The sulfonyl chloride is consecutively reacted with NH 4 OH and tetra-n-butyl ammonium fluoride to yield a novel compound of the invention represented by the general formula: ##STR3##
I may be oxidized by Jones' reagent to yield a novel compound of the invention represented by the general formula: ##STR4##
That is, II represents the alpha carbonyl derivatives of the invention, i.e., wherein R 1 and R 2 together, represent O (oxygen).
II may be reacted with H 2 NOH.HCl in pyridine to provide compounds of the invention represented by the general formula: ##STR5##
That is, in the compounds represented by Formula III, R 1 and R 2 , together, represent NOH.
Alternatively, compounds represented by Formula I may be reacted with acetic anhydride in pyridine to yield compounds of the invention represented by the general formula: ##STR6##
That is, in the compounds represented by Formula IV, R 1 represents OCOCH 3 and R 2 represents hydrogen. Of course, other anhydrides may be used, e.g. benzoic anhydride, to provide compounds wherein R 1 represents a radical derived from said other anhydride, e.g. R 1 is OCOC 6 H 5 .
An alternative to the above general reaction scheme relies on the Wittig reaction as follows:
(Alkyl)triphenylphosphonium bromide is reacted with 4-bromo-2-thiophene carboxaldehyde in THF, in the presence of potassium tertiary butoxide to yield ##STR7## wherein R is an unsaturated alkenyl radical derived from the above alkyl phosphonium bromide. The 2-(alk-1-enyl)-4-bromothiophene of Formula V may be hydrogenated in the presence of Wilkenson's catalyst to yield the saturated derivative. The saturated derivative is consecutively reacted with n-butyl lithium, SO 2 , NCS and NH 4 OH/tetra-n-butyl ammoniumfluoride to yield ##STR8## wherein R 1 =R 2 =H and R 3 is alkyl.
Specific compounds within the scope of this invention include:
1-[5-(3-sulfamoyl thienyl)] pentanone oxime
5-(4-hydroxybenzoyl)3-thiophene sulfonamide
5-(3-N,N-dimethylamino-4-hydroxybenzhydrol)-3-thiophene sulfonamide
5-(1-hydroxy-n-pentyl)-3-thiophene sulfonamide
5-(1-hydroxy-n-heptyl)-3-thiophene sulfonamide
5-(4-acetoxymethylbenzhydrol)-3-thiophene sulfonamide
5(4-formylbenzhydrol)-3-thiophene sulfonamide
5-(4-carboxylbenzhydrol)-3-thiophene sulfonamide
5-(benzhydrol)-3-thiophene sulfonamide
5-(4-methoxybenzhydrol)3-thiophene sulfonamide
5-(2-methoxybutyl)-3-thiophene sulfonamide
5-(4-chlorohexyl)-3-thiophene sulfonamide
5-(3-phenylpentyl)-3thiophene sulfonamide
5-(3-methylpentyl)-3-thiophene sulfonamide
5-benzoyl-3-thiophene sulfonamide
5-[benzhydrol]-3-thiophene sulfonamide
When administered for the treatment of elevated intraocular pressure of glaucoma, the active compound is most desirably administered topically to the eye, although systemic treatment is also satisfactory.
When given systemically, the drug can be given by any route, although the oral route is preferred. In oral administration the drug can be employed in any of the usual dosage forms such as tablets or capsules, either in a contemporaneous delivery or sustained release form. Any number of the usual excipients or tableting aids can likewise be included.
The active drug of this invention is most suitably administered in the form of ophthalmic pharmaceutical compositions adapted for topical administration to the eye such as a suspension, ointment, or as a solid insert. Formulations of these compounds may contain from 0.01 to 15% and especially 0.5% to 3% of medicament. Higher dosages as, for example, about 10%, or lower dosage can be employed provided the dose is effective in reducing or controlling elevated intraocular pressure. As a unit dosage from 0.001 to 10.0 mg, preferably 0.005 to 2.0 mg, and especially 0.1 to 1.0 mg of the compound is generally applied to the human eye, generally on a daily basis is single or divided doses so long as the condition being treated exists.
The hereinbefore described dosage values are believed accurate for human patients and are based on the known and presently understood pharmacology of the compounds, and the activity of other similar entities in the human eye. As with all medications, dosage requirements are variable and must be individualized on the basis of the disease and the response of the patient.
The pharmaceutical preparation which contains the active compound may be conveniently admixed with a non-toxic pharmaceutical organic carrier, or with a non-toxic pharmaceutical inorganic carrier. Typical of pharmaceutically acceptable carriers are, for example, water, mixtures of water and water-miscible solvents such as lower alkanols or aralkanols, vegetable oils, polyalkylene glycols, petroleum based jelly, ethyl cellulose, ethyl oleate, carboxymethylcellulose, polyvinylpyrrolidone, isopropyl myristrate and other conventionally employed acceptable carriers. The pharmaceutical preparation may also contain non-toxic auxiliary substances such as emulsifying, preserving, wetting agents, bodying agents and the like, as for example, polyethylene glycols, antibacterial components such as quaternary ammonium compounds, phenylmercuric salts known to have cold sterilizing properties and which are non-injurious in use, thimerosal, methyl and propyl paraben, benzyl alcohol, buffering ingredients such as sodium chloride, sodium borate, sodium acetate, and other conventional ingredients such as sorbitan monolaurate, polyoxyethylene sorbitan monopalmitylate, dioctyl sodium sulfosuccinate, monothioglycerol, thiosorbitol, ethylenediamine tetracetic acid, and the like. Additionally, suitable ophthalmic vehicles can be used as carrier media for the present purpose including conventional phosphate buffer vehicle systems, isotonic boric acid vehicles, isotonic sodium chloride vehicles, isotonic sodium borate vehicles and the like. The pharmaceutical preparation may also be in the form of a solid insert.
While many patients find liquid medication to be entirely satisfactory, other may prefer a solid medicament that is topically applied to the eye, for example, a solid dosage form that is suitable for insertion into the cul-de-sac. To this end the carbonic anhydrase inhibiting agent can be included with a non-bioerodable insert, i.e., one which after dispensing the drug remains essentially intact, or a bioerodable insert, i.e., one that either is soluble in lacrimal fluids, or otherwise disintegrates.
For example, one may use a solid water soluble polymer as the carrier for the medicament. The polymer used to form the insert may be any water soluble non-toxic polymer, for example, cellulose derivatives such as methylcellulose, sodium carboxymethyl cellulose, or a hydroxy lower alkyl cellulose such as hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose and the like; acrylates such as polyacrylic acid salts, ethyl acrylates, polyacrylamides; natural products such as gelatin, alginates, pectins, tragacanth, karaya, chondrus, agar, acacia; the starch derivatives such as starch acetate, hydroxyethyl starch ethers, hydroxypropyl starch, as well as other synthetic derivatives such as polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl methyl ether, polyethylene oxide, neutralized carbopol and xanthan gum, and mixtures of said polymers.
The invention is further illustrated by the following examples which are illustrative of a specific mode of practicing the invention and is not intended as limiting the scope of the appended claims.
EXAMPLE 1
2-(n-Hex-1-enyl)-4-bromo thiophene
2.0 grams (10.5 mmols) of (n-pentyl) triphenyl phosphonium bromide was added to 105 ml. of tetrahydrofuran (THF) with stirring. 1.86 gms (15.8 mmol.) of potassium tertiary butoxide was then added to the mixture while stirring at room temperature under an argon atmosphere. After one hour of continued stirring, 2.0 gms (10.5 mmol) of 4-bromo-2-thiophene carboxaldehyde, dissolved in 20 ml of THF, was added to the phosphonium bromide solution. After an additional one hour, the reaction was quenched with water. The organic layer was then separated, washed twice with water and then with brine. After drying over MgSO 4 and filtering, the filtrate was concentrated. The concentrate was flushed through a silica plug and eluted with hexane to yield 2.2 gms of a yellow liquid. This liquid included a mixture of cis and trans isomers of the named compound and had the following NMR spectra:
1 HNMR (CDCl 3 ): 7.12 (s), 6.98 (s), 6.88 (s), 6.42 (app. d), 6.03-6.14 (m), 5.52-5.64 (m), 2.32-2.42 (m), 2.12-2.22 (m), 1.28-1.74 (m), 0.90-0.98 (m).
EXAMPLE 2
2-(hexyl)-4-bromo thiophene
2.2 gms (9.0 mmol) of the product of Example 1 were dissolved in 25 ml of ethanol and 0.22 gms of Wilkenson's catalyst were added. (Wilkenson's catalyst is tris(triphenylphosphine) rhodium (I) chloride.) The mixture was stirred at room temperature under atmospheric hydrogen pressure overnight. The reaction product was concentrated and separated by flash chromatography, using hexane, as the eluant, to yield 2.2 gms of a colorless liquid. The NMR spectra of said liquid was as follows:
1 HNMR (CDCl 3 ): 7.01 (s), 6.98 (s), 6.78 (s), 6.71 (s), 6.42 (d, J=15 Hz), 6.09 (d, t, J=8, 15 Hz), 2.77 (t, J=7 Hz), 2.12-2.22 (m), 1.60-1.70 (m), 1.29-1.35 (m), 0.87-0.91 (m).
From said spectra it was determined that 2-(n-hex-1-enyl)-4-bromothiophene was still present in the reaction product. The reaction product was again treated with Wilkenson's Catalyst and hydrogen, overnight. The re-treated reaction mixture was passed through a silica gel plug and eluted with hexane to yield 2.1 gms of a clear, colorless liquid having the following NMR spectra: 7.01 (s, 1H), 6.71 (s, 1H), 2.77 (t=7 Hz, 2H), 1.65 (m, 2H), 1.29-1.35 (m, 6H), 0.89 (t, J=7 Hz, 3H).
EXAMPLE 3
5-n-Heptyl-3-thiophene sulfonamide
1.93 gms (7.8 mmol) of the bromothiophene of Example 2 were added to 78 ml. of THF and the solution was cooled to -100° C., while under an argon atmosphere. 4.9 ml of a 1.6M solution of n-butyl lithium (n-BuLi) in hexane were added to the cooled solution and stirred at -100° C. under an argon atmosphere. After a few minutes, SO 2 was bubbled into the solution. When the solution became saturated with SO 2 , it was allowed to warm to room temperature and 20 ml. of ethyl ether were then added. After about two and one-half hours, the solution was transferred to a roto-evaporator and concentrated. The resulting concentrate was dissolved in 78 ml of methylene dichloride (CH 2 Cl 2 ) and 1.15 gms (8.6 mmol) of N-chlorosuccinamide (NCS) were added. The resulting mixture was stirred, under argon, at room temperature for two hours. The resulting mixture was filtered and the filtrate was concentrated. The concentrate was dissolved in 50 ml of acetone and 10 ml of concentrate NH 4 OH (aqueous) were added. After 10 minutes, the mixture was diluted with ethyl acetate and washed with water three times and then with a saturated salt solution, i.e. brine. The organic phase was separated, dried over MgSO 4 , filtered and the filtrate concentrated. The concentrate was subjected to flash chromatography utilizing a 3 to 1, by volume, mixture of hexane and ethyl acetate eluant to yield 1.24 gms of a light yellow solid having the following NMR spectra:
1 H NMR (CDCl 3 ): 7.76 (d, J=1.4 Hz, 1H), 7.07 (d, J=1.4 Hz, 1H), 5.21 (bs, 2H), 2.76 (q, J=7.7 Hz, 2H), 1.65 (p, J=7.7 Hz, 2H), 1.28-1.38 (m, 6H), 0.87 (t, J=6.8 Hz, 3H).
EXAMPLE 3(a)
5-n-Pentyl-3-thiophene sulfonamide
The reactions set forth in Examples 1 through 3 are repeated except that (n-butyl)triphenylphosphine bromide is substituted for (n-pentyl)triphenylphosphine bromide to yield the named compound.
EXAMPLE 3(b)
5-(3-methylpentyl)-3-thiophene sulfonamide
The reactions set forth in Examples 1 through 3 are repeated except that (2-methylbutyl)triphenylphosphine bromide is substituted for (n-pentyl)triphenylphosphine bromide to yield the named compound.
EXAMPLE 3(c)
5-(3-phenylpentyl)-3-thiophene sulfonamide
The reactions set forth in Examples 1 through 3 are repeated except that (2-phenylbutyl)triphenylphosphine bromide is substituted for (n-pentyl)triphenylphosphine bromide to yield the named compound.
EXAMPLE 3(d)
5-(4-chlorohexyl)-3-thiophene sulfonamide
The reactions set forth in Examples 1 through 3 are repeated except that (3-chloropentyl)triphenylphosphine bromide is substituted for (n-pentyl)triphenylphosphine bromide to yield the named compound.
EXAMPLE 3(e)
5-(2-methoxybutyl)-3-thiophene sulfonamide
The reactions set forth in Examples 1 through 3 are repeated except that (3-methoxypropyl)triphenylphosphine bromide is substituted for (n-pentyl)triphenylphosphine bromide to yield the named compound.
EXAMPLE 4
5-[(4-t-butyldimethylsiloxyphenyl)(trimethylsiloxy)methyl]-3-bromothiophene
5.9 gms (0.02 mol) of 4-bromo t-butyldimethylsiloxybenzene were dissolved in 42 ml of dry THF. The solution was cooled to -78° C. while under an argon atmosphere and 13.1 ml (0.02 mol) of a 1.6M solution of n-butyl lithium in hexane were added. After stirring for fifteen minutes under argon the solution was combined over a twenty-five-minute period with a solution of 4.0 gms (0.02 mol) of 4-bromo-2-thiophene carboxaldehyde in 50 ml. of THF at -78° C. The resulting solution was stirred for one hour and fifteen minutes at -78° C. 1.95 ml of trimethylsilylchloride (TMSCI) were added and the solution was allowed to warm to room temperature overnight with stirring. An additional 10 ml of TMSCl were added and the solution was stirred for six hours. The reaction was quenched with water; the organic phase was separated from the brine, dried over MgSO 4 , filtered, concentrated and separated by flash chromatography, utilizing hexane as the eluant. 2.5 gms of a clear colorless liquid were recovered having an NMR spectra of:
1 H NMR (acetone-d 6 ): 7.21 (d, J=8.5 Hz, 2H), 7.11 (d, J=1.5 Hz, 1H), 6.80 (d, J=8.5 Hz, 2H), 6.65 (d, J=1.5 Hz, 1H), 5.84 (s, 1H), 0.99 (s, 3H), 0.21 (s, 6H), 0.10 (s, 9H).
EXAMPLE 5
5-(4-hydroxybenzhydrol)3-thiophene sulfonamide
2.34 gms (5.0 mmol) of the bromothiophene, prepared in Example 4, were dissolved in 50 ml of dry THF. The resulting solution is cooled to -78° C. while under an argon atmosphere. 3.1 ml of a 1.6M solution of n-BuLi, in hexane, is added and stirring was continued for a few minutes. SO 2 was bubbled into the solution until the solution was saturated with SO 2 . 20 ml of ethyl ether were added and the solution was allowed to warm to room temperature. After about two hours at room temperature, the solution was concentrated, the residue dissolved in 50 ml of methylene dichloride and 0.73 gms (5.5 mmol) of NCS were added. After about one-half hour, the resulting mixture was filtered, the filtrate concentrated and the concentrate was dissolved in a solution of 5 ml concentrated NH 4 OH (aqueous) and 25 ml of acetone. After one-half hour, the resulting solution is diluted with ethyl acetate, washed with water, three times, and then with brine. The resulting organic phase is separated, dried over MgSO 4 , filtered and the filtrate concentrated. The concentrate was subjected to flash chromatography utilizing a 3:1 mixture of hexane and ethyl acetate, as the eluant, to yield 1.41 gms of a light yellow oil having the following NMR spectra:
1 H NMR (acetone-d 6 ): 7.88 (s, 1H), 7.33 (d, J=9 Hz, 2H), 7.10 (s, 1H), 6.88 (d, J=9 Hz, 2H), 6.55 (bs, 2H), 6.07 (s, 1H), 0.97 (s, 9H), 0.20 (s, 6H), 0.07 (s, 9H).
0.52 gms (1.1 mmol.) of the product light yellow oil was dissolved in 11 ml of THF and 2.3 ml of a 1.0M solution of tetra-n-butyl ammonium fluoride (TBAF) in THF is added. After one-half hour, the reaction was quenched with water and extracted with ethyl acetate. The organic layer was separated, washed three times with water and then with brine. The organic phase was separated, dried over MgSO 4 , filtered and the filtrate concentrated. The concentrate was subjected to flash chromatography, utilizing the above hexane/ethyl acetate mixture to yield 0.26 gms of a white foam having the following NMR spectra:
1 H NMR (acetone-d 6 ): 8.43 (bs, 1H), 7.88 (s, 1H), 7.28 (d, J=9 Hz, 2H), 7.05 (s, 1H), 6.82 (d, J=9 Hz, 2H), 6.57 (bs, 2H), 5.95 (s, 1H), 5.32 (bs, 1H).
EXAMPLE 5(a)
5-(4-methoxybenzhydrol)-3-thiophene sulfonamide
The reactions set forth in Examples 4 and 5 are repeated except that 4 -methoxybromobenzene is substituted for 4-bromo t-butyldimethyl-siloxy-benzene to yield the named compound which has the following NMR spectra:
1 H NMR (acetone-d 6 ): 7.88 (d, J=1.5 Hz, 1H), 7.38 (d, J=8.6 Hz, 2H), 7.07 (m, 1H), 6.92 (d, J=8.6 Hz, 2H), 6.54 (bs, 2H), 5.99 (d, J=4.3 Hz, 1H), 5.34 (d, J=4.3 Hz, 1H), 3.78 (s, 3H).
EXAMPLE 5(b)
5-(benzhydrol)-3-thiophene sulfonamide
The reactions set forth in Examples 4 and 5 are repeated except that bromobenzene is substituted for 4-bromo t-butyldimethylsiloxybenzene to yield the named compound. This compound may be subsequently reacted with acetic anhdyride in the presence of pyridine, as described above, to yield the acylated derivative, i.e. 5-[(phenyl)(acetoxy)methyl]-3-thiophene sulfonamide, having the following NMR spectra:
1 H NMR (acetone-d 6 ): 7.90 (s, 1H), 7.30-7.50 (m, 5H), 7.10 (s, 1H), 6.55 (bs, 2H), 6.05 (d, J=4.3 Hz, 1H), 5.46 (d, J=4.3 Hz, 1H).
EXAMPLE 5(c)
5-(1-hydroxy-n-heptyl)-3-thiophene sulfonamide
The reactions set forth in Examples 4 and 5 are repeated except that 1-bromohexane is substituted for 4-bromo t-butyldiimethylsiloxybenzene to yield the named compound, having the following NMR spectra:
1 H NMR (CDCl 3 ): 7.88 (s, 1H), 7.24 (s, 1H), 5.06 (bs, 2H), 4.88-4.89 (m, 1H), 2.43-2.45 (m, 1H), 1.79-1.81 (m, 2H), 1.25-1.31 (m, 8H), 0.86-0.88 (m, 3H).
EXAMPLE 5(d)
5-(1-hydroxy-n-pentyl)-3-thiophene sulfonamide
The reactions set forth in Examples 4 and 5 are repeated except that 1-bromobutane is substituted for 4-bromo t-butyldimethylsiloxybenzene to yield the named compound, having the following NMR spectra:
1 H NMR (CDCl 3 ): 7.82 (s, 1H), 7.20 (s, 1H), 5.35 (bs, 2H), 4.80 (t, J=4.5 Hz, 1H), 1.70-2.88 (m, 2H), 1.24-1.48 (m, 4H), 0.88 (t, J=4.5 Hz, 3H).
EXAMPLE 5(e)
5-(3-hydroxybenzhydrol)-3-thiophene sulfonamide
The reactions set forth in Examples 4 and 5 are repeated except that 3-bromo t-butyldimethylsiloxy is substituted for 4-bromo t-butyldi-methylsiloxybenzene to yield the named compound, having the following NMR spectra:
1 H NMR (acetone-d 6 ): 8.40 (bs, 1H), 7.89 (d, J=1.5 Hz, 1H), 7.18 (t, J=7.7 Hz, 1H), 7.11 (d, J=1.5 Hz, 1H), 6.92-6.97 (m, 2H), 6.75-6.78(m, 1H), 6.56 (bs, 2H), 5.97 (s, 1H), 5.40 (bs, 1H).
EXAMPLE 6
5-(4-hydroxybenzoyl)-3-thiophene sulfonamide
0.10 gms (0.35 mmol) of 5-(4-hydroxybenzhydrol) 3-thiphene sulfonamide, as prepared in Example 5, were dissolved in 5 ml of acetone and to this solution 0.13 ml (0.35 mmol) of a 2.67M solution of Jones' Reagent were added. (Jones' Reagent is aqueous chromic acid.) The resulting mixture was stirred for about forty minutes at room temperature and then quenched with isopropyl alcohol. The resulting solution was diluted with ethyl acetate, washed three times with water and then with brine. The organic layer was separated, dried over MgSO 4 , filtered and the filtrate concentrated. The concentrate was subjected to flash chromatography, utilizing a 1:1 mixture of hexane and ethyl acetate, as the eluant, to yield 78 mg of a clear colorless oil having the following NMR spectra:
1 H NMR (acetone-d 6 ): 9.45 (bs, 1H), 8.43 (d, J=1.3 Hz, 1H), 7.95 (d, J=1.3 Hz, 1H), 7.89 (d, J=9 Hz, 2H), 7.04 (d, J=9 Hz, 2H), 6.81 (bs, 2H).
EXAMPLES 6(a)-(j)
The compounds of Examples 5(a)-(j) are converted into the corresponding alpha carbonyl derivatives by the method of Example 6. The compounds were identified by the NMR spectra given below.
EXAMPLE 6(a)
5-(4-methoxybenzoyl)-3-thiophene sulfonamide
1 H NMR (acetone-d 6 ): 8.43 (s, 1H), 7.92-7.95 (m, 3H), 7.12 (d, J=9.0 Hz, 2H), 6.77 (bs, 2H), 3.93 (s, 3H).
EXAMPLE 6(b)
5-benzoyl-3-thiophene sulfonamide
1 H NMR (acetone-d 6 ): 8.48 (s, 1H), 7.90-7.95 (m, 3H), 7.60-7.75 (m, 3H), 6.80 (2H).
EXAMPLE 6(c)
5-(1-heptanoyl)-3-thiophene sulfonamide
1 H NMR (CDCl 3 ): 8.21 (s, 1H), 7.94 (s, 1H), 5.01 (bs, 2H), 2.89 (t, J=7.3 Hz, 2H), 1.73 (p, 7.2 Hz, 2H), 1.30-1.34 (m, 6H), 0.88 (t, J=8.3 Hz, 3H).
EXAMPLE 6(d)
5-(1-pentanoyl)-3-thiophene sulfonamide
1 H NMR (CDCl 3 ): 8.22 (s, 1H), 7.96 (s, 1H), 5.10 (bs, 2H), 2.90 (t, J=7.5 Hz, 2H), 1.73 (p, J=7.5 Hz, 2H), 1.40 (sex., J=7.5 Hz, 2H), 0.95 (t, J=7.5 Hz, 3H).
EXAMPLE 6(e)
5-(3-hydroxybenzoyl)-3-thiophene sulfonamide
1 H NMR (acetone-d 6 ): 8.46 (d, J=1.3 Hz, 1H), 7.93 (d, J=1.4 Hz, 1H), 7.32-7.46 (m, 3H), 7.15-7.19 (m, 1H), 6.86 (bs, 2H).
Examples 6(f) to (j) were prepared by a process analogous to the preparation of Examples 6(a) to (e) with the appropriate bromo reactant substituted for the 4-bromotrimethylsiloxybenzene.
EXAMPLE 6(f)
5-(4-butylbenzoyl)-3-thiophene sulfonamide
1 H NMR (acetone-d 6 ): 8.45 (d, J=1.4 Hz, 1H), 7.93 (d, J=1.4 Hz, 1H), 7.85 (d, J=8.2 Hz, 2H), 7.45 (d, J=8.2 Hz, 2H), 6.78 (bs, 2H), 2.74 (t, J=7.5 Hz, 2H), 1.60-1.68 (m, 2H),. 1.38 (sex., J=7.8 Hz, 2H), 0.93 (t, J=7.3 Hz, 3H).
EXAMPLE 6(g)
5-(3-trifluoromethylbenzoyl)-3-thiophene sulfonamide
1 H NMR (acetone-d 6 ): 8.52 (d, J=1.4 Hz, 1H), 8.22 (d, J=7.9 Hz, 1H), 8.17 (s, 1H), 8.06 (d, J=8.3 Hz, 1H), 7.95 (d, J=1.4 Hz, 1H), 7.88 (t, J=7.8 Hz, 1H), 6.78 (bs, 2H).
EXAMPLE 6(h)
5-(2-fluorobenzoyl)-3-thiophene sulfonamide
1 H NMR (acetone-d 6 ): 8.50 (d, J=1.2 Hz, 1H), 7.79 (t, J=1.5 Hz, 1H), 7.68-7.73 (m, 2H), 7.34-7.44 (m, 2H), 6.80 (bs, 2H).
EXAMPLE 6(i)
5-(3-fluorobenzoyl)-3-thiophene sulfonamide
1 H NMR (acetone-d 6 ): 8.49 (s, 1H), 7.95 (s, 1H), 7.60-7.77 (m, 3H), 7.47-7.53 (m, 1H), 6.79 (bs, 2H).
EXAMPLE 6(j)
5-(3.5-difluorobenzoyl)-3-thiophene sulfonamide
1 H NMR (acetone-d 6 ): 8.51 (s, 1H), 7.99 (s, 1H), 7.49-7.56 (m, 2H), 7.37-7.44 (m, 1H), 6.79 (bs, 2H).
EXAMPLE 7
5-(4-hydroxy-3-(N,N-dimethylaminomethyl)benzoyl)-3-thiophene sulfonamide
5-(4-hydroxy-3,5-(bis-N,N-dimethylaminomethyl)benzoyl)-3-thiophene sulfonamide
0.25 g (0.88 mmol) of 5-(4-hydroxybenzoyl)-3-thiophene sulfonamide, 0.21 mL (2.6 mmol)of aqueous formaldehyde (37%) and 0.89 mL (7.9 mmol)of aqueous dimethylamine (40%) were added to 3 mL of ethanol. The solution was heated at reflux for 15 1/2 h and then cool to room temperature. Solvent was removed under vacuum and the crude product subjected to flash chromatography. Utilizing 5:1 chloroform/methanol as the eludent 49 mg of 5-(4-hydroxy-3-(N,N-dimethylaminomethyl)benzoyl)-3-thiophene sulfonamide was recovered as a yellow color solid.
1 H NMR (acetone-d 6 ): 8.39 (d, J=1.4 Hz, 1H), 7.92 (d, J=1.4 Hz, 1H), 7.81 (dd, J=8.5, 2.3 Hz, 1H), 7.67 (d, J=2.3 Hz, 1H), 6.85 (d, J=8.5 Hz, 1H), 3.82 (s, 2H), 2.38 (s, 6H).
The eluant was switched over to 2:1 methanol/chloroform (with 5% triethylamine) and 0.18 g of 5-(4-hydroxy-3,5-(bis-N,N-dimethylamino-methyl)benzoyl)-3-thiophene sulfonamide was recovered as a yellow color solid.
1 H NMR (acetone-d 6 ): 8.39 (d, J=1.4 Hz, 1H), 7.93 (d, J=1.4 Hz, 1H), 7.75 (s, 2H), 3.66 (s, 4H), 2.32(s, 12H).
EXAMPLE 8
4-bromo-2-[tetrahydropyronyl) (4-t-butyldimethylsiloxymethylphenyl)methyl] thiophene
6.5 g (22 mmol) of 4-bromobenzyl alcohol, t-butyldimethylsilyl ether was added to 40 mL of THF. The solution was cool to -78° C. 15.3 mL (22 mmol) of a 1.42M n-BuLi solution was added. The solution was transferred via cannula to 4.2 g (22 mmol) of 4-bromo-2-thiophene carboxaldehyde in 70 mL THF at -78° C. Reaction was stirred at -78° C. for 30 min before quenching with 5 mL of saturated NH 4 Cl. The reaction was diluted with ethyl acetate and washed with water (3×) followed with brine. Solution was dried over MgSO 4 and the solvent removed under vacuum. The product, 10 mL (o.11 mol) of DHP and a catalytic amount of TsOH were added to 88 mL of dichloromethane. The reaction was stirred at rt for 18 1/2 h. The reaction was washed with water (3×) followed with brine. The solution was dried over MgSO 4 and the solvent removed under vacuum. Flash chromatography utilizing 20:1 hexane/ethyl ether as the eluant recovered 9.3 g of the product as a light yellow color oil.
1 H NMR (CDCl 3 ): mixture of diastereomers; 7.27-7.40 (m), 7.12-7.18 (m), 6.90 (s), 6.58 (s), 5.95 (s), 5.90 (s), 4.84-4.88 (m), 4.75 (s), 4.72 (s), 4.62-4.66 (m), 3.96-4.05 (m), 3.74-3.82 (m), 3.48-3.62 (m), 1.48-2.02 (m), 0.94 (s), 0.93 (s), 0.12 (s), 0.10 (s).
EXAMPLE 9
5-[(tetrahydropyranyl)(4-t-butyldimethylsiloxymethylphenyl)methyl]-3-thiophene sulfonamide
8.8 g (18 mmol) of the product obtained in Example #8 was added to 180 mL of THF. The solution was cool to -100° C. 12.7 mL (18 mmol) of a 1.42M n-BuLi solution was added dropwise. After a few minutes SO 2 was passed through the reaction flask until the solution became saturated. 30 mL of ethyl ether was added and the liquid nitrogen/ethyl ether bath removed. After 2 h the solvent was removed under vacuum. The crude product and 2.6 g (19.8 mmol) NCS were added to 180 mL of dichloromethane. After stirring at rt for 11/2 h the mixture was filtered and the filtrate concentrated. The crude product was added to 30 mL of concentrated ammonium hydroxide in 180 mL of acetone. Upon stirring for 31/2 h the solution was dilutd with ethyl acetate and washed with water (3×) followed with brine. The solution was dried over MgSO 4 and the solvent removed under vacuum. Flash chromatography utilizing 2:1 hexane/ethyl acetate recovered 2.9 g of the product as a yellow color oil.
1 H NMR (CDCl 3 ): mixture of diastereomers; 7.96 (s), 7.94 (s), 7.49-7.34 (m), 7.01 (s), 6.07 (s), 6.01 (s), 4.83-4.86 (m), 4.78 (s), 4.60-4.64 (m), 3.90-3.99 (m), 3.68-3.77 (m), 3.43-3.58 (m), 1.43-1.98 (m), 0.96 (s), 0.15 (s), 0.13 (s).
EXAMPLE 10
5-(4-hydroxymethylbenzhydrol)-3-thiophene sulfonamide
0.36 g (0.72 mmol) of the product from Example #9 and a catalytic amount of TsOH were added to 10 mL of methanol. After 2 h of stirring at rt the solution was diluted with ethyl acetate and washed with water (3×) followed with brine. The solution was dried over MgSO 4 and the solvent removed under vacuum. Flash chromatography utilizing 2:1 ethyl acetate/hexane as the eluant recovered 87 mg of 5-(4-hydroxymethylbenzhydrol)-3-thiophene sulfonamide as a clear colorless oil.
1 H NMR (acetone-d 6 ): 7.88 (d, J=1.4 Hz, 1H), 7.44 (d, J=7.5 Hz, 2H), 7.35 (d, J=7.5 Hz, 2H), 7.08 (d, J=1.4 Hz, 1H), 6.54 (bs, 2H), 6.04 (d, J=4.3 Hz, 1H), 5.42 (d, J=4.3 Hz, 1H), 4.62 (d, J=5.7 Hz, 2H), 4.19 (t, J=5.8 Hz, 1H).
EXAMPLE 11
5-(4-carboxybenzoyl)-3-thiophene sulfonamide
0.53 g (1.8 mmol) of 5-(4-hydroxymethylbenzhydrol)-3-thiophene sulfonamide was added to 8.8 mL of acetone. The solution was cool to 0° C. and 1.35 mL (3.7 mmol) of Jone's reagent was added. After 15 min the solvent was removed under vacuum and the mixture filtered. The solid was washed with water. Flash chromatography utiling 20% methanol/chloroform as the eluant recovered 0.48 g of 5-(4-carboxybenzoyl)-3-thiophene sulfonamide as a white solid.
1 H NMR (acetone-d 6 ): 8.51 (d, J=1.4 Hz, 1H), 8.23 (d, J=8.3 Hz, 2H), 8.01 (d, J=8.3 Hz, 2H), 7.94 (d, J=1.4 Hz, 1H),6.79 (bs, 2H).
EXAMPLE 11(a)
5-(3-carboxylbenzoyl)-3-thiophene sulfonamide
1 H NMR (acetone-d 6 ): 8.51 (d, J=1.4 Hz, 1H), 8.50 (s, 1H), 8.34 (d, t, J=7.8, 1.3 Hz, 1H), 8.16 (d, t, J=7.8, 1.3 Hz, 1H), 7.96 (d, J=1.3 Hz, 1H), 7.77 (t, J=7.8 Hz, 1H), 6.81 (bs, 2H).
EXAMPLE 12
5-[(tetrahydropyranyl)(4-hydroxymethylphenyl)methyl]-3-thiphene sulfonamide
0.45 g (0.91 mmol) of the product from Example #9 was added to 10 mL of THF. 1.0 mL (1.0 mmol) of a 1M tetra-n-butylammonium fluoride solution was added. After stirring at rt for 1 h the solution was diluted with water and extracted with ethyl acetate. The organic phase was washed with water (3×) followed with brine. The solution was dried over MgSO 4 and the solvent removed under vacuum. Flash chromatography utilizing 1:1 hexane/ethyl acetate as the eluent recovered 0.33 g of the product as a clear colorless oil.
1 H NMR (acetone-d 6 ): mixture of diastereomers; 7.97 (s), 7.95 (s), 7.32-7.48 (s), 6.97 (s), 6.60 (bs), 6.55 (bs), 6.05 (s), 5.98 (s), 4.82-4.85 (m), 4.58-4.68 (m), 4.17-4.28 (m), 3.90-3.97 (m), 3.68-3.75 (m), 3.40-3.56 (m), 1.44-1.98 (m).
EXAMPLE 13
5-(4-acetoxymethylbenzhydrol)-3-thiophene sulfonamide
0.74 g (1.9 mmol) of the product from Example #12, 0.23 mL (2.9 mmol) of pyridine and 0.23 mL (2.9 mmol) of acetic anhydride were added to 19 mL of dichloromethane. After stirring at rt for 15 h the solution was diluted with ethyl acetate and washed with water (3×) followed with brine. The solution was dried over MgSO 4 and the solvent removed under vacuum. The 0.60 g of the crude product and a catalytic amount of TsOH were added to 14 mL of methanol. After stirring at rt for 31/2 h the solution was diluted with water and extracted with ethyl acetate. The organic phase was washed with water (2×) followed with brine. The solution was dried over MgSO 4 and the solvent removed under vacuum. Flash chromatography utilizing 1:1 hexane/ethyl acetate as the eluant recovered 0.37 g of 5-(4-acetoxymethyl-benzhydrol)-3-thiophene sulfonamide as a clear colorless oil.
1 H NMR (acetone-d 6 ): 7.90 (s, 1H), 7.48 (d, J=7.5 Hz, 2H), 7.37 (d, J=7.5 Hz, 2H), 7.12 (s, 1H), 6.55 (bs, 2H), 6.08 (s, 1H), 5.50 (bs, 1H), 5.10 (s, 2H), 2.08 (s, 3H).
EXAMPLE 14
5-(4-acetoxymethylbenzoyl)-3-thiophene sulfonamide
0.20 g (0.6 mmol) of 5-(4-acetoxymethylbenzhydrol)-3-thiophene sulfonamide was added to 6 mL of acetone. 0.22 mL (0.6 mmol) of a 2.67M TBAF solution was added. After stirring at rt for 15 min the reaction was quenched with isopropyl alcohol. The mixture was diluted with water and extracted with ethyl acetate. The organic phase was washed with water (3×) followed with brine. The solution was dried over MgSO 4 and the solvent removed under vacuum. Recrystallization from ethyl acetate/hexane afforded 0.17 g of 5-(4-acetoxymethylbenzoyl)-3-thiophene sulfonamide as white crystals.
1 H NMR (acetone-d 6 ): 8.47 (d, J=1.4 Hz, 1H), 7.93 (s, 1H), 7.92 (d, J=8.3 Hz, 2H), 7.62 (d, J=8.3 Hz, 2H, 6.80 (bs, 2H), 5.22 (s, 2H), 2.10 (s, 3H).
EXAMPLE 15
5-(4-hydroxymethylbenzoyl)-3-thiophene sulfonamide
14 mg (41.3 mmol) of 5-(4-acetoxymethylbenzoyl)-3-thiophene sulfonamide and 9 mg (61.8 mmol) of K 2 CO 3 were added to 3 mL of methanol. After stirring at rt for 11 h the solution was diluted with ethyl acetate and washed with 1N HCl followed with water (2×) and brine. The solvent was removed under vacuum to afford 12.5 mg of 5-(4-hydroxymethylbenzoyl)-3-thiophene sulfonamide as a white solid.
1 H NMR(acetone-d 6 ): 8.46 (d, J=1.4 Hz, 1H), 7.93 (d, J=1.4 Hz, 1H), 7.89 (d, J=8.3 Hz, 2H), 7.59 (d, J=7.9 Hz, 2H), 6.79 (bs, 2H), 4.77 (d, J=5.4 Hz, 2H), 4.51 (t, J=5.7 Hz, 1H).
EXAMPLE 16
5-(4-formylbenzoyl)-3-thiophene sulfonamide
30 mg (0.1 mmol) of 5-(4-hydroxymethylbenzoyl)-3-thiophene sulfonamide and 300 mg of MnO2 were added to 5 mL of THF. After stirring at rt for 30 min the mixture was filtered through a bed of celite and eluted with ethyl acetate. The filtrate was concentrated and the crude product subjected to flash chromatography utilizing 1:1 ethyl acetate/hexane as the eluent to recover 16 mg of 5-(4-formylbenzoyl)-3-thiophene sulfonamide as a yellow solid.
1 H NMR(acetone-d 6 ): 10.21 (s, 1H), 8.52 (d, J=1.3 Hz, 1H), 8.12 (q, J=9.7 Hz, 4H), 7.94 (d, J=1.3 Hz, 1H), 6.79 (bs, 2H).
EXAMPLE 16(a)
5-(3-formylbenzoyl)-3-thiophene sulfonamide
1 H NMR(acetone-d6): 10.18 (s, 1H), 8.52 (d, J=1.3 Hz, 1H), 8.14 (s, 1H), 8.23 (d, t, J=1.4, 8.0 Hz, 2H), 7.97 (d, J=1.4 Hz, 1H), 7.85 (t, J=8.0 Hz, 1H), 6.80 (bs, 2H).
EXAMPLE 17
5-(4-formylbenzhydrol)-3-thiophene sulfonamide
0.12 g (0.32 mmol) of the product from Example #12, 4A molecular sieves and 56 mg (0.48 mmol) of NMO were added to 6 mL of dichloromethane. After stirring at rt for 15 min 5.6 mg (0.016 mmol) of TPAP was added. After 4 h at rt the mixture was filtered through a plug of celite and eluted with ethyl acetate. The filtrate was concentrated and the crude product subjected to flash chromatography utilizing 1:1 ethyl acetate/hexane as eluant to recover 42 mg of the desired product and 41 mg of starting material.
63 mg (0.17 mmol) of the product and a catalytic amount of TsOH were added to 5 mL of methanol. After 4 h at rt the solution was diluted with ethyl acetate and washed with saturated NaHCO 3 followed with water (3×) and brine. The solution was dried over MgSO 4 and the solvent removed under vacuum to afford 47 mg of 5-(4-formylbenzhydrol)-3-thiophene sulfonamide as a clear colorless oil.
1 H NMR(acetone-d 6 ): 10.04 (s, 1H), 7.94 (d, J=8.3 Hz, 2H), 7.93 (s, 1H), 7.73 (d, J=8.3 Hz, 2H), 7.18 (s, 1H), 6.58 (bs, 2H), 6.20 (d, J=4 Hz, 1H), 5.77 (d, J=4 Hz, 1H).
EXAMPLE 18
5-[(methoxy)(3-trifluoromethylphenyl)methyl]-3-thiophene sulfonamide
0.20 g (0.6 mmol) of 5-(3-trifluoromethylbenzhydrol)-3-thiophene sulfonamide and 0.11 g (0.6 mmol) of TsOH were added to 10 mL of methanol. The solution was heated at reflux for 12 h. The solvent was removed under vacuum and the crude product subjected to flash chromatography utilizing 2:1 hexane/ethyl acetate as the eluant to recover 0.16 g of 5-[(methoxy)(3-trifluoromethylphenyl)methyl]-3-thiophene sulfonamide as a white solid.
1 H NMR (acetone-d 6 ): 7.99 (d, J=1.5 Hz, 1H), 7.66-7.80 (m, 4H), 7.23-7.24 (m, 1H), 6.59 (bs, 2H), 5.76 (s, 1H), 3.41 (s, 3H).
EXAMPLE 18(a)
5-[(methoxy)(4-hydroxymethylphenyl)]methyl-3-thiophene sulfonamide
1 H NMR (acetone-d 6 ): 7.94 (d, J=1.1 Hz, 1H), 7.39 (s, 4H), 7.08 (d, J=1.1 Hz, 1H), 6.56 (bs, 2H), 5.56 (s, 1H), 4.64 (d, J=5.9 Hz, 2H), 4.24 (t, J=5.9 Hz, 1H), 3.35 (s, 3H).
EXAMPLE 19
5-(1-pentanoyl)-3-thiophene sulfonamide, oxime
0.10 gms (0.4 mmol) of 5-(1-pentanoyl)-3-thiophene sulfonamide and 0.28 gms (4 mmol) of NH 2 OH.HCl were dissolved in 5 ml of pyridine. The reaction vessel was sealed and heated at 60° C. overnight. The reaction solution was cooled to room temperature, diluted with ethyl acetate, washed three times with water and finally with brine. The organic phase was separated, dried over MgSO 4 , filtered and concentrated. Thin liquid chromatography showed that the starting compounds were present. The concentrate was redissolved in 5 ml of pyridine, 0.25 gms of NH 2 OH.HCl were added and the reaction vessel was sealed and heated at 60° C. overnight. The resulting reaction solution was cooled to room temperature, extracted with ethyl acetate, washed with water and brine as described above. After drying with MgSO 4 and filtering, the organic phase was concentrated and subjected to flash chromatography, utilizing a 2 to 1 mixture of hexane and ethyl acetate, as the eluant, to yield 78 mgs. of a white solid having the following NMR spectra:
1 H NMR (acetone-d 6 ): mixture of Isomers: 11.11 (bs), 10.50 (bs), 8.16 (s), 7.92 (s), 7.78 (s), 7.55 (s), 6.64 (bs), 2.68-2.80 (m), 1.35-1.67 (m), 0.89-0.95 (m).
EXAMPLES 19(a)-(b)
The compounds of Examples 6(a) and (b) are converted into the corresponding oxime derivatives by the method of Example 19.
EXAMPLE 19(a)
5-(4-methoxybenzoyl)-3-thiophene sulfonamide, oxime
1 H NMR (acetone-d 6 ): 11.55 (s), 10.58 (s), 8.22 (d, J=1.4 Hz), 7.96 (d, J=1.4 Hz), 7.40-7.47 (m), 7.00-7.07 (m), 6.61-6.64 (m), 3.87 (s), 3.86 (s).
EXAMPLE 19(b)
5-benzoyl-3-thiophene sulfonamide, oxime
1 H NMR (acetone-d 6 ): mixture of Isomers: 11.69 (bs), 10.65 (bs), 8.24 (d, J=1.4 Hz), 7.98 (d, J=1.4 Hz), 7.37-7.59 (m), 7.02 (d, J=1.4 Hz), 6.58-6.64 (m).
EXAMPLE 20
5-(4-ethoxycarbonylbenzoyl)-3-thiophene sulfonamide
0.1 g (0.32 mmol) of 5-(4-carboxylbenzoyl)-3-thiophene sulfonamide was added to 0.19 g (1.13 mmol) of N,N'-diisopropyl-O-ethyl isourea 1.6 mL of THF. Solution was heated at 50° C. for 2 h. An additional 0.19 g of the isourea was added and the reaction stirred at 50° C. for 48 h. The mixture was filtered through a plug of celite and the filtrate collected and concentrated. Flash chromatography (35% ethyl acetate/hexane) recovered 80 mg of 5-(4-ethoxycarbonylbenzoyl)-3-thiophene sulfonamide as a white color solid.
1 H NMR (acetone-d 6 ): 8.50 (d, J=1.4 Hz, 1H), 8.20 (d, J=8 Hz, 2H), 8.10 (d, J=8 Hz, 2H), 7.92 (d, J=1.4 Hz, 1H), 6.80 (bs, 2H), 4.40 (q, J=7 Hz, 2H), 1.39 (t, J=7 Hz, 3H).
EXAMPLE 20(a)
5-(3-butoxycarbonylbenzoyl)-3-thiophene sulfonamide
8.50 (d, J=1.4 Hz, 1H), 8.43 (m, 1H), 8.25 (m, 1H), 8.12 (m 1H), 7.94 (d, J=1.4 Hz, 1H), 7.74 (m, 1H), 6.80 (bs, 2H), 1.60 (s, 9H).
EXAMPLE 20(b)
5-(4-(2-N,N-dimethylamino-1-ethoxy)carbonylbenzoyl)-3-thiophene sulfonamide
1 H NMR (CD 3 OD):
8.47 (d, J=1.4 Hz, 1H), 8.29 (d, J=8.5 Hz, 2H), 8.00 (d, J=8.5 Hz, 2H), 7.89 (d, J=1.4 Hz, 1H), 4.73 (t, J=5 Hz, 2H), 3.65 (t, J=5 Hz, 2H), 3.03 (s, 6H).
EXAMPLE 20(c)
5-(4-t-butoxycarbonylbenzoyl)-3-thiophene sulfonamide
1 H NMR (acetone-d 6 ):
8.50 (d, J=1.4 Hz, 1H), 8.16 (d, J=8.5 Hz, 2H), 8.00 (d, J=8.5 Hz, 2H), 7.93 (d, J=1.4 Hz, 1H), 6.79 (bs, 2H), 1.61 (s, 9H).
EXAMPLE 21
5-(4-acetoxybenzoyl)-3-thiophene sulfonamide
58 mg (0.20 mmol) of 5-(4-hydroxybenzoyl)-3-thiophene sulfonamide, 81 mL (1.0 mmol) of pyridine and 94 mL (1.0 mmol) of acetic anhydride were added to 4 mL of THF. The reaction was stirred at rt for 1 1/4 h and then diluted with ethyl acetate. The organic phase was washed with water (2×) followed with brine. The solution was dried over MgSO 4 and the solvent removed under vacuum. Flash chromatography utilizing 1:1 hexane/ethyl acetate as the eluant recovered 51 mg of 5-(4-acetoxybenzoyl)-3-thiophene sulfonamide as tan color crystals.
1 H NMR (acetone-d 6 ):
8.47 (d, J=1.3 Hz, 1H), 7.98 (d, J=8.6 Hz, 2H), 7.96 (d, J=1.3 Hz, 1H), 7.37 (d, J=8.6 Hz, 2H), 6.78 (bs, 2H), 2.32 (s, 3H).
EXAMPLE 21(a)
5-(3-acetoxybenzoyl)-3-thiophene sulfonamide
1 H NMR (acetone-d 6 ):
8.22 (d, J=1.3 Hz, 1H), 7.69 (d, J=1.3 Hz, 1H), 7.53 (d,d, J=7.8, 1.3 Hz, 1H), 7.37 (t, J=7.8 Hz, 1H), 7.39 (s, 1H), 7.18-7.22 (m, 1H), 6.50 (bs, 2H), 2.04 (s, 3H).
EXAMPLE 22
5-(4-propionoxybenzoyl)-3-thiophene sulfonamide
0.10 g (0.35 mmol) of 5-(4-hydroxybenzoyl)-3-thiophene sulfonamide, 85 mL (1.05 mmol) of pyridine, 26 mL (0.35 mmol) of propionic acid and 70 mg (0.37 mmol) of EDCI were added to 3.5 mL of THF. The reaction was stirred at rt for 46 h. The solution was diluted with ethyl acetate and washed with water (3×) followed with brine. The solution was dried over MgSO4 and the solvent removed under vacuum. Flash chromatography utilizing 1:1 ethyl acetate/hexane recovered 77 mg of 5-(4-propionoxybenzoyl)-3-thiophene sulfonamide as a clear colorless oil.
1 H NMR (acetone-d 6 ):
8.47 (s, 1H), 7.99 (d, J=8.7 Hz, 2H), 7.95 (s, 1H), 6.79 (bs, 2H), 2.67 (q, J=7.4 Hz, 2H), 1.21 (t, J=7.4 Hz, 3H).
EXAMPLE 22(a)
5-(3-benzoxybenzoyl)-3-thiophene sulfonamide
1 H NMR (acetone-d 6 ): 8.50 (d, J=1.4 Hz, 1H), 8.21 (d, J=7.2 Hz, 2H), 8.00 (d, J=1.4 Hz, 1H), 7.59-7.88 (m, 7H), 6.78 (bs, 2H).
The compounds of the invention were assayed for biological activity as follows:
Carbonic anhydrase activity was assayed according to the micromethod of Maren (J. Pharmacol. Exptl. Therap., 130, 26-29, 1960). All solutions and reagents were maintained at 0°-4° C. The final assay mixture contained 16 mM phenol red, added enzyme and 62.5 mM sodium carbonate/bicarbonate. Its volume was kept constant at 0.8 mL. The time required for the added enzyme to lower the pH of CO 2 -saturated carbonate/bicarbonate buffer from pH 9.9 to 6.8 was measured using the color change of phenol red as endpoint. T 1 is the time recorded for the reaction containing no enzyme. T 2 is the time recorded for the reaction containing pure CA11 enzyme from human erythrocyte, or an unknown amount in a sample. Enzyme activities (unit) were calculated using the formula:
Unit/ug=(T.sub.1 -T.sub.2)/(T.sub.2 *ug protein used in assay)
IC50 of a carbonic anhydrase inhibitor is the concentration that lowers the enzyme activity to half.
The results of this assay are reported in Table 1, below.
______________________________________Structures IC50nM______________________________________5-(4-acetoxybenzoyl)-3-thiophene sulfonamide 12 nM5-(4-hydroxy-3-(N,N-dimethylaminomethyl) 30 nMbenzoyl)-3-thiophene sulfonamide5-(4-hydroxy-3,5-(bis-N,N-dimethylaminomethyl) 155 nMbenzoyl)-3-thiophene sulfonamide5-(hydroxymethylbenzoyl)-3-thiophene sulfonamide 17 nM5-(4-propionoxybenzoyl)-3-thiophene sulfonamide 9 nM5-(3-hydroxybenzoyl)-3-thiophene sulfonamide 6.7 nM5-(3-carboxybenzoyl)-3-thiophene sulfonamide 11, 14 nM5-(3-formylbenzoyl)-3-thiophene sulfonamide 7.3 nM5-(4-butylbenzoyl)-3-thiophene sulfonamide 8.7 nM5-(3-trifluoromethylbenzoyl)-3-thiophene sulfonamide 8.3 nM5-(2-N,N-dimethylamino-1-ethoxy)carbonylbenzoyl)- 25 nM3-thiophene sulfonamide5-(3-butoxycarbonylbenzoyl)-3-thiophene sulfonamide 25 nM5-(4-acetoxybenzoyl)-3-thiophene sulfonamide 3.6 nM[5-(3-sulfonamidothienyl)][2-pyridyl] ketone 19 nM5-(4-ethoxycarbonylbenzoyl)-3-thiophene sulfonamide 6 nM5-(4-t-butoxycarbonylbenzoyl)-3-thiophene 3 nMsulfonamide5-(3-benzoxybenzoyl)-3-thiophene sulfonamide 5.3 nM5-(4-formylbenzoyl)-3-thiophene sulfonamide 13 nM5-benzoyl-3-thiophene sulfonamide 13 nM5-(4-methoxybenzoyl]-3-thiophene sulfonamide 26 nM5-(1-heptanoyl)-3-thiophene sulfonamide 14 nM5-(1-pentanoyl)-3-thiophene sulfonamide 27 nM5-(4-carboxybenzoyl)-3-thiophene sulfonamide 3.4, 5 nM5-(4-hydroxybenzoyl)-3-thiophene sulfonamide 17 nM5-(4-acetoxymethylbenzoyl)-3-thiophene sulfonamide 6 nM5-(2-fluorobenzoyl)-3-thiophene sulfonamide 18 nM5-(3-fluorobenzoyl)-3-thiophene sulfonamide 12 nM5-(3,5-difluorobenzoyl)-3-thiophene sulfonamide 15 nM5-(1-hydroxypentyl)-3-thiophene sulfonamide 32 nM5-(4-hydroxymethylbenzhydrol)-3-thiophene 41 nMsulfonamide5-(4-formylbenzhydrol)-3-thiophene sulfonamide 18 nM5-(1-hydroxyheptanyl)-3-thiophene sulfonamide 31 nM5-(4-methoxybenzhydrol)-3-thiophene sulfonamide 16 nM5-benzhydrol-3-thiophene sulfonamide 74 nM5-(4-acetoxymethylbenzhydrol)-3-thiophene 21 nMsulfonamide5-(4-hydroxybenzhydrol)-3-thiophene sulfonamide 26 nM5-(3-hydroxybenzhydrol)-3-thiophene sulfonamide 37 nM5-[(hydroxy)(pyridyl)methyl]-3-thiophene 240 nMsulfonamide5-(acetoxyphenylmethyl)-3-thiophene sulfonamide 90 nM5-(4-methoxybenzoyl)-3-thiophene sulfonamide, oxime 31 nM5-heptyl-3-thiophene sulfonamide 21 nM5-(1-pentanoyl)-3-thiophene sulfonamide, oxime 22 nM5-[(methoxy)(4-hydroxymethylphenyl)]methyl- 13 nM3-thiophene sulfonamide5-[(methoxy)(3-trifluoromethylphenyl)methyl]- 18 nM3-thiophene sulfonamide5-benzoyl-3-thiophene sulfonamide, oxime 53 nM______________________________________
While particular embodiments of the invention have been described it will be understood of course that the invention is not limited thereto since many obvious modifications can be made and it is intended to include within this invention any such modifications as will fall within the scope of the appended claims. | The present invention provides novel carbonic anhyrase inhibitors represented by the structural formula: ##STR1## wherein R 1 and R 2 are, for example, independently (a) hydrogen; or
(b) OR 4 , wherein R 4 is hydrogen or C 1-7 alkyl; or
(c) NR 5 R 6 , wherein R 5 and R 6 are independently hydrogen, or C 1-7 alkyl, or C 1-7 alkyl substituted with one or more halogen or OR 4 ; or
(d) --COR 7 , wherein R 7 is hydrogen, C 1-7 alkyl, or NR 5 R 6 ; or
(e) --SR 8 , wherein R 8 is hydrogen or C 1-7 alkyl, or C 1-7 alkyl substituted with one or more halogen, or OR 4 ; or
(f) C 1-7 alkyl, or C 1-7 alkyl substituted with one or more halogen, or OR 4 or NR 5 R 6 ; or
(g) R 1 and R 2 are together
(i) ═O, or
(ii) ═NOR 8 or
(iii) ═S;
and R 3 is
(h) C 1-7 alkyl or C 1-7 substituted with one or more halogen, OR 4 or NR 5 R 6 . | 53,613 |
This is a division, of application Ser. No. 749,589, filed June 27, 1985, now abandoned.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates in general to integrated circuits and in particular to integrated circuits in complementary circuit technology comprising at least two MIS field effect transistors of different channel types wherein the first is mounted in a doped semiconductor body of a first conductivity type and the second is mounted in a tub-shaped semiconductor body of a second conductivity type mounted in the semiconductor body.
2. Description of the Prior Art
In integrated circuits of the complementary circuit technology wherein two field effect transistors of different channel types with the first one mounted in a doped semiconductor body of a first conductivity type and the second mounted in a tub-shaped semiconductor body of a second conductivity type and wherein the semiconductor body 2 of the second conductivity type is electrically connected to a supply voltage and the first field effect transistor is provided with a source terminal which lies at a reference potential there is a difficulty in that four successive semiconductor layers of alternating conductivity type are generally present between a terminal of a field effect transistor of the first channel type which is mounted in the tub-shaped semiconductor region and a terminal of a field effect transistor of the second channel type which is mounted outside of this zone such that the one connecting region of the first transistor forms the first semiconductor layer and the tub-shaped semiconductor region forms the second with the semiconductor body forming the third and the one connecting region of the second transistor forming the first semiconductor layer. When an overvoltage which exceeds the supply voltage by a specific amount, as for example 500 mV, occurs on the mentioned terminal of the transistor of the first channel type, the pn-junction between the first and second semiconductor layers can be positively biased to a degree such that a current path occcurs between the transistor terminals and this current path is attributable to a parasitic thyristor effect (latchup) within the four layer structure. This current path will also remain in effect after the decay of the overvoltage and can thermally overload the integrated circuit.
SUMMARY OF THE INVENTION
It is an object of the present invention to eliminate the disadvantages of the prior art described above. A feature of the invention is to provide a metal contact at the surface of a semiconductor region inserted into the semiconductor body and doped oppositely thereto with the metal contact forming a Schottky diode together with the semiconductor region and the metal contact is connected to a connecting region of the second field effect transistor whereas the semiconductor region is electrically connected to the supply voltage V DD .
The advantages obtainable with the invention lie particularly in that the parasitic thyristor effect is avoided by means of a simple structure which particularly during manufacture of the circuit does not require any additional method steps but only slight modifications of the prior art steps:
Other objects, features and advantages of the invention will be readily apparent from the following description of certain preferred embodiments thereof taken in conjunction with the accompanying drawings although variations and modifications may be effected without departing from the spirit and scope of the novel concepts of the disclosure and in which:
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an exemplary embodiment of the invention;
FIG. 2 is a circuit diagram of the exemplary embodiment of FIG. 1;
FIG. 3 is a modified form of the invention;
FIG. 4 is another embodiment of the invention; and
FIGS. 5, 6 and 7 illustrate various steps in the method of manufacturing the embodiment of FIG. 1.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
As illustrated in FIG. 1 an integrated circuit comprises a body 1 of doped semiconductor material, as for example, p-conductivity type silicon. The semiconductor body 1 contains a n-conductive tub-shaped conductor region 2 which extends up to the boundary layer 1a of the body 1. Mounted at the boundary surface 1a are field insulated regions 3a, 3b, 3c, 3d, and 3e which may be made of, for example, SiO 2 and between these insulation regions 3a through 3e, respective gate insulation regions which cover the active regions of the semiconductor circuit are mounted. There is provided in a first active region which is mounted in the lateral boundaries of the semiconductor region 2 a small p+ doped region 4 and a p+ doped region 5 which respectively form the source and drain regions of p- channel type field effect transistor T1. The channel region lying between regions 4 and 5 is covered by gate 6 which is provided with a terminal E and is separated from the boundary surface 1a by a thin gate insulation layer 7 of, for example, SiO 2 . A conductive coating 9 is applied to an intermediate insulation layer 8 which covers the gate 6 and it contacts the source region 4 through a window 10 formed in insulation layer 8 and is provided with a terminal 11. The terminal 11 is therefore is electrically connected to a supply voltage V DD . Another conductive coating 12 is connected to the intermediate insulation layer 8 and contacts the drain region 5 in the area of a window 13 and is electrically connected to a terminal A.
An n-channel field effect transistor T2 is mounted in an active region lying between the insulation regions 3d and 3e and field effect transistor T2 is formed with n+ doped regions 14 and 15 which are formed in the body 1 as shown. A gate region 16 lies between the regions 14 and 15 and is separated by gate insulation layer 17. The gate 16 is connected to terminal E. A conductive coating 18 which contacts the drain region 15 through a window 19 of the intermediate insulating layer 8 is connected to terminal A and a conductive coating 20 which contacts the source region 14 through a window 21 is connected to a terminal 22 to which is applied a reference potential V SS .
An n+ doped connecting region 23 is inserted into the semiconductor region 2 and this region 23 is contacted in the region of a window 24a by a conductive coating 24 mounted above the intermediate insulation layer 8 and the conductive coating 24 is connected to terminal 11.
In the region of an additional window 25 of the intermediate insulation layer 8 a part of the conductive coating 12 forms a metal contact on the surface of the n-conductive semiconductor region 2 and this metal contact comprises a Schottky diode together with semiconductor region 2. Assuming an n-doping concentration about 10 16 cm -3 in the semiconductor region 2, the conductive coating 12 is expediently composed of aluminum. It is also advantageous if the conductive coating 12 is composed of tantalum silicide (TaSi 2 ) or it can be designed as a double layer which comprises a first layer of TaSi 2 and a second layer of aluminum which overlies the first layer. Other materials which are employed in a known fashion for Schottky diodes such as, for example, platinum or molybdenum may also be used for the conductive coating 12. Aluminum or the double layer of TaSi 2 and Al, however, have the advantage that they can also be employed for the coatings 9, 18, 20 and 24 such that all of the coatings on the intermediate insulation layer 8 can be applied in a single process step. It is essential that the leading threshold voltage V D of the Schottky diode D be lower than the leading threshold voltage of the pn-junction between the semiconductor region 5 and the semiconductor region 2 and this is referenced as V pn .
As is illustrated in FIG. 2 the p-channel transistor T1 and n-channel transistor T2 are series connected with their source and drains connected to the supply voltage V DD which is supplied via 11 and 22 and their gates are electrically connected to the common terminal E. The Schottky diode D which is composed of parts 12 and 2 is inserted between terminals A and 11. In case a voltage which exceeds the supply voltage V DD by amount that is equal to or greater than the leading threshold voltage V D of the Schottky diode D appears at the inverter output A during operation, then D becomes conductive and limits the voltage V A to the value V A =V DD +V D . Thus, it is avoided that V A continues to increase and reaches or exceeds a value V A =V DD +V pn which causes parasitic thyristor effects to occur in the region of the four layer structures 5, 2, 1 and 14 with such thyristor effects potentially leading to the formation of a current path between terminals A and 22 and to a thermal overload of the entire structure.
FIG. 3 illustrates a modification of the exemplary embodiment of FIG. 1 and differs from FIG. 1 in that the windows 13 and 25 are combined to a single window 13' and the conductive coating 12 which is designated by 12' in FIG. 3 contacts both the drain region 5' of T1 as well as the semiconductor region 2 in the area of this window. Since the drain region 5' is significantly higher doped than the semiconductor region 2, the coating 12' forms an ohmic contact on 5' and forms the Schottky diode D with the semiconductor zone 2. Another embodiment of the invention is illustrated in FIG. 4 wherein the Schottky diode D is arranged differently than in FIG. 1 and it lies in its own n-conductive semiconductor region 2' which is inserted into the semiconductor body next to the n-conductive semiconductor region 2. The region 2' has approximately the same doping concentration as region 2. The field insulation region 3b and 3c of FIG. 1 are combined into a single field insulation region 3b' and the coating 12" which replaces the coating 12 of FIG. 1 contacts only the drain region 5 of transistor T1. The field insulation regions 3d is divided into two regions 3d' and 3d" and the semiconductor region 2' is mounted therebetween. An n+ doped connecting region 26 is inserted into the semiconductor region 2' and this is contacted by conductive coating 27 in the area of a window 28 of the intermediate insulation layer 8. The coating 27 is connected to terminal 11. A conductive coating 29 which is composed of the same material as the coating 12 illustrated in FIG. 1 forms a metal contact in the area of a window 30 of the intermediate insulation layer 8 on the semiconductor region 2' and this metal contact comprises the Schottky diode D together with semiconductor region 2'. The coating 29 is connected to terminal A.
In FIGS. 3 and 4, those parts which were described with reference to FIG. 1 are provided with the same reference characters as in FIG. 1. The modifications of FIGS. 3 and 4 operate in the same manner as that described for FIG. 1 and the electrical schematic of FIG. 2.
In order to manufacture the circuit according to FIG. 1 an n-doped tub-shaped semiconductor region 2 which, for example, has a doping concentration of 10 16 cm -3 is inserted by means of a diffusion process into a body 1 of p-conductive silicon which has a basic doping concentration of about 10 15 cm -3 . Subsequently, a thin Si 3 N 4 layer is applied to the boundary surface 1a and such Si 3 N 4 layer being structured such by means of a photolithographic step that it remains only on the active semiconductive regions. Field oxidation regions 3a through 3e of SiO 2 are formed by means of thermal oxidation at those locations on the body 1 that are not covered by the Si 3 N 4 layer. After removal of the Si 3 N 4 layer portions, gate oxide layers S1 through S4 are grown on the active regions of the semiconductor body 1 by thermal oxidation process and these gate oxide layers form the previously mentioned gate oxide regions. The gates 6 and 16 of the field effect transistor T1 and T2 are then formed on the gate oxide layers S1 and S4 by using photolithographic steps and are formed therefrom with a polycrystalline silicon layer that has been applied on the surface.
As is illustrated in FIG. 5 the n+ doped regions 14 and 15 of transistor T2 and the connecting region 23 are generated by means of ion implantation which is indicated by the arrows Im1. The lefthand part of the semiconductor body 1 extending up to the middle of the thick film region 3c is covered with a photoresist layer L1 during this time.
Then the photoresist layer L1 is removed and as shown in FIG. 6, a further photoresist layer L2 is applied which covers the righthand portion of the body 1 up to the middle of the thick film region 3b whereby p+doped region 4 and 5 of transistor T1 are formed by means of ion implantation which is indicated by arrows Im2.
As is illustrated in FIG. 7, an intermediate insulation layer of SiO 2 is applied using a deposition technique in a following method step and this layer 8 is provided with windows 10, 13, 21, 19, 24a and 25 above the regions 4, 5, 14 and 15 as well as above the connecting region 23 and between the field insulation regions 3b and 3c. These windows are etched through to the boundary layer 1a so that the gate insulation layers S1 through S4 indicated in FIG. 6 are also opened. For reasons of a simplified illustration the gate insulation layers S1 and S4 are not separately illustrated but are provided with the reference characters 7 and 17 since they lie under the gates 6 and 16. The remaining parts of S1 and S4 as well as the layers S2 and S3 are incorporated into the intermediate insulation layer 8 and are shown together with the insulation layer 8 as a uniform insulation layer.
The conductive coatings 9, 12, 24, 18 and 20 are subsequently applied with this preferably occurring by means of a corresponding structuring of a surface wide coating by means of photolithographic steps. The coatings 9 and 24 finally are provided with the terminal 11 and the coating 20 is provided with the terminal 22 and the gates 6 and 16 are provided with the terminal E. The coatings 12 and 18 are provided with a terminal A.
Other embodiments of the invention differ from those described in that the individual semiconductor parts are replaced by those of the respectively opposite conductivity types whereby the voltage of the opposite polarity can then be applied.
In addition to these embodiments, the inventive concept also encompasses other integrated circuits in complementary circuit technology wherein at least two field effect transistors having different channel types are integrated in a semiconductor body such that at least one of them belongs to a first channel type and lies in a tub-shaped zone which is of a conductivity type opposite to that of the semiconductor body and where as least one other field effect transistor has a second channel type and is mounted in the semiconductor body outside of this zone. The tub-shaped zone is thereby always electrically connected to a supply voltage. The parasitic thyristor effect which was described under the Prior Art with reference to the transistors T1 and T2 which can occur in any circuit of this type is suppressed by the insertion of a Schottky diode between a connecting region of the field effect transistor lying in the tub-shaped zone and the terminal of the supply voltage when the leading threshold voltage V D of the Schottky diode is selected to be lower than the leading threshold voltage of the pn-junction between this connecting region in the tub-shaped zone.
Although the invention has been described with respect to preferred embodiments, it is not to be so limited as changes and modifications can be made which are within the full intended scope of the invention as defined by the appended claims. | An integrated circuit in complementary circuit technology comprising two field effect transistors (T1, T2) of different channel types with the first one (T2) mounted in a doped semiconductor body (1) having a first conductivity type and the other FET (T1) mounted in a semiconductor zone 2 of a second conductivity type which is arranged in said body. The object is to provide a protection against thermal overloads which can appear due to "latch up" influences when overvoltages at the one connecting region of the field effect transistor (T1) mounted in the semiconductor zone occur. This is accomplished by the mounting of a metal contact (12) on the surface of a semiconductor region (2') inserted into the semiconductor body 1 and doped oppositely thereto with such metal contact forming a Schottky diode (D) with the semiconductor region (2') which can be connected to the connecting region of the field effect transistor T1 mounted in the semiconductor region 2 whereas the semiconductor region (2') is electrically connected to the supply voltage (V DD ). The circuits are applied in CMOS circuits. | 16,046 |
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