Two sets of a high speed differential amplifier and a low speed differential amplifier are prepared, and frequency response speeds of these high speed/low speed differential amplifiers are different from each other. Both an oscillating frequency and a frequency modulation sensitivity of a ring oscillator type voltage-controlled oscillator circuit can be separately set by adding two outputs of these differential amplifiers to each other and by varying the selection ratio of these high speed/low speed differential amplifiers in a linear manner. Thus, the setting ranges for the oscillating frequency and the frequency modulation sensitivity are enlarged. At this time, since a summation of currents flowing through the high speed/low speed differential amplifiers is continuously made constant, the oscillating frequency depending characteristic of the output amplitude of the VCO circuit can be canceled. Furthermore, since control signals are supplied in a differential structure, increasing of jitter components caused by the common mode noise can be suppressed.

The present invention is related to a voltage-controlled oscillator circuit (VCO) for constituting a phase-locked loop (PLL) circuit. This phase-locked loop circuit produces a clock signal in synchronism with input data and/or an input clock in an optical transmitter module and an optical receiver module used in an optical communication.
A voltage-controlled oscillator circuit (VCO) for constituting a phase-locked loop (PLL) circuit which produces a clock signal in synchronism with input data and also an input clock, corresponds to such an oscillator. An oscillating frequency of this VCO circuit is varied in response to a control voltage. In general, there are a multivibrator type VCO and a ring oscillator type VCO with respect to a VCO used in an integrated circuit (IC). In the case of a ring oscillator type VCO, since this VCO may be constructed only of transistors and resistors, this ring oscillator type VCO may be manufactured in the form of an IC. Also, in principle, since 4-phase clocks are outputted in which a phase of an oscillator signal is shifted by xcfx80/2, xcfx80, and 3xcfx80/2, this ring oscillator type VCO owns the following merit. That is, when a frequency comparator is arranged by employing such a ring oscillator type VCO, a necessary xcfx80/2-delay signal can be produced without employment of an additional circuit.
In FIG. 1, a typical ring oscillator circuit is indicated. An oscillation is initiated by such a way that outputs derived from two-staged differential amplifiers are supplied as inputs to the corresponding differential amplifiers in a positive feedback manner, so that V0, V90, V180, and V270 corresponding to 4-phase clock signals can be obtained. As an item indicative of a characteristic of a VCO circuit, there are an oscillating frequency and a frequency modulation sensitivity. This frequency modulation sensitivity represents a degree of changes in the oscillating frequencies with respect to a control voltage. In this type of system, an oscillating frequency is determined by a transition (cut-off) frequency xe2x80x9cfTxe2x80x9d of a transistor. In general, a transition frequency of a bipolar type transistor is expressed by the below-mentioned equation (1), assuming now that a collector-to-base capacitance is xe2x80x9cCbcxe2x80x9d, a base-to-emitter capacitance is xe2x80x9cCbexe2x80x9d, and a mutual conductance is xe2x80x9cgmxe2x80x9d:
fT=gm/2xcfx80(Cbc+Cbe)xe2x80x83xe2x80x83(1)
where the values of xe2x80x9cCbcxe2x80x9d and xe2x80x9cCbexe2x80x9d depend upon a device fabrication technology. Also, assuming now that an elementary electric charge is xe2x80x9cqxe2x80x9d, a collector current is xe2x80x9cIcxe2x80x9d, the Boltzmann constant is xe2x80x9ckxe2x80x9d, and an absolute temperature is xe2x80x9cTxe2x80x9d, the mutual conductance xe2x80x9cgmxe2x80x9d may be expressed by the following equation (2), and is directly proportional to the collector current:
gm=(qxc2x7Ic)/(kxc2x7T)xe2x80x83xe2x80x83(2)
As a consequence, the oscillating frequency can be controlled by controlling the voltage xe2x80x9cVcontxe2x80x9d shown in FIG. 1, and by varying an amount of a current xe2x80x9cI1xe2x80x9d flowing through the differential amplifier, and this ring oscillator may function as a voltage-controlled oscillator. As apparent from the above-described equation (1), the frequency modulation sensitivity indicative of a change in the oscillating frequencies with respect to a change in the control voltages will depend upon both Cbc and Cbe. Both Cbc and Cbe may be controlled in such a manner that while a plurality of transistors are employed, base, collector, and emitter terminals thereof are connected in parallel to each other. For example, when xe2x80x9cnxe2x80x9d pieces of transistors are connected in parallel to each other, a collector-to-base capacitance becomes xe2x80x9cnCbcxe2x80x9d and a base-to-emitter capacitance becomes xe2x80x9cnCbexe2x80x9d. In this ring oscillator circuit, the parallel element number of the transistors which constitute the differential transistor pairs is varied so as to change these capacitances xe2x80x9cCbcxe2x80x9d and xe2x80x9cCbexe2x80x9d, so that the frequency modulation sensitivity can be set. Such a system for controlling the oscillating frequency by controlling the currents of the differential transistor pairs is known from, for example, JP-A-9-326676.
In the related ring oscillator type VCO circuit, both Cbc and Cbe are changed by the parallel element number of the transistors of the differential pairs, so that the frequency modulation sensitivity is set. However, these capacitance values Cbc and Cbe are also related to the transition frequency, and therefore may give an adverse influence to the oscillating frequency. To set the oscillating frequency, this oscillating frequency is controllable by the collector current value in accordance with the above-explained equations (1) and (2). In a practical transistor, a range capable of satisfying the above-explained equation (2) is finite, and therefore, a setting width of an oscillating frequency is also finite. As previously explained, in this system, it is practically difficult to set both the oscillating frequency and the frequency modulation sensitivity to desirable values, respectively. In other words, in this VCO circuit, as to the oscillating frequency, the transition frequency xe2x80x9cfTxe2x80x9d of the transistor is varied by controlling the values of the currents flowing through the differential transistor pairs so as to control the oscillating frequency, whereas as to the frequency modulation sensitivity, this frequency modulation sensitivity is set to a desirable value by varying the capacitance values. However, since the capacitance values are also related to the oscillating frequency, it is practically difficult to design both the oscillating frequency and the frequency modulation sensitivity to the desirable values at the same time.
Also, in the related system, since the frequency of the oscillator is controlled by the values of the currents flowing through the differential pairs, the output amplitude of the oscillator becomes Rxc3x97(I1+xcex94I), assuming now that the resistance values R1 to R4 connected to the differential transistor pairs are equal to xe2x80x9cRxe2x80x9d, and a change amount of currents is xe2x80x9cxcex94Ixe2x80x9d. As a result, there are such problems that the output amplitude of the oscillator owns the current depending characteristic, and therefore, the phase detection sensitivity at the phase comparator may change due to this behavior.
Furthermore, in the circuit system shown in FIG. 1, when noise is mixed with the current source control voltage Vcont, both the oscillating frequency and the output amplitude are changed, the jitter contained in the output signal are readily increased.
The present invention has been made to solve the above-described problems, and therefore, has an object to provide a frequency response controllable amplifier, a voltage-controlled oscillator (VCO), and a phase-locked loop (PLL) circuit, capable of increasing a flexibility of design, while enlarging a range for setting an oscillating frequency, and also a range for setting a frequency modulation sensitivity.
Another object of the present invention is to provide a frequency response controllable amplifier, a voltage-controlled oscillator (VCO), and a phase-locked loop (PLL) circuit, capable of increasing a flexibility of design, while enlarging ranges for setting both an oscillating frequency and a frequency modulation sensitivity, and moreover an oscillating frequency depending characteristic of an output amplitude can be canceled.
Another object of the present invention is to provide a frequency response controllable amplifier, a voltage-controlled oscillator (VCO), and a phase-locked loop (PLL) circuit, capable of increasing a flexibility of design, while enlarging ranges for setting both an oscillating frequency and a frequency modulation sensitivity, and moreover suppressing an increase of jitter caused by common mode noise.
A further object of the present invention is to provide a digital optical receiver module and a digital optical transmitter module, in which a phase-locked loop (PLL) circuit can be applied to an optical communication.
To achieve the above-explained objects, a voltage-controlled oscillator, according to an aspect of the present invention, is featured by such a ring oscillator type voltage-controlled oscillator wherein: the ring oscillator type voltage-controlled oscillator is arranged in such a manner that both an oscillating frequency and a frequency modulation sensitivity can be separately set to desirable values.
Also, a voltage-controlled oscillator, according to another aspect of the present invention, is featured by such a ring oscillator type voltage-controlled oscillator comprising: at least two sets of a high speed differential amplifier and a low speed differential amplifier, the frequency response speeds of which are different from each other; and an adder for calculating a summation of outputs of the at least two high speed and low speed differential amplifiers; wherein: a selection ratio of the at least two high speed/low speed differential amplifiers is varied in a linear manner, so that both an oscillating frequency and a frequency modulation sensitivity can be separately set to desirable values, respectively.
Also, in the above-described voltage-controlled oscillator of the present invention, this voltage-controlled oscillator is featured by arranging that while a summation between a current flowing through the high speed differential amplifier and a current flowing through the low speed differential amplifier is made constant, an oscillating frequency depending characteristic of an output amplitude is canceled.
Also, in the above-described voltage-controlled oscillator of the present invention, this voltage-controlled oscillator is featured by arranging that control signals are supplied in a differential structure to at least the two high speed/low speed differential amplifiers.
Also, a voltage-controlled oscillator, according to another aspect of the present invention, is featured by comprising: a first frequency response controllable amplifier equipped with a current source for producing a DC current; a DC current distributer for distributing the DC current of the current source into two DC currents in a ratio depending upon an input control signal; a high speed current distributor in response to an input switching signal; a low speed current distributor in response to the input switching signal; an adder for adding the output from the high speed current distributor to the output from the low speed current distributor; and an output buffer for an output signal from the adder; and a second frequency response controllable amplifier equipped with a current source for producing a DC current; a DC current distributer for distributing the DC current of the current source into two DC currents in a ratio depending upon an input control signal; a high speed current distributor in response to an input switching signal; a low speed current distributor in response to the input switching signal; an adder for adding the output from the high speed current distributor to the output from the low speed current distributor; and an output buffer for output voltage of the adder; wherein: a positive feedback circuit is arranged by using the output signal derived from the first frequency response variable amplifier as an input signal for the second frequency response variable amplifier; and also by using the output signal derived from the second frequency response variable amplifier as an input signal for the first frequency response amplifier.
Also, a phase-looked loop circuit, according to another aspect of the present invention, is featured by comprising the above-explained voltage-controlled oscillator.
Further, a phase-locked loop circuit, according to another aspect of the present invention, is featured by comprising: the above-explained voltage-controlled oscillator; a phase/frequency comparator for comparing phases/frequencies as to the oscillating frequencies outputted from this voltage-controlled oscillator and the entered data; and a loop filter for rejecting high frequency noise from this phase/frequency comparator; wherein a control voltage signal from the loop filter is entered into the above-explained voltage-controlled oscillator.
Also, a digital optical receiver module, according to another aspect of the present invention, is featured by such an optical receiver module arranged by a photodetector for receiving a transmitted optical signal, an amplifier for amplifying the optical signal received by photodetector, and the above-explained phase-locked loop circuit; and in which the optical receiver module is comprised of: a timing extraction circuit for producing and outputting a clock signal in synchronism with a data signal derived from the amplifier; and a decision and regeneration circuit for deciding and regenerating the data signal derived from the amplifier by employing a clock signal derived from the timing extraction circuit.
Moreover, a frequency response controllable amplifier, according to another aspect of the present invention, is featured by comprising: a current source for producing a DC current; a DC current distributer for distributing the DC current of the current source into two DC currents in a ratio depending upon an input control signal; a high speed current distributor in response to an input switching signal; a low speed current distributor in response to the input switching signal; an adder for adding the output from the high speed current distributor to the output from the low speed current distributor; and an output buffer for an output signal from the adder.
As previously described, the ring oscillator type voltage controller, according to the present invention, is arranged in""such a manner that the parallel connection number of the transistors is changed; two sets of the high speed/low speed differential amplifiers having the different frequency response speeds from each other are prepared; the output signals derived from the high speed/low speed differential amplifiers are summed; and then the selection ratio of these high speed/low speed differential amplifiers is varied in a linear manner. As a result, both the oscillating frequency and the frequency modulation sensitivity can be separately set. In other words, both the oscillating frequency of the high speed differential amplifier and the oscillating frequency of the low speed differential amplifier are set in such a manner that the desirable oscillating frequency variable ranges can be obtained. The selection ratio of these high speed/low speed differential amplifiers is voltage-controlled so as to set the control sensitivities thereof. As a consequence, the desirable frequency modulation sensitivities can be obtained.
Also, when the high speed differential stage and the low speed differential stage are selectively controlled, since the VCO circuit is arranged in such a manner that the summation of the current flowing through the high speed differential stage and the current flowing through the low speed differential stage is made constant, the oscillating frequency depending characteristic of the output amplitude can be canceled.
Also, since the voltage used to control the oscillating frequency may be applied by the differential arrangement, increasing of the jitter caused by the common mode noise can be suppressed.

Optical receiver module optical transmitter module phase-locked loop circuit voltage-controlled oscillator and frequency response controllable amplifier


The method for preparing a deep trench uses a dry etching process to form a trench in a silicon substrate, and an etching mixture is then coated on the surface of the silicon substrate and inside the deep trench. A portion of etching mixture is removed from the surface of the silicon substrate and the trench above a predetermined depth from the surface of the substrate, and an etching process is then performed using the etching mixture remaining inside the trench to etch the silicon substrate below the predetermined depth so as to form the deep trench. The etching mixture comprises a conveying solution and an etchant, and the viscosity of the conveying solution is higher than that of the etchant. The conveying solution is spin-on-glass or a photoresist, and the etchant is tetramethylammonium hydroxide, ammonium, or hydrofluoric acid. The volume ratio of the conveying solution and the etchant is preferably between 50:1 and 20:1.

(A) Field of the Invention
The present invention relates to a method for preparing a deep trench and an etching mixture for the same, and more particularly, to a method for preparing a deep trench of a DRAM cell and an etching mixture for the same.
(B) Description of the Related Art
A memory cell of the DRAM consists of a metal oxide field-effect transistor and a capacitor on the silicon substrate, and the source of the transistor is electrically connected to the upper storage plate of the capacitor. There are two types of capacitors: stack and deep trench. The stack capacitor is fabricated directly on the surface of the silicon substrate, while the deep trench capacitor is fabricated inside the silicon substrate. Recently, the integrity of the DRAM has increased with the innovation of semiconductor process technology rapidly. However, the size of the memory cell must be shrunk to achieve the purpose of high integrity, i.e., increasing the integrity needs to reduce the size of the transistor and the capacitor.
FIG. 1 is a cross-sectional diagram of a deep trench 10 according to the prior art. As shown in FIG. 1, the method for preparing the deep trench 10 first forms a hard mask layer 14 and a photoresist layer 16 on a silicon substrate 12, and a photolithography process is then performed to form two openings 18 in the photoresist layer 16. An anisotropic etching process, such as the reactive ion etching process or the plasma etching process, is performed to remove a portion of the hard mask layer 14 and silicon substrate 12 under the two openings 18 to form two deep trenches 10 in the silicon substrate 12. As the diameter of the deep trench 10 shrinks, the deep trench 10 deviates from being the same diameter, but tends to have a larger diameter at the upper portion and a smaller diameter at the bottom portion.
The capacitance is proportional to the surface area of the electrode, and the surface area of the electrode for the deep trench capacitor is a product of the depth and the circumference of the deep trench, wherein the circum area depends on the diameter of deep trench. With the continuous reduction of the DRAM cell, the diameter of the deep trench is reduced accordingly, and the deep trench 10 cannot provide a sufficient surface area according to the prior art. In addition, with the continuous reduction of the DRAM cell, the width of a local silicon substrate 20 separating the two deep trenches 10 becomes smaller. Consequently, the local silicon substrate 20 may be removed during the subsequent etching process to result in the direct connecting of the two deep trenches 10, which invalidate the subsequent formed capacitor due to electrical connecting.

Method for preparing a deep trench and an etching mixture for the same


A transmitter device of the content distribution system transmits content portions of a content message to a receiver device using respective multicast channels within a network. In such an arrangement, by using multiple multicast channels for transmission of the content portions forming the content message, the transmitter device limits the ability for an unauthorized user, monitoring a particular multicast channel, to distinguishing the content portions from noise or to retrieve the complete content message from the transmitter device, thereby providing security to the content message. Furthermore, the content distribution system utilizes multicast channels within a network to deliver the content portions to all receiver devices in communication with the network, thereby minimizing the power requirements needed by the transmitter device to deliver the content portions to a receiver device farthest from the transmitter device.

In general, content distributor devices (e.g., radio transmitters, cellular wireless transmitters) transmit audio, images, or text, (e.g., content or content messages) to end user or receiver devices (e.g., radio receivers, cellular wireless receivers) using a variety of distribution mechanisms.
One conventional mechanism for content distribution involves broadcast transmission of content. In broadcast transmission, such as radio or satellite broadcast, a single content source transmits content to many receivers (one-to-many transmission). Certain broadcast transmissions, such as shared-medium broadcasts or Code-Division Multiple Access (CDMA) transmissions, for example, utilize spread-spectrum techniques in broadcasting the content. Spread-spectrum is a modulation technique that uses a pseudo-noise (PN) code sequence to "spread" a signal over multiple frequencies within a channel for transmission (e.g., broadcast) to a receiver device. For example, a transmission device combines an input signal with a user-specific pseudo-noise code and transmits the combined signal to a receiver device. The receiver device locally produces a correlated signal by generating the same PN code sequence and synchronizing its code sequence with that of the received code sequence. The receiver device, therefore, tracks the received encoded signal to recover the input signal.
The spread-spectrum technique provides security to a signal transmitted to a receiver device. For example, the spread-spectrum technique provides antijam capabilities to the transmitted signal. In spread-spectrum, the transmitter transmits the signal, to a receiver device, using several frequencies. In such a transmission, an unauthorized user can have difficulty in distinguishing the signal from noise. The spread-spectrum technique, therefore, limits the ability for an unauthorized user to "jam" or inject noise within the transmission.
The spread-spectrum technique, furthermore, provides low probability of interception (LPI) capabilities to the transmitted signal. For example, when using the spread-spectrum technique, the transmitter device transmits a signal to a receiver device using several frequencies. In such a transmission, an unauthorized user can have difficulty in retrieving the complete signal from the transmitter device. The spread spectrum technique, therefore, minimizes interception of the transmitted signal.
Another conventional mechanism for content distribution involves multicast transmission. In multicast transmission, such as Internet Protocol (IP) multicast or application-level multicast, a content source transmits content to many receivers (e.g., one-to-many) using a multicast-enabled network. For example, assume a content source (e.g., content server) receives, over a computer network, requests for content from multiple requesting devices (e.g., client devices). The content source provides content to the network in response to the content requests. In multicast transmission, multicast-enabled data communications devices within the network distribute the content to all of the multiple requesting devices. The content source, therefore, provides the requested content to the network once and allows the multicast-enabled data communications devices within the network to distribute the content to the requesting devices. Multicast distribution of content over the network limits loading of a particular content source with the task of providing, for multiple iterations, identical content to multiple requesting devices, thereby allows for a more efficient operation of the content source.

Methods and apparatus for multicasting content


A manufacturing method of a semiconductor device of this invention includes forming metal pads on a Si substrate through a first oxide film, bonding the Si substrate and a holding substrate which bolsters the Si substrate through a bonding film, forming an opening by etching the Si substrate followed by forming a second oxide film on a back surface of the Si substrate and in the opening, forming a wiring connected to the metal pads after etching the second oxide film, forming a conductive terminal on the wiring, dicing from the back surface of the Si substrate to the bonding film and separating the Si substrate and the holding substrate.

1. Field of the Invention
This invention relates to a manufacturing method of a semiconductor device, specifically to a manufacturing method of a BGA (Ball Grid Array) type semiconductor device which has ball-shaped conductive terminals.
2. Description of the Related Art
A BGA type semiconductor device has been known as a kind of surface-mount type semiconductor device. A plurality of ball-shaped conductive terminals made of a metal material such as solder is arrayed in a grid pattern on one principal surface of a package substrate and is connected with a semiconductor die bonded on the other principal surface of the substrate in the BGA type semiconductor device. When the BGA type semiconductor device is mounted into electronic equipment, the semiconductor die and external circuit on a printed circuit board are electrically connected by thermally bonding each of the conductive terminals to each of wiring patterns on the printed circuit board.
Such a BGA type semiconductor device is known to have advantages in providing a large number of connection terminals as well as reducing the size over other surface-mount type semiconductor devices such as an SOP (Small Outline Package) and a QFP (Quad Flat Package), which have lead pins protruding from their sides.
The BGA type semiconductor device was adopted into a CCD image sensor in recent years, and has been used as an image sensor chip mounted in a mobile telephone which is strongly required to reduce the size.
On the other hand, three-dimensional packaging technologies have come to attention, which use a wafer level CSP (Chip Size Package) or a technology to make through-hole interconnection in silicon substrate. These technologies include a method to make through-hole interconnection in silicon substrate after bonding multi layers of chips and a method to stack silicon wafers after making through-hole interconnections in the silicon substrate from the surface.
However, conventional three-dimensional packaging technologies have shortcomings of increased process steps. That is, because processing to make through-hole interconnection in silicon substrate starts from the surface and a via hole is filled with copper, CMP (Chemical Mechanical Polishing) processing from the top surface and re-distribution to connect the copper and a pad after forming the via hole are required. Although copper wiring technology is suitable for fine patterning, increased cost is unavoidable because copper itself is expensive and it is necessary to purchase a specific apparatus additionally.


A display device is disclosed. The display device includes a display panel; a first substrate positioned in a rear of the display panel; a second substrate positioned in the rear of the display panel and adjacent to the first substrate; a plurality of first light sources mounted on the first substrate and configured to provide light to the display panel; a plurality of second light sources mounted on the second substrate and configured to provide light to the display panel; and a first reflective sheet positioned on the first substrate, the first reflective sheet including a plurality of first holes formed corresponding to positions of the plurality of first light sources, wherein in the plurality of first holes, an area of a first hole formed corresponding to a position of a first light source close to a boundary of the first substrate and the second substrate may be greater than an area of a second hole formed corresponding to a position of a second light source far from the boundary of the first substrate and the second substrate.

With the development of the information society, various demands for display devices are increasing. Various display devices such as a liquid crystal display (LCD), a plasma display panel (PDP), an electroluminescent display (ELD), and a vacuum fluorescent display (VFD) have been recently studied and used in response to the various demands for the display devices.
Out of the display devices, a liquid crystal display panel of the LCD includes a liquid crystal layer and a TFT substrate and a color filter substrate that are opposite to each other with the liquid crystal layer interposed between them, and can display an image using light provided by a backlight unit.


A transmission circuit alleviates the frequency characteristics of a group delay and an attenuation amount in a transmission signal band and expands a dynamic range to a high frequency band. A ladder-type resistance-type attenuator includes switching elements, 2R resistor elements and R resistor elements. The 2R and R resistor elements are respectively connected to variable capacitor elements in parallel. The variable attenuator having such a connection structure is connected to an amplitude modulation loop of the transmission circuit. By controlling the capacitance value of the variable capacitor elements using the capacitance value control section when the switching elements are ON/OFF switched based on the transmission power control signal, the influence of parasitic capacitances of the variable capacitor elements is suppressed and the group delay between the amplitude modulation and the phase modulation is reduced.

1. Field of the Invention
The present invention relates to a transmission circuit usable for a communication apparatus, such as a mobile phone, a wireless LAN device or the like, and more specifically to a transmission circuit for alleviating the frequency characteristics of a group delay and an attenuation amount in a transmission signal band and also for expanding the dynamic range to a high frequency band, and a communication apparatus using the same.
2. Description of the Background Art
As a conventional transmission circuit for a mobile phone, a transmission circuit of a quadrature modulation system as shown in FIG. 9 is used. FIG. 9 is a block diagram showing an exemplary structure of a conventional transmission circuit of the quadrature modulation system. As shown in FIG. 9, the conventional transmission circuit of the quadrature modulation system includes D/A converters 101 and 104, low pass filters 102 and 105, mixers 103 and 106, a local oscillator 107, a phase shifter 108, an adder 109, an RF filter 110, an attenuator 111, a power amplifier 112, and an isolator 113.
I and Q signals which are input from a baseband circuit (not shown) are respectively input to the mixers 103 and 106 via the D/A converters 101 and 104 and the low pass filters 102 and 105. The signals which are input to the mixers 103 and 106 are mixed together by a signal divided by a phase frequency division circuit including the local oscillator 107 and the phase shifter 108 and then processed with quadrature modulation by the adder 109. An output signal from the adder 109 passes through the RF filter 110 for suppressing an unnecessary harmonic, is amplified by the power amplifier 112 via the attenuator 111, and then is output to an antenna duplexer (not shown) via the isolator 113 for suppressing the load fluctuation of the power amplifier 112.
Various communication systems are widely used in the world today, and a multi-mode wireless communication system compatible with a plurality of communication systems is desired. However, a multi-mode wireless communication terminal based on the conventional technology has an increased size due to a large number of components especially in a wireless section, and thus has a high cost. Therefore, being able to use one component for different purposes is an important issue in realizing a multi-mode wireless communication terminal.
In the EDGE (Enhanced Data GSMEnvironment) system, which was developed for the purpose of raising the communication speed based on GSM (Global System for Mobile Communications) and is one standard of the mobile phone, a polar modulation system is often used as a modulation system in a wireless transmission section for the following reasons. The polar modulation system has a high level of affinity with a transmission circuit structure of GMSK (Gaussian filtered Minimum Shift Keying) modulation, which is a conventional modulation system. By adopting a polar modulation system in a multi-mode wireless communication terminal compatible with the GSM system and UMTS (Universal Mobile Telecommunications System), the system is simplified because a single platform can be used.
With such a background, a transmission circuit of the polar modulation system has been proposed. FIG. 10 is a block diagram showing an exemplary structure of a conventional transmission circuit of a polar modulation system. As shown in FIG. 10, I and Q signals which are input from a baseband circuit (not shown) are separated into an amplitude signal and a phase signal by a CODEC 114. The amplitude signal is amplitude-modulated by an amplitude modulator 115 and is input to a voltage control circuit 118 via a D/A converter 116 and an attenuator 117. The voltage control circuit 118 outputs a signal which is preset in accordance with the magnitude of the amplitude signal to a power amplifier 119. The phase signal is input to a phase modulator 120. The phase modulator 120 performs phase modulation on the input phase signal and outputs the resultant signal as a phase modulated signal. The power amplifier 119 performs amplitude modulation on the phase modulated signal which is output from the phase modulator 120 with a signal which is output from the voltage control circuit 118, and outputs the resultant signal to an antenna duplexer (not shown) as an amplitude modulated signal.
As compared with the transmission circuit by the quadrature modulation system described above with reference to FIG. 9, the transmission circuit of the polar modulation system does not need an analog quadrature modulator and thus does not need the RF filter 110. In addition, the transmission circuit of the polar modulation system can reduce power consumption because the power amplifier 119 does not need to provide linearity. The transmission circuit using the polar modulation system does not need an isolator 113 either because the influence of the load fluctuation is alleviated.
Despite the above-described advantages, the transmission circuit of the polar modulation system has the problem that because the amplitude signal and the phase signal are separate, the transmission circuit cannot provide functions thereof sufficiently if the amplitude signal and the phase signal are different in group delay, even though the amplitude signal and the phase signal are synthesized by the power amplifier 119.
One exemplary circuit for reducing the group delay included in a high frequency signal is, for example, a group delay compensation circuit disclosed in Japanese Laid-Open Patent Publication No. 2001-53631 (hereinafter, referred to as "patent document 1"). FIG. 11 is a block diagram showing an exemplary structure of a conventional group delay compensation circuit 122 disclosed in patent document 1. As shown in FIG. 11, the conventional group delay compensation circuit 122 includes a fixed delay device 123, a variable phase device 124, a variable attenuator 125, a frequency displacement detector 126, and a signal converter 127. The fixed delay device 123 outputs a high frequency signal which passed through an analog filer 121 with a delay of a certain length of time. The frequency displacement detector 126 detects a displacement amount, from the central frequency, of the high frequency signal which passed through the analog signal 121. The signal converter 127 generates a control signal for controlling the delay amount of the variable phase device 124 and a control signal for controlling the amplitude level of the variable attenuator 125, based on the displacement amount detected by the frequency displacement detector 126. The variable phase device 124 controls the phase of the output signal from the fixed delay device 123 by the control signal. The variable attenuator 125 controls the amplitude of the output signal from the variable phase device 124 by the control signal.
As described above, in the conventional group delay compensation circuit 122, the signal converter 127 controls the phase amount of the variable phase device 124 such that the delay time in the transfer signal band is flattened based on the displacement amount detected by the frequency displacement detector 126. Namely, the conventional group delay compensation circuit 122 matches the delay time at and around the cut-off frequency on the low frequency side, the delay time at and around the central frequency, and the delay time at and around the cut-off frequency on the high frequency side, by controlling the phase amount of the variable phase device 124. As a result, the high frequency signal which passed through the analog filter 121 is output as a signal having the group delay deviation flattened by the group delay compensation circuit 122 although the overall delay amount is increased.
As an exemplary structure of a conventional variable attenuator 125, a structure of a 4-bit variable attenuator 130 using resistor elements will be shown. FIG. 12 shows an exemplary structure of the conventional 4-bit variable attenuator 130. As shown in FIG. 12, the 4-bit variable attenuator 130 includes an input terminal 131, an output terminal 132, switching elements 133 through 136, 2R resistor elements 137 through 141, and R resistor elements 142 through 144.
The 2R resistor elements 137 through 141 each have a resistance value twice as high as that of each of the R resistor elements 142 through 144. Therefore, a 2R resistor element may have a structure of two R resistor elements connected in series. Control terminals D1 through D4 of the switching elements 133 through 136 are connected to a transistor-transistor logic (TTL) circuit (not shown) and perform ON/OFF switching operations in accordance with a control signal (binary data) which is output from the TTL circuit.
Specifically, the 4-bit variable attenuator 130 of a ladder type as shown in FIG. 12 has the following connection structure. In the 4-bit variable attenuator 130, the switching element 133 and the 2R resistor element 138 are connected in series, the switching element 134 and the 2R resistor element 139 are connected in series, the switching element 135 and the 2R resistor element 140 are connected in series, and the switching element 136 and the 2R resistor element 141 are connected in series. The switching elements 133 through 136 are each connected to the input terminal 131. One output of the 2R resistor element 138 is grounded via the 2R resistor element 137, and other output of the 2R resistor element 138 is connected to the 2R resistor element 139 via the R resistor element 142. The 2R resistor element 139 is connected to the 2R resistor element 140 via the R resistor element 143. The 2R resistor element 140 is connected to the 2R resistor element 141 via the R resistor element 144. The connection point between the 2R resistor element 141 and the R resistor element 144 is connected to the output terminal 132.
The attenuation amount which is set for the 4-bit variable attenuator 130 having the ladder structure shown in FIG. 12 is represented by expression (1) .Attenuation amount dB=20 log(control signal/24)  expression (1)
where 0≦control signal≦24−1
When the control signal is 3, the binary thereof is "0011", and the value of "0" or "1" at each level represents the state of D4, D3, D2 or D1. Namely, at "0", the switching element is controlled to be grounded; and at "1", the switching element is controlled to be connected to the input terminal 131 of the 4-bit variable attenuator 130. By switching the four switching elements 133 through 136 to ON or OFF in this manner, the 4-bit variable attenuator 130 can output a signal shaped by an attenuation amount of one of 16 stages of "0000" through "1111" from the output terminal 132.
However, the conventional 4-bit variable attenuator 103 shown in FIG. 12 has the following problem. When the switching elements 133 through 136 are each formed of, for example, a MOS transistor, unless the ON resistance value of the MOS transistor is sufficiently smaller than the resistance value of the 2R resistor elements 137 through 141 and the R resistor elements 142 through 144, the output signal is distorted.
The 2R resistor elements 137 through 141 and the R resistor elements 142 through 144 do not have a frequency characteristic. However, when the switching elements 133 through 136 are each formed of, for example, a MOS transistor, the switching elements 133 through 136 are influenced by the parasitic capacitance of the MOS transistor and the frequency characteristics thereof are deteriorated.
With reference to FIG. 13, the influence of the parasitic capacitance of a switching element in a conventional variable attenuator will be described. FIG. 13 shows operation simulation results of a conventional 8-bit variable attenuator. Although not shown, the 8-bit variable attenuator may include 10 switching elements, 11 2R resistor elements, and 9 R resistor elements based on the structure of the 4-bit variable attenuator 130 shown in FIG. 12. Namely, the attenuation amount of the 8-bit variable attenuator can be controlled to be any one of 256 stages by a transmission power control signal.
In FIG. 13, (a) shows the phase characteristics, (b) shows the gain characteristics, and (c) shows the group delay characteristics. It is understood that by the influence of the parasitic capacitance of the switching elements, the group delay deviation is −2.4 nsec. at the maximum when the transmission power control signal=1, is 1.4 nsec. at the maximum when the transmission power control signal=3, and is 0.3 nsec. at the maximum when the transmission power control signal=255.
As the transmission power control signal is increased, i.e., as the number of the resistor elements is increased, the influence of the parasitic capacitance of the switching elements becomes conspicuous. As the transmission power control signal is increased, i.e., as the number of the resistor elements is increased, it becomes difficult for the gain characteristics to be kept flat to the high frequency area.

Transmission circuit by polar modulation system and communication apparatus using the same


The present invention relates to a novel flavone derivative, pharmaceutically acceptable salt, hydrate, solvate and isomer thereof which is useful as an inhibitor against Cyclin Dependent Kinase (CDK), a process for preparation thereof, and a composition of anti-cancer agent or agent for treating neurodegenerative disease comprising this compound as an active ingredient.

The present invention relates to a novel flavone derivative represented by the following formula (1):
in which
R1, R3 and R4 each independently represent hydrogen, halogen, hydroxy, alkyl, lower alkoxy, amino or nitro,
R2 represents hydrogen, halogen, hydroxy, lower alkyl, lower alkoxy, amino, nitro or
xe2x80x83wherein
A represents amino which may be optionally substituted with alkyl, cycloalkyl, aralkyl, acyl, or aryl which is optionally substituted with one or two substituents selected from the group consisting of halogen, cyano, nitro and amino; or 1,2,3,4-tetrahydroisoquinoline which may be optionally substituted with halogenoalkylcarbonyl; or alkyl, aryl, aralkyl or heteroaryl each of which may be optionally substituted with one or two substituents selected from the group consisting of alkyl, halogenoalkyl, halogen, dialkylamino, phenyl, nitro, amino, isooxazole, pyridine, carboxy, morpholine, methylpiperazine and cyano,
Y represents SO2 or CO,
B represents hydrogen or alkyl,
R5 represents hydrogen or hydroxy, and
R6 and R7 are substituted at o-, m- or p-position from each other and each independently represents hydrogen, hydroxy, halogen or lower alkoxy or together represent lower alkylenedioxy,
pharmaceutically acceptable salt, hydrate, solvate and isomer thereof which is useful as an inhibitor for Cyclin Dependent Kinase (hereinafter, referred to as xe2x80x9cCDKxe2x80x9d),
In addition, the present invention relates to a process for preparing the flavone derivative of formula (1) and also relates to an anti-cancer agent or an agent for treating neurodegenerative disease characterized by comprising the compound of formula (1) as an active ingredient.
Researches on cell division process in molecular level have been extensively performed from the late 1980""s through study of division of frog oocytes, analysis several yeast cell growth or characterization of induced mutants by radiation and study of the tumor suppressor Rb. In the 1990""s, it is discovered that small molecular cell growth regulator controls cell division process (i.e. growth, differentiation, cytogenesis, aging and apoptosis etc.) through its own regulatory function. These results were very useful for more precise understanding of the pathology of several diseases.
A representative example is cancer. In transformation process from normal cells to cancer cells, it was frequently observed that cell growth regulator loses its own function. That is to say, in cancer cells, the cell growth regulator shows an abnormal activity, which is deeply associated with invasion/metastasis which is crucial in the cancerpathology. Particularly, cell cycle deregulation is recognized to be a direct cause of cancer since cancer occurs in experimental animal when overexpression or knock-out of cell growth regulator is induced by using tranformed animal.
The cell growth is under positive or negative regulation in the same manner as other biological regulations. The major pathway of cell cycle regulation known up to now is based on CDK activity and as a result of studies on many cancer cells and carcinogenesis mechanisms, it was confirmed that problems of positive or negative regulation on CDK activity result in carcinogenesis in many cases. That is, cancer may occur when positive or negative regulation and timely regulation which is important for cell growth regulation are disrupted.
The representative CDKs of mammals are CDK4 (Cyclin dependent kinase 4) which shows its activity in mid-G1 phase of cell cycle, CDK2 which shows its activity in mid-1 and S phases, CDC2 (CDK1) which shows its activity in G2-M phase, and so on. It is known that CDK4 and CDK2 activities are regulated by check point of G1-S cell cycle and CDC2 activity by check point of G2-M. In many cancer cells, abnormalities appear in the regulatory mechanism of CDK4, CDK2 and CDC2 (CDK 1) and in fact, it was confirmed that induced abnormalities cause cancer in the transformed animal. Therefore, CDK4, CDK2 and CDC2 (CDK1) among several kinds of CDKs are suitable as a target of anti-cancer agents.
The results of studies on relation between these CDKs and carcinogtenesis will be explained in more detail in the following.
The relation between the abnormal regulation of CDK4 activity and carcinogenesis is observed in several cancer tissues. The deletion of p16 and p15 genes in several kinds of cancer is reported and particularly, overexpression of cyclin D1 is observed, which has close relation with the fact that breast cancer has a metastatic proper and which suggests that malignant phenotype may be expressed when CDK4 activity is deregulated.
Furthermore, it was reported that p16 knocked-out mouse has such a high carcinogenesis rate as p53 knocked-out mouse, which suggests that malfunction of p16 on CDK4 regulation is a cause of carcinogenesis. It gives the possibility that p16 plays a role in the downstream in NIH 3T3 cell with overexpressed ras or src. Reversely it was observed that modified phenotype wherein p16 or p21 is transformed with ras is repaired into wild phenotype. From these experimental results, deregulation of CDK4 activity may be a cause of carcinogenesis and play a role in maintenance of phenotype of cancer cell. Therefore, CDK4 inhibitors may have anti-cancer effects.
It was reported that overexpression of cyclin E is observed in some breast cancers, deeply associated with metastasis of breast cancer, inhibits cell apoptosis under low serum condition and induces anchorage independent growth, and that hyperproliferation (neoplasia) of mammary epithelial cells is observed in transformed animal with overexpressed CDK2 by MMTV promoter, which suggests that CDK2 activity is related with the progress or maintenance of cell transformation and CDK2 inhibitors may also have anti-cancer effects.
It is recently discovered that CDK5 among these CDKs may cause neurodegenerative diseases by phosphorylation of tau protein of the brain. Therefore, CDK5 inhibitor may be useful as an agent for treating neurodegenerative diseases (e.g. Alzheimer""s disease). CDK2 inhibitors may have inhibitory effects on CDK5 in that CDK2 and CDK5 are homologous in the same family (Ref.: John Leu et al., xe2x80x9cNeuronal CDC2-like kinasexe2x80x9d, TIBS, January 1995, pp33xcx9c37).
Furthermore, it is discovered that CDC2 (CDK1), CDK3, CDK6 and CDK7 play an important role in each phase of cell division. These are classified into CDKs family. In addition, to cyclin D1 and E, cyclin A, B, C, D2, D3, D4, F and G are also calssified into the same family.
On the basis of the above-mentioned research, efficient inhibitors of these CDKs may be useful as anti-cancer or anti-neurodegenerative agents. Therefore, recently, these inhibitors have been developed.
As effective CDK inhibitors developed hitherto, there exists Flavopiridol, compound of the formula (2)
which is under clincal trials [Ref.: EP 0,241,003 and 0,336,061]. In addition, a purine derivative of the formula (3)
has been recently developed [Ref: WO 97/16447].
However, the CDK inhibitors developed up to now could not have satisfactory effects.
So, the present inventors have made widespread and concentrative researches on CDK inhibitors and as a result, found that the above flavone derivative of formula (1) which has a quite different structure from any other known CDK inhibitors inhibits CDKs effectively and finally. complete the present invention.
The object of the present invention is to provide a novel flavone derivative of formula (1), pharmaceutically acceptable salt, hydrate, solvate and isomer thereof having an inhibitory activity for CDK.
Another object of the present invention is to provide a process for preparing the compound of formula (1). Still another object of the present invention is to provide an anti-cancer agent and an agent for treating neurodegenerative disease each of which is characterized by comprising as an active ingredient the compound of formula (1) with a pharmaceutically acceptable carrier.
In this specification, CDKs includes all of CDK2, CDK4, CDC2 (CDK1), CDK3, CDK5, CDK6, CDK7 etc., and cyclin includes cyclin D1, E, A, B, C, D2, D3, D4, F, and G.
The present invention is explained in detail hereinafter.
The present invention relates to a novel flavone derivative represented by the following formula (1):
in which
R1, R3 and R4 each independently represent hydrogen, halogen. hydroxy, alkyl, lower alkoxy, amino or nitro.
R2 represents hydrogen, halogen, hydroxy, lower alkyl, lower alkoxy, amino, nitro or
xe2x80x83wherein
A represents amino which may be optionally substituted with alkyl, cycloalkyl, aralkyl, acyl, or aryl which is optionally substituted with one or two substituents selected from the group consisting of halogen, cyano, nitro and amino; or 1,2,3,4-tetrahydroisoquinoline which may be optionally substituted with halogenoalkylcarbonyl; or alkyl, aryl, aralkyl or heteroaryl each of which may be optionally substituted with one or two substituents selected from the group consisting of alkyl, halogenoalkyl, halogen, dialkylamino, phenyl, nitro, amino, isooxazole, pyridine, carboxy, morpholine, methylpiperazine and cyano,
Y represents SO2 or CO,
B represents hydrogen or alkyl,
R5 represents hydrogen or hydroxy, and
R6 and R7 are substituted at o-, m- or p-position from each other and each independently represents hydrogen, hydroxy, halogen or lower alkoxy or together represent lower alkylenedioxy,
pharmaceutically acceptable salt, hydrate, solvate and isomer thereof which has efficacies on treating cancer or neurodegenerative disease through a mechanism of inhibiting CDKs activity,
In addition, the present invention relates to a process for preparing the flavone derivative of formula (1) and also relates to an anti-cancer agent or an agent for treating neurodegenerative disease each of which is characterized by comprising the compound of formula (1) as an active ingredient.
Among the compound of formula (1) according to the present invention, the preferred compounds include those wherein
(1) R1, R2, R3 and R4 each independently represent hydrogen, halogen. hydroxy, lower alkoxy or nitro (provided that two or more of these four substituents are hydrogen),
R5 represents hydrogen or hydroxy, and
R6 and R7 are substituted at o-, m- or p-position from each other and each independently represents hydrogen, hydroxy, halogen or lower alkoxy or together represent lower alkylenedioxy, or
(2) R1 represents hydrogen, hydroxy, lower alkoxy or amino,
R2 and R3 each independently represent hydrogen, halogen, hydroxy, lower alkyl, lower alkoxy or amino,
R4 represents hydrogen, halogen, hydroxy or lower alkoxy,
R5 represents hydroxy, and
R6 and R7 represent 3-hydroxy and 4-hydroxy respectively, or
(3) R1, R3 and R4 each independently represent hydrogen, halogen, hydroxy, alkyl or amino (provided that two or more of these three substituents are hydrogen),
R2 represents
xe2x80x83wherein
A represents amino which may be optionally substituted with alkyl, cycloalkyl, aralkyl, acyl, or amyl which is optionally substituted with one or two substituents selected from the group consisting of halogen, cyano, nitro and amino; or 1,2,3,4-tetrahydroisoquinoline which may be optionally substituted with halogenoalkylcarbonyl; or alkyl, aryl, aralkyl or heteroaryl each of which may be optionally substituted with one or two substituents selected from the group consisting of alkyl, halogenoalkyl, halogen, dialkylamino, phenyl, nitro, amino, isooxazole, pyridine, carboxy, morpholine, methylpiperazine and cyano,
Y represents SO2 or CO,
B represents hydrogen or alkyl,
R5 represents hydroxy, and
R6 and R7 represent 3-hydroxy and 4-hydroxy respectively.
More preferred compounds include those wherein
(1) R1, R2, R3 and R4 each independently represent hydrogen, chloro, hydroxy, methoxy or nitro(provided that two or more of these four substituents are hydrogen),
R5 represents hydrogen or hydroxy, and
R6 and R7 are substituted at o-, m- or p-position from each other and each independently represents hydrogen, hydroxy, chloro or methoxy or together represent methylenedioxy, or
(2) R1 represents hydrogen, hydroxy or lower alkoxy,
R2 represents hydrogen, halogen, hydroxy, lower alkyl, lower alkoxy or amino,
R3 represents hydrogen, hydroxy, lower alkyl, lower alkoxy or amino,
R4 represents hydrogen, halogen or hydroxy,
R5 represents hydroxy, and
R6, and R7 represent 3-hydroxy and 4-hydroxy respectively, or
(3) R1, R3 and R4 each represent hydrogen,
R2 represents
xe2x80x83wherein
A represents amino which may be optionally substituted with cycloalkyl; or 1,2,3,4-tetrahydroisoquinoline which may be optionally substituted with halogenoalkylcarbonyl; or alkyl, aryl, aralkyl or heteroaryl each of which may be optionally substituted with one or two substituents selected from the group consisting of alkyl, halogenoalkyl, halogen, dialkylamino, phenyl. nitro, amino isooxazole, pyridine carboxy, morpholine and methylpiperazine,
Y represents SO2,
B represents hydrogen,
R5 represents hydroxy, and
R6 and R7 represent 3-hydroxy and 4-hydroxy respectively, or
(4) R1, R3 and R4 each represent hydrogen
R2 represents
xe2x80x83wherein
A represents amino which may be optionally substituted with cycloalkyl, aralkyl, acyl, or aryl which is optionally substituted with one or two substituents selected from the group consisting of halogen, cyano, nitro and amino; or alkyl or aryl each of which may be optionally substituted with halogen,
Y represents CO,
B represents hydrogen,
R5 represents hydroxy, and
R6 and R7 represent 3-hydroxy and 4-hydroxy respectively.
Most preferred compounds include those wherein
(1) R1 represents hydrogen, hydroxy or methoxy,
R2 represents hydrogen, bromine, hydroxy, methyl or amino,
R3 represents hydrogen, hydroxy, methyl, methoxy or amino,
R4 represents hydrogen, halogen or hydroxy,
R5 represents hydroxy, and
R6 and R7 represent 3-hydroxy and 4-hydroxy respectively, or
(2) R1, R3 and R4 each represent hydrogen,
R2 represents
xe2x80x83wherein
A represents 1,2,3,4-tetrahydroisoquinoline which may be optionally substituted with halogenoalkylcarbonyl or aryl or heteroaryl each of which may be optionally substituted with one or two substituents selected from the group consisting of alkyl, halogenoalkyl, halogen, dialkylamino, phenyl, nitro, amino, isooxazole, pyridine, carboxy, morpholine and methylpiperazine,
Y represents SO2,
B represents hydrogen,
R5 represents hydroxy, and
R6 and R7 represent 3-hydroxy and 4-hydroxy respectively, or
(3) R1, R3 and R4 each represent hydrogen,
R2 represents
xe2x80x83wherein
A represents amino which is substituted with aryl which is substituted with one or two substituents selected from the group consisting of halogen, cyano, nitro and amino,
Y represents CO,
B represents hydrogen,
R5 represents hydroxy, and
R6 and R7 represent 3-hydroxy and 4-hydroxy respectively.
Typical examples of the flavone derivative of formula (1) according to the present invention are
compound 1) 2-(4-chloro-phenyl)-7-methoxy-chromen-4-one,
compound 2) 7-methoxy-2-phenyl-chromen-4-one,
compound 3) 7-hydroxy-2-phenyl-chromen-4-one.
compound 4) 2-(benzo[1,3]dioxol-5-yl)-3-hydroxy-5-methoxy-chromen-4-one,
compound 5) 2-(benzo[1,3]dioxol-5-yl)-3-hydroxy-6-methoxy-chromen-4-one,
compound 6) 2-(benzo[1,3]dioxol-5-yl)-3-hydroxy-7-methoxy-chromen-4-one,
compound 7) 3-hydroxy-7-methoxy-2-(4-methoxy-phenyl)-chromen-4-one,
compound 8) 2-(4-chloro-phenyl)-3-hydroxy-7-methoxy-chromen-4-one,
compound 9) 6-chloro-3-hydroxy-2-(4-methoxy-phenyl)-8-nitro-chromen-4-one,
compound 10) 6,8-dichloro-3-hydroxy-2-(4-methoxy-phenyl)-chromen-4-one,
compound 11) 3-hydroxy-2-(4-methoxy-phenyl)-chromen-4-one,
compound 12) 6-chloro-2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-one,
compound 13) 6-bromo-2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-one,
compound 14) 2-(3,4-dihydroxyphenyl)-3,6-dihydroxy-4H-chromen-4-one,
compound 15) 6-amino-2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-one,
compound 16) 2-(3,4-dihydroxyphenyl)-3-hydroxy-6-methoxy-4H-chromen-4-one,
compound 17) 6-fluoro-2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-one,
compound 18) 6-methyl-2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-one,
compound 19) 6,8-dichloro-2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-one,
compound 20) 6,8-dibromo-2-(3,4-dihydoxyphenyl)-3-hydroxy-4H-chromen-4-one,
compound 21)6,8-difluoro-2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-one,
compound 22) 6-chloro-2-(3,4-dihydroxyphenyl)-3-hydroxy-7-methyl-4H-chromen4-one,
compound 23) 2-(3,4-dihydroxyphenyl)-3-hydroxy-7-methoxy4H-chromen-4-one,
compound 24) 2-(3,4-dihydroxyphenyl)-3,8-dihydroxy-7-methoxy-4H-chromen-4-one,
compound 25) 2-(3,4-dihydroxyphenyl)-3,8-dihydroxy-4H-chromen-4-one,
compound 26) 2-(3,4-dihydroxyphenyl)-6,7-dimethyl-3-hydroxy-4H-chromen-4-one,
compound 27) 2-(3,4-dihydroxyphenyl)-3-hydroxy-5-methoxy-4H-chromen-4-one,
compound 28) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-4-methylbenzenesulfonamide,
compound 29) 4-bromo-N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]benzenesulfonamide,
compound 30) 3-bromo-N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]benzenesulfonamide,
compound 31) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-2-naphthalenesulfonamide,
compound 32) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-5-(dimethylamino)-1-naphthalenesulfonamide,
compound 33) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-2-(1-naphthyl)-1-ethanesulfonamide,
compound 34) 4,5-dibromo-N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-41-1-chromen-6-yl]-2-thiophenesulfonamide,
compound 35) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-[1,1xe2x80x2-diphenyl]-4-sulfonamide,
compound 36) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-5-(isooxazolyl)-2-thiophenesulfonamide,
compound 37) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-5-(2-pyridinyl)-2-thiophenesulfonamide,
compound 38) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-3,4-difluorobenzenesulfonamide,
compound 39) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-4-(trifluoromethyl)benzenesulfonamide,
compound 40) 4-chloro-N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-3-nitrobenzenesulfonamide,
compound 41) 3-chloro-N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-1-propanesulfonamide,
compound 42) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-2,4-difluorobenzenesulfonamide,
compound 43) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-4-fluorobenzenesulfonamide,
compound 44) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-2-(2,2,2-trifluoroacetyl)-1,2,3,4-tetrahydro-7-isoquinolinesulfonamide,
compound 45) 4-({[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]amino}sulfonyl)benzoic acid,
compound 46) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-1,2,3,4-tetrahydro-7-isoquinolinesulfonamide,
compound 47) N-cyclohexyl-Nxe2x80x2-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-sulfide,
compound 48) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-4-(4-morpholinyl)-3-nitrobenzenesulfonamide,
compound 49) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-4-(4-methyl-1-piperazinyl)-3-nitrobenzenesulfonamide,
compound 50) 3-amino-N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-4-(4-methyl-1-piperazinyl)benzenesulfonamide,
compound 51) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]acetamide,
compound 52) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]benzamide,
compound 53) 4-chloro-N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]benzamide,
compound 54) N-benzyl-Nxe2x80x2-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]urea,
compound 55) N-(4-bromophenyl)-Nxe2x80x2-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]urea,
compound 56) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-Nxe2x80x2-phenylurea,
compound 57) N-benzoyl-Nxe2x80x2-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]urea,
compound 58) N-(3-bromophenyl)-Nxe2x80x2-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]urea,
compound 59) N-(2,4-dichlorophenyl)-Nxe2x80x2-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-urea,
compound 60) N-(3-cyanophenyl)-Nxe2x80x2-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]urea,
compound 61) N-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]-Nxe2x80x2-(4-nitrophenyl)urea,
compound 62) N-(4-aminophenyl)-Nxe2x80x2-[2-(3,4-dihydroxyphenyl)-3-hydroxy-4-oxo-4H-chromen-6-yl]urea,
compound 63) 2-(3,4-dihydroxyphenyl)-3-hydoxy-4H-chromen-4-one,
compound 64) 2-(3,4-dihydroxyphenyl)-3,7-dihydroxy-4H-chromen-4-one,
compound 65) 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one, and
compound 66) 2-(3,4-dihydroxyphenyl)-3,7,8-trihydroxy-4H-chromen-4-one.
The above compound of formula (1) may also form a pharmaceutically acceptable salt. Such a salt includes non-toxic acid addition salt containing pharmaceutical acceptable anion, for example a salt with inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, hydroiodic acid, etc., a salt with organic carboxylic acids such as tartaric acid, formic acid, citric acid, acetic acid, trichloroacetic acid, trifluoroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid, etc., or a salt with sulfonic acids such as methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, etc. The compound of formula (1) may also exist in the form of hydrate or solvate.
Since the compounds according to the present invention may have asymmetric carbon centers, they can be present in the form of racemate, diastereomer or mixtures thereof. Therefore, the present invention also includes all these isomers and their mixtures.
The compound of the formula (1) according to the present invention may be prepared by process described in the following.
First, the compound of formula (1) wherein R5 is hydrogen, namely the compound of the following formula (1a):
wherein R1, R2, R3, R4; and R7 are defined as previously described, or a salt thereof may be prepared characterized by
a) cyclizing a compound of the following formula (4):
wherein R1, R2, R3, R4, R6 and R7 are defined as previously described, in the presence of trifluoroacetic acid to give a compound of the following formula (5):
wherein R1, R2, R3, R4, R6 and R7 are defined as previously described, then reducing the resulting compound of formula (5) in the presence of a reducing agent in a solvent or
b) cyclizing a compound of the following formula (6):
wherein R1, R2, R3, R4, R6 and R7 are defined as previously described, in the presence of sodium acetate in a solvent.
The processes are depicted in the following Schemes (1) and (2).
wherein R1, R2, R3, R4, R6 and R7 are defined as previously described.
In the reaction depicted in Scheme (1), the compound of formula (5) is prepared from cyclization of the compound of formula (4) during which the compound (4) is heated under reflux in the presence of trifluoroacetic acid. This reaction is carried out for an enough time, usually for a day, to complete the reaction depending on the kind of reactant. After the cyclization is completed, the chromane derivative of formula (5) thus obtained is oxidized with a oxidizing agent in a solvent to produce the chromene derivative of above formula (1a). As the solvent, one or more selected from the group consisting of benzene and toluene may be preferably used. As the oxidizing agent, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is used preferably.
In the reaction according to Scheme (2). the compound of formula (1a) wherein R5 is hydrogen is prepared by cyclizing the compound of formula (6) in the presence of sodium acetate in a solvent. At this time, acetic acid is preferably used as the solvent.
Second, the compound of formula (1) wherein R5 is hydroxy, namely the compound of following formula (1b):
wherein R1, R2, R3, R4, R6 and R7 are defined as previously described, or a salt thereof may be prepared characterized by cyclizing the compound of following formula (4):
wherein R1, R2, R3, R4, R6 and R7 are defined as previously described, in the presence of a base and hydrogen peroxide in a solvent.
Especially, the compound of formula (1b) wherein R6 and R7 together represent methylenedioxy, namely the compound of formula (1cc):
wherein R1, R2, R3 and R4 are defined as previously described, can be prepared from the compound of following formula (4a):
wherein R1, R2, R3 and R4 are defined as previously described, according to the above method.
The process of the above reaction is depicted in the following Scheme (3).
wherein R1, R2, R3, R4, R6 and R7 are defined as previously described.
In the reaction according to the Scheme (3), the compound of formula (1b) is prepared by cyclizing compound of formula (4) in the presence of hydrogen peroxide. In this process, a solvent and a base are used. As the solvent, the one which does not adversely affect the reaction, such as for example, one or more selected from the group consisting of methanol and ethanol, particularly methanol is used. The base includes one or more selected from the group consisting of sodium hydroxide and potassium hydroxide. Particularly an aqueous sodium hydroxide solution having a concentration of 10% is preferable. This reaction should be conducted inevitably by using hydrogen peroxide which is used in excess amount, preferably in an amount of 5 to 10 times molar equivalents with respect to the compound of formula (4). Suitably, it is used in an aqueous solution of 30%. The reaction may be promoted by optionally adding acid catalyst, such as hydrochloric acid. The reaction is usually carried out at room temperature or under warming, and about 3 hours are usually required to complete the reaction at room temperature.
Deprotection reaction may also be carried out to remove the amino- or hydroxy-protecting group which exists optionally.
That is to say, the compound of formula (1) wherein one or more of the substituents R1, R2, R3 and R4 are hydroxy or amino may be prepared characterized by selectively deprotecting the hydroxy or amino group which is protected by lower alkyl or alkanoyl in the presence of boron tribromide or by hydrolyzing with aqueous sulfuric acid solution or alcohol solvent.
Moreover, the compound of formula (1) wherein R2 is
namely the compound of the following formula (1h):
wherein R1, R3, R4, R5 and A, Y, B are defined as previously described, may be prepared by reacting the compound of formula (9):
wherein R1, R3, R4, R5 and B are defined as previously described, with the compound of formula (10):
Axe2x80x94Yxe2x80x94Xxe2x80x83xe2x80x83(10)
wherein A and Y are defined as previously described and X is a leaving group, or with the compound of formula (11):
Axe2x80x2xe2x80x94Nxe2x95x90Cxe2x95x90Oxe2x80x83xe2x80x83(11)
wherein Axe2x80x2 represents aralkyl, acyl or aryl which is optionally substituted with one or two substituents selected from the group consisting of halogen, cyano and nitro.
Especially, the compound of formula (1h) wherein R5 is hydroxy, namely the compound of formula (1hh):
wherein R1, R3, R4, A, Y and B are defined as previously described, can be prepared from the compound of formula (9a):
wherein R1, R3, R1and B are defined as previously described, according to the above method.
The compound of formula (9), especially the compound of formula (9a) used in the above method can be prepared by process described in the following.
A compound of formula (4b):
wherein R1, R3, R4 and B are defined as previously described, is prepared by reacting 2-hydroxyacetophenone derivative of formula (7a):
wherein R1, R3, R4 and B are defined as previously described, the piperonal of formula (8a):
and sodium hydroxide in the aqueous ethanol solution solvent, then thus obtained compound of formula (4b) is reacted with aqueous sodium hydroxide and hydrogen peroxide in methanol solvent to produce a compound of formula (1e):
wherein R1, R3, R4 and B are defined as previously described.
Then, the above obtained compound of formula (1e) is hydrolyzed with aqueous sulfuric acid solution in alcoholic solvent to give a compound of formula (9a):
wherein R1, R3, R4 and B are defined as previously described.
The compound of formula (1) wherein one to six of the substituents R1, R2, R3, R4, R6 and R7 are hydroxy may be prepared characterized by selectively deprotecting one to six lower alkoxy groups or lower alkylenedioxy group in the compound of formula (1) in order to convert them into hydroxy of dihydroxy group in the presence of boron tribromide.
For example, the compound of formula (1) wherein R6 and R7 represent 3-hydroxy and 4-hydroxy respectively, namely compound of formula (1d):
wherein R1, R2, R3, R., and R5 are defined as previously described, may be prepared from the compound of formula (1c):
wherein R1, R2, R4, R4, and R5 are defined as previously described, according to the reaction as depicted in the following Scheme (4).
wherein R1, R2, R3, R4, and R5 are defined as previously described.
Especially, the compound formula (1d) wherein R5 is hydroxy, namely the compound of formula (1dd):
wherein R1, R2, R3 and R4 are defined as previously described, can be prepared from the compound of formula (1cc):
wherein R1, R2, R3 and R4 are defined as previously described, according to the above method.
In addition, the compound of formula (1cc) wherein R2 is
namely the compound of formula (1i):
wherein R1, R3, R4, A, Y and B are defined as previously described, can be prepared from the compound of formula (1hh):
wherein R1, R3, R4, A, Y and B are defined as previously described, according to the above method.
In the reaction according to Scheme 4, the compound of formula (1d) is prepared by opening the dioxolane ring of the compound of formula (1c) to convert it into dihydroxy group. The opening of dioxolane ring is accomplished by a reaction with boron tribromide which is usually used in an amount of 2 to 5 equivalents, preferably 3 equivalents or more, with respect to the compound of formula (1c). This opening reaction is preferably carried out in a solvent and as the solvent, one or more selected from the group consisting of methylenechloride, dioxane, benzene and toluene, preferably methylenechloride, may be mentioned. The reaction is usually carried out at room temperature or under warming and the reaction is completed at room temperature for about 2 hours.
The compound of formula (4) used as a starting material in the above process for preparation of the compound of formula (1) according to the present invention may be produced by reacting a 2-hydroxyacetophenone derivative of the following formula (7)
wherein R1, R2, R3, and R4 are defined as previously described, with a compound of the following formula (8):
wherein R6 and R7 are defined as previously described, in the presence of a base in a solvent.
Especially, the compound of formula (4a) can be prepared by reacting the compound of the formula (7) with piperonal of formula (8a)
according to the above method.
The above reaction is depicted in the following Scheme (5).
wherein R1, R2, R3, R4, R6 and R7 are defined as previously described.
In the reaction according to Scheme 5, the compound of formula (4) is prepared by coupling the 2-hydroxyacetophenone derivative of formula (7) with the compound of formula (8) in an amount of 1 to 3 equivalents, preferably 3 equivalents. As the solvent which can be used, one or more selected from the group consisting of water, methanol, ethanol, propanol, butanol and dioxane may be exemplified, and methanol, ethanol or aqueous ethanol solution (80%) is more preferable. As the base, one or more selected from the group consisting of sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate and calcium carbonate, preferably sodium hydroxide, may be mentioned. The amount of base is not particularly restricted, however it is generally used in an amount of 2 to 5 equivalents, preferably 3 equivalents with respect to the compound of formula (7). The reaction is usually carried out at room temperature or under warming and reaction time is variable according to the kind of used solvent or base used, or reaction temperature. The reaction is usually completed at room temperature for about 15 hours.
In the processes as explained in above, the reaction conditions including the amount of reactants, reaction temperature, reaction time, etc. are easily determined depending on the reactants selected by a person having ordinary skill in this art. In general, as for solvent, any one can be used unless it adversely affect the reaction. The reaction temperature may be changeable in variety, however the reaction is preferably carried out at temperatures ranging from 0 to 120xc2x0 C.
The free compound of formula (1) prepared in the reaction according to the present invention may be converted into the above-mentioned salt in a conventional manner well-known in the art. In addition, after the reaction is completed, the product may be isolated or purified by conventional work up procedures such as chromatography, recrystallization, etc.
The compound of the present invention prepared according to the above method has an inhibitory activity against CDK, and thus may be put to a good use as an anti-cancer agent. Accordingly, another object of the present invention is to provide an anti-cancer agent or an agent for treating neurodegenerative disease which comprises the compound of formula (1), pharmaceutically acceptable salt, hydrate, solvate or isomer thereof as an active ingredient together with pharmaceutically acceptable carrier.
In case the compound of the present invention is administered for clinical purpose, it is preferably administered in an amount ranging from 0.01 to 50 mg/kg of body weight a day. The total daily dosage may be administered in one time or over several times. However, the specific dosage for a specific patient can be varied according to the specific compound used, body weight of the subject patient, sex, hygienic condition, diet, time or method of administration, excretion rate, mixing ratio of the medicine, severity of the disease to be treated, etc.
The compound of the present invention may be administered in the form of injections or oral preparations. Injections such as sterilized aqueous or oily suspension for injection may be prepared by using suitable dispersing agent, humectant or suspension agent according to the known method. As solvents to be used for preparing injections, water, Ringer""s fluid and isotonic NaCl solution can be mentioned, and sterilized fixing oil is also used as the solvent or suspension medium. Any non-stimulative fixing oil including mono- or di-glyceride can be used for this purpose, and also fatty acid such as oleic acid can be used for injection formulation.
As the solid preparation for oral administration, capsules, tablets, pills, powders and granules, preferably capsules and tablets can be mentioned. It is desirable for tablets and pills to be formulated into enteric-coated preparation. Solid preparations may be prepared by mixing the active compound of formula (1) according to the present invention with least one carrier selected from a group consisting of inert diluents(e.g. sucrose. lactose, starch, etc.), lubricants(e.g. magnesium stearate), disintegrators, and binders.


One embodiment of the present invention includes a system comprising to determine a direction of tracking a fiber based on a vector corresponding to a largest value of a set of values for a tensor, if an anisotropy value of the tensor is greater than or equal to a first threshold; and to apply a weighted function to the vector of the tensor to select the direction of tracking the fiber, if the anisotropy value of the tensor is less than or equal to the first threshold and larger than or equal to a second threshold. In one embodiment, the system is to generate the weighted function comprises a linear interpolation to be performed on the vector. In one embodiment, a weight of the linear interpolation is in part dependent on the anisotropy value of the tensor, wherein the weight corresponds to the anisotropy value relative to the first threshold. One embodiment of the invention is also executable as a method.

Diffusion Tensor Imaging (DTI) visualization is a growing field of research. The scanners are collecting better data all the time, and doctors and scientists are constantly discovering new applications for the data. The success of diffusion magnetic resonance imaging (MRI) is rooted in the powerful concept that during their random, diffusion-driven displacements, molecules probe tissue structure at a microscopic scale well beyond the usual image resolution. As diffusion is a three dimensional process, molecular mobility in tissues may be anisotropic, as in brain white matter.
The diffusion anisotropy effects can be extracted, characterized, and exploited, providing details on tissue microstructure. One such advanced application is that of fiber tracking in the brain, which may provide insight into the issue of connectivity. DTI has also been used to demonstrate subtle abnormalities in a variety of diseases (including stroke, multiple sclerosis, dyslexia, and schizophrenia) and is currently becoming part of many routine clinical protocols.
However, there exist a need for a more intuitive input interface to let the user specify the tracts of interest, so as to make them part of the surgical planning and subsequent navigation.


Bootstrapping a microservices container registry. A computing system node receives an installation package. The receiving computing system node bootstraps an initial invocation of the microservice by first installing a local container registry from the installation package and then by installing the microservice from the installation package. The installation package contains additional components that can be extracted, installed and invoked by executing the microservice at the computing system node after extracting from the local container registry. The installation package is generated by any node of the computing system and contains code corresponding to infrastructure microservices that are installed before invoking microservices that depend on the infrastructure. Temporary domain name services are installed from the installation package at a node-local IP address. The temporary domain name services are switched over to a different domain name service at a different IP address. A second computing system node is designated as a failover node.

As applications move from virtual machines to executable containers, their deployment models also change. Unlike virtual machine images, executable container images are deployed in observance of a layered file system. Executable containers use these layered file systems. The executable containers and constituent components taken from the layered file system are building blocks for applications, where each executable container is a READ/WRITE image having access to many read-only layers. The are several possible approaches to addresses this problem, some of which are discussed hereunder:
One approach relies on a download of an executable container image from some container registry. However, in order to access the executable container for download, the registry needs to exist, and this registry has to be populated before the application that will be in and/or using the executable containers is started. The registry and its components as well as a protocol to access the registry serve to access and assemble only those layers that are both (1) needed by the containerized application, and (2) not already downloaded. Most applications are delivered in multiple executable containers and, as such, and most of the time, there are many common layers. As such, each of the multiple executable containers that form the application may differ only in their respective container-specific layer. This can result in a very efficient and fast download mechanism, however this model suffers from several deficiencies as detailed below.
Other approaches package the container images as a "tar" or "gzip" file, such as the well-known "tar.gz". The tar file includes all of the layers required to bring up the container in a single download including all the layers of the container as mentioned above. These saved images then need to be downloaded at an application deployment site and loaded into a local executable instance which, in turn, will load the images into a container-friendly file system.
Deficiencies in these Approaches
Many applications that are deployed as microservices use the former approach that relies on a download of an executable container image from some container registry. To facilitate efficiency when following this approach, highly available container registries are made available (e.g., in other on-premises facilities and/or in various computing clouds). Enterprise-managed systems operate to push the pre-built container images into this highly available container registry. Applications that use these containers download them through one of the highly available container registry sites at the time of their deployment. However, there is a class of applications called "infrastructure applications," that have to be operational before any other (non-infrastructure) classes of applications (e.g., business applications) can be made operational. In the situation where these "infrastructure applications" are deployed as microservices, they rely on certain computing infrastructure being available at the time of the invocation. In such situations, these non-infrastructure microservices cannot run in the absence of such relied-on infrastructure. This sets up a "chicken-and-egg" problem such that any "infrastructure application" that is deployed as a microservice cannot bootstrap itself.
In circumstances where an infrastructure microservice is to be deployed, the latter tar.gz approach could be used instead of the former download approach. Unfortunately, the tar.gz approach often results in very large images for each and every container. As such, the total size of downloaded image data often becomes huge and thus the download times are correspondingly huge, which leads to poor performance. What is needed is a way to deploy infrastructure microservices in a manner that overcomes the "chicken-and-egg" problem as well as the performance problems and limitations of download approaches.


A compound having a bisazo moiety and a polyester moiety is provided. The compound can be provided as a pigment dispersant to improve the dispersion of an azo pigment in a water-insoluble solvent.

A reduction in the size of pigment particles so as to improve its spectral characteristics, such as tinting strength and transparency, results in an increase in the growth or transformation of crystals caused by thermal history or contact with a solvent in a dispersion process and subsequent processes, resulting in a decrease in the tinting strength and transparency of the pigment.
Various pigment compositions and pigment dispersants have been proposed in order to improve the dispersibility of pigments. PTL 1 discloses the use of a comb polymer dispersant having an acidic or basic portion known as Solsperse (registered trademark). PTL 2 discloses the use of a polymer dispersant for an azo pigment in an ink jet recording method. The polymer dispersant is a water-soluble polymer having a chromophore bonded to its side chain or end. The chromophore has a molecular weight of less than 95% of the molecular weight of the azo pigment.
PTL 3 discloses the use of a mixture of at least two organic pigments in red (R), green (G), and blue (B) color filters in order to achieve desired color characteristics. Particularly in the case of the green color filter, a main pigment, a copper phthalocyanine green pigment, is combined with an azo yellow pigment for tone adjustment.
However, the pigment dispersant described in PTL 1 cannot sufficiently disperse an azo pigment because of insufficient affinity for the azo pigment. The pigment dispersant described in PTL 2 is a water-soluble polymer and therefore results in poor dispersion in a system using a water-insoluble solvent as a dispersion medium.
There has been a problem that the use of an azo pigment in a color filter resist results in poor and unstable pigment dispersion and consequently poor color characteristics of the color filter.

Compound having bisazo dye skeleton, pigment composition containing the same, pigment dispersion, ink, and color filter resist composition


A transmitting apparatus and method in a transmit diversity system, which transmits a plurality of block-coded symbols over a plurality of antennas are provided. The transmitting apparatus includes N+M antennas where N is an integer equal to or greater than two and M is an integer equal to or greater than one; a switch which forwards N-ary block-coded symbols to N-ary antennas of the N+M antennas; and a switch controller which controls switching of the switch, and when a receiving end which receives the N-ary block-coded symbols informs the switch controller of a poor reception state, the switch controller forwards the N-ary block-coded symbols to other N-ary antennas which include at least one antenna different from the N-ary antennas. The block-coded symbols can be transmitted by selectively using more antennas than block-coded symbols.

1. Field of the Invention
Methods and apparatuses consistent with the present invention relate to a transmit diversity system, and more particularly, a transmit diversity system which transmits a plurality of block-coded symbols over a plurality of antennas.
2. Description of the Related Art
A transmit diversity system transmits block-coded symbols to a receiver over a plurality of antennas. The transmit diversity system is prevalently used due to its excellent transmission performance over wireless channels.
FIG. 1 is a block diagram of a related art transmitting apparatus adopted in the transmit diversity system. In FIG. 1, the transmitting apparatus includes a space-time block coder (STBC) 10, a first antenna 21 and a second antenna 22.
The STBC 10 generates two STBC symbols by space-time block coding a source symbol. The two STBC symbols generated by the STBC 10 are transmitted to a receiver over the first antenna 21 and the second antenna 22, respectively.
In FIG. 1, it is explained that the transmit diversity system transmits the two STBC symbols generated by the STBC 10 over the two antennas, by way of example. As shown in FIG. 1, the number of the STBC symbols to be transmitted equals to the number of the antennas transmitting the symbols in the transmit diversity system according to the related art.
Accordingly, if four STBC symbols are to be transmitted, four antennas are required, and if eight STBC symbols are to be transmitted, eight antennas are required.

Transmitting apparatus and method in transmit diversity system


The present invention provides a method for producing (+)-estrone derivatives, characterized in that it comprises starting from a certain cyclopentadiene derivative, reacting the derivative with a certain diene compound by an asymmetric Diels-Alder reaction, and via intermediates obtaining a (+)-estron derivative represented by the following formula: ##STR1## wherein R is alkyl of 1-20 carbon atoms. According to the present invention, (+)-estron derivatives can be obtained by limited steps from the starting materials of dicyclopentadiene derivatives.

1. Field of the Invention
The present invention relates to a method for producing (+)-estrone derivatives useful for oral contraceptives by using dicyclopentadiene derivatives as starting materials, and to intermediates which is used for the production of (+)-estrone derivatives.
2. Description of the Prior Art
(+)-Estrone is a compound useful for oral contraceptives, and it has been known from a long time to obtain the compound by methods in which natural materials are used (U.S. Pat. Nos. 1,967,350 (1934) and 135,992 (1962). However, the efficiency and yields of the methods are too inferior to those of synthetic methods to compare with.
Synthetic methods of (+)-estrone whose configuration is a natural type have been developed. Posner et al. (J. Am. Chem. Soc., 108,1239(1986) disclosed that a compound having an AB ring skeleton and a compound having a D ring skeleton which is asymmetrically derived are reacted by an asymmetric Michael addition reaction, and a C ring skeleton is formed by an intramolecular Diels-Alder reaction to construct an estron skeleton having a diastereo selectivity of 91-94%. However, the total yield is low, 6.3%, and the process has inefficiently nine steps.
Moreover, Taber et al. (J. Org. Chem.,52 28(1987)) constructed a .beta.-ketoester having a D ring skeleton by using a camphor derivative as a chiral source, combined the compound with a benzocyclobutene derivative, and constructed a BC ring skeleton by internal cyclization reaction in one step to synthesize (+)-estrone having an optical purity of 91% ee. However, the process has many reaction steps. To construct the .beta.-ketoester, it needs five steps. To synthesize the benzocyclobutene derivative, it needs three steps. To combine the both compounds and to obtain the objective skeleton, it needs three steps. The yield of the ring formation is low, 41%, and the total yield from the .beta.-ketoester precursor is 9.8%. The stereoselectivity of the (+)-estrone is comparatively good, but the efficciency of the process is no good.
Before the present invention, (+)-estrone was much in demand, but it was not provided well.

Method for producing (+)-estrone derivatives