MXPA06010624A - Substituted phenoxy- and phenylthio- derivatives for treating proliferative disorders - Google Patents

Abstract

Substituted phenol derivatives of Formula (I) are useful as antiproliferative agents including, for example, anticancer agents, and as radioprotective and chemoprotective agents.

Description

DERIVATIVES PHENOXY- AND PENETYL-REPLACED TO TREAT PROLIFERATIVE DISORDERS CROSS REFERENCE TO RELATED REQUEST This application claims the benefits of the copending US Provisional Application Serial No. 60 / 554,008, filed on March 16, 2004, a full description which is incorporated herein by reference.

FIELD OF THE INVENTION The invention relates to compositions and methods for the treatment of proliferative diseases, which include but are not limited to cancer. The invention further relates to compositions that provide protection from the cytotoxic effects of ionizing radiation and cytotoxic chemotherapeutic agents.

BACKGROUND OF THE INVENTION Sulfone α, ß-ns-unsaturated compounds Certain α, β-unsaturated compounds, particularly certain styrylbenzyl sulfones, have been shown to possess antiproliferative, radioprotective and chemoprotective activity. The chemoprotective effect is shown by protecting normal cells from the cytotoxic side effects of mitotic phase cell cycle inhibitors and topoisomerase inhibitors, used in the treatment of cancer and other proliferative disorders. See, U.S. Patents 6,599,932, 6,576,675, 6,548,553, 6,541, 475, 6,486,210, 6,414,034, 6,359,013, 6,201, 154, 6,665,973, and 6,667,346 full descriptions of which are incorporated herein.

Sulfonamide a, ß-lnsaturated compounds Certain a, ß-unsaturated sulfonamide compounds, particularly styrylbenzyl sulfonamides, have been shown to possess antiproliferative, radioprotective and chemoprotective activity (normal cells protected from the cytotoxic side effects of phase cell cycle inhibitors mitotic and topoisomerase inhibitors). See, U.S. Patent 6,646,009 and PCT publications WO 03072063, complete descriptions which are incorporated herein.

Aromatic Propenamide Compounds Certain aromatic propenamide compounds, particularly N-aromatic cinnamides, have been shown to possess antiproliferative, radioprotective and chemoprotective activity (normal cells protected from the cytotoxic side effects of mitotic phase cell cycle inhibitors and topoisomerase inhibitors). See PCT publication WO 04037751, the full disclosure which is incorporated herein by reference.

Treatment of Proliferative Disorders Several growth factors have been shown to play a significant role in cell proliferation and differentiation. Proliferative disorders, particularly cancers, arise as a result of an event progression. Such events may include breakage of regulated expression of factors or growth components of their signaling path. The tyrosine phosphorylation events initiated by the receptor, cytoplasmic and nuclear kinases and regulated by phosphatases, are central to these procedures. The mutation, hyper-activation, translocation and overexpression of tyrosine kinase protein are all associated with tumorigenesis. Certain compounds have been shown to be tyrosine kinase inhibitors. Due to their ability to inhibit tyrosine phosphorylation, these compounds can alter cellular responses, which include unregulated proliferation by growth factors or other procedures associated with tyrosine kinase activity. Inhibition of tyrosine kinase associated with signaling pathways associated with proliferative disorders, may be sufficient to interrupt a cancer cell from a proliferative cell cycle in programmed cell death, or apoptosis.

Selective inhibition of specific tyrosine kinase offers a method to treat cancer cell growth with a high degree of specificity and minimal toxicity for normal cells. Thus, specific tyrosine kinase inhibitors have greater potential as clinical anti-carcinogenic treatments. Inhibition of tyrosine kinase offers a mechanism by which cell proliferation can be inhibited. One skilled in the art will appreciate that other mechanisms of inhibition may also be involved. There is a need in the art to identify compounds that inhibit cell proliferation.

Health Risks by Ionizing Radiation Ionizing radiation has an adverse effect on cells and tissues, mainly through cytotoxic effects. In humans, exposure to ionizing radiation occurs mainly through therapeutic techniques (such as anticancer radiotherapy) or through occupational and environmental exposure.

Radiation Therapeutic Administration A major source of exposure to ionizing radiation is the administration of therapeutic radiation in the treatment of cancer or other proliferative disorders. Depending on the course of treatment prescribed by the treating physician, multiple doses may be received by an individual over the course of several weeks to several months. Therapeutic radiation is generally applied to a defined area of the individual's body which contains abnormal proliferative tissue, to maximize the dose absorbed by the abnormal tissue and to minimize the dose absorbed by the closest normal tissue. However, it is difficult (if not impossible) to selectively administer the therapeutic ionizing radiation to the abnormal tissue. Thus, normal tissue near the abnormal tissue is also exposed to potentially harmful doses of ionizing radiation throughout the course of treatment. There are also some treatments that require exposure of the individual's entire body to radiation, in a procedure called "total body irradiation," or "TBI." The effectiveness of radiotherapy techniques in destroying abnormal proliferative cells is therefore balanced by associated cytotoxic effects in closer normal cells. Because of this, radiotherapy techniques have an inherently narrow therapeutic index which results in inadequate treatment of more tumors. Even the best radiotherapeutic techniques can result in incomplete tumor reduction, tumor recurrence, increased tumor burden and induction of radiation-resistant tumors. Numerous methods have been designed to reduce the injury of normal tissue while still providing the effective therapeutic doses of ionizing radiation. These techniques include brachytherapy, fractionated and hyperfractionated dosing, complicated dose scheduling and delivery systems, in high voltage therapy with a linear accelerator. However, such techniques only attempt to direct a balance between the therapeutic and undesirable effects of radiation, and full efficacy has not been achieved. For example, a treatment for individuals with metastatic tumors does not collect their haematopoietic stem cells and then treat the individual with high doses of ionizing radiation. This treatment is designed to destroy the individual's tumor cells, but it has side effects of also destroying their normal hematopoietic cells. Thus, a portion of the individual's bone marrow (which contains the haematopoietic stem cells) is removed before radiation therapy. Once the individual has been treated, the autologous hematopoietic stem cells are returned to their body. However, if the tumor cells have metastasized away from the primary tumor site, there is a high probability that some tumor cells may contaminate the hematopoietic cell population collected. The hematopoietic cell population collected may also contain neoplastic cells if the subject suffers from bone marrow cancers such as the various French-American-British (FAB) subtypes of acute myelogenous leukemia (AML), chronic myelodontic leukemia (CML) or lymphocytic leukemia. acute (ALL). Thus, metastasized tumor cells or resident neoplastic cells can be removed or eliminated before reintroduction of the stem cells to the individual. If some of the living tumorigenic or neoplastic cells are reintroduced into the individual, they can lead to a relapse. Methods of the prior art for removing tumorigenic or neoplastic cells from the bone marrow collected, are based on a strategy of separation or elimination of tumor cells from the entire population, which typically does not eliminate or remove all contaminating malignant cells. Such methods include leukopheresis of mobilized peripheral blood cells, selection and elimination based on immunoaffinity of tumor cells, or the use of cytotoxic or photosensitizing agents to selectively eliminate tumor cells. In the best case, the malignant cell burden may still be 1 to 10 tumor cells per 100000 cells present in the initial collection (Lazarus et al., J. of Hematotherapy, 2 (4): 457-66, 1993) . Thus, there is a need for a purging method designed to selectively destroy the malignant cells present in the bone marrow, while preserving the normal hematopoietic stem cells necessary for hematopoietic reconstitution in the transplant subject.

Occupational / Environmental Radiation Exposure Exposure to ionizing radiation can also occur in the occupational situation. Occupational doses of ionizing radiation can be received by a person whose role involves exposure (or potential exposure) to radiation, for example in the nuclear power and nuclear weapons industries. Military personnel located on ships propelled by nuclear reactors, or soldiers required to operate in areas contaminated by radioactive fallout, have a similar risk of exposure to ionizing radiation. Occupational exposure can occur in rescue calls and personal emergencies that operate with catastrophic events that involve a nuclear reactor or radioactive material. Other sources of occupational exposure can be from machine parts, plastics and solvents left by the manufacturer of radioactive medical products, smoke alarms, emergency signals and other consumer goods. Occupational exposure can also occur in person which you serve on nuclear-powered ships, particularly those that monitor nuclear reactors, on military personnel operating in areas contaminated by nuclear weapons precipitation, and on personal emergency operating with nuclear accidents. Environmental exposure to ionizing radiation can also result from detonations of nuclear weapons (either experimental or during wartime), actinide discharges from nuclear waste storage and processing and reprocessing of nuclear fuel, and from radioactive materials that originate from natural gas such as radon or uranium. There is also increased interest, that the use of artillery containing depleted uranium results in low level radioactive contamination of combat areas. Exposure to radiation from any source can be classified as acute (a single long exposure) or chronic (a series of small low level exposures or continuous low level exposures lasting for a while). Radiation diseases generally result from an acute exposure of an efficient dose, and present with a series of characteristics of symptoms that appear in an orderly manner, including hair loss, weakness, vomiting, diarrhea, skin burns and bleeding of the skin. gastrointestinal tract and mucous membranes. Genetic defects and cancers (particularly, bone marrow cancer) often develop after a while. Chronic exposure is usually associated with delayed medical problems such as cancer and premature aging. An acute or total body exposure of 125,000 millirem can cause radiation diseases. Localized doses as used in radiation therapy can not cause radiation diseases, but can result in the injury or death of exposed normal cells. For example, a dose of acute total body radiation of 100000 - 125000 millirem (equivalent to 1 Gy) received in less than a week may result in observable physiological effects such as burn or skin eruptions, mucosal bleeding and Gl, nausea , diarrhea and / or excessive fatigue. Long-term cytotoxic and genetic effects such as hematopoietic cell and immune component destruction, hair loss (alopecia), oral and gastrointestinal mucosal detachment, veno-occlusive liver disease and chronic vascular hyperplasia of the cerebral cavity, cataracts, pneumonites, changes in the skin and an increased incident of cancer, may also manifest itself after a while.

Acute doses of less than 10,000 millirem (equivalent to 0.1 Gy) will typically not result in immediately observable biological or physiological effects, although long-term cytotoxic or genetic effects may occur. A sufficiently long acute dose of ionizing radiation, for example 500,000 to over 1 million millirem (equivalent to 5 - 10 Gy), can kill an individual immediately. Doses in the hundreds of thousands of millirems can kill within 7 to 21 days, of a condition called "acute radiation poisoning". According to reports, some of the Chernobyl firefighters died of acute radiation poisoning, having received acute doses on the scale of 200,000 - 600,000 millirem (equivalent to 2 -6 Gy). Acute doses below approximately 200,000 millirems do not result in death, but the exposed individual will likely suffer long-term cytotoxic or genetic effects as discussed above. Acute occupational exposures usually occur in. workers in nuclear power plants exposed to accidental release of radiation, or in firefighters and rescue personnel and who respond to catastrophic events involving nuclear reactors or other sources of radioactive material. The suggested limits for acute occupational exposures in emergency situations were developed by Brookhaven National Laboratories, and are given in Table 1.

TABLE 1 * 100000 millirem equal to a sievert (Sv). For penetrating radiation such as gamma radiation, a Sv equal to approximately one Gray (Gy). Thus, the dosage in Gy can be estimated as 1 Gy for every 100,000 millirem.

A dose is a dose of radiation that is increased or is continued at a low level (ie, 100 - 5000 milliem) received for a time. Examples of chronic doses include a full body dose of ~ 5000 millirem per year, which is the dose typically received by an adult working at a nuclear power plant. On the contrary, the Atomic Energy Commission recommends that members of the general public should not receive more than 100 millirems per year. Chronic doses can cause long-term cytotoxic and genetic effects, for example, that manifest as an increased risk of cancer induced by radiation developed later in life. The recommended limits for chronic exposure to ionizing radiation are given in Table 2.

TABLE 2 By comparison, Table 3 shows the radiation dose from common sources.

TABLE 3 Chronic doses greater than 5000 millirem per year (0.05 Gy per year) may result in long-term cytotoxic or genetic effects similar to those described by people receiving acute doses. Some cytotoxic or genetic adverse effects may also originate in chronic doses significantly less than 5000 millirem per year. For purposes of radiation protection, it is assumed that any dose over zero may increase the risk of cancer induced by radiation (ie, there is no threshold). Epidemiological studies have found that the estimated lifetime risk of death from cancer is greater than approximately 0.04% per rem dose of radiation to the whole body. While anti-radiation suits or other protective equipment can be effective in reducing exposure to radiation, such equipment is expensive, bulky and generally not available to the public. However, protective equipment will not protect normal tissue adjacent to a tumor from exposure to deviated radiation during radiation therapy. What is needed, therefore, is a practical way to protect individuals who are scheduled to incur, or are at risk of incurring, ionizing radiation exposure. In the context of therapeutic radiation, it is desired to improve the protection of normal cells while causing the tumor cells to remain vulnerable to the harmful effects of radiation. In addition, it is desired to provide a systermic protection for anticipated or inadvertent total body irradiation, such as may occur with occupational or environmental exposures, or with certain therapeutic techniques. Pharmaceutical radioprotectors offer a cost-efficient, effective and easily available alternative to radioprotective equipment. However, previous efforts in radioprotection of normal cells with pharmaceutical compositions have not been completely successful. For example, cytosines directed to peripheral blood progenitor cells confer a myeloprotective effect when administered before radiation (Neta et al., Semin. Radiat, Oncol 6: 306-320, 1996), but do not confer protection systemic Other chemical radioprotectors administered alone or in combination with biological response modifiers have shown less protective effects in mice, but the application of these compounds to large mammals is less successful, and it is questioned whether chemical radioprotection is of any value (Maisin, JR , Bacq and Alexander Award Lecture. "Chemical radioprotection: past; present and future prospects", Int J. Radiat Biol. 73: 443-50, 1998). Pharmaceutical radiation synthesizers, which are known to preferentially improve the effects of radiation on cancerous tissues, are clearly unsuitable for the general systemic protection of normal tissues from exposure to ionizing radiation. What is needed are therapeutic agents to protect individuals who have incurred, or are at risk of incurring exposure to ionizing radiation. In the context of therapeutic irradiation, it is desired to improve the protection of normal cells while causing the tumor cells to remain vulnerable to the harmful effects of radiation. In addition, it is desired to provide systemic protection of anticipated or inadvertent total body irradiation, such as may occur with occupational or environmental exposures, or with certain therapeutic techniques.

Protection of Toxic Side Effects of Experimental Chemotherapy Experimental chemotherapy has been the mainstay of treatment offered to patients diagnosed with advanced cancers capable of being surgically removed, or cancers immune to standard chemotherapy and radiation therapy. Of the most effective classes of drugs, the healing properties are still limited. This is due to its relatively narrow therapeutic index, restricted dosage, delayed treatments and a relatively large proportion of only partial tumor reductions. This state is usually followed by reoccurrence, increased tumor limit, and drug resistant tumors.

A. Mitotic cell phase inhibitors Mitotic cell phase inhibitors constitute a class of chemotherapeutic compounds used in cancer therapy. The usual description of the cell cycle describes the cycle in terms of a series of phases - interfaces and M phase (mitotic) - and the interface subdivision into the times when the DNA synthesis is performed, known as the S phase (for phase synthesis), and the openings that separate the S phase from the mitosls. G1 is the opening after mitosis but before initiating DNA synthesis, and G2 is the opening after the DNA synthesis is complete before mitosis and cell division. The interface is thus composed of successive phases G1, S and G2, and normally comprises 90% or more of the total cell cycle time. The M phase consists of nuclear division (mltosis) and cytoplasmic division (cytokinesis). During the early part of the M phase, the replicated chromosomes condense from their prolonged interphase condition. The nuclear envelope is broken, and each chromosome undergoes movements that result in the separation of pairs of sister chromatids as the nuclear contents are divided. Then two new nuclear envelopes are formed, and the cytoplasm divides to generate two daughter cells, each with a single nucleus. This procedure of cytokinesis ends the M phase and marks the beginning of the interphase of the next cell cycle. The daughter cells that result from the termination of the M phase start the interface of a new cycle. A mitotic phase cell cycle inhibitor is a chemical agent whose mechanism of action includes the inhibition of a cellular passage through any portion of the M phase of the cell cycle.

B. Topoisomerase Inhibitors A topoisomerase inhibitor is a chemical agent whose mechanism of action includes interfering with the function of a topoisomerase. Topoisomerases constitute a group of enzymes that catalyze the conversion of DNA from one topological form to another, introducing temporal breaks in one or both strands of a DNA duplex. Topological isomers are molecules that differ only from their supercoiling state. Topoisomerases serve to relieve torsional stress during replication and transcription. They can alter the DNA structure, but not the sequence. Three different types of topoisomerases have been reported in humans. They are topoisomerase I (monomer 91 kDa), and topoisomerase II, which are also subclassified as lla (dimer 170 kDa) and llβ (dimer 180 kDa). The different differential types are encoded by genes on separate chromosomes. The simplest organisms possess only topoisomerase I; however, higher organisms have all three types of iopoisomerases. As long as the iopoisomerase is present in all eukaryotes, it is present only in vertebrates and seems to be more closely associated with cell differentiation than with proliferation. Ilpoisomerase llß seems to be very homologous to the lipo. The iopoisomerases acíúan caíalizando breaking reactions and again union in the structure of fosfodiésíer of DNA molecules. Ipopoesomerase I reversibly unfolds a single strand into the duplex DNA molecule, while iopoisomerase II breaks and unites both strands of DNA again. These reactions are thought to proceed via femmediary reaction mediators, known as "split complexes," where enzymes (or enzyme subunits) form covalenid bonds that involve an inosine and the phosphodiester linkage unfolded from the DNA subsystem. In recent years, iopoisomerases have become important chemo-therapeutic targets for cancer eradication. Campy2ecine and its derivatives are reported to be specific to the level of lopoisomerase I - DNA complexes and to minimize the DNA unfolding. Agents, such as β-lapacona, act by blocking the formation of topoisomerase I - DNA complex. Several new compounds have been developed that may be objecive, be it isoforms of iopoisomerase I or lo-isomerase lla- / llß, or the three types of topoisomerases. The inhibition of topoisomerase II is considered to be more stimulated due to the complexity of interactions. Most inhibitors of iopoisomerase II block the ligation pathway, which leads to stabilized "split complexes" between DNA and the enzyme. Most inhibitors work by coupling in the active site of the enzyme or near the allogeneic site to block the reaction of normal subsidence. Inhibition of lopoisomerase 11 involves two pairs: the aromatic part of the inhibitor molecule is intercalated between the base pairs of DNA and another more polar portion in line with lopoisomerase. Due to topoisomerase inhibitors (eg, doxorubicin and etoposide), they act as poisons preferably as classic competitive inhibitors, their action depends on the level of the enzyme in cells. The cells rapidly proliferate, which contain relatively high levels of iopoisomerase II, seem to be more sensitive to these organisms. On the other hand, the differentiated cells have relativly low levels of iopoisomerase II and are much more resistant to the action of these inhibitors.

C. Agencies Croproviders A number of research agencies have been proposed to improve the epidemiological index of anticancer drugs. For methotrexan toxicity, agents include asparginase, leucovorus factor, thymidine, and carbipepidase. Due to the excessive use of anticyclics, specific and non-specific cyto-molecular agents have been proposed, which have degrees of efficacy; corticosteroids, desrazoxane and silaurosporin are included. The last one is of inferes because it includes a G1 / S resiiction block in normal cells. (Chen et al., Proc AACR 39: 4436A, 1998). The cisplaíino is widely used and has a small therapeutic index which has stimulated research and search for cylindro-segreces. List the cycloprotectors for cisplatin with clinical poíencials esíán, mesna, gluíaíiona, íiosulfaío of sodium and amiphosíina (Griggs, Leuk, Res. 22 Suppl 1: S27-33, 1998; Lisí et al., Semin. Oncol. 23 (4 suppl 8 ): 58-63, 1996, Taylor et al., Eur. J. Cancer 33 (10): 1693-8, 1997). None of the other proposed substances, such as oxic acid for fluoropyrimidine toxicity, or prosapide for PC12 pacliaxel cell toxicity, seem to function by a mechanism which gives cells of normal replication in a high quiescent state. What are needed are new efficient molecular agents that are effective on animals, including humans prolegged from the cyto-toxic effects of chemo-therapist agencies.

Definitions General The term "individual" or "subject" includes humans and non-human animals. With respect to the methods of radioprojection and described above, these terms refer, unless the context indicates in another way, to an organism that is programmed to incur, is at risk of incurring, or has incurred, radiation exposure. Ionizing or exposure to one or more cytoioxic chemo-therapeutic agents. The term "effective quality" when used to describe therapy for patients suffering from a proliferative frasiorno, refers to the canineity of a compound according to Formula I, of a conjugate according to Formula l-Ab, which inhibits the growth of tumor cells or alternatively induces apoplasis of cancer cells, preferably blood cells, resulting in a selective and selective epidural effect in proloplasty cells when administered to a patient suffering from a cancer or other disease which manifests abnormal cell proliferation. The term "effective canine" is inclusive of canines of a compound of the invention that can be metabolized to an acidic metabolism in an amount that inhibits the growth of tissue cells or induces apoptosis of cancer cells. The term "antibody" as used herein, refers to a long-term immunoglobulin complex, or to an immunologically active portion of a long-term immunoglobulin complex, i.e., a molecule that contains a site that binds the antigen which is not specifically identified. it binds an antigen of an object of interest, that is, cells that proliferate abnormally, particularly cancer cells. The antibody can be of any type, for example, IgG, IgE, IgM, IgD, IgA or IgY; of any kind, for example, IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2 or immunoglobulin subclass. The antibody can be derived from any species. Preferably, the antibody is human or murine, more preferably human. Antibodies can include antibody fragments, single chain, chimeric, humanized, human, bispecific, monoclonal, polyclonal antibodies, eg, Fab, F (ab '), F (ab) 2, and fragments produced by an expression library. Fab. The term "humanized antibody" refers to a microorganism derived from its immunoglobulin-derived regions of complementarity (CDR's) derived from non-human species, and the rest of the antibody molecule derived from a human immunoglobulin. The term "chimeric antibody" refers to a monoclonal antibody comprising a variable region, i.e., region of attachment, of a source or species and at least a portion of a region derived from a different source or species. The term "humanized chimeric antibody" means a chimeric antibody, in which at least the human region is derived from human.

The term "monospecific polyclonal antibody" means an antibody preparation comprising multiple species of ananthibody that have specificity for an animal. The term "proliferative írasíorno" means an írasíorno where the cells are elaborated by the body to a rate aíípicamente accelerated.

Radioprotection As used herein, "ionizing radiation" is radiation of sufficient energy which, when absorbed by cells and tissues, induces the formation of reactive oxygen species and DNA damage. This type of radiation includes X-rays, gamma rays, and particle bombardment (eg, neutron beam, electron beam, protons, mesons, and others), and is used for medical testing and traceability, scientific purposes, industrial testing, manufacturing, and sterilization, weapons and weapons development and many other uses. Radiation is typically measured in units of absorbed doses, such as rad or gray (Gy), where 1 rad = 0.01 Gy, or in units of dose equivalence, such as rem or sievert (Sv), where 1 rem = 0.01 Sv. The Sv is the Gy dose multiplied by a factor that includes the lesion made in ilex. For example, ionizing radiation (eg, gamma and bela radiation) have a factor of about 1, so 1 Sv = ~ 7 Gy. Alpha rays have a factor of 20, so that 1 Gy of alpha radiation = 20 Sv. By "effective ionizing radiation" means a canon of effective ionizing radiation in the destruction, or in the reduction of proliferation, of cells that they proliferate abnormally in an individual. As used with respect to bone marrow clearance, "effective amount of ionizing radiation" means a quantity of effective ionizing radiation in the desirucción, or in the reduction of the proliferation of malignant cells in a sample of bone marrow removed from an individual. By "acute exposure to ionizing radiation" or "acute dose of ionizing radiation", it means a dose of ionizing radiation absorbed by an individual in less than 24 hours. The acute dose can be localized as in radiotherapy techniques, or it can be absorbed by the body's complement of the individual. Acute doses are typically above 10000 millirem (0.1 Gy), but may be lower. "Chronic exposure to ionizing radiation" or "chronic dose of ionizing radiation" means a dose of ionizing radiation absorbed by an individual during a period of time greater than 24 hours. The dose may be intermittent or continuous, and may be localized or absorbed by the entire body of the individual. The chronic doses are typically less than 10,000 millirem (0.1 Gy), but may be higher. By "at risk of exposure to ionizing radiation," it means that an individual may initially, for example, through scheduled radiotherapy sessions, or inadvertently, be exposed to ionizing radiation in the future. Inadvertent exposure includes accidental or occupational exposure or ambidential exposure. By "effective amount" of a radioprolectronic compound "means a compound quantity according to Formula 1, effective to reduce or eliminate the toxicity associated with radiation in normal cells of the individual, and also to impart a direct cyto-toxic effect to cells that promote Abnormally in the individual As used with respect to purging the bone marrow, "effective toxicity" of the radioprobe compound according to Formula I means an effective compounding to reduce or eliminate the toxicity associated with radiation in the removed bone marrow. of an individual, and also impart a cytotoxic effect to malignant cells in the bone marrow, removed from the individual.

Cytoprojection By "myofovic phase cell cycle inhibitor" means a chemical agent whose mechanism of action includes inhibition of a cell passage through any portion of the mitotic phase (M) of the cell cycle. By "effective amount" of a mifotic phase cell inhibitor or topoisomerase inhibitor means a certain amount of said effective inhibitor in the elimination or reduction of the proliferation of cancer cells in a host animal. By "effective amount" of the cyclopropyl compound according to Formula I means a quantity of effective compound to reduce the toxicity of the cell cycle inhibitor of mitogenic phase or topoisomerase inhibitor in normal cells of the animal. The term "cell cycle" refers to the usual description of cell development in terms of a cycle consisting of a series of phases -inferial phase M (mitotic) and the subdivision of the inferred phase at the time when the synthesis of DNA performed, known as the S phase (for synthesis phase), and the openings that separate the S phase from mitosis. G1 is the opening after miyosis but before starting the synthesis of DNA, and G2 is the opening after the synthesis of DNA anis of mitosis and cell division was completed. The interface consists of successive phases G1, s and G2, and normally comprises 90% or more of the time of the cellular cycle. The M phase consists of nuclear division (mitosis) and cytoplasmic division (cytokinesis). During the early part of the M phase, the replicated chromosomes condense from their prolonged in? Ampere condition. The nuclear envelop is broken, and each chromosome is subjected to movements that result in the separation of pairs of chromaid brothers as the nuclear contents are divided. Then two new nuclear envelopes are formed and the cytoplasm is divided to generate two daughter cells, each with a unique nucleus. This procedure of cyclokinesis ends the M phase and marks the beginning of the in? Uephase of the next cell cycle. The daughter cells of the termination of the M phase initiate the inception of a new cycle. By "iopoisomerase" it means an enzyme that catalyzes the conversion of DNA from one lopological form to another, introducing temporary breaks in one or both strands of a DNA complex. By "inhibitor of iopoisomerase" means a chemical agent whose mechanism of action includes interfering with the function of a fopoisomerase. "Iopological isomers" are molecules that differ only in their supercoiling state. Ipopoeomerase I cleaves a strand of DNA and relaxes the supercoiled negaíivamenie DNA, but does not aclúa in posiíivamenle DNA coiled. Ipoolsomerases lipo II cut both strands of DNA and increase the degree of negative supercoiling in DNA.

Chemistry The term "alkyl", by itself or as part of another subsystem, for example, alkoxy, haloalkyl or aminoalkyl, means, unless otherwise stated, a saturated hydrocarbon radical having the number of carbon atoms designated (ie, CrC6 means one, two, irides, quart, five or six carbons) and includes cyclic or polycyclic groups, straight chain, branched. Examples include: meilyl, efyl, propyl, isopropyl, buyl, isobuyl, érc-bufyl, pentiol, neopenilyl, hexyl, cyclohexyl, norbomyl and cyclopropylmethyl. Preferred alkyl groups are (CrC6) alkyl. More (C 1 -C 3) alkyl is preferred, particularly ethylene, mephyl or isopropyl. "Alkylated alkyl" means alkyl, as defined above, subsituted by one, two or three, preferably independently selected from the group consisting of halogen, -OH, -O-alkyl of (C-rC ^, -NH2, -N (CH3 ) 2, -C02H, -C02alkullo of (CC ^, -CF3, -CONH2, -S02NH2, -C (= NH) NH2, -CN, and -N02 More preferably, the substituted alkyl contains one or two substituents independently selected from halogen, -OH, -NH2, -N (CH3) 2, urea fluoride and -C02H, more preferably, independently selected from halogen and -OH Examples of solid alkyls include, but not limited to, 2,2-difluoropropyl, -carboxyclopenyl and 3-chloropropyl The term "alkylene", by itself or as part of other substitutions, means, unless it is declared in one form, a straight, branched or cyclic hydrocarbon radical having the designated number of A suspension of another group or alkylene may be at any suitable carbon, that is, the expression -C (= 0) (Cr C4 alkylene) RW may include, for example: The term "alkoxy" used alone or in combination with other terms means, unless otherwise stated, an alkyl group having the designated number of carbon atoms, as defined above, connected to the rest of the molecule via a oxygen atom, eg as, for example, meioxy, eioxy, 1 -propoxy, 2-propoxy (isopropoxy) and homologues and higher isomers. Preferred are (C 1 -C 3) alkoxy, particularly ethoxy and methoxy.

The term "amine" or "amino" refers to radicals of the general formula -NRR ', wherein R and R' are independently selected from hydrogen or a hydrocarbyl radical, or wherein R and R 'combined form a heterocycle. Examples of amino groups include: -NH2, methyl amino, diethyl amino, anilino, benzyl amino, piperidinyl, piperazinyl and indolinyl. The term "aqueous base", as used for a hydrolysis reaction, refers to a base contained in a solvency medium which may be water or may be a mixture of water and at least one organic solvent misdible in water such as, for example, methanol, propanol or telrahydrofuran. The term "aromatic" refers to a carbocycle or heterocycle having one or more polyunsaturated rings that have delocalized aromatic (4n + 2) p (pi) elecigrees). The term "aryl" used alone or in combination with other terms means, unless otherwise stated, a carbocyclic aromatic system containing one or more rings (typically one, two or three rings) in which the rings may extend. joined together in a pending manner, such as a biphenyl, or they may be fused, such as naphthalene. Examples include: phenyl; anthracyl; and naphthyl. Phenyl and naphthyl are preferred, more phenyl is preferred. The term "(C 1 -C 3) arylalkyl means a radical wherein one or more alkylene carbon chains are attached to an aryl group, for example, -CH 2 CH 2 -phenyl." - (CH 2) aryl and - (CH (CH 3) are preferred. ) "aryl" The term "arylalkyl of (C1-C3) susyiluido" means an arylalkyl radical of (Cp C3) in which the aryl group is susphiuido.It is preferred - (CH2) aryl susíiluido.Similarly, the term "heteroarylalkyl" (C1-C3) "means a radical wherein one to three carbon alkene chains bind to a heteroaryl group, for example, -CH2CH2-pyridyl. Preferred - (CH2) heteroaryl. The term "heteroaryl-substituted (C1-C3) alkyl" means a heteroarylalkyl radical of (C1-C3) in which the heteroaryl group is substituted. Preferred - (CH2) substituted heteroaryl. The term "arylene", by itself or as part of another subscript, means, unless it is declared in a different form, a radical aryl divalent. Divalent phenyl radicals, particularly 1,4-divalent phenyl radicals, are preferred. The term "cycloalkyl" refers to alkyl radicals that contain a ring. Examples include cyclohexyl, cyclopentyl, cyclopropyl methyl and norbornyl. The term "exocyclic double bond", unless stated otherwise, refers herein to an external carbon-carbon double bond to a chemical ring structure. Especially, the expression refers to the carbon-carbon double bond in compounds of the invention, which are not contained in either the phenyl ring or the aromatic ring, Q, but rather the double bond which is alpha to the aromatic ring , Q; The terms "halo" or "halogen" by themselves or as part of another substitute, for example, haloalkyl, mean, unless stated otherwise, a fluorine, chlorine, bromine or iodine atom, preferably fluorine, chlorine or bromine, more preferably, fluorine or chlorine. The term "haloalkyl" means, unless otherwise stated, an alkyl group as defined herein which contains at least one halogen substituent and is not different from halogen. Multiple halogen substituents, for the substitution of all the hydrogens susiible in the alkyl group can be the same or differentiate. Preferred haloalkyl groups include, for example, perfluoroalkyl of (C? -C), gem-difluoroalkyl of (C C4) and chloroalkyl of (C C4). More preferred haloalkyl groups include, for example, -CF3, -C2F5, -CH2F3, -CHF2, -CF2CH3 and -CH2CI. The term "heyeroalkullo" by itself or in combination with another term, means, unless stated otherwise, a stable straight or branched chain radical consisting of the declared number of carbon atoms and one or two hetero-atoms selected from the group. A group consisting of O, N, and S, and in which sulfur can optionally be oxidized and the nitrogen heleroatomes optionally quaternized or oxidized. Oxygens bound to sulfur or oxidized nihologen may also present one or two heterogeneous in the hephenoalkyl group. Heteroazymes can be placed at any position in the heleroalkyl group, which include the heteroalkyl group and the fragment to which they are attached, to join the more dissimilar carbon atom in the heteroalkyl group. Examples include: -OH-CH2- CH2-CH3, -CH2-CH2CH2-OH, -CH2-CH2-NH-CH3, -CH2-S02-NH-CH3, -CH2-S-CH2-CH3 and -CH2CH2-S (= 0) -CH3. Up to two atoms may be consecutive, such as, for example, -CH 2 -NH-OCH 3, O -CH 2 -CH 2 -S-S-CH 3. The term "heterocycle" or "heterocyclic" or "heterocyclic" by itself or as part of other terms means, unless otherwise stated, a heterocyclic, unsubstituted or substituted, monocyclic or unsubstituted, stable, ring system. which consists of carbon atoms and at least one heteroamomyl selected from the group consisting of N, O and S, and wherein the heterohydrides of nylogen and sulfur may optionally be oxidized, and the nitrogen atom may optionally be quaternized. The heterocyclic system may be attached, unless otherwise stated, to any heterogeneous or carbon atom which provides a stable structure. The term "heeroeroil" or "heieroaromáfico" refers to a helerocycle that is aromatic carácíer. A monocyclic heyanoaryl group is a 5-, 6- or 7-membered ring, examples of which are pyrrolyl, furyl, thienyl, pyridyl, pyrimidinyl and pyrazinyl. A polycyclic heeroaryl may comprise multiple aromatic rings or may include one or more rings which are partially unsaturated. Examples of polycyclic heteroaryl groups that contain a partially saturated ring include tetrahydroquinolyl and 2,3-dihydrobenzofuryl. For compounds of Formula I, the point of attachment in the Q ring will be understood to be in an atom which is part of an aromatic monocyclic ring or a ring component of a polycyclic aromatic which is an aromatic ring. The point of attachment or ring Q may be a carbon ring or a nitrogen ring and includes binding to form aromatic quaternary ammonium salts such as pyridinium. Examples of non-aromatic heterocycles include monocyclic groups such as aziridine, oxirane, thiirane, azetidine, oxetane, manganese, pyrrolidine, pyrrolin, imidazoline, plrazolidine, dioxolane, sulfolane, 2,3-dihydrofuran, 2,5-dihydrofuran, hydro-hydrofuran, lycopene , piperidine, 1, 2,3,6-eeryhydropyridine, 1,4-dihydropyridine, piperazine, morpholine, iomorpholine, pyran, 2,3-dihydropyran, hydro-pyridine, 1,4-dioxane, 1,3-dioxane, homopiperizine, homopiperidine, 1,3-dioxepane, 4,7-dihydro-1,3-dioxepine and hexamethylene oxide. Examples of heteroaryl groups include: pyridyl, pyrazinyl, pyrimidinyl, particularly 2- and 4-pyrimidyl, pyridazinyl, thienyl, furyl, pyrrolyl, particularly 2-pyrrolyl, imldazolyl, thiazolyl, oxazole, pyrazolyl, particularly 3- and 5-pyrazolyl, isothiazollol, 1,2,3-triazolyl, 1,4-2,4-triazolyl, 1,4-triazolyl, 1,4-triazolyl, 1,4-triazolyl, 1,4-triazolyl, 1,4-triazolyl, 1,4-triazolyl, 1,4-triazolyl, 1,2,4-triazolyl, 1,4-triazolyl, 1,2,4-triazolyl, 1,4-triazolyl, 1,2,4-triazolyl Iiadiazolyl and 1,4-oxadiazollol. Examples of polycyclic compounds include indolyl, particularly 3-, 4-, 5-, 6- and 7-indolyl, indolinyl, quinolyl, telrahydroquinolyl, isoquinolyl, particularly 1- and 5-isoquinolyl, 1,2,4,4-eeryhydroisoquinolyl. , cinnolinyl, quinoxalinyl, particularly 2- and 5-quinoxalinyl, quinazolinyl, phthalazinyl, 1,8-naphthyridinyl, 1,4-benzodioxanyl, coumarin, dihydrocoumarin, benzofuryl, particularly 3-, 4-, 1,5-naphthyridinyl, 5- , 6- and 7-benzofuryl, 2,3-dihydrobenzofuryl, 1,2-benzisoxazolyl, benzothienyl, particularly 3-, 4-, 5-, 6-, and 7-benzothienyl, benzoxazolyl, benzothiazolyl, particularly 2-benzoiazolyl and benzoliazolyl, purinyl, benzimidazolyl, in particular 2-benzimidazolyl, benzolriazolyl, thioxanthinyl, carbazolyl, carbolinyl, acridinyl, pyrrolizidinyl, and quinolizidinyl. The term "heteroarylene" by itself or as part of another substitution means, unless it is declared in a different form, a divalent heteroaryl radical. Five- or six-membered monocyclic heteroarylene is preferred. More preferred are portions comprising divalent heteroaryl rings selected from pyridine, piperazine, pyrimidine, pyrazine, furan, thiophene, pyrrole, thiazole, imidazole and oxazole. For compounds of Formula I, when an aromatic or heleroaromatic ring is attached to a position and the ring comprises a polycyclic ring which is partially unsaturated, the point of attachment on the aromatic or heteroaromatic ring is on a ring atom of a component of aromatic ring of the polycyclic ring. For example, in the partially sacralized heteroaromatic ring, 1, 2,3,4-leihydroisoquinoline, the binding points are at the ring atoms in positions 5-6-, 7-, and 8. The aforementioned list of of heterocyclic and heteroaryl is intended to be representative, not limiting. The term "hydrocarbon" refers to any portion that comprises only hydrogen and carbon atoms. Preferred hydrocarbyl groups are hydrocarbyl of (C -C- | 2), more preferred are hydrocarbyl of (C? -C7), very preferred are benzyl and alkyl of (CrC6). The term "hydrocarbylene" by itself or as part of another substitute means, unless otherwise indicated, a divalent moiety comprising only hydrogen and carbon atoms. A substitution of another group on hydrocarbylene may be on any substitutable carbon, that is, the expression - (hydrocarbylene of C -? - C6) Rw may include, for example: The term "terminally bound carboxy peptidyl residue" refers to a peptide radical such as a sustiluyenle in a mule of Formula I. The radical is attached to the carboxy functionality of a peptidyl residue to form a carboxamide, carboxylic ester or sulfide of acyl (-SC (= 0) -). Reaction Scheme 1 illustrates how an exemplary peptidyl residue can be carboxyl-linked as a subsitute in a compound according to Formula I.

REACTION SCHEME 1 Terminally bound peptidyl carboxy residue Peptidyl residue The amino acid residues comprising the terminally linked peptidyl carboxy residue may comprise natural or unnatural amino acids or a combination thereof. The non-natural amino acids are amino acids different from the twenty essential amino acids. An example of an unnatural amino acid is a D-amino acid, that is, an amino acid having an opposite stereochemistry, the stereochemistry of natural L-amino acids. Another example of a non-natural amino acid is an amino acid having a side chain that differs from the side chains that originate from natural amino acids, for example a-etll glycine or a-phenyl glycine. A third example is an amino acid that has a structure variation. Examples of amino acid structure variations include ß-alanine mimetics and ß-alanine mimics such as Freidinger's lama. See Freidinger et al., Science, 1980, 210, 656, the full description which is incorporated herein by reference. A fourth example of a non-naive amino acid is an amino acid which has two α-amino acids, for example, a, α-dimethylsulin. The amino termini of the bonded carboxy residue can be an amino group unsubstituted, or it can be substituted.

Substitutions in the amino termini include mono- and di- (Ci-Cß alkyl), - C (= 0) (Ci-Cß alkyl), -C (= 0) 0 (hydrocarbyl (C C7)) and commonly employed protective groups of iohols such as urea-buoxycarbonyl (BOC), carbobenxyloxy (CBZ), 2,4-dimethioxybenzyl and fluorenylmethoxycarbonyl (FMOC). The term "amino-linked amino-peplidyl residue" refers to a peptide moiety as a substituent in a compound according to Formula I. The moiety is linked to the amino-terminal functionality of the peptidyl residue to form a carboxamide, sulfonamide, urea or thiourea. The reaction scheme 2 illustrates how an exemplary peptidyl residue can be amino-terminally linked as a substituent in a compound according to Formula I.

REACTION SCHEME 2 The carboxy terms of the amino-terminally-linked petridyl residue can be a free carboxyl group or a salt thereof, or they can be derivatized as an ester or amide. Suitable esters include alkyl, preferably alkyl of (CrC6); and arylalkyl, preferably benzyl esters. Suitable amides include the primary and secondary amide and the tertiary amides comprising one or two substituents on the amide nitrogen independently selected from (C3) alkyl, preferably methyl or ethyl; aryl, preferably phenyl; and arylalkyl groups of (C 1 -C 3), preferably benzyl or substituted benzyl. As with the terminally linked peptidyl carboxy residues, the amino acids comprising the strictly bound amino peptidyl residue may comprise naïve or unnatural amino acids or a combination thereof. The term "perfluoroalkyl of (Cx-Cy)", wherein x < and, it means an alkyl group with a minimum of carbon atoms x and a maximum of carbon atoms and, wherein all hydrogen atoms are replaced by fluorine atoms. Preferred is perfluoroalkyl of (C Cß), more preferred is perfluoroalkyl of (C -? - C3), most preferred is -CF3. The term "fluoroalkyl of (Cx-Cy)", means an alkyl group with a minimum of carbon atoms x and a maximum of carbon atoms and, where the lower hydrogen atoms at the terminal carbon (-CH3) are replaced by fluorine atoms. Examples include -CH2CF3, - (CH2) 2-CF3 and -CH (CH3) -CF3. The term "difluoroalkyl of (Cx-Cy)" means an alkyl group with a minimum of carbon atoms x and a maximum of carbon atoms, and wherein a carbon atom is germinally substituted with two fluorine atoms. The fluorine removed carbon can be any carbon in the chain having at least two substitutable hydrogens, which include the terminal -CH3 group and the proximal carbon through which the difluoroalkyl of (C? -Cy) is attached to the remainder of the chain. the molecule. Examples include -CH2CF2H, - (CH2) 2-CF2H and -CF2-CH3 and 3,3-difluorocyclohexyl. The term "subsituted" means that one atom or group of atoms have hydrogen replaced as the substituent attached to another group. For aryl and heteroaryl groups, the term "susíifuido" refers to any level of subsumption, called mono-, di-, iri-, tetra- or penta-substitution, where it is permitted to suspend it. Substituents are selected independently, and the substitution can be in any chemically accessible position. The term "isolated optical isomer" means a compound which has been substantially purified from the corresponding optical isomer of the same formula. Preferably, the isolated isomer is at least about 80%, more preferably at least 90% pure, even more preferably at least 98% pure, most preferably at least 99% pure by weight. The denomination of compounds described in this document was done using the program of denomination of structure included in CHEMDRAW® software packages. The compounds, excepted for α-unsaturated sulfonamides, were named using the "Name for Structure" program within ChemDraw Ultra Version 8.0 (© 1985-2003, CambridgeSoft Corporation, 100 Cambridgepark Drive, Cambridge, MA 02140 USA). The structures of the α, β-unsaturated sulfonamides described in this document were named using the Nomenclature Plug-in poor ChemDraw 7.0.

BRIEF DESCRIPTION OF THE INVENTION It is an object of the invention to provide compounds, conjugates, pharmaceutical compositions and therapeutic methods. The biologically active compounds are in the form of aromatic olefins, structurally linked via an optionally substituted methylene sulfone linker, an optionally substituted methylene sulfoxide linker, and optionally N-suslyl sulfonamide linker, or an optionally substituted carboxamide linker, for a functionality of phenol or thiophenol, or a derivative of such functionality of phenol or iiophenol. It is an object of the invention to provide compounds, conjugates, compositions and methods for the treatment and / or prevention of cancer and other proliferative disorders. It is an object of the invention to provide compounds and conjugates which are selective in eliminating tumor cells at therapeutically useful concentrations. *: It is an object of the invention to provide compounds, conjugates, compositions and methods to induce neoplastic cells to selectively subject them to apoptosis.

It is an additional objection of the invention to provide compounds, conjugates, compositions and methods which are capable of prophylactic treatment of proliferative disorders. It is a further object of this invention to provide compounds, compositions and methods to protect normal cells and tissues from the cltotoxic and genital effects of exposure to ionizing radiation, in which individuals have incurred, will incur the fuluro, or are at risk of incurring exposure by ionizing radiation. Exposure to ionizing radiation can occur in controlled doses, during the treatment of cancer and other proliferative disorders. Alternately, exposure to ionizing radiation may occur in uncontrolled doses beyond the accepted norm for the population in activities of high risk or prolonged environmental exposure. It is an object of the invention to provide compounds, compositions and methods for providing individuals with the cytoxic side effects of miyotic phase cell cycle inhibitors and topoisomerase inhibitors, used in the treatment of cancer and proliferative urastoma cells. It is an object of the invention to provide a method for tracing proliferative cancers or urans which reduce or eliminate cytotoxic effects in normal cells. It is an object of the invention to improve the effects of mitochondrial phase cell cycle inhibitors and topoisomerase inhibitors, used for cancer traumatization or other proliferative disorders. It is an object of the present invention to provide a therapeutic program for treating cancer and other proliferative disorders, which include the administration of a cytoprotective compound before the administration of a chemotherapeutic agent, said cytoproleny compound induces an irreversible cyclic quiescent state in tissue without tumor . It is an object of the invention to provide a method for safely increasing the dosage of cell cycle inhibitors in the mitogenic phase and topoisomerase inhibitors used in the trafficking of cancer and proliferative cells.

I. Compounds of Conformity with Formula I In accordance with one aspect, the invention is directed to new compounds in accordance with Formula I: wherein, A is -S- or -O-; R1 is selected from the p consisting of -H; alkyl halogen of (C C6), preferably trifluoroalkyl of (C C6), difluoro alkyl (C -? - C6) and chloroalkyl of (C C6), more preferably trifluoro alkyl of (C1-C3), difluoroalkyl of (C-) C3) and chloroalkyl of (C C3), most preferably -CF3, -CHF2 and -CH2CI; -C (= 0) Rw; -S (= 0) Rw; -S02Rw; - (hydrocarbylene C C6) Rz, preferably -alkylene of (C C6) Rz, more preferably -alkylene of (C C3) -Rz; -P (= 0) (ORv) 2; -C (Ra) (Rv) -C (= 0) -Rn; substituted and unsubstituted aryl, preferably substituted and unsubstituted phenyl; substituted and unsubstituted heteroaryl, preferably substituted and unsubstituted monocyclic heteroaryl; -Yi [(CrC6) alkyl] 3, preferably, -Yi (CH3) 2-C (CH3) 3; and -CH2CH2Si [(C6) alkyl] 3, preferably -CH2CH2Si (CH3) 2-C (CH3) 3 and -CH2CH2Si (CH3) 3; each Rv is independently selected from the group consisting of -H and -hydrocarbyl of (C C7), preferably benzyl and -alkyl of (C ^ Ce), more preferably benzyl and -alkyl of (C- | -C3), most preferably -CH3 or -C2H5; Rw is selected from the group consisting of -hydrocarbyl of (C- | -C7), preferably -alkyl of (CrC6), more preferably -alkyl of (C C3), most preferably -CH3 or -C2H5; -NRV2; -ORv; halo (C1-C3 alkyl), preferably chloro (Cs alkyl) and trifluoro (CrCl alkyl); -NRvCRvRa-C (= 0) -Rn; -CRvRa-N (Rv) -Rc; substituted and unsubstituted aryl, preferably substituted and unsubstituted phenyl; (CrC3) substituted and unsubstituted arylalkyl, preferably phenylalkyl of (CrC3) substituted and unsubstituted; substituted and unsubstituted heteroaryl, preferably monocyclic and unsubstituted monocyclic heteroaryl; Substituted and unsubstituted (C C 3) heteroarylalkyl, preferably heteroarylalkyl of unsubstituted and unsubstituted monocyclic (C C 3); Substituted and unsubstituted heterocyclyl; unsubstituted and substituted (CrC3) heterocyclylalkyl; - (CrC3 alkylene) P (= 0) (ORv) 2; -perfluoroalkylene (C 1 -C 3) -N (CH 3) 2, - -alkylene (C 3) -N ((CrC 3) alkyl) 2; -alkylene of (CrC3) -N + (CrCs) 3; -alkylene of (C C3) -N + (CH2CH2OH) 3; - (C C alkylene) -C (= 0) -halogen; -perfluoroalkylene of (CrC) -C02Rv; - (CrC3 alkylene) C (= 0) ORv; and - (C C3 alkylene) OC (= 0) - (C C3 alkylene) C (= 0) Ry; Ry is selected from the group consisting of -ORv, -NRV2 and -alkyl (CI-Ce); R7 is selected from the group consisting of -C (= 0) Ry; - NRvCRvRa-C (= 0) -Rn; -NRV2; -0RV; unsubstituted and unsubstituted aryl, preferably substituted and unsubstituted phenyl; substituted and unsubstituted heteroaryl, preferably substituted and unsubstituted monocyclic heteroaryl; substituted and unsubstituted (CrC3) heterocyclylalkyl, preferably heterocyclylalkyl (CrC3) unsubstituted, more preferably heterocyclylalkyl (C1-C3) 6-substituted, most preferably piperazin-1-ylalkyl (C3) and mofolin-1- ilalqullo of (C1-C3); and -C (= 0) alkyl of (CrC3); each Ra is independently selected from the group consisting of -H; -alkyl of (CrC6); -heteroalkyl of (CrC6), particularly -CH2SH, - (CH2) 2C (= 0) -NH2, -CH2-OH, -CH (OH) -CH3, - (CH2) 4-NH2, and - (CH2) 2 -S-CH3; - (CH2) 3-NH-C (NH2) (= NH); -CH2C (= 0) NH2; -CH2COOH; - (CH2) 2COOH; substituted and unsubstituted aryl, preferably substituted and unsubstituted phenyl; substituted and unsubstituted (C C 3) arylalkyl, preferably phenylalkyl of (CrCl 3) unsubstituted and unsubstituted, more preferably unsubstituted and substituted benzyl, particularly 4-hydroxybenzyl; substituted and unsubstituted heterocyclyl, preferably substituted and unsubstituted heteroaryl, more preferably substituted and unsubstituted monocyclic heteroaryl; and (C 1 -C 3) heterocyclyl unsubstituted and unsubstituted heterocyclylalkyl (CrC 3) substituted and unsubstituted, particularly -CH 2 - (3-indolyl), more preferably heteroarylalkyl (C 1 -C 3) substituted and unsubstituted monocyclic, most preferably heteroaryl- Unsubstituted and unsubstituted monocyclic CH2, particularly -CH2-inidazolyl; each Rp is independently selected from the group consisting of -ORv, -NRV2, and an N-terminally linked peptidyl residue containing from 1 to 3 amino acids in which the terminal carboxyl group of the peptidyl residue is present as a functional group, selected from the group consisting of group consisting of -C02Rv and -C (= 0) NRv2; each Rc is independently selected from the group consisting of -H and a peptidyl carboxy-linked terminal residue containing 1 to 3 amino acids in which the terminal amino group of the peptidyl residue is present as a functional group selected from the group consisting of -NH2; -NHC (= 0) alkyl of (CrC6); -NHalkyl of (C C6); -NH (CrC6 alkyl) 2; and -NHC (= 0) Ohdrocarbon of (CrC7), preferably -NHC (= 0) Oalkyl of (C C6) and -NHC (= 0) 0-benzyl; Q is aryl or heteroaryl; each R2 and R3 is independently selected from the group consisting of halogen; -hydrocarbyl of (CrC7), preferably -alkyl of (CrC6), more preferably -alkyl of (C C3), very preferably -CH3 and -C2H5; -C (= 0) Rv; -NRV2; -NHC (= 0) Rv: -NHS02Rv; -NHRa; -NHCRvRaC (= 0) Rn; -NHS02Rv; -C (= 0) ORv; -C (= 0) NHRv; -N02; -CN; -ORv; -P (= 0) (ORv) 2; -C (= NH) NH2, dimethylamino (C2-C6 alkoxy); -NHC (= NRV) NHRV; haloalkyl of (CrCβ), preferably trifluoroalkyl of (CrCβ) and difluoroalkyl of (CrC 6), more preferably trifluoroalkyl of (CrC 3) and difluoroalkyl of (CrC 3), most preferably -CF 3 and -CHF 2; and -haloalkoxy (CrCß), preferably (C? -C6) trifluoroalkoxy and (CrC?) difiuoroalkoxy, more preferably (C3) trifluoroalkoxy and (CrC3) difluoroalkoxy, most preferably -OCFs and -OCHF2; the two groups Rv in -P (= 0) (ORv) 2 and -NR 2 may optionally together form a heterocyclic ring of five or six elements, preferably a ring of five elements, which may optionally also be fused with an aryl ring or carbocyclic, preferably an aryl ring, more preferably a phenyl ring; a is 0, 2, 2 or 3; b is 0, 1, 2 or 3; wherein the sum of a and b is preferably at least 1; the conformation of the substituents in the exocyclic carbon-carbon double bond is either E- or Z-; X is -C * H (RX) Y- or -NRX-Z-; Z is -C (= 0) - or -SO2-; Rx is selected from the group consisting of -H; -alkyl of (C C6), preferably -alkyl of (C C3), more preferably methyl and ethyl; and -C (= 0) alkyl of (CrCß), preferably -C (= 0) alkyl of (C C3), more preferably acetyl and propionyl; and * indicates that, when Rx is different from H, the conformation of the substituents at the designated carbon atom is (R) -, (S) - or any mixture of (R) - and (S) -; or a salt of such a compound, preferably a pharmaceutically acceptable salt of such a compound; provided that: (a) when A is -O- and R1 is -H: b is greater than 0; and R3 is different from alkyl of (CrC6), -OH and -N02. (b) when X is -NRX-Z- and A is -O-; Rz is different from -C (= 0) Ry, -NRV2 and aryl insustiluido; and Rw is different from -alkyl of (C Cß); and (c) when X is -C * H (RX) Y- and A is -O-: R1 is different from haloalkyl of (CrCß); Rz is different from -NRV2 and insoluble aryl; and Rw is different from -hydrocarbyl of (C C7). In accordance with one embodiment of the compounds of the invention: R1 is selected from the group consisting of -H; haloalkyl of (CrC6), preferably trifluoroalkyl of (CrC6), difluoroalkyl of (CrC6) and chloroalkyl of (CrC6), more preferably trifluoroalkyl of (CrC3), difluoro (C1-C3) alkyl and chloro (CrC3) alkyl, very preferably CF3, -CHF2 and -CH2CI; -C (= 0) Rw; -S (= 0) Rw; -S02Rw; - (CrC6 hydrocarbylene) R2, preferably -alkylene of (CrC6) Rz, more preferably - (C6C) alkyleneCORy; -P (= 0) (ORv) 2; -C (Ra) (Rv) -C (= 0) -Rn; substituted and unsubstituted aryl, preferably unsubstituted and unsubstituted phenyl; unsubstituted and unsubstituted heteroaryl, preferably monocyclic heterocyclic unsubstituted and unsubstituted; -Yi [(CrC6) alkyl] 3, preferably, -Yi (CH3) 2-C (CH3) 3; and -CH2CH2Si [(CrC6) alkyl] 3, preferably -CH2CH2Si (CH3) 2-C (CH3) 3 and -CH2CH2Si (CH3) 3; Rw is selected from the group consisting of (C C7) hydrocarbyl, preferably - (CrC6) alkyl, more preferably - (CrC3) alkyl, most preferably -CH3 or -C2H5; -NRV2; -ORv; halo (d-C3 alkyl), preferably chloro (C3 alkyl) and lrifluoro (C1-C3 alkyl); -NRvCRvRa-C (= 0) -Rn; -CRvRa-N (Rv) -Rc; substituted and unsubstituted aryl, preferably substituted and unsubstituted phenyl; substituted and unsubstituted (C C3) arylalkyl, preferably phenylalkyl of (CrC3) unsubstituted and unsubstituted; unsubstituted and unsubstituted heteroaryl, preferably substituted and unsubstituted monocyclic heteroaryl; heteroarylalkyl (CrCl3) susilided and unsubstituted, preferably heteroarylalkyl (CrCl3) monocyclic substituted and unsubstituted; substituted and unsubstituted heteroaryclic; substituted and unsubstituted (C1-C3) heterocyclylalkyl; - (C C3 alkylene) P (= 0) (ORv) 2; -perfluoroalkylene of (CrC3) -N (CH3) 2; -alkylene of (CrC3) -N + (CrC3) 3; -alkullen of (d-C3) -N + (CH2CH2OH) 3; - (C 4 C alkylene) -C (= 0) -halogen; -perfluoroalkylene of (C C4) -C02Rv; - (alkylene of d-C3) C (= 0) ORv; and - (C C3 alkylene) OC (= 0) - (C C3 alkylene) C (= 0) Ry; Rz is selected from the group consisting of -C (= 0) Ry; - NRvCRvRa-C (= 0) -Rn; -NRV2; -ORv; substituted and unsubstituted aryl, preferably substituted and unsubstituted phenyl; substituted and unsubstituted heteroaryl, preferably unsubstituted and unsubstituted monocyclic heteroaryl; and -C (= O) alkyl of (d-C3); and each Rv is independently selected from the group consisting of -H and -hydrocarbyl of (d-C7), preferably -alkyl of (d-C6), more preferably -alkyl of (d-d), most preferably -CH3 or -C2H5; and (c) when X is -C * H (RX) Y- and A is -O-; R1 is different from alkyl halo of (d-d) and unsubstituted aryl; Rz is different from -NRV2 and unsubstituted aryl; and Rw is different from -hydrocarbyl of (d-d). According to some embodiments of compounds of Formula I, Q is aryl, preferably phenyl or naphthyl, more preferably phenyl. According to other modalities of the compounds of Formula I, Q is heeroaryloyl, preferably monocyclic heleroaryl. According to some embodiments of compounds of Formula I, compounds of Formula IE are provided: wherein in the exocyclic carbon-carbon double bond is in the (E) -configuration. According to other embodiments of compounds of formula I, compounds of Formula IZ are provided: where the exocyclic carbon-carbon double bond is in the (Z) -configuration. According to some modalities of compounds of Formula I, R1 is -H. According to some embodiments of compounds of Formula I, R1 is different from H. Preferably, when one or more of Q, R1, Rw or Rz is a monocyclic heteroaryl group, the monocyclic heteroaryl group is independently selected from the group consisting of pyridyl. , pyrazinyl, pyrimidinyl, pyridazinyl, thienyl, furyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, pyrazolyl, isothiazolyl, 1,2,3-triazolyl, 1,4-triazolyl, 1,4-triazolyl, theyrazolyl, , 2,3-thiadiazolyl, 1, 2,3-oxadiazolyl, 1,4-thiadiazolyl and 1,4-oxadiazolyl. More preferably, when one or more of Q, R1, Ra, Rw or Rz is a monocyclic heeroaryl group, the monocyclic heteroaryl group is independently selected from the group consisting of pyridyl, thienyl, furyl, pyrrolyl, midazolyl, thiazolyl, oxazolyl, pyrazolyl and siatylolyl. More preferably, when one or more of Q, R1, Ra, Rw or Rz is a monocyclic heteroaryl group, the monocyclic heteroaryl group is independently selected from the group consisting of pyridyl, thienyl and furyl. Preferably, when one or more of Q, R, Ra, Rw or Rz is a heteroaryl group other than monocyclic heteroaryl group, the heleroaryl group is selected from the group consisting of indolyl, quinolyl, isoquinolyl, cinolinyl, quinoxalinyl, quinazolinyl, phthalazinyl, 1,8-naphthyridinyl, 1,4-benzodioxanyl, coumarin, benzofuryl, 1,2-benzisoxazolyl, benzoyienyl, benzoxazolyl, benzoiazolyl, purinyl, benzimidazolyl, benzolriazolyl, ioxanilinyl, carboxyl, carbolinyl, acridinyl, pyrrolizidinyl and quinolizidinyl. More preferably, when one or more Q, R1, Ra, R or Rz is a heteroaryl group differentiates the monocyclic heteroaryl group, the heteroaryl group is selected from the group consisting of indolyl, quinolyl, isoquinolyl, benzofuryl, benzothienyl, benzoxazole, benzothiazolyl and benzimidazolyl. More preferably, when one or more Q, R1, Ra, Rw or Rz is a heteroaryl group different from the monocyclic heteroaryl group, the heteroaryl group is selected from the group consisting of indolyl, quinolyl, isoquinolyl, benzofuryl and benzothienyl. Preferably, substituted aryl and heteroaryl ring in groups R1, Ra, Rw and Rz are mono-, di-, or Iri-susiloyl, more preferably mono- or di-substituted by substituents selected from the group consisting of halogen; hydrocarbyl (d-d), preferably benzyl and (d-C6) alkyl, more preferably benzyl and (d-d) alkyl, more preferably benzyl, methyl and ethyl; -NRV2; -N0; -CN; heterocyclyl, preferably N-methylpiperazinyl, morpholinyl and thiomorpholino; -ORv and -O-hydrocarbyl (d-C7), preferably -O-alkyl (d-d) and -O-benzyl, more preferably -O-alkyl (d-d), more preferably benzyl, methoxy and ethoxy. More preferably, aryl and heteroaryl rings substituted in groups R1, Ra, Rw and Rz are mono-, di- or Iri-susliuides, more preferably mono- or di-substituted by substituents selected from the group consisting of: chloro: fluoro; bromine; alkyl (d-d), preferably alkyl (d-d), more preferably methyl and ethyl; -NH2; -N02; -CN; heterocyclyl, preferably N-methylpiperazinyl, morpholinyl and liomorpholinyl; -OH; and -Oalkyl of (d-d), preferably -O-alkyl (d-d), more preferably mefoxy and ethoxy. More preferably, aryl and heleroaryl rings substituted in groups R1, Ra, Rw and Rz are mono-, di- or trisubstituted, preferably mono- or di-substituted by substituents selected from the group consisting of chloro, fluoro, bromo, meiyl. , -N02, -CN, -OH and meloxi.

Preferably, suscylidyl heterocyclic groups contained in groups Rz, Ra and Rw are mono-, di- or Iri-susiiuides, more preferably mono- or di-susitutes, by substituents selected from the group consisting of -hydrocarbyl (dd), preferably benzyl and - (dd) alkyl, more preferably methyl, ethyl and benzyl; -C (= 0) alkyl of (d-C6), preferably C (= 0) alkyl of (d-d), more preferably acelyl; and -perfluoroalkyl of (d-d), preferably -perfluoroalkyl of (d-d), more preferably -CF3. More preferably, substituted heterocyclic groups contained within groups Rz, Ra and Rw are mono- or di-substituted by substituents selected from the group consisting of (d-C6) alkyl, preferably me yl and ethyl, and -C (= 0) alkyl (dd), preferably acetyl. According to some embodiments of the invention, the sum of a and b is at least 2. In accordance with other embodiments of the invention, the sum of a and b is at least 3. In accordance with still further embodiments of the invention, the sum of a and b it is at least 4. According to some modalities of the invention, a and b are at least 1. In accordance with other embodiments of the invention, a is at least 1 and b is at least 2. In accordance with other modalities of the invention, b is at least 1 and is at least 2. In accordance with still other embodiments of the invention, both a and b are at least 2. According to preferred embodiments of the compounds of Formula I: when b is 1, the substitution of groups R3 in Q is in the ortho or para position. when b is 2, the substitution of groups R3 in Q is in either ortho and para positions, or in both ortho positions; and when b is 3, the substitution of groups R3 in Q is in the position para and in both ortho positions. Preferably, for compounds according to Formula I, Q is aryl; b is 1, 2 or 3; and each R2 is -ORv or halogen, wherein multiple groups OROR or halogens may be the same or different. More preferably, for composites in accordance with Formula I, Q is phenyl; b is 2 or 3; and each R2 is -ORv, where multiple -ORv groups can be the same or different. More preferably, each R2 is -OCHs. The compounds of the invention further comprise embodiments of Formula I, described below in Formulas II, III, IV, V and VI. It will be understood that the preferred modalities and embodiments defined above for compounds according to Formula I are also preferred embodiments and embodiments of the compounds in accordance with Formulas II, III, IV, V and VI, as described below.

II. Compounds in accordance with Formula II In accordance with one embodiment of the compounds according to Formula I, compounds according to Formula II are provided: wherein R2, R3, A, a, b, X and Q are as defined hereinabove for compounds according to Formula I; or a salt of them.

A. Compound in accordance with Formula HA In accordance with one embodiment of the compounds according to Formula II, compounds are provided in accordance with the Formula HA: wherein R2, R3, Rx, a, b, A, Y, Q and * are as defined above in this document for compounds according to Formula I, and the exocyclic carbon-carbon double bond is in (E) -conformation. In accordance with some embodiments of compounds according to the Formula HA, Rx is -H.

Preferred compounds according to the Formula HA include, for example: (E) -5 - ((2,4,6-trimethoxysilyl-sulfonyl) -methyl) -2-methoxyphenol; (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-meioxybenzenefol; (E) -5 - ((2,4,6-tri-methoxy-styrylsulfinyl) methyl) -2-melioxyphenol; (E) -5 - ((2,4,6-trimethoxy-styrylsulphonyl) -methyl) -2-methoxy-benzothiol; and you come out of them.

B. Compounds in accordance with Formula IIB In accordance with another embodiment of the comps in accordance with Formula II, compounds are provided in accordance with Formula IIB: wherein R2, R3, Rx, a, b, A, Z and Q are as defined hereinabove for compounds according to Formula I, and carbon-carbon double bond is in (E) -formation. In accordance with a preferred embodiment of compounds according to Formula IIB, Rx is -H. Preferred compounds according to Formula llb include, for example: (E) -5 - ((2,4,6-trimethoxy-styryl) sulfonamido) -2-methoxyphenol; (E) -5 - ((2,4,6-trimethoxystyryl) sulfonamido) -2-methoxybenzothiol; (E) -N- (3-hydroxy-4-methoxyphenyl) -3- (2,4,6-trimethoxyphenyl) acrylamide; (E) -N- (3-mercapto-4-methoxy-phenyl) -3- (2,4,6-trimethoxyphenyl) -acrylamide; and you come out of them.

II. Compounds in accordance with Formula III In accordance with other embodiments of the compounds according to Formula I, there are provided compounds according to Formula III: wherein R2, R3, Rv, A, a, b, X and Q are as defined hereinabove for compounds of Formula I; or a salt of them.

A. Compounds according to Formula I HA In accordance with one embodiment of the compounds according to Formula III, there are provided compounds according to Formula IIIA: wherein R2, R3, Rv, Rx, a, b, A, Y, Q and * are as defined hereinabove for compounds according to Formula I, and the exocyclic carbon-carbon double bond is in the ( E) -formation. According to a preferred embodiment of the compounds according to Formula IIIA, Rx is -H. Preferred compounds according to Formula I HA include, for example: dihydrogen phosphate of (E) -5 - ((2,4,6-imyroxystyrylsulfonyl) methyl) -2-meioxyphenyl; dimellyl phosphate of (E) -5 - ((2,4,6-imyroxystyrylsulfonyl) methyl) -2-methoxyphenyl; diethyl phosphate of (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) meily) -2-methoxyphenium; dibenzyl phosphate of (E) -5 - ((2,4,6-trimelloxyesilyrisulfonyl) -mellyl) -2-methoxyphenyl; phosphorothioate of (E) -S-5 - ((2,4,6-trimoxysilyl-sulfonyl) -methyl) -2-methoxyphenyl-0,0-dihydrogen; phosphorothioate of (E) -S-5 - ((2,4,6-trylperoxysilyl-sulfonyl) -methyl) -2-mexoxyphenyl-0,0-dimethyl; phosphorothioaio of (E) -S-5 - ((2,4,6-dimethoxystyrylsulfonyl) methy1) -2-methoxy-phenyl-0, O-diethyl; phosphorothioalo of (E) -S-5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenyl-O.O-dibenzyl; dihydrogen phosphate of (E) -5 - ((2,4,6-trimethoxy-silyl-sulfinyl) -methyl) -2-meloxyphenyl; dimethyl phosphate of (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenyl; diethyl phosphate of (E) -5 - ((2,4,6-trimethioxy-ylsilyl-sulfinyl) -methyl) -2-methoxy-phenyl; phospho-dibenzyl of (E) -5 - ((2,4,6-trimethoxy-syrylsulfonyl) -methyl) -2-methoxyphenyl; phosphorolioalole of (E) -S-5 - ((2,4,6-trimethoxystyryl-suI-nyl) -methyl) -2-mexoxyphenyl-0,0-dihydrogen; phosphoroaioaio of (E) -S-5 - ((2,4,6-trimethoxystiryl sulphonyl) methyl) -2-methoxyphenyl-0, 0-dimethyl; phosphorothioate of (E) -S-5 - ((2,4,6-trimethoxy-styrylsulfinyl) methyl) -2-methoxy-phenyl-0,0-diethylol; phosphoroaioaio of (E) -S-5 - ((2,4,6-methyxy-styryl-sulfinyl) methyl) -2-methoxyphenyl-0,0-d? -benzyl; and you come out of them.

B. Compounds in accordance with Formula 1I1B In accordance with another embodiment of the compounds according to Formula III, compounds according to Formula 11 IB are provided: wherein R2, R3, Rx, Rv, a, b, A, Z and Q are as defined hereinabove for compounds according to Formula I, and the exocyclic carbon-carbon double bond is in (E) -conformation. In accordance with a preferred embodiment of compounds according to the Formula HIB, Rx is -H. Preferred compounds according to Formula IIIB include, for example: dihydrogen phosphate of (E) -5- (2,4,6-trimethoxy-sulphonylsulfonamido) -2-methoxy-phenyl; dimethyl phosphate of (E) -5- (2,4,6-trimethoxy-styrylsulfonamido) -2-methoxyphenyl; diethyl phosphate of (E) -5- (2,4,6-yl-methoxystyrylsulfonamido) -2-meloxophenyl; di-benzylphosphate of (E) -5- (2,4,6-trimethoxystirylsulfonamido) -2-methoxyphenyl; phosphorothioate of (E) -S- (5- (2,4,6-trimethoxybutyryl-sulfonamido) -2-methoxy-phenyl) -0,0-dlhydrogen; phosphorothioate of (E) -S- (5- (2,4,6-trimoxysilyl-sulfonamido) -2-methoxyphenyl) -0,0-dimethyloyl; phosphoroaioaio of (E) -S- (5- (2,4,6-ynedimoxy-styrylsulfonamido) -2-methoxyphenyl) -0, O-diethyl; phosphoroaioaio of (E) -S- (5- (2,4,6-lime-mexysilyl-sulfonamido) -2-mexoxyphenyl) -0,0-dibenzyl; 5 - ((E) -3- (2,4,6-lyrimethoxyphenyl) acrylamido) -2-methoxyphenyl dihydrogen phosphate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) -acrylamido) -2-methoxyphenyl dimethyl phosphate; 5 - ((E) -3- (2,4,6-methoxy-phenyl) -acrylamido) -2-methoxyphenyl diethyl phosphate; 5 - ((E) -3- (2,4,6-trimethoxy-phenyl) acrylamido) -2-methoxyphenyl phospho-dibenzyl; phosphorothioate of S-5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxyphenyl-0,0-dihydrogen; S-5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-mexoxyphenyl-0,0-dimethylol phosphorothioate; phosphorothioate of S-5 - ((E) -3- (2,4,6-trimelloxyphenyl) acrylamido) -2-mexoxyphenyl-0,0-dielyl; phosphorothioate of S-5 - ((E) -3- (2,4,6-trimelloxyphenyl) acrylamido) -2-mexoxyphenyl-0,0-dibenzyl; and you come out of them.

IV. Compounds in accordance with Formula IV In accordance with another embodiment of the compounds according to Formula I, there are provided compounds according to Formula IV: wherein R2, R3, Rw, A, a, b, X and Q are as defined above in this document for compounds according to Formula I; or a salt of them.

A. Compounds in accordance with Formula VA In accordance with one embodiment of the compounds according to Formula IV, compounds are provided in accordance with the Formula IVA: as defined above in this document for compounds according to Formula I, and exocyclic carbon-carbon double bond is in (E) -formation. In accordance with a preferred embodiment of compounds according to the Formula IVA, Rx is -H. Preferred compounds according to the Formula IVA include, for example: (E) -2 - ((5 - ((2,4,6-trimethoxy-styrylsulphonyl) meily) -2-methoxyphenoxy) -carbonyl) acetic acid; (E) -5 - ((2,4,6-L-dimethyloxystyrylsulfonyl) methyl) -2-methoxyphenyl-3,5-dinitrobenzoal; (E) -5 - ((2,4) 6-Rlymethyxystyrylsulfonyl) -methyl) -2-methoxyphenyl-3,5-diaminobenzoate; (E) -5 - ((2,4,6-lrimethoxystyrylsulfonyl) methyl) -2-methoxyphenyl-2-chloroacety; (E) -5 - ((2,4,6-trimethoxy-styrylsulphonyl) meily) -2-mexoxyphenyl-2- (4-methyl-piperazin-1-yl) -acetyl; benzoaio of (E) -5 - ((2,4,6-trimethoxystylsulphonyl) methyl) -2-methoxyphenyl; (E) -5 - ((2,4,6-Tr! Methoxystyrylsulfonyl) methyl) -2-methoxyphenyl-4-nitrobenzoate; (E) -5 - ((2,4,6-lrimethoxystyrylsulfonyl) methyl) -2-methoxy-phenyl-4-amino-benzoate; (E) - (R) -5 - ((2,4,6-Iryoxystyrylsulfonyl) methy1) -2-methoxyphenyl-2,6-diaminohexanoaio; (E) - (R) -5 - ((2,4,6-Rlymethyloxy-phenyrylsulfonyl) methyl) -2-methoxy-phenyl-2-amino-3-hydroxypropanoane; (E) - (5) -5 - ((2,4,6-ynedioxy-esyrylsulfonyl) methyl) -2-methoxyphenyl-2-amino-3-hydroxypropanoane; carbamate of (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) meily) -2-methoxy-phenyl; (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-mexoxyphenyl-2- (di-meitylamino) -acetate; (E) -5- ((2,4,6-yrimoxystyrylsulfonyl) -methyl) -2-methoxyphenyl-4- (4-methylpiperazin-1-ii) benzoaio; (E) -5 - ((2,4,6-uro-methoxystyrylsulfonyl) methyl) -2-methoxyphenyl-2-hydroxyacetate; (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) -methyl) -2-meioxyphenii-2- (pyridinium-1-yl) acetate; (E) -5 - ((2,4,6-LR-methoxy-styrylsulfonyl) methyl) -2-methoxyphenyl-2-acetyxyacetate; (E) -5 - ((2,4,6-tri-methoxy-styrylsulfonyl) methyl) -2-methoxy-phenyl-2-hydroxypropanoate; (E) -5 - ((2,4,6-trimethoxystirylsulfonyl) methyl) -2-methoxyphenyl-2- (trieryl-ammonium) -aceto; (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methy1) -2-mexoxyphenyl-2- (tris (2-hydroxy-yl) ammonium) -acetate; (E) -5 - ((2,4,6-trimethoxystyryl-sulfonyl) methyl) -2-methoxyphenyl-2-hydroxy-2-methyl-propanolane; (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenyl-2-acetoxy-2-methylpropanoate; (E) -5 - ((2,4,6-Trimethioxysulfylsulfonyl) meily) -2-methoxy-phenyl-2,2,2-trifluoroacetate; (E) -3 - ((5 - ((2,4,6-Trimethioxysphyr-sulfonyl) -methyl) -2-meioxyfenoxy) -carbonyl) propanoic acid; (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-mexoxyphenyl-3- (chlorocarbonyl) -propanoate; 2- (3-carboxypropanoic) acetamide of (E) -5 - ((2,4,6-ylmethyloxy-sulphonylsulfonyl) meily) -2-meloxyphenyl; (E) -4 - ((5 - ((2,4,6-trimethyloxystyrylsulfonyl) -methyl) -2-meloxyphenoxy) -carbonyl) butanoic acid; dihydrogen phosphate of (E) - ((5 - ((2) 4,6-trimethoxystirylsulfonyl) methyl) -2-methoxyphenoxy) -carbonyl) meityl; methylated carbonate of (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenyl; (E) -5 - ((2,4,6-ylmeyoxy-ylsulfonyl) -methyl) -2-methoxy-phenyl-2-acetoxypropanoate; Methyl succinate of (E) -5 - ((2,4,6-trimethoxy-styrylsulfonyl) methyl) -2-methoxyphenyl; ethyl ester of (E) -5 - ((2,4,6-trimethyloxystyrylsulfonyl) methyl) -2-methoxyphenyl; (E) -5 - ((2,4,6-Trimethioxysulfylsulfonyl) methyl) -2-methoxyphenyl-2,2,3,3,3-penta-fluoropropanoate; (E) -1- (5 - ((2,4,6-urimaxysilylsulfonyl) methyl) -2-methoxyphenyl) -3-methyl-2,2-difluoromalonade; (E) -3 - ((5 - ((2,4,6-methyxy-styrylsulfonyl) methyl) -2-methoxyphenoxy) -carbonyl) -2,2,3,3-tetrafluoro-propanoic acid; (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxy-phenyl-2-aminoacetate; (E) -2 - ((5 - ((2,4,6-Tr! methoxystyrylsulfonyl) -methyl) -2-methoxyphenoxy) carbonyl) -2,2-difluoroacetic acid; (E) -5 - ((2,4,6-trimellinoxy-silyl-sulfonyl) -methyl) -2-mexoxyphenyl-2- (dimethylamino) -2,2-difluoro-acetylene; 5 - ((2,4,6-ylmedeoxy-ylsilylsulfonyl) meily) -2-methoxyphenyl-2- (dimethylamino) acetate; (E) -2 - ((5 - ((2,4,6-trimeioxy) -syrylsulfinyl) methyl) -2-mexoxyphenoxy) carbonyl) acidic acid; (E) -5 - ((2,4,6-N-methoxystyrylsulfinyl) -methyl) -2-mexoxyphenyl-3,5-dinitrobenzoaio; (E) -5 - ((2,4,6-trimethoxystyryl-sulfinyl) methyl) -2-mexoxyphenyl-3,5-diaminobenzoaio; (E) -5 - ((2,4,6-trimelloxistyrylsulfonyl) methyl) -2-methoxyphenyl-2-chloroacetal; (E) -5 - ((2,4,6-trimethoxystyrylsulfinyl) methyl) -2-methoxyphenyl-2- (4-methyl-piperazin-1-yl) acetate; benzoate of (E) -5 - ((2,4,6-trimethoxystyrylsulfinyl) methy1) -2-methoxyphenyl; (E) -5 - ((2,4,6-trimethoxystirylsulfinyl) methyl) -2-methoxyphenyl-4-nitrobenzoal; (E) -5 - ((2,4,6-Trimethyloxy-ylsilyl-sulfonyl) -methyl) -2-methoxyphenyl-4-aminobenzoate;. 2,6-diaminohexanoaio of (E) - (R) -5 - ((2,4,6-uroimyoxystilsulfinyl) -methyl) -2-methoxyphenyl; 2-amino-3-hydroxypropanoate of (E) - (R) -5 - ((2,4,6-trimethyloxy-styrylsulfonyl) -methyl) -2-methoxyphene; (E) - (S) -5 - ((2,4,6-Irido-xyrylsilyl-sulfinyl) -methyl) -2-methoxyphenyl-2-amino-3-hydroxypropanoate; carbamate of (E) -5 - ((2,4,6-trimethoxystyrylsulfinyl) methy1) -2-methoxy-phenyl; 2- (di-methylamino) acetyl of (E) -5 - ((2,4,6-dimethoxystyrylsulfinyl) methyl) -2-methoxy-phenyl; 4- (4-Melyl-piperazin-1-yl) -benzoate of (E) -5 - ((2,4,6-trimethoxystirylsulfinyl) -methyl) -2-methoxyphenyl; (E) -5 - ((2,4,6-trimethoxystiryl sulfinyl) methyl) -2-methoxyphenyl-2-hydroxyacetate; (E) -5 - ((2,4,6-trimethoxy-styrylsulfinyl) methyl) -2-methoxyphenyl-2- (pyridinium-1-yl) -acelate; (E) -5 - ((2,4,6-trimethoxy-silyl-sulfinyl) -methyl) -2-methoxyphenyl-2-acetoxyacetate; (E) -5 - ((2,4,6-Trimethioxysilylsulfinyl) methyl) -2-methoxy-phenyl-2-hydroxypropanoate; (E) -5 - ((2,4,6-Trimethioxy-syrylsulfinyl) -methyl) -2-methoxyphenyl-2- (triethylammonium) acetyl; 2- (Iris (2-hydroxyethyl) -ammonium) acetamide of (E) -5 - ((2,4,6-trimethoxystyryl-sulfinyl) methyl) -2-methoxyphenyl; 2-hydroxy-2-methylpropanoic acid ester of (E) -5 - ((2,4,6-ylmeyoxy-ylsilyl-sulfinyl) methyl) -2-methoxy-phenyl; (E) -5 - ((2,4,6-trimethoxystyrylsulfinyl) -methyl) -2-methoxy-phenyl-2-acetyloxy-2-methylpropanoaio; (E) -5 - ((2,4,6-Trimethyloxystyrylsulfinyl) -methyl) -2-methoxyphenyl-2,2,2-trifluoroacetylane; (E) -3 - ((5 - ((2,4,6-trimethoxy-styrylsulfinyl) methyl) -2-methoxyphenoxy) -carbonyl) -propanoic acid; (E) -5 - ((2,4,6-Tr ymethoxystiryl sulphonyl) methyl) -2-methoxy-phenyl-3- (chlorocarbonyl) -propanoaiole; (E) -5 - ((2,4,6-irimidoxy-syrylsulfinyl) -methyl) -2-methoxyphenyl-2- (3-carboxypropanoic) acetyl; (E) -4 - ((5 - ((2,4,6-trimethoxy-syrylsulfinyl) -methyl) -2-methoxyphenoxy) -carbonyl) butanoic acid; dihydrogen phosphate of (E) - ((5 - ((2,4,6-trimethoxystirylsulfinyl) methyl) -2-methoxy-phenoxy) -carbonyl) -methyl; meityl carbonation of (E) -5 - ((2,4,6-irimethyoxysilyl-sulfinyl) -methyl) -2-methoxyphenyl; (E) -5 - ((2,4,6-trimethoxystyrylsulfinyl) -methyl) -2-mexoxyphenyl-2-acetoxypropanoate; methyl succinate (E) -5 - ((2,4,6-trimethoxy-sulphyr-sulfinyl) methyl) -2-methoxyphenyl; ethyl malonal from (E) -5 - ((2,4,6-trimethioxy-ylsilyl-sulfonyl) -methyl) -2-meloxyphenyl; (E) -5 - ((2,4,6-trimethoxy-sysilyl-sulfonyl) methyl) -2-methoxyphenyl-2,2,3,3,3-penne-fluoropropanoyl; (E) -1- (5 - ((2,4,6-lyrimethoxy-ylsily-sulfinyl) methyl) -2-methoxyphenyl) -3-methyl-2,2-difluoromalonate; (E) -3 - ((5 - ((2,4,6-L-methoxy-styrylsulfinyl) methyl) -2-methoxyphenoxy) -carbonyl) -2,2,3,3-tetrafluoro-propanoic acid; (E) -5 - ((2,4,6-Tr ymethystyrylsulfonyl) methyl) -2-methoxy-phenyl-2-aminoacetate; (E) -2 - ((5- ((2,4,6-Trimethoxystyrylsulfinyl) -methyl) -2-methoxyphenoxy) -carbonyl) -2,2-difluoroacetic acid; (E) -5 - ((2,4,6-trimethoxy-styrylsulfonyl) methyl) -2-methoxyphenyl-2- (dimethylamino) -2,2-difluoroacetate; 5 - ((2,4,6-trimethoxy-silyl-sulfinyl) -methyl) -2-methoxyphenyl-2- (dimethylamino) -acetamide; and you come out of them.

B. Compounds in accordance with Formula IVB In accordance with another embodiment of the compounds according to Formula IV, compounds are provided in accordance with Formula IVB: wherein R2, R3, Rx, A, Rw, a, b, Z and Q are as defined above in this document for compounds according to Formula I, and the exocyclic carbon-carbon double bond is in (E) -conformation. In accordance with a preferred embodiment of compounds according to Formula IVB, Rx is -H. Preferred compounds according to Formula IVB include, for example: 2- acid. { [5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl}. Amino) -2-methoxy-phenyl] oxycarbonyl} acéíico; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) -vinyl] sulfonyl} amino) -2-methoxyphenyl-3,5-dinitrobenzoate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl.] Amino) -2-methoxy-phenyl-3,5-diamino-benzoate; 5- ( { [(1 E) -2- (2,4,6-trimethoxypheni) vinyl] sulfonyl.} Amino) -2-mexoxyphenyl-2-chloroacetate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) -vinyl] -sulfopyl}. Amino) -2-methoxyphenyl 2- (4-methylpiperazinyl) acetate; 5- ( { [(1 E) -2- (2,4,6-Trimethioxyphenyl) vinyl] sulfonyl} amino) -2-methoxyphenyl benzoate; 5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl) -vinyl] -sulfonyl} -amino) -2-methoxyphenyl-4-nitrobenzoate; 5- ( { [(1 E) -2- (2,4,6-uroimidoxyphenyl) vinyl] -sulfonyl] amino) -2-methoxyphenyl-4-aminobenzoate; 5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl) vinyl] -sulfonyl.] Amino) -2-methoxyphenyl- (2R) -2 , 6-diamino-hexanoate; 5- ( { [(1 E) -2- (2,4,6-lrimethoxyphenyl) vinyl] sulfonyl}. Amino) -2-methoxyphenyl- (2R) -2-amino-3-hydroxypropanole; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] -sulfonyl}. Amino) -2-methoxyphenyl- (2S) -2-amino-3-hydroxypropanoate; 5- ( { [(1 E) -2- (2,4,6-Trimethioxyphenyl) vinyl] sulfonyl] -amino) -2-mexoxyphenyl carbamate; 5- ( { [(1 E) -2- (2,4,6-trimellidoxyphenyl) vinyl] sulfonyl.} Amino) -2-methoxyphenyl-2- (dimethylamino) -acetate; 5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl) vinyl] sulfonyl}. Amino) -2-methoxy-phenyl-4- (4-methylpiperazinyl) - benzoate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) -vinyl] sulfonyl}. Amino) -2-methoxyphenyl-2-hydroxyacetate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) viny] -sulfonyl.}. Amino) -2-methoxyphenyl-2-pyrid-1-ylacetate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl] amino] -2-methoxyphenyl-2-acetyloxyacelate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl} -amino) -2-methoxyphenyl 2-hydroxypropanoate; 5- ( { [(1 E) -2- (2,4,6-lrimethoxy-phenyl) vinyl] sulfonyl] -amino) -2-methoxyphenyl-2- (triethylammonium) acetate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl}. Amino) -2-methoxyphenyl-2- [tris (2-hydroxyethyl) ammonium] acetamide; 5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl) vinyl] -sulfonyl} -amino) -2-methoxyphenyl-2-hydroxy-2-methylpropanoate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) viny] sulphonyl}. Amino) -2-methoxyphenyl-2-acyloxy-2-methylpropanoate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) viny] sulphonyl] -amino) -2-methoxyphenyl-2,2,2-trifluoroacetate; acid 3-. { [5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl] -amino) -2-methoxyphenyl] oxycarbonyl} -propanoic; 5- ( { [(1 E) -2- (2,4,6-trimethioxyphenyl) vinyl] sulfonyl}. Amino) -2-methoxyphenyl-3- (chlorocarbonyl) -propanoate; 3 - [( { [5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl} amino) -2-methoxyphenyl] oxycarbonyl. .methyl) oxycarbonyl] propanol; 4- acid. { [5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) -vinyl] sulfonyl}. Amino) -2-methoxyphenyl] -oxocarbonyl} butanoic; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] -sulfonyl] amino) -2-methoxyphenyl-2- (phosphonooxy) acelaide; meioxyformate of 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl] -amino) -2-meloxyphenyl; 5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl-vinyl] sulfonyl} -amino) -2-mexoxyphenyl-2-acetyloxypropanoane; buanary-1,4-dioate mephyl of 5- ( { [(1 E) -2- (2,4,6-uroimidoxyphenyl) -vinyl] sulfonyl}. amino) -2-methoxy-phenol; propan-1,3-dioate ethyl of 5 - ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] -sulfonyl}. Amino) -2-methoxy-phenyl; 5- ( { [(1 E) - 2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl.] - amino) -2-methoxy-phenyl-2,2,3,3,3-pentafluoropropanoate; 2,2-difluoropropane-1,3-dioate methyl 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl] -amino) -2-methoxy-phenyl; {. [5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] -sulfonyl}. Amino) -2-meloxophenyl] -oxycarbonyl.} -2, 2,3,3-tetrafluoropropanoic; 5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl) vinyl] sulfonyl.} Amino) -2-methoxy-phenyl-2-aminoacetamide; 2- acid. { [5- ( { [(1 E) -2- (2,4,6-uroimidoxyphenyl) vinyl] -sulfonyl}. Amino) -2-mexoxyphenyl] -oxocarbonyl} - 2,2-difluoroacetic; 5- ( { [(1 E) -2- (2,4,6-lrimethoxyphenyl) -vinyl] sulfonyl}. Amino) -2-methoxy-phenyl-2- (dimethylamino) -2.2 -difluoro-aceíalo; 5 - ((E) -3- (2,4,6-trimeioxyphenyl) -acrylamido) -2-methoxyphenyl-2- (carboxy) acetate; 5 - ((E) -3- (2,4,6-Trimethioxyphenyl) acrylamido) -2-methoxy-phenyl-3,5-diniirobenzoate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxyphenyl-3,5-dinoxybenzoate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acryl-amido) -2-methoxyphenyl-2-chloroacetate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) -acrylamido) -2-methoxyphenyl-2- (4-methylpiperazin-1-yl) acetyl; benzoaio of 5 - ((E) -3- (2,4,6-lyrimethoxyphenyl) acrylamido) -2-methoxyphenyl; 5 - ((E) -3- (2,4,6-Tr ~ methoxyphenyl) acrylamide) -2-methoxy-phenyl-4-nitrobenzoate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamide) -2-methoxy-phenyl-4-aminobenzoate; (R) -5 - ((E) -3- (2,4,6-trylmeloxyphenyl) acrylamido) -2-methoxyphenyl-2,6-di-aminohexanoate; (R) -5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxy-phenyl-2-amino-3-hydroxypropanoate; (S) -5 - ((E) -3- (2,4,6-trimethoxyphenyl) -acrylamido) -2-methoxyphenyl-2-amino-3-h idroxy propanoate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-meloxyphenyl carbamate; 5 - ((E) -3- (2,4,6-lrimeioxyphenyl) acrylamide) -2-mexoxyphenyl-2- (dimethylamino) acetate; 5 - ((E) -3- (2,4,6-trimethoxy-phenyl) -acrylamide) -2-meloxyphenyl-4- (4-methyl-piperazin-1-yl) -benzoane; 5 - ((E) -3- (2,4,6-ynedioxyphenyl) acrylate) -2-meloxyphenyl-2-hydroxyacetate; 2- (pyridin-1-yl) acelaio of 5 - ((E) -3- (2,4,6-trimethoxyphenyl) -acyl-amide) -2-meioxyphene; 5 - ((E) -3- (2,4,6-uroimyoxy-phenyl) acrylamido) -2-methoxyphenyl-2-acetyloxy-acetamide; 5 - ((E) -3- (2,4,6-tri-methoxyphenyl) acrylamido) -2-methoxyphenyl-2-hydroxypropanoate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamide) -2-methoxyphenyl-2- (N, N, N-triethyl-amino) acetate; 5 - ((E) -3- (2,4,6-Trimethioxyphenyl) acrylamido) -2-meioxy-phenyl-2- (N, N, N-yl- (2-hydroxyethyl) amino) acetylane; 5 - ((E) -3- (2,4,6-Rlymethio-phenyl) acrylamido) -2-methoxyphenyl-2-hydroxy-2-methyl-propanoate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-meloxyphenyl-2-acetoxy-2-methyl-propanoaio; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxy-phenyl-2,2,2-и fluoroacetate; 5 - ((E) -3- (2,4,6-Trimethioxyphenyl) -acrylamido) -2-mexoxyphenyl-3-carboxypropanole; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acryl-amido) -2-methoxyphenyl-3- (chlorocarbonyl) propanoate; 5 - ((E) -3- (2,4,6-lri-methoxyphenyl) acrylamide) -2-meloxyphenyl-2- (3-carboxypropanoic) acetate; 5 - ((E) -3- (2,4,6-lrimethoxyphenyl) acrylamido) -2-methoxyphenyl- (4-carboxy-butyral); 5 - ((E) -3- (2,4,6-trimellidoxyphenyl) acrylamido) -2-methoxyphenoxy) -carbonyl) methyl phosphate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) -acrylamido) -2-methoxyphenyl methyl carbonate; 5 - ((E) -3- (2,4,6-trimethoxy-phenyl) acrylamido) -2-methoxyphenyl-2-acetoxypropanoate; 5 - ((E) -3- (2,4,6-trimethoxy-phenyl) -acrylamido) -2-methoxyphenyl methyl succinate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxyphenyl ethyl malonate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxy-phenyl-2,2,3,3,3-penta-fluoropropanole; 3- (5 - ((E) -3- (2,4,6-trimethioxyphenyl) acrylamido) -2-meloxyl-phenyl) -3-metll-2,2-d-fluoro-morphonate; 5 - ((E) -3- (2,4,6-lyrimethoxyphenyl) acrylamido) -2-meioxyphenyl- (3-carboxy-2,2,3,3-tetrafluorobulirate); 5 - ((E) -3- (2,4,6-trimethoxy-phenyl) acrylamido) -2-methoxyphenyl-2-aminoacetate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxyphenyl- (2-carboxy-2,2-difluoroacetate); 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxy-phenyl-2- (dimethylamino) -2,2-difluoroacetate; 5 - ((E) -3- (2,4,6-trimethoxy-phenyl) acrylamido) -2-methoxy-phenyl acetate; 5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl) vinyl] sulfonyl.] Amino) -2-methoxyphenyl-2- (dimethylamino) -acetamide; 5 - ((2,4,6-uroimethoxy-sulfonylsulfonyl) amino) -2-meloxyphenyl-2- (dimethylamino) -acetylane; and you come out of them.

V. Compounds according to Formula V In accordance with another embodiment of the compounds according to Formula I, compounds according to Formula V are provided: wherein R2, R3, Rw, A, a, b, X and Q are as defined above in this document for compounds of Formula I; and you come out of them.

A. Compounds in accordance with Formula VA In accordance with one embodiment of the compounds according to Formula V, compounds are provided in accordance with Formula VA: wherein R2, R3, Rx, Rw, A, a, b, Q and * are as defined hereinabove for compounds of Formula I, and the exocyclic carbon-carbon double bond is in the (E) -formation. In accordance with a preferred embodiment of compounds according to Formula VA, Rx is -H. Preferred compounds according to the Formula VA include, for example: carboxy-methanesulfonated of (E) -5 - ((2,4,6-trimethoxy-styrylsulfonyl) methy1) -2-methoxyphenyl; (E) -5 - ((2,4,6-trimethoxy-styrylsulfonyl) meily) -2-methoxy-phenyl-2,4-dinitrobenzenesulfonate; (E) -5 - ((2,4,6-trimethoxy-srylyl-sulfonyl) -mellyl) -2-methoxyphenyl-2,4-diaminobenzenesulfonate; trifluoromethanesulfonate of (E) S - ((2,4,6-trimethoxystyrylsulfonyl) mell) -2-methoxyphenyl, (E) -5 - ((2,4,6-trimethoxystirylsulfonyl) methyl) -2-methoxyphenyl-4 -methoxy-benzenesulfonate; carboxymethanesulfonate of (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) melyl) -2-methoxy-phenyl; (E) -5 - ((2,4,6-trimelloxistirylsulfinyl) -metl) -2-methoxyphenyl-2,4-dlnitrobenzenesulfonate; (E) -5 - ((2,4,6-trimethoxystirylsulfinyl) methyl) -2-methoxyphenyl-2,4-diaminobenzenesulfonale; (E) -5 - ((2,4,6-trimethoxystiryl-sulfinyl) -methyl) -2-methoxyphenyl-trifluoromethylene sulfonate; (E) -5 - ((2,4,6-trimethoxystyrisyl-sulfinyl) methyl) -2-methoxyphenyl-4-meioxybenzenesulphone; (E) -5 - ((2,4,6-dimethoxystyrylsulfonyl) mephyl) -2-mexoxyphenyl-4-methylbenzenesulfonate; (E) -5 - ((2,4,6-ylmethioxyesyl) ylsulfinyl) methyl) -2-methoxyphenyl-4-methylbenzenesulfonate; and you come out of them.

B. Compounds according to Formula VB In accordance with another embodiment of the compounds according to Formula V, compounds according to Formula VB are provided: wherein R2, R3, Rw, Rx, a, b, A, Z and Q are as defined hereinabove for compounds according to Formula I, and the carbon-carbon double bond exocyclic is in (E) -conformation. In accordance with a preferred embodiment of compounds according to Formula VB, Rx is -H. Preferred compounds according to Formula VB include, for example: 2- acid. { [5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl}. Amino) -2-methoxy-phenyl] oxysulfonyl} acetic; 5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl) vinyl] -sulfonyl}. Amino) -2-methoxyphenyl-2,4-dinylrobencenesulfonaio; 5- ( { [(1 E) -2- (2,4,6-lrimethoxyphenyl) vinyl] sulfonyl.] Amino) -2-methoxyphenyl-2,4-diamino-benzenesulfonalo; 5- ( { [(1 E) -2- (2,4,6-tr.methoxyphenyl) vinyl] -sulfonyl}. Amino) -2-methoxyphenyl- (trifluoromethyl) sulfonate; 5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl) vinyl] sulfonyl.] Amino) -2-methoxyphenyl-4-methoxy-benzenesulfonate; 5- ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxy-phenylcarboxy-methanesulfonate; 5 - ((E) -3- (2,4,6-trimethoxy-phenyl) -acrylamido) -2-methoxy-phenyl-trifluoromethanesulfonate; 5 - ((E) -3- (2,4,6-trimethoxy-phenyl) acryl-amido) -2-rethoxyphenyl-2,4-dinitrobenzenesulfonate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxyphenyl-2,4-diaminobenzenesulfonate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxyphenyl-4-methoxy-benzenesulfonate; 5 - ((E) -3- (2,4,6-uroimidoxyphenyl) acrylamido) -2-methoxy-phenyl-4-methylbenzenesulphone; (E) -5 - ((2,4,6-trimethoxystirylsulfonyl) -amino) -2-methoxyphenyl-4-methylbenzenesulfonate; and you come out of them.

SAW. Compounds in accordance with Formula V In accordance with another embodiment of the compounds according to Formula I, there are provided compounds according to Formula VI: wherein R2, R3, Rz, A, a, b, X, and Q are as defined hereinabove for compounds of Formula I; or a salt of them.

A. Compounds of Formula VIA In accordance with one embodiment of the compounds according to Formula VI, compounds are provided in accordance with the VIA Formula: wherein R2, R3, Rx, Rz, a, b, A, Y, Q and * are as defined hereinabove for compounds according to Formula I, and the exocyclic carbon-carbon double bond is in the ( E) -formation. In accordance with a preferred embodiment of the comps in accordance with the Formula VIA, Rx is -H. Preferred compounds according to the Formula VIA include, for example: (E) -2- (5 - ((2,4,6-trimoxysilyl-sulfonyl) -methyl) -2-methoxyphenoxy) -acetic acid; (E) -2- (5 - ((2,4,6-lrimethoxystyrylsulfonyl) methyl) -2-meloxyphenoxy) -propanoic acid; (E) -4- (5 - ((2,4,6-trimethoxystirylsulfonyl) -methyl) -2-methoxy-phenoxy) -butanoic acid; (E) -3- (5 - ((2,4,6-Trimethoxystyryl-sulfinyl) methyl) -2-methoxyphenoxy) -propanoic acid; (E) -2- (5 - ((2,4,6-trimethoxystirylsulfinyl) -methyl) -2-methoxyphenoxy) -acetic acid; (E) -2- (5 - ((2,4,6-trimethoxystiryl-sulfinyl) methyl) -2-methoxyphenoxy) -propanoic acid; (E) -4- (5 - ((2,4,6-trimethoxystiryl-sulfinyl) methyl) -2-methoxyphenoxy) -butanoic acid; (E) -3- (5 - ((2,4) 6-trimethoxystirylsulfinyl) methyl) -2-meioxlfenoxy) -propanoic acid; (E) -4- (2- (5 - ((2,4,6-Trimethioxysphsylsulfonyl) methyl) -2-methoxyphenoxy) ethyl) -morpholine; (E) -4- (2- (5 - ((2,4,6-dimethoxystyrylsulfinyl) methyl) -2-methoxy-phenoxy) eyl) morpholine; and you come out of them.

B. Compounds in accordance with Formula VIB In accordance with another embodiment of the compounds according to Formula VI, there are provided compounds according to Formula VIB: wherein R2, R3, Rx, Rz, a, b, A, Z and Q are as defined above in this document, and the exocyclic carbon-carbon double bond is in (E) -configuration. According to a preferred embodiment of compounds according to Formula VIB, Rx is -H. Preferred compounds according to Formula VIB include, for example: 2- [5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl} amino] -2 -methoxy-phenoxy] acetic; 2- [5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl.] -amino) -2-meloxyphenoxy] propanoic acid; 4- [5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl) vinyl] -sulfonyl}. amino) -2-methoxy-phenoxybutanoic acid; 3- [5 - (([(1 E) -2- (2,4,6-Trimethioxyphenyl) vinyl] sulfonyl.] amino) -2-methoxy-phenoxy] -propanoic acid; (E) -N ~ (3- (carboxymethoxy) -4-methoxyphenyl) -3- (2,4,6-trimethoxyphenyl) acrylamide; (E) -N- (3- (1-carboxyethoxy) -4-methoxyphenyl) -3- (2, 4,6-methyloxyphenyl) -acrylamide; (E) -N- (3- (3-carboxypropoxy) -4-methoxyphenyl) -3- (2,4,6-trimethoxyphenyl) acrylamide; (E) -N- (3 - (2-carboxy-ethoxy) -4-methoxy-phenyl-3- (2,4,6-trimethoxyphenyl) acrylamide; (E) -N- (3- (2-morpholinoethoxy) -4-methoxyphenyl) -3 - (2,4,6-trimethoxyphenyl) acrylamide: (E) -4- (2- (5 - ((2,4,6-trimethoxystyrylsulfonyl) amino) -2-methoxyphenoxy) ethyl) -morpholine; and salts thereof same.

Vll. New Synthetic Intermediates The invention is also directed to intermediates, useful in the preparation of certain compounds of Formula I.

A. Intermediates in the Preparation of Compounds of Formula IE wherein X is -C * RXY- In accordance with some embodiments of the invention, synthetic intermediates useful in the preparation of compounds of Formula IE are provided: Synthetic intermediates have the formula Vll: or a salt of the compound, wherein: R1, R2, RX, A, a and * are as defined above in this document for compounds of Formula I; n is 0, 1 or 2; and R is -H or -alkyl of (d-d); or a salt thereof; provided that: R1 is different from haloalkyl of (d-d); Rz is different from -NRV2 and substituted aryl; and Rw is different from Hydrocarbon of (d-d). In accordance with one embodiment of the compounds of Formula Vll, A is -O-. In accordance with another embodiment of compounds of Formula Vll, RX is -H. Compounds according to Formula Vll, wherein n is 1, include for example: 2- (3-hydroxy-4-methoxybenzylsulfinyl) acetic acid; 2- (3-mercapto-4-methoxybenzylsulfinyl) acetic acid; 2- (3-tert-butyldimethylsilyloxy-4-methoxybenzylsulphonyl) acetic acid; 2- (3 - ((tert-Butyldimethylsilyl) sulfanyl) -4-methoxybenzylsulfinyl) acetic acid; dihydrogen phosphate 0-2-methoxy-5- (carboxymethylsulfinylmethyl) phenyl; dimethylsilyl 0-2-meloxy-5- (carboxymethyl-sulfinylmethyl) phenyl phosphate; diethyl phosphate 0-2-methoxy-5- (carboxymethylsulfinylmethyl) phenyl; Dibenzyl 0-2-methoxy-5- (carboxymethylsulfinylmethyl) phenyl phosphate; phosphorothioate S-2-methoxy-5- (carboxymethylsulfinylmethyl) phenyl-0,0-dihydrogen; phosphorus-thioaio S-2-methoxy-5- (carboxymethylsulfinylmethylphenyl-0,0-dimethyl; phosphorothioate S-2-methoxy-5- (carboxymethylsulfinylmethyl) phenol-0,0-diethyl; phosphorothioate S-2-methoxy- 5- (carboxymethylsulfinylmethyl) phenyl-0,0-dibenzyl, and salts thereof Compounds according to Formula Vll, wherein n is 2, include, for example: 2- (3-hydroxy-4-methoxybenzylsulfonyl) acetic acid 2- (3-mercaplo-4-methoxybenzylsulfonyl) acidic 2- (3-tert-butyldimethylsilyloxy-4-methoxy-benzylsulfonyl) -acetic acid 2- (3 - ((tert-butyldimethylsilyl) sulfanic acid; l) -4-methoxy-benzisulfonyl) acetic acid, dihydrogen phosphate 0-2-methoxy-5- (carboxymethylsulfonyl-methyl) -phenyl, dimethyl phosphate 0-2-methoxy-5- (carboxymethyl-sulfonyl-methyl) phenyl; diethyl phosphate 0-2-methoxy-5- (carboxymethylsulfonyl-methyl) phenyl; dibenzyl phosphate 0-2-methoxy-5- (carboxymethylsulfonyl-methyl) phenol; phosphorothioaio S-2-meloxy-5- (carboxymethylsulfonyl-meth) phenyl-0,0-dihydrogen; phosphorus-thioate S-2-methoxy-5- (carboxymethyl) sulfonylmethyl) phenol-0,0-dimethyl; phosphorothioate S-2-methoxy-5- (carboxymethylsulfonylmethyl) phenyl-0,0-dethyl; phosphorothioate S-2-methoxy-5- (carboxymethylsulfonylmethyl) phenyl-0.0-dibenzyl; and you come out of them. Compounds of Formula Vll, wherein n is 1 or 2, and R is -alkyl of (d-d) include, for example, methyl and ethyl esters of the exemplary compounds of Formula Vll listed above.

Compounds of Formula Vll can be prepared, wherein R is -H, for example, by: (1) reacting the compound according to Formula Vll, wherein R is -alkyl of (dd), under conditions capable of hydrolyzing an ester of the carboxylic acid to the corresponding carboxylic acid, preferably in an aqueous base such as, for example, aqueous lithium hydroxide, aqueous sodium hydroxide or potassium hydroxide harassment; and (2) isolating a compound according to Formula Vll, wherein R is -H, from the reaction mixture. Compounds of Formula Vll can be prepared, wherein n is 1 and A is -O-, for example, by: (1) reacting an intermediate of Formula Vll, wherein n is 0 and A is -O-, or a salt thereof, with an oxidizing agent capable of oxidizing a sulphide for a sulfoxide; and (2) isolating a compound according to Formula Vll, where n is 1, from the products of the reaction. Compounds of Formula Vll can be prepared, where n is 2 and A is -O-, for example by (1) reacting either (a) an intermediate of Formula Vll, wherein n is O and A is -O-, with an oxidizing agent capable of oxidizing a sulfide for a sulfone; or (b) an intermediate of Formula Vll, wherein n is 1 and A is -O-, with an oxidizing agent capable of oxidizing a sulfoxide to a sulfone; and (2) isolating a compound according to Formula Vll, where n is 2, from the reaction products. Compounds according to Formula Vll, wherein n is 0, include, for example: 2- (3-hydroxy-4-methoxybenzylsulfanyl) acetic acid; 2- (3-tert-Butyldimethylsilyloxy-4-methoxybenzylsulfanyl) acetic acid; dihydrogen phosphate 0-2-methoxy-5- (carboxymethylsulfanylmethyl) phenyl; 0-2-dimethyloxy-5- (carboxymethyl sulfanylmethyl) phenyl dimethyl phosphate; diethyl phosphate 0-2-methoxy-5- (carboxymethylsulfanylmethyl) phenyl; dibenzyl phosphate 0-2-methoxy-5- (carboxymethylsulfanylmethyl) phenyl; and you come out of them. Compounds of Formula Vll, wherein n is 0, and R is -alkyl of (d-d) include, for example, methyl or ethyl esters of the exemplary compounds of Formula Vll listed above. Compounds of Formula Vll can be prepared, wherein n is 1 or 2 and A is -S- or -O-, or salts thereof, for example, by (a) reacting a compound according to Formula IX: wherein: R1, R2, Rx, A, a and * are as defined for the compounds of Formula Vll, provided that R1 is different from H; and L is a leaving group, preferably selected from the group consisting of halogen, halo, nosyl, iryl, and mesyl; With a compound in accordance with Formula X; wherein: R is -alkyl of (C C6), preferably methyl or ethyl; n is 1 or 2; and M + is a counter ion, preferably selected from the group consisting of alkali metals, preferably lithium, sodium and potassium; alkaline earth metals, preferably calcium and magnesium; and transition metals, preferably, zinc, iron, nickel, copper, titanium, manganese, cadmium and tin. (b) isolating a compound according to Formula Vll, wherein, n is 1 or 2, and R is -alkyl of (d-d), of the reaction products; (c) reacting the compound according to Formula Vll, isolated in step (b), under conditions capable of hydrolyzing a carboxylic acid ester to the corresponding carboxylic acid, preferably in a fai aqueous base such as, for example, hydroxide aqueous lithium, aqueous sodium hydroxide or aqueous poisonous hydroxide; and (d) isolating a compound according to Formula Vll, wherein n is 1 or 2, of the reaction mixture. Compounds of Formula VII can be prepared, wherein n is 0 and A is -S- or -O-, for example, by (a) reacting a compound according to Formula IX: with a compound in accordance with HIV formula: wherein, R is -H or -alkyl of (d-d) or a salt thereof; (b) isolating a compound according to Formula Vll, wherein n is 0, product of the reaction. (c) optionally, if R is -alkyl of (dd), reacting the compound according to Formula Vll isolated in step (b) under conditions capable of hydrolyzing a carboxylic acid ester to the corresponding carboxylic acid, preferably in an aqueous base such as, for example, aqueous lithium hydroxide, aqueous sodium hydroxide or aqueous potassium hydroxide; and (d) isolating a compound according to Formula Vll, wherein n is 0, of the reaction mixture. Preferred compounds according to Formula IX include, for example: 5- (bromomethyl) -2-meioxyphenoxy (tert-butyl) dimethylsilane; 5- (chloromethyl) -2-methoxyphenoxy (tert-butyl) dimethylsilane; (5- (bromomethyl) -2-methoxy-phenylthio) (tert-butyl) dimethylsilane; (5- (chloromethyl) -2-methoxyphenylthio) - (tert-butyl) dimethylsilane; dihydrogen phosphate 5- (bromomethyl!) - 2-methoxyphenyl; dihydrogen phosphate 5- (chloromethyl) -2-methoxyphenyl; 5- (bromomethyl) -2-methoxyphenyl dimethyl phosphate; phosphorylated dimethyl 5- (chloromethyl) -2-methoxyphenyl; diethyl phosphate 5- (bromomethyl) -2-meloxyphenyl; phosphonyl diethyl 5- (chloromethyl) -2-methoxyphenyl; 5- (chloro-methyI) -2-methoxyphenyl phosphate dibenzyl; dibenzyl phosphate 5- (bromomethyl) -2-methoxyphenyl; phosphorothioate S-5- (chloromethyl) -2-methoxyphenyl-0,0-dihydrogen; phosphorolioalo S-5- (bromomethyl) -2-methoxyphenyl-0,0-dihydrogen; phosphorothioate 0, O-dibenzyl-S-5- (chloromethyl) -2-methoxy-phenyl; phosphorothioane 0.0-dibencll-S-5- (bromomethyl) -2-mexoxyphenyl; phosphoroioate 0.0-dimethyl-S-5- (chloromethyl) -2-methoxyphenyl; phosphorolioate 0.0-dimethyl-S-5- (bromomethyl) -2-methoxyphenyl; phosphorothioate 0, O-diethyl-S-5- (chloromethyl) -2-methoxyphenyl; phosphorothioate 0.0-diethyl-S-5- (bromomethyl) -2-methoxyphenyl; and you leave it. Compounds in accordance with the HIV Formula include, for example, 2-mercaptoacetic acid, methyl 2-mercaptoacetate and ethyl 2-mercaptoacetoacetate.

B. Intermediates in the preparation of compounds of Formula IZ wherein X is -C * -Rx-Y- The invention is also directed to synthetic intermediates, useful in the preparation of certain compounds of Formula IZ.

The synthetic intermediate compounds have Formula XI: wherein R1, R2, Rx, A, a and * are as defined above for the compounds of Formula IX; Already-. In accordance with one embodiment of compounds of Formula XI, Rx is -H. Compounds according to Formula XI include, for example, (Z) -5 - ((2,4,6-trimethoxystyrylthio) methyl) -2-methoxyphenol; dihydrogen phosphate (Z) -5 - ((2,4,6-tri-methoxystyryl) -methyl) -2-methoxyphenyl; dimethyl phosphate (Z) -5 - ((2,4,6-trimethoxystyrylthio) methyl) -2-methoxyphenyl; diethyl phosphate (Z) -5 - ((2) 4,6-trimoxysylthyl) methyl) -2-methoxy-phenyl; dibenzyl phosphate (Z) -5 - ((2,4,6-trimethoxystyrylthio) methyl) -2-methoxyphenyl; and you leave it. The invention is also directed to synthetic intermediates, useful in the preparation of certain compounds of the invention. The compounds of the synthetic intermediate have the Formula XII: where: R1, R2, Rx, A, a and * are as defined herein for compounds of Formula IX; and M + is a counter ion, preferably selected from the group consisting of alkali metals, more preferably lithium, sodium and potassium; alkaline earth metals, more preferably calcium and magnesium; and transition metals, more preferably zinc, iron, nickel, copper, tilanium, manganese, cadmium and tin. In accordance with one embodiment of compounds of Formula XII, Rx is -H. Compounds in accordance with Formula XII include, for example, alkali metal and ferrous melanoalkali salts of: (2-methoxy-5-mercaptomethylene) (tert-butyl) dimethylsilane; (3- (tert-Butyldimethylsilyloxy) -4-methoxyphenyl) -methanediol; (3 - ((tert-Butyldimethylsilyl) sulfanyl) -4-methoxyphenyl) methan-thiol; dimephyl 2-meloxy-5- (mercaptomethyl) phenyl phosphate; diethyl phosphate 2-methoxy-5- (mercaptomethyl) phenyl; dibenzyl phosphate 2-methoxy-5- (mercapto-methyl) phenol; dihydrogen phosphate 2-methoxy-5- (mercaptomethyl) -phenyl; phosphoryl diethyl 5- (mercaptomethyl) -2-methoxyphenyl; dibenzyl phosphate 5- (mercaptomethyl) -2-methoxyphenyl; phosphorothioate S-5- (mercaptomethyl) -2-methoxyphenyl-0,0-dimethyl; phosphorothioaio S-5- (mercaptomethyl) -2-methoxyphenyl-0,0-diethyl; phosphorothioate S-5- (mercaptomethyl) -2-methoxyphenyl-O, 0-dibenzyl; and S-5- (mercaptomethyl) -2-methoxyphenyl-0,0-dihydrogen phosphorothioate.

C. Intermediates in the Preparation of Compounds of Formula 1E. where X is -NR -Z-. The invention is also directed to synthetic intermediates, useful in the preparation of certain sulfonamide and propenamide compounds of Formula IE, in particular, in the preparation of α, β-unsaturated sulfonamide and propenamide compounds of Formulas 1IB, IIIB, IVB, VB and VIB. Synthetic intermediates have the Formula Xlll: wherein R1, R2, Rx, A, Z and a are as defined herein for compounds of Formula I, and R is -H or -alkyl of (d-d); or a salt of them. According to one embodiment of the compounds of Formula Xlll, A is -O-. According to another embodiment of compounds of Formula Xlll, Rx is -H. A compound according to Formula Xlll wherein R is -H, or a salt of such a compound, can be prepared by: (a) reacting a corresponding compound according to Formula Xlll, wherein R is -alkyl of ( dd) under conditions capable of hydrolyzing a carboxylic acid ester to the corresponding carboxylic acid, preferably in an aqueous base such as, for example, aqueous lithium hydroxide, aqueous sodium hydroxide or aqueous potassium hydroxide; and (b) isolating a compound according to Formula Xlll from the reaction products, wherein R is -H. In accordance with one embodiment of the compounds of Formula Xll, a compound according to Formula XIIIA is provided: wherein R1, R2, Rx, A, a and R are as defined above in this document for compounds of Formula XIII; or a salt of such compound. In accordance with another embodiment of the compounds of Formula Xll, a compound according to Formula XIIIB is provided: wherein R, R, Rx, a, R and A are as defined above in this document for compounds of Formula Xll; or salts of such compound. Compounds according to Formula XIIIA include, for example: N- (3-hydroxy-4-mexoxyphenyl) carboxymethylsulfonamide; N- (3-mercapto-4-methoxyphenyl) carboxymethylsulfonamide; N- (3-tert-butyldimethylsilyloxy-4-methoxyphenyl) carboxymethylsulfonamide; 3 - ((tert-butyldimethylsilyl) -sulfanyl) -4-methoxyphenylsulphamoylacetic acid; 2- (3-tert-butyldimethyl-silyloxy-4-methoxyphenylsulfamoyl) acetic acid; 2-methoxy-5- (N- (carboxymethyl) sulfamoyl) phenyl phosphate; phosphoryloxy-2-meioxy-5- (N- (carboxymethyl) sulfamoyl) phenol; diethyl phosphate 2-methoxy-5- (N- (carboxymethyl) sulfamoyl) phenyl; dibenzyl phosphate 2-methoxy-5- (N- (carboxymethyl) sulfamoyl) phenyl; phosphorus-thioate S- (2-methoxy-5- (N- (carboxymethyl) -sulfamoyl) phenyl) -0,0-dimethyl; phosphoroiioaio S- (2-meioxy-5- (N- (carboxymethyl) -sulfamoyl) phenyl) -0, Odimethyl; phosphoroiioaio S- (2-methoxy-5- (N- (carboxymethyl) sulfamoyl) phenyl) -0,0-diethyl; phosphorus thioate S- (2-methoxy-5- (N- (carboxymethyl) sulfamoyl) phenyl) -0,0-d-benzyl; and you come out of them. Compounds according to Formula XIIIB include, for example: 2- (3-mercapto-4-methoxyphenylcarbamoll) acrylic acid; 2- (3-hydroxy-4-methoxy-phenylcarbamoyl) -acetic acid; 3 - ((tert -buyldimethylsilyl) sulfanyl) -4-meioxy-phenylcarbamoylaseic acid; 2- (3-urea-butyldimethylisillloxy-4-methoxyphenyl-carbamoyl) -acetic acid; 5-N- (carboxymethyl) carbamoyl-2-mexoxyphenyl phosphate; dimethyl 5-N- (carboxymethyl) carbamoyl-2-mexoxyphenyl phosphate; diethyl phosphate 5-N- (carboxymethyl) carbamoyl-2-methoxyphenyl; dibenzyl phosphate 5-N- (carboxymethyl) carbamoyl-2-methoxyphenyl; phosphorus-thioate S-5-N- (carboxymethyl) carbamoyl-2-mexoxyphenyl; dimethyl phosphorothioate S-5-N- (carboxymethyl) carbamoyl-2-methoxyphenyl; phosphorothioate diethyl S-5-N- (carboxymethyl) carbamoyl-2-methoxyphenyl; phosphorothioate dibenzyl S-5-N- (carboxymethyl) carbamoyl-2-mexoxyphenyl; and you come out of them. Compounds of Formula Xlll and salts thereof can be prepared, wherein R is -alkyl of (d-d), for example, by (a) reacting a compound according to Formula XIV: wherein R1, R2, Rx, A and a are as defined herein for compounds of Formula Xll; or a salt thereof; with a compound in accordance with Formula XV: wherein it is as defined in this document for compounds of Formula I; R is -alkyl of (d-d); and L is a leaving group, preferably selected from halogen, more preferably chlorine; and (b) isolating a compound according to Formula Xlll, or a salt thereof, from the reaction mixture.

HIV Methods for Preparing Compounds of Formula In accordance with another aspect of the invention, methods for preparing compounds according to Formula I are provided.

A. Preparation of compounds of Formula IE, wherein X is -CH * RX-Y- According to one embodiment, a compound according to Formula IE: or a salt thereof, wherein R1, R2, R3, A, Q, a and B are as defined herein for compounds of Formula I, and X is -CH * RX-Y-, can be prepared by: ( a) reacting a compound in accordance with Formula Vll: or a sai uei same, in uopue n is i or 2, with a compound according to Formula XVI: (b) isolating a compound according to Formula IE, or a salt thereof, from reaction products.

B. Preparation of compounds of Formula IZ, wherein X is CH * RX-Y- (i) Preparation of compounds wherein A is -O- In accordance with one embodiment of the invention, a compound according to Formula IZ: or a salt of such compound; wherein R1, R2, R3, A, Q, a and B are as defined herein for compounds of Formula I wherein X is -CH * RX-Y-, Y is-S (= 0) -; and A is -O-, can be prepared by: (a) reacting a compound in accordance with Formula XI: or a salt thereof, with an oxidizing agent capable of oxidizing a sulphide for a sulfoxide; and (b) isolating a compound according to Formula IZ, or a salt thereof, from the reaction products. According to another embodiment, a compound according to Formula IZ, or a salt thereof, wherein R1, R2, A, Q, a and b are as defined in this document, X is -CH * RX-Y-, And it is -S02-, and A is -O-, it can be prepared either: (a) reacting a compound according to Formula XI, or a salt of! same, with an oxidizing agent capable of oxidizing a sulfide to a sulfone; and (b) isolating a compound according to Formula IZ, or a salt thereof, from the products of the reaction; or by (a) reacting a compound according to Formula IZ, or a salt thereof, wherein R1, R2, R3, A, Q, a and b are as defined herein; X is -CH * RX-Y-, Y is -S (= O) -, and A is -O-; with an oxidizing agent capable of oxidizing a sulfoxide for a sulfone; and (b) isolating a compound according to Formula IZ, or a salt thereof, from the reaction products. The compound of Formula XI can be prepared, for example, by: (a) reacting a compound in accordance with Formula Xll: with a compound in accordance with Formula XVll: (b) isolating a compound according to Formula XI from the reaction products.

C. Preparation of compounds of Formula IE, wherein X is -NRX-Z-. According to another embodiment of the invention, there is provided a process for preparing a compound according to Formula IE, or a salt thereof, wherein X is -NRX-Z-, which comprises: (a) reacting a compound according to formula XIV: or a salt thereof, with a compound according to Formula XVlll: wherein, Z is as defined herein for compounds of Formula I, R is -alkyl of (d-d), and L is a leaving group selected from halogen, preferably chlorine; (b) isolating a compound according to Formula Xlll, wherein R is -alkyl of (d-d); (c) hydrolyzing the compound according to Formula Xlll, isolated in step (b), for the corresponding carboxylic acid, preferably in an aqueous base such as, for example, aqueous lithium hydroxide, aqueous sodium hydroxide or potassium hydroxide. aqueous; (d) isolating from the reaction products of efapa (c), a compound according to Formula Xlll, or a salt thereof, wherein R is -H; (e) optionally, if R1 is a protecting group comprising - Si [(C6) alkyl] 3, or -CH2CH2Si [(C3) alkyl] 3, remove said protecting group, preferably with a reagent selected from the group consisting of tetrabutylammonofluoride (TBAF) and triethylamine trihydrofluoride; (f) isolating a compound according to Formula XIIIA, or a salt thereof, from the reaction products of step (e): (g) coupling either the compose in accordance with the Formula Xlll isolated in step (b), or the compound corresponding to Formula XIIA formed in step (f), with an aromatic aldehyde of formula XVI: preferably, in an acidic solvent or acidic solvent mixture, more preferably, glacial acetic acid at high lemmaperaurate; and (h) isolating a compound according to Formula IE, wherein X is -NRX-Z-, or a salt of such compound.

D. Preparation of compounds of Formula IZ or IE, wherein X is -NRX-Z. According to another embodiment of the invention, there is provided a process for preparing a compound according to Formula IZ or Formula IE, or a salt thereof comprising: (1) derivitizing a carboxylic acid of Formula XVIII, or a salt thereof; same: wherein Q, R3 and b are as defined by Formula I and the carbon-carbon double bond can be either (E) - or (Z) -formation; to form a carboxylic acid derivative of Formula XVIIIA: wherein L1 is a leaving group selected from halogen, preferably chloro, and -OC (= 0) alkyl of (d-d); (2) coupling the carboxylic acid derivative of Formula XVIIIA for a compound according to Formula XIV: (3) isolate from the reaction products, either: (a) a compound according to Formula IE, if the exocyclic carbon-carbon double bond of formula XVlll is in (E) -formation; or (b) a compound according to Formula IZ, if the exocyclic carbon-carbon double bond of Formula XVlll is in the (Z) -formation; or a salt of the compound according to Formula IE or IZ.

IX. Conjugates of Compounds of the Invention In accordance with another embodiment of the invention, there is provided a conjugate of Formula I-L-Ab, wherein I is a compound according to Formula I; Ab is an antibody; u -L- is a single bond or a linking group covalently linked to said compound according to Formula I for said antibody. In accordance with the sub-modalities of conjugates of Formula I-Ab, the compound according to Formula I, which forms the conjugate is a compound according to Formula HA, IIB, HIA, IIIB, IVA, IVB, VA , VB. VlA and VIB. In a preferred sub-modality of the aforementioned conjugates, the antibody (Ab) is a monoclonal antibody or a specific polyclonal antibody. In more preferred sub-modalities of the aforementioned conjugates, the antibody (Ab) is a tumor specific anylibody.

X. Pharmaceutical Compositions In accordance with another embodiment of the invention, compositions are provided, comprising a pharmaceutically acceptable carrier and a compound according to Formula I: wherein R1, R2, R3, A, X, Q, a and B are as described above by Formula I; or a salt of such compound. Also provided are pharmaceutical compositions comprising a pharmaceutically acceptable carrier and at least one conjugate according to Formula l-L-Ab, wherein I, L and Ab are as defined herein.

XI. Methods of Treatment According to other embodiments of the invention, there is provided a method for treating an individual for a proliferative disorder, particularly cancer, which comprises administering to the individual an effective amount of at least one compound in accordance with Formula I or at least a conjugate of Formula I-Ab, alone or in combination with a pharmaceutically acceptable carrier. According to a further embodiment of the invention, there is provided a method for inducing apoptosis of tumor cells in an individual affected with cancer, comprising administering to the individual an effective amount of at least one compound according to Formula I, or at least a conjugate of Formula I-Ab, either alone or in combination with a pharmaceutically acceptable carrier. According to another embodiment of the invention, there is provided a method for inhibiting the growth of tumor cells in an individual afflicted with cancer, comprising administering to the individual an effective amount of at least one compound according to Formula I, or at least a conjugate of Formula I-Ab, alone or in combination with a pharmaceutically acceptable carrier. In accordance with another embodiment of the invention, there is provided a method for reducing or eliminating the effects of ionizing radiation on normal cells in an individual who has incurred or is at risk of incurring exposure to ionizing radiation. This method comprises administering to the individual either before or after exposure to ionizing radiation, at least one compound according to Formula I, alone or in combination with a pharmaceutically acceptable carrier. In accordance with another embodiment of the invention, there is provided a method for safely increasing the dose of therapeutic ionizing radiation used in the treatment of cancer or other proliferative disorder, comprising admixing an effective amount of at least one radioprotective compound according to the Formula I, alone or in combination with a pharmaceutically acceptable carrier. Without wishing to be bound by any theory, it is believed that the radioprotective compound induces a temporarily radioresistant phenotype in the normal tissue of the individual. In accordance with another embodiment of the invention, there is provided a method for treating an individual who has incurred, or is at risk of incurring remediable radiation injury from exposure to ionizing radiation. This method comprises administering an effective amount of at least one radioprotective compound according to Formula I, alone or in combination with a pharmaceutically acceptable carrier, either before, or after the individual incurs injury by remediable radiation by exposure to radiation. ionizing According to another embodiment of the invention, there is provided a method for treating an individual for a proliferative disorder, particularly cancer, comprising: (1) administering to the individual an effective amount of at least one radioprotechlor compound according to Formula I , or at least one conjugate of Formula I-Ab; and (2) administer an effective therapeutic ionizing radiation. In accordance with another embodiment of the invention, there is provided a method for reducing the number of malignant cells in the bone marrow of an individual, comprising: (1) removing a portion of the individual's bone marrow; (2) administering an effective amount of at least one radioprotective compound according to Formula I, to remove the bone marrow; and (3) irradiate the removed bone marrow with an effective amount of ionizing radiation. In accordance with a sub-modality, the above method is provided to reduce the number of malignant cells in the bone marrow of an individual, further comprising replacing the bone marrow with the irradiated bone marrow. According to another embodiment of the invention, there is provided a method for protecting an individual from cytotoxic side effects of the administration of a cytoxy agent, particularly a mitotic phase or topoisomerase inhibitor cell cycle inhibitor, which comprises administering to the individual, during the administration of the cyto-toxic agent, an effective amount of at least one cytoproctor compound according to Formula I; wherein the mitotic phase or topoisomerase inhibitor cell cycle inhibitor is not a compound according to Formula I. In accordance with another sub-modeling thereof, the described method is provided above, wherein the cylco-toxic agent is a topoisomerase inhibitor. Topoisomerase inhibitors may be inhibitors of topoisomerase I, topoisomerase II, or both. Inhibitors of iopoisomerase I include, but are not limited to, adriamycin and etoposide. Topoisomerase II inhibitors, include but are not limited to, camptothecin, irinotecan, topotecan and mitoxantrone. In accordance with another embodiment of the invention, there is provided a method of treating an individual for a pro-inflammatory disorder, particularly cancer, comprising: (1) administering to the individual an effective amount of at least one cytoprotein compound according to Formula I , or at least one conjugate of Formula I-Ab; and (2) administering an effective amount of at least one mitotic cell phase inhibitor or topoisomerase inhibitor after administration of at least one cytoprotective compound according to Formula I, or at least one conjugate of Formula I-L-Ab. According to another embodiment of the invention, there is provided the use of at least one compound according to the Formula I, or at least one conjugate in accordance with Formula I-Ab, either alone or as part of a pharmaceutical composition, for the preparation of a medicament for: (a) bringing a proliferative disorder in an afflicted individual with a proliferative transloid; (b) inhibiting the growth of tumor cells in an individual afflicted with cancer; (c) induce apoptosis of tumor cells in an individual afflicted with cancer; (d) bringing an individual who has incurred, or is at risk of incurring remediable radiation injury from exposure to ionizing radiation; (e) reducing or eliminating the effects of ionizing radiation on normal cells in an individual who has incurred or is at risk of incurring radiation exposure; (f) safely increase the dosage of therapeutic ionizing radiation used in treatment with cancer or other proliferative disorder; (g) protect an individual from the cytotoxic side effects of the administration of a cytotoxic agent.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows the dose response curve for the compound (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenol (Example 1) in six different cancer cell lines.

DETAILED DESCRIPTION OF THE INVENTION I. Treatment of Proliferative Disorders In accordance with the present invention, it is believed that the compounds of Formula I and salts thereof, and conjugates according to Formula l-Ab, are selective for inhibiting the proliferation of cancer cells, and eliminate several types of tumor cells without elimination (or with reduced elimination of) normal cells. It is believed that cells are removed at concentrations where normal cells can temporarily stop growth but not eliminate them.

A. Cancer Treatment The compounds and conjugates of the invention can be administered to individuals (mammals, including animals and humans) afflicted with cancer. The compounds and conjugates of the invention are believed to inhibit the proliferation of tumor cells, for some compounds or conjugates, to induce cell death. Cell death is believed to result from the induction of apoptosis. It is believed that the compounds and conjugates are effective against a broad scale but are not limited to the following: ovarian cancer; cervical cancer; breast cancer; prostate cancer; Testicular cancer; lung cancer; Kidney cancer; Colorectal cancer; skin cancer; brain cancer; leukemia, which includes acute myeloid leukemia, chronic myeloid leukemia, acute lymphoid leukemia, and chronic lymphoid leukemia. More particularly, cancers can be treated by the compounds, conjugates, compositions and methods of the invention including, but not limited to the following: cardiac cancers, including, for example, sarcoma, eg, angiosarcoma, fibrosarcoma, rhabdomyosarcoma and liposarcoma; myxoma; rhabdomyoma; fibroma; lipoma and teraíoma; lung cancers, including, for example, bronchogenic carcinoma, eg, squamous cell, undifferentiated small cell, undifferentiated large cell and adenocarcinoma; alveolar and bronchial carcinoma; bronchial adenoma; sarcoma; lymphoma; chondromatose hamartoma; and mesothelioma; gastrointestinal cancer, which includes, for example, cancers of the esophagus, for example, squamous cell carcinoma, adenocarcinoma, leiomyosarcoma and lymphoma; stomach cancers, for example, carcinoma, lymphoma and leiomyosarcoma; cancers of the pancreas, for example, ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumors, and vipoma; small bowel cancers, eg, adenocarcinoma, lymphoma, carcinoid tumors, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, and fibroma; cancers of the large intestine, for example, adenocarcinoma, tubular adenoma, hairy adenoma, hamartoma and leiomyoma; cancers of the genitourinary tract, which include, for example, kidney cancers, eg, adenocarcinoma, Wilm's tumor (nephroblastoma), lymphoma and leukemia; bladder and ureral cancers, for example, squamous cell carcinoma, intermediate cell carcinoma and adenocarcinoma; cancers of the prostate, for example, adenocarcinoma and sarcoma; lesion cancer, for example, seminoma, teratoma, embryonal carcinoma, teratocarcinoma, coroosarcoma, sarcoma, interstitial cell carcinoma, fibroma, fibroadenoma, adenomatoid and lipoma tumors; liver cancers that include, for example, hepaíoma, for example, hepatocellular carcinoma; cholangiocarcinoma; hepatoblastoma; angiosarcoma; hepatocellular adenoma and hemangioma; bone cancer, which includes, for example, osteogenic sarcoma (westosarcoma), fibrosarcoma, malignant fibrous histocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticulum cell sarcoma), multiple myeloma, giant malignant cell tumor chordoma, osteochondroma (osteocartilaginous exostoses), chondroma beninga, chondroblastoma, chondromyofibroma, osteoid osteoma, and giant cell tumors; cancers of the nervous system including, for example, skull cancers, eg, osteoma, hemangioma, granuloma, xanthoma and osteitis deformities; cancers of the meninges, for example, meningioma, meningiosarcoma and gliomatosis; cancers of the brain, for example, astrocytoma, medulloblastoma, glioma, ependioma, gerrninoma (pinealoma), multiform glioblasloma, oligodendroglioma, eschwanoma, retinoblastoma and congenital tumors; and spinal cord cancers, eg, neurofibroma, meningioma, glioma and sarcoma; gynecological cancers including, for example, ureiral cancers, for example, endomelial carcinoma; cervical cancers, for example, cervical carcinoma and cervical pre-tumoral dysplasia; cancers of the ovaries, for example, ovarian carcinoma, which includes serous cystadenocarcinoma, mucosal cystadenocarcinoma, unclassified carcinomas, granulosa-thecal cell tumors, sertoli-leydig cell lumps, dysgermoma and malignant omegalamy; vulvar cancers, for example, squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma and melanoma; cancers of the vagina, for example, clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma and embryonal rhabdomyosarcoma; and cancers of the fallopian tubes, eg, carcinoma; hematologic cancers including, for example, blood cancers, for example, acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative diseases, multiple myeloma and myelodysplastic syndrome, Hodgkin's lymphoma, non-Hodgkin's lymphoma (malignant lymphoma) ) and Waldentrom's macroglobulinemia; skin cancers including, for example, malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, nevi dysplastic moles, lipoma, angioma, dermatofribroma, keloid, psoriasis; and cancers of the adrenal gland including, for example, neuroblastoma. Cancers can be solid tumors that may or may not be metasytic. Cancers can also occur, as in leukemias, as a diffuse tissue. Thus, the term "cellular murmur" as provided herein, includes a cell afflicted by any of the disorders identified above. In accordance with one modality of the methods for the treatment according to the invention, the treated proliferative disorder is hepatoma. According to another embodiment of the treatment methods according to the invention, the treated proliferative transient is breast cancer.

B. Treatment of Non-cancerous Proliferative Disorders The compounds and conjugates of the invention are also believed to be useful in the treatment of non-cancerous proliferative disorders, i.e., proliferative disorders which are characterized by benign indications. Such disorders are also known as "cytoproliferative" or "hyperproliferative", in which the cells are elaborated by the body at an atypically high rate. It is believed that non-cancerous proliferative disorders amenable to compounds and conjugates of the invention include, for example: hemangiomatosis in newborns, secondary progressive multiple sclerosis, atherosclerosis, chronic progressive myelodegenerative disease, neurofibromatosis, ganglioneuromaiosis, keloid formation, Pageís' disease. bone, fibrocystic disease of the breast, uterine fibrosis, fibrosis Peronies and Duputren, restenosis, benign proliferafive breast disease, benign prostatic hyperplasia, lymphoproliferative disorder such as X (Duncan's disease), lymphoproliferative disorder after transplantation (PTLD), macular degeneration and retinopathies, such as diabetic retinopathies and proliferative vitreoretinopathy (PVR). Other non-cancerous proliferative disorders are believed to be treatable by compounds and conjugates of the invention, including the presence of pre-cancerous lymphoproliferative cells associated with a high risk of progression to a cancerous disorder. Many noncancerous lymphoproliferative disorders are associated with latent viral infections such as Epstein-Barr virus (EBV) and Hepatitis C. These disorders often begin as a benign pathology and progress in lymphoid neoplasia as a function of time. The treatment of tumor cells with the compounds and conjugates of the invention is believed to lead to the inhibition of cell proliferation and the induction of apoptotic cell death.

II. Radioprotective Treatment The compounds of Formula I are also believed to protect normal cells and tissues from the effects of acute and chronic exposure to ionizing radiation. Individuals may be exposed to ionizing radiation when they are under therapeutic irradiation for the treatment of proliferative disorders. It is believed that the compounds are effective in protecting normal cells during the therapeutic irradiation of abnormal tissues. It is also believed that the compounds are useful in the protection of normal cells during the radiation trampling for leukemia, especially in the purging of malignant cells from autologous bone marrow grafts with ionizing radiation. In accordance with the invention, therapeutic ionizing radiation can be administered to an individual in any scheme and in any dose consistent with the prescribed course of tracing, as soon as the radioprotective compound according to the invention is administered before radiation. The training course differs from individual to individual, and those of ordinary skill in the art can easily determine the appropriate dose and therapeutic radiation scheme in a given clinical situation. lll. Chemoproyecto treatment To others, the compounds of Formula! It is believed that normal cells and tissues are protected from effects of exposure to miicidal phase cell cycle inhibitors and lopoisomerase inhibitors. Miicidal cell phase inhibitors include, but are not limited to, vinca alkaloid, for example vincrisine and vinblastine, particularly vincristine; estramustine; taxanes, for example, paclitaxel and paclitaxel analogs, particularly paclitaxel; macrolens that originate naturally, for example, rhizoxin, maitasin, ansamitocin P-3, fomopsin A, dolastatin 10 and halicrondins B; Colchicine and Colchicine derivatives. Paclitaxel is an anti-mitotic drug which has been used as an initial for ovarian, breast and lung cancer, with moderate success.

Vincristine is a well-established anti-miotic drug widely used for the treatment of breast cancer, Hodgkin's lymphoma and childhood cancers. Topoisomerase inhibitors include compounds that inhibit topoisomerase I, compounds that inhibit topolsomerase II, and compounds that inhibit both topoisomerase I and II. Iopoisomerase I inhibitors include, for example, adrlamycin, eloposide, ß-lapacone (Calbiochem No. 428022). AG-555 (Calbiochem No. 112270), 10-hydroxycatothecin (Calbiochem No. 390238), AG-1387 (Calbiochem No. 658520), rebeccamycin (Calblochem No. 553700), nagalamicin (Calblochem No. 488200) and topotecan (Calbiochem No 614800). Topoisomerase II inhibitors include, for example, camptolecine, irinotecan and topotecan, amsacrine (Calbiochem No. 171350), aurintricarboxylic acid (Calbiochem No. 189400), bruneomycin (Calbiochem No. 571120), ellipticine (Calblochem No. 324688), epirubicin (Calbiochem). Do not. 324905), etoposide (Calbiochem No. 341205), genistein (Calbiochem No. 345834) and merbarone (Calbiochem No. 445800). Inhibitors of both topoisomerases I and II include, for example, aclarubicin (Calbiochem No. 112270), congocidin (Calblochem No. 480676), daunomycin (Calbiochem No. 251800), ellagic acid (Calbiochem No. 324683), and suramin (Calbiochem No. 574625). The compounds of the present invention are believed to not only protect normal cells, but are also operationally cytotoxic in tumor cells. In normal cells, the cytoprotective compounds of the invention are believed to induce a reversible resting state by providing normal cells relatively refractory to the cytotoxic effect of mitotic phase cell cycle inhibitors and topoisomerase inhibitors.

IV. Formula Compounds A. Ring Substitution The substitution pattern for hydrogens of the phenyl ring ring and aromatic ring Q of Formula I can comprise any substitution pattern as soon as the functionality -A-R1 is placed at position 3 of the relative ring fenllo a -X-. For example, when ring Q is phenyl, the tri-substitution in Q may comprise substitution in positions 2, 3 and 4, positions 2, 4 and 5, positions 3, 4 and 5, positions 2, 5 and 6 or positions 2 , 4 and 6. The substitution of a phenyl Q may include substitution, for example, in positions 2 and 3, positions 2 and 4, positions 2 and 5, positions 2 and 6, positions 3 and 4 , positions 3 and 5 or positions 3 and 6. The substitution pattern in a heteroaryl ring Q of five elements must also count for the number of heyeroaltones contained in the ring heieroaromáíico and point of union of the heteroaryl ring. The substitution in a heteroaromatic ring of five elements contains a heteroatom, in which the heteroaryl ring is joined via its 2 positions, serves to exemplify the variety of substitution patterns. The suspension in the aforementioned five-membered heteroaryl ring Q may be, for example, in position 3, 4 or 5 for mono-substitution; and in positions 3 and 4, 3 and 5, or 4 and 5 for di-substitution. When b is 1 in Formula I, R3 is preferably located in the ortho- or para positions. When b is 2, the R3 substituents are preferably located in ortho- or para-positions, or in both ortho-positions. When b is 3, the substituents R3 are preferably located in the para- position and at least one ortho-, more preferably, in the para positions and in both ortho. When b is 1 in Formula I, R2 is preferably placed para- to -X or para- to -A-R1; more preferably, para- to -X. When a is 2 or 3, the R3 substituents are preferably placed para- to -X and para- to -A-R1. The terms substitution positions "para-", "meta-" and "ortho-" in a ring are also denoted by a number system. However, numerical systems are often not consistent between different ring systems. In aromatic systems of six elements, the spatial arrangements are specified as described above by the common nomenclature "para-" for 1.4-substitution, "meta-" for 1, 3-substitution and "ortho-" for 1, 2- substitution as shown below in Reaction Scheme 3.

REACTION SCHEME 3 "para-" meta- "" ortho- Recci Scheme ii 3 Since the aromatic rings are essentially flat, ortho-meta- and para- designations, they essentially define geometric positions in a ring of six elements that correlate geometrically to the planar angles. Thus, a substitute is formed by a flat angle of 60 ° with a reference substituent referred to as being ortho. Similarly, a target substituent defines a plane angle of 120 ° and a substituent to define an angle of 180 °. The designation of substitute patterns as ortho, meta and para nomenclature as angles of 60, 120 and 180 is descriptive for six-element unicycles. There is no substituent in a six-element aromatic ring or a bicyclic ring, which forms an angle of 60, 120 or 180 ° C. However, the definition of a flat angle or a scale of flat angles between two substituents is a convention which easily communicates a particular substitution pattern that is independent of the nature of the particular ring involved. A susfituyenie for in an aromatic ring of six elements, is closely approximated in other flat monocyclic or bicyclic rings by any substituent, which, with the reference substituent, forms a flat angle between about 144 ° and about 180 °. Similarly, a target substituent in a six element ring is approximated in other flat mono or bicyclic rings by any substituent which, with the reference substituent, forms a flat angle of between about 90 ° and about 144 °. Several examples of subservient patterns which could be communicated in this way were represented in Reaction Scheme 4.

REACTION SCHEME 4 Reaction Scheme 4 In some cases, a true angle is not formed between a substituent and a reference substituent. An example of this is a naphthalene system substituted at positions 1 and 5 as shown in structure (e) above. In the structure (e) there is no geometric intersection between the lines defined by the links in positions 1 and 5. However, it is reasonable with respect to these "parallel" links, to define an angle of 180 ° and in this way, to approximate the arrangement for a flat ring of six elements. Thus, for the references described above for the positions of substituents R2 and R3, the substitution preference for, corresponds to substituents forming a flat angle of between about 144 ° C and about 180 °, or the bonds are parallel as in structure (e) of Reaction Scheme 4. Similarly, meta substitution preferences correspond to substituents that form a plane angle of glare approximately 90 ° and approximately 144 °. Ortho substitution preferences, always refer to a substitution in a position adjacent to the position used as a reference position.

B. E- / Z- Isomerism in Compounds of the Invention Compounds of Formula I are characterized by somerism resulting from the presence of an exocyclic carbon-carbon double bond. That isomerism is commonly referred to as a cis-rans isomerism, but the more comprehensive naming convention employs E- and Z- designations. The compounds are named in accordance with the Cahn-Ingold-Prelog system, Recommendations lUPAC 1874, Section E: Stereochemistry, in Nomenclature of Organic Chemistry, John Wiley & Sons, Inc., New York, NY, 4th. Ed., 1992, p. 127-138, complete contents which are incorporated herein by reference. Using this system of nomenclature, the four groups approximately to a double bond, are groups prioritized in accordance with a series of rules. Then, such an isomer with the two higher ranked groups on the same side of the double bond, is designated Z (by the German word "zusammen", which means altogether). The other isomer, in which the two higher classification groups are on opposite sides of the double bond, is designated E (by the German word "enigence", which means "opposite"). Thus, if the four groups in a carbon-carbon double bond are classified, A is the lowest classification and D is the highest A > B > C > D, the isomers may be named as in Reaction Scheme 5.

REACTION SCHEME 5 configuration Z configuration E Reaction Scheme 5 Unless indicated otherwise, both configurations are represented below in Reaction Scheme 6, and mixtures thereof, are included in the scope of compounds of Formula I.

REACTION SCHEME 6 configuration (Z) configuration (E) Reaction Scheme 6 C. Optical Isomerism The present invention is also directed to isolated optical isomers of compounds according to Formula I. The isomers resulting from the presence of a chiral center comprise a pair of non-superimposable isomers., which are called "enaníiómeros". The unique enantiomers of a pure compound are optically active, that is, they are capable of rotating the plane of polarized light. Unique enantiomers are designated in accordance with the Cahn-Ingold-Prelog system. See, March, Advanced Organic Chemistry, 4ía. Ed., (1992) p.109. Once the priority classification of the groups is determined, the molecule is oriented so that the lowest classification group is indicated away from the observer. Then, if the ranking order descends from the other groups proceeds in clockwise direction, the molecule is designated (R) and if the descending classification of the other groups proceeds counterclockwise, the molecule is designated (S). In the example in Reaction Scheme 7, the Cahn-lngold-Prelog classification is A >; B > C > D. The lowest classification atom D is oriented away from the observer.

REACTION SCHEME 7 configuration (R) configuration (S) Reaction Scheme 7 The sulfoxides of Formula I (for example, sulfoxides of Formulas HB, HIB, IVB, VB and VIB), have at least one chiral center, which is the sulfoxide sulfur atom. In addition, for the compounds of Formula I, where X is -C * H (RX) S02, or -C * H (Rx) SO-, and RX is different from hydrogen, the carbon atom (C *) to which Rx is attached, is a chiral center.

For the chiral sulfoxide center present in the compounds of the present invention (compounds of Formula I, wherein Y is -S (= 0) -), the atoms of lower priority (an empty orbit), and higher priority ( the sulfoxide oxygen) approximated to the chiral sulfur, are fixed. Thus, the absolute configuration of the compounds of the invention depends on the priority classification of the two carbon atoms attached to the sulfoxide group as shown in Reaction Scheme 8.

REACTION SCHEME 8 and Evade Reaction Scheme 8 Certain compounds of Formula I may have more than one chiral center, for example, when X is -C * H (Rx) SO2, or -C * H (Rx) SO-, and Rx is other than -H. If a compound has more than one chiral center, it results in diastereomeric isomerism, as exemplified in Reaction Scheme 9, by the urodal structures of Formula 1.

REACTION SCHEME 9 The present invention means encompassing diastereomers, as well as their racemic and resolved, diastereomerically and enantiomerically pure forms and salts thereof. Diastereomeric pairs can be resolved by known separation techniques including reverse and abnormal phase chromatography, and crystallization. The isolated optical isomers can be purified from racemic mixtures by well-known chiral separation techniques. According to such a method, a racemic mixture of a compound having the structure of Formula I, or a chiral inermidiary thereof, is separated into 99% by weight of pure optical isomers by HPLC, using a suitable chiral column, as an element of the family series of columns DAICEL CHIRALPAK (Daicel Chemical Industries, Ltd., Tokyo, Japan). The column is operated in accordance with the manufacturer's instructions.

V. Preparation of Compounds of the Invention Compounds of Formula I can be prepared via synthetic organic chemistry methods, within the capacity of a chemist of ordinary skill. The compounds of Formula I wherein the carbon-carbon double bond is (E) and wherein the exocyclic carbon-carbon double bond is (Z), are preferably prepared via processes that are selective for the preparation of olefins (E) or ( Z), respectively.

A. Preparation of a, ß-lnsaturated Sulphoxides and Sulfones Formula (i) Preparation of Compounds of Formula IE A preferred preparation of compounds (E) of Formula I, wherein X is -C * H (R *) SO- or -C * H (R *) S02-, is for a Knoevenagel condensation of Q-aldehydes 8j with substituted phenyl- (CHRx) n-sulfinyl acetic acids 7b, or substituted phenyl- (CHRx) n-sulfonyl acetic acid acids 7a, respectively, in accordance with Reaction Scheme 10 below, wherein R1, R2, R3, Rx, A, Q, a, b, n, and * are as defined herein by Formula I.

REACTION SCHEME 10 n = 2; Formula I wherein X = -C * (R ") S02- n = 1; Formula I wherein X = -C * (R") SO- The synthesis route illustrated in Reaction Scheme 10, serves to produce compounds of Formulas 9a and 9b, which are themselves, compounds of Formula I. In addition, the compounds of Formulas 9a and 9b, serve as advanced intermediates, which they may also be derivatized to provide additional new compounds of Formula I, via derivatization of the 3-hydroxy or 3-mercapto portion. In accordance with Reaction Scheme 10, a starting phenol or thiophenol 1 is first derivatized to protect the phenol or thiophenol moiety. The compounds of phenol and thiophenol 1 are reacted with trlalkylsilyl halide, preferably urea-butyldimethylsilyl chloride (t-BDMS-CI), or with a vinyltralkyl silane, preferably vinyl urea-butyldimethylsilane or vinyl trimethylsilane, to produce the corresponding protected trialkylsilylethyl phenol or thiophenol 2. The protected compound 2, is treated with a reducing agent capable of reducing a ketone or aldehyde to the corresponding alcohol. Suitable reducing agents include hydride reducing agents, for example, NaBH and NaBH3CN. Preferably, the reaction is carried out in a solvent, for example, tetrahydrofuran (THF). The reduction provides the benzyl alcohol derivative 3. The benzyl alcohol 3 is reacted with a halogenating agent, for example, thionyl chloride, to provide the benzyl halide derivative 4. In accordance with Reaction Scheme 10, the composed of benzylmercaponeclic acid 5, is formed by the reaction of mercapioacetic acid (or salt thereof) with 4, wherein R2, Rx and a, are as defined herein for Formula I and L is a leaving group. Suitable mercaptoacetic acid salts include alkali metal salts such as sodium and potassium salts. Suitable leaving groups for 4 include, for example, halogen, tosyl, nosyl, trifly or mesyl. The reaction is preferably carried out, in a polar solvent, more preferably, a (C 1 -C 4) alkyl alcohol, for example methanol. The reaction is preferably carried out, at ambient or higher temperature, more preferably, greater than 50 ° C, more preferably, at reflux temperature of the solvent. The benzylmercaptoacetic acid compound 5 is then deprotected to remove the lyophenol or phenol proponent, PG, to provide 3-hydroxy or 3-mercaptobenzylmercaptoacetic acid 6. Suitable deprotection reagents include TBAF and triethylamine trihydrofluoride. The deprotected compound 6 is then oxidized with a suitable oxidizing agent to give a corresponding sulfinyl acetic acid compound 7b, or sulfonyl acetic acid compound 7a. A suitable oxidation agent is any oxidant capable of selectively oxidizing a sulfide to a sulfoxide (e.g., 7a), or capable of selectively oxidizing a sulfide to a sulfone (e.g., 7b). Examples include 3-chloroperbenzoic acid (MCPBA) (Aldrich 27,303-1) and potassium peroxymonosulfate (Aldrich 22, 803-6). Oxidation to form sulfoxide 7b is preferably carried out at low temperature, preferably from -40 ° C to 0 ° C. Oxidation to form sulfone 7a is preferably carried out at room temperature or higher, more preferably from 30 ° C to 50 ° C. The reaction is preferably carried out in a suitable solvent. Suitable solvents are preferably non-polar organic solvents, more preferably, halogenated solvents, for example, dichloromethane (DCM). The condensation of sulfoxide 7b or sulphone 7a with Q-aldehydes 8, via a Knoevenagel reaction in the presence of benzylamine and glacial acetic acid, yields the desired (E) -a-β-unsaturated sulfoxide 9b, or sulfone (E) ) -a, ß-unsaturated 9a, respectively. Compounds 9b or 9a are compounds of formula I, wherein R 1 is H. Compounds 9b and 9a can be subsequently derivatized to provide the additional compounds of Formula I as described in this document. (ii) Preparation of Compounds of Formula IZ A preferred preparation of compounds of Formula IZ wherein X is -C * H (Rx) SO- or -C * H (Rx) S02-, is by oxidation of the sulfide compound corresponding to either the sulfoxide or the sulfone. The Q-acetylenes 10 are reacted with anions of benzyl mercaptans 1 1, according to Reaction Scheme 1 below, wherein R 1, R 2, R 3, R x, A, Q, a, b, n and * are as defined in this document by Formula I.

REACTION SCHEME 11 According to Reaction Scheme 11, the α, β-unsaturated and α, β-unsaturated sulfoxides of Formula IZ are preferably prepared by a nucleophilic addition of an appropriate thiol salt of Formula XI to an optionally substituted aryl or heteroaryl acetylene. of Formula XVll. In Formula XVll, R1, R2, R3, Rx, Q, a and b are defined as for the compounds of Formula I, A is -S, and M + is a counterion, preferably an alkali metal, eg, sodium, lithium or potassium , an alkaline earth metal, for example, calcium or magnesium or a transition metal, for example, zinc or copper. The synthesis represented in Reaction Scheme 11 is analogous to the procedure described by Reddy et al., Sulfur Letters 13: 3-90 (1991), for the production of (Z) -styryl benzylsulfoxides. The full description of Reddy et al., Is incorporated in this document by reference. The sulfide intermediate XVI is then oxidized with a suitable oxidation agent. A suitable oxidizing agent is one capable of oxidizing a sulfide to a sulfoxide of Formula IZ. Oxidation agents suitable for the reaction to produce sulfoxide or sulfone compounds of Formula IZ include meta-chloroperoxybenzoic acid (MCPBA) and potassium peroxymonosulfate. Oxidation to form the sulfoxide of Formula IZ is preferably carried out at low temperature, preferably from -40 ° C to 0 ° C. The oxidation to form the sulfone of Formula IZ is preferably carried out at room temperature or higher, more preferably from 30 ° C to 50 ° C. Because the sulfoxide is an intermediate oxidation state in the oxidation of the sulphoxide to the sulfone, the reaction to oxidize the sulfone must be monitored and terminated before further oxidation to the sulfone. Similarly, for oxidation to the sulfone, the reaction must be monitored to make sure that all of the sulfoxide of Formula XVI is consumed and that the intermediate sulfoxide of Formula IZ is consumed. The reaction is preferably carried out in a suitable solvent. Suitable solvents are preferably non-polar organic solvents, more preferably, halogenated solvents, for example, dichloromethane (DCM).

B. Preparation of sulfonamides and α-β-unsaturated aryl propenamides of Formula I (i) Preparation of Compounds of Formula IE A preferred preparation of compounds of Formula IE, wherein X is -NR C (= O) - or -NRxS02-, is by reaction of an appropriately substituted aniline compound, to form either a compound of sulfonamide or an arylpropenamide according to Formula XIX. The compound of Formula XIX is then hydrolyzed, deprotected and reacted with an aryl or heteroaryl aldehyde of Formula XV, to form a sulfonamide compound or an arylpropenamide according to Formula IE, as shown in Reaction Scheme.

REACTION SCHEME 12 In accordance with Reaction Scheme 2, a 3-nitrophenol or 3-Nitrothiophenol starting 10, is first derivatized to protect the portion of phenol or thiophenol. The phenol and iiophenol compounds 10 are reacted with a trialkylsilyl halide, preferably urea-butyldimethylsilylchloride (t-BDMS-CI), or with a vinylinalkylsilane, preferably vinyl urea-butyldimethylsilane or vinyl trimethylsilane, to produce the protected trialkylsilylethyl compound correspond, 11b. The protected compound 11_ is treated with a reducing agent capable of reducing an aromatic nitro group to the corresponding aromatic amino group. Suitable agents include noble metal catalyst reducing agents, for example, palladium metal and hydrazine. Preferably, the reaction is carried out in a solvent, for example, THF or a lower alcohol, such as, for example, methanol or ethanol. The reduction provides the aniline derivative 12. The aniline derivative 12 is optionally alkylated to provide an intermediate having a substituent -R x on the aniline nitrogen. Suitable alkylations of an aniline nitrogen include: (a) alkylation with an alkyl moiety having a leaving group, eg, an alkyl halide or an alkyl mesylate; and (b) reductive amination, that is, reaction with an aldehyde or a ketone in the presence of a reduction agent capable of selectively reducing the mine formed by reaction of an aldehyde or ketone with the aniline. By "selective reduction", it means that a suitable reducing agent, under the reaction conditions, will reduce the imine intermediate faster than it will reduce the starting aldehyde. Suitable reducing agents include, for example, NaBHsCN and sodium idriacetoxy borohydride. Alternatively, a reductive amination reaction can be performed directly on the aromatic nitro compound 1_1, wherein the nitro group is reduced and alkylated in a one-pot process. The optionally alkylated aniline is then reacted with a compound according to Formula Xll, wherein the leaving group is preferably chlorine. Particular compounds of Formula XII include elylammonium chloride (to form a compound in accordance with Formula 13, wherein Z is -C (= O) -) and ethyl-2-chlorosulfonylacetate (to form a compound in accordance with Formula 13, where Z is - S02-). According to Reaction Scheme 12, the carboxylic ester compound 13 is hydrolyzed to form the solvent of the corresponding carboxylic acid compound. The hydrolysis is preferably formed under basic conditions. Suitable bases include LiOH, NaOH and KOH. The hydrolysis is preferably carried out in an aqueous solvent, which may be water or a mixture of water and an organic solvent miscible in water such as methanol, ethanol, THF or mixtures thereof. Compound 13 is also deprotected to remove the protecting group of thiophenol or phenol, PG, to provide the 3-hydroxy or 3-mercapide compound 14. Suitable deprotection reagents include TBAF and triethylamine hydrohydride. The deprotected carboxylic acid compound 14 is then reacted with a suitable aryl or heleroaryl aldehyde in the presence of an amine, preferably piperidine, to produce a compound according to Formula I, wherein R 1 is -H and X is -NRX-Z-. The reaction is preferably carried out in an organic solvent which forms an azeotrope with water. Such solveníes include, for example, benzene, íoluene and DCM. The reaction is preferably carried out with some means to remove water, as they form in the reaction. Suitable means for removing water include the use of a Dean-Stark rag or the use of a water scrubbing agent, such as a molecular sieve. The compound, wherein R1 is -H, may subsequently be derivatized to provide additional compounds of Formula I as described herein. (ii) Preparation of α, β-unsaturated sulfonamides and propenamides of Formula IZ Compounds of Formula IZ, wherein X is -NR x C (= 0) - or -NR x SO 2 -, can be prepared according to the method of Reddy et al. ., WO 03/072063, the full description of which is incorporated herein by reference. The synthesis comprises the reaction of an appropriately suslidated aniline with a compound according to Formula XXA, wherein the exocyclic carbon-carbon double bond, is in conformation (Z), to form either a sulfonamide or an arylpropenamide compound in accordance with the Formula IZ. This process can also serve to produce compounds of Formula IE, wherein the exocyclic carbon-carbon double bond of the intermediate compound according to Formula XXA, is in conformation (E). The synthesis is shown in Reaction Scheme 13.

REACTION SCHEME 13 According to Reaction Scheme 13, an aromatic acryloylhalide intermediate (E) or (Z), XXA, or α, β-unsaturated sulfonyl halide XXA, can be prepared from the corresponding aromatic acrylic acid XX, or sulfonic acid a, β- unsaturated XX. To do this, sulfonic acid XX is reacted with a halogenating agent such as, for example, thionyl chloride or phosphorus pentachloride to form an XXA Intermediate. An aromatic amine of Formula Xll is reacted with XXA. The reaction is preferably carried out in the presence of an acid scavenger. Suitable acid scavengers include, for example, tertiary amines such as TEA, DIPEA, pyridine or lutidine; inorganic bases such as sodium carbonate or potassium carbonate, or bases on a solid support, such as? /,? / - di'sopropylethylamnomethylpolystyrene (PS-DIPEA). The reaction is preferably carried out in an organic solvent such as THF, íoluene or DCM. If R1 is a propylene glycol or phenol group, such as, for example, a trialkylsilyl or an alkylsilylethyl group, the product can be optionally deprotected and derivatized to produce additional compounds of Formula I.

C. Preparation of Formula Compounds by derivatization of thiophenol or phenol compounds of Formula ll The compounds of Formula II are derivatized by reacting the 3-hydroxy or 3-mercapto portion of a compound according to Formula I, wherein R 1 is -H, with various reactants to produce compound digests of Formula I. Thus, in accordance with a further embodiment of the invention, a method is provided for providing a compound according to Formula I, or a salt thereof, via derivatization of a 3-hydroxy or 3-mercapto portion of a compound such as, for example, a compound according to Formula II: which comprises reacting the compound according to Formula II, or a salt thereof with an electrophysical compound according to Formula XXI: R1-L wherein R1 is as defined for the compounds of Formula I, as long as R1 is not -H; and L comprises a leaving group, so that the reaclivo XXI, will react with the phenol or thiophenol group of the compound according to Formula II, thereby, derivatizing the thiophenol or phenol group thereof and forming a compound according to Formula I, wherein R 1 is H-distinguished. Compounds of Formula XXI include, for example: (a) compounds wherein R 1 is alkyl functionalized by the leaving group L; (b) compounds in which R1 is aryl or heeroaryl functionalized by the leaving group L, wherein L is acyl distinguished; (c) the compounds in which R1 is a carboxylic acid, which is activated by the group leaving L; (b) compounds wherein R 1 is a sulfonic acid, the lime is activated by the leaving group L; (d) compounds wherein R1 is a carbamic acid, which is activated by the leaving group L; (e) compounds wherein R1 is a trialkyl silyl group which is activated by the leaving group L; or (f) compounds wherein R is a dihydrocarbylphosphityl group, which is activated by the leaving group L. Suitable leaving groups L, include for example, halogen, mesyl, tosyl, nosyl, trifyl and acyl groups. Compounds of Formula XXI include, for example, silylhalides, such as t-BDMS-CI; alkyl and arylalkyl halides such as alkyl bromides and benzyl bromides; acyl halides, such as acetyl chloride and other acid chlorides; sulfonyl halides, such as sulfonyl chlorides; acid anhydrides, sulfonic anhydrides; substituted alkanes having a sulphonate leaving group, eg as mesyl or ioosyl; and phosphite esters, such as diethylphosphites. Representative examples of the types of derivatizations which can be used to generate compounds of the invention, such as compounds according to Formulas III, IV, V and VI, are shown in Table 4.

TABLE 4 Accordingly, a method is provided for preparing a compound according to Formula III, or a salt thereof: wherein R2, R3, X, A, Q, a and b are as defined in this document for the compounds of Formula I; and Rv is hydrocarbyl of (CrC7). The method comprises the steps of: (a) reacting a compound according to Formula II: wherein, R2, R3, X, A, Q, a and b are as defined herein for compounds of Formula I, with a dihydrocarbylphosphyl halide: (b) isolating from the reaction products, a compound of Formula III, or a salt of! same, where Rv is hydrocarbyl of (CrC7). Further provided is a process for preparing a compound according to Formula III, or a salt thereof, wherein R2, R3, X, A, Q, a and b are as defined herein for compounds of Formula I; and Rv is -H. The method comprises the steps of: (a) reacting a compound of Formula III; wherein Rv is hydrocarbyl of (-C7), with a halotrialkylsilane: alkyl (C -) - C6) halogen - Si alkyl of (C-tC6) alkyl of (C, -C6) - and (b) isolating from the reaction products, a compound of Formula III, or a salt thereof, wherein Rv is -H. Preferably, the haloalkylsilane is selected from trialkylsilyl chlorides and trialkylsilyl bromides, more preferably, trimethylsilylbromide.

SAW. Conjugated Compounds of Formula I The compounds according to Formula I can be selected to form conjugates with an antibody (Ab). The antibody acts to deliver the therapeutically active drug molecule to the particular target cell population, with which the antibody reacts.

A. Suitable Antibodies for Conjugation with Compounds of Formula I The antibody can be any antibody that binds to, forms complexes with or reacts with a receptor, antigen and other receptive portion associated with an abnormally proliferative cell population sought to be treated and, the which has at least one chemically reactive portion, preferably a sulfhydryl (-SH), amino (-NH) or carboxyl group (-C02H) free reagent. Particularly, preferred antibodies are those which can recognize an antigen associated with the tumor. The antibody can belong to any recognized class or subclass of immunoglobulins such as IgG, IgA, IgM, IgD, or IgE. The antibody can be derived from any species. Preferably, however, the antibody is of human, murine, or rabbit origin, more preferably, of human origin. The antibody can be polyclonal or monoclonal, preferably monoclonal. The invention also encompasses the use of antibody fragments that recognize antigens. Such fragments may include, for example, Fab ', F (ab') 2, Fv or Fab fragments, or other antibody fragments that recognize antigens. Such antibody fragments can be prepared for example, by proteolytic enzymatic digestion, for example, by digestion of pepsin or papain, reductive alkylation, recombinant techniques. Monoclonal antibodies (Mabs) can be advantageously split by proteolytic enzymes to generate fragments that retain the antigen binding site. For example, a proteolytic fragment of IgG antibodies with papain at neutral pH generates two identical "Fab" fragments, each containing an intact light chain linked to a disulfide fragment of the heavy chain (Fd). Each Fab fragment confers a binding site to the animal. The resigating portion of the IgG molecule is a dimer known as "Fc". Similarly, the splitting of pepsin at pH 4 results in an F (ab ') 2 fragment. The materials and methods for preparing the fragments are well known to those skilled in the art. See, generally, Parham, J. Immunology, 131, 2895 (1983); Lamoyi et al., J. Immunological Methods, 56, 235 (1983); Parham, Id., 53, 133 (1982); Goding, Monoclonal Antibodies Principies and Practice, Academic Press (1983), p. 119-123; and Matthew went to., Id., 50, 239 (1982). The antibody can be a single chain antibody ("SCA"). This may consist of single chain Fv fragments ("scFv") in which the variable light (VL) and heavy variable (VH) domains are linked by a peptide bridge or by disulfide bonds. The anficibody may consist of unique VH domains (dAbs), which possess antigen binding activity. See for example, G. Winter and C. Milstein, Nature, 349, 295 (1991); R. Glockshuber et al., Biochemistry 29, 1362 (1990); and E. S. Ward et al., Nature 341, 544 (1989), the full descriptions of which are incorporated herein by reference. Also, the antibody can be a "bi-functional" or "hybrid" antibody, that is, an antibody which can have an arm that has a specificity for an antigenic site, such as an antigen associated with the tumor, while the other arm recognizes an antibody. different target, for example, a hapten which is, or to which it is attached, a lethal agent to the tumor cell carrying the antigen. Alternatively, a bifunctional antibody may be one in which each arm has specificity for a different epitope of an antigen associated with the tumor of the abnormally proliferating cell to be treated. Bifunctional antibodies are described, for example, in European Patent Publication, EP 0105360, the full disclosure of which is incorporated herein by reference. Such hybrid or bifunctional antibodies can be derived, biologically, by cell fusion techniques, or chemically, particularly with crosslinking agents or reagents that form disulfide bridges. The bifunctional antibodies may comprise antibodies and complete fragments thereof. The methods for obtaining such hybrid hybrids are described, for example, in PCT application WO83 / 03679, published on October 27, 1983, and published European Application EPA 0 217 577, published on April 8, 1987, full descriptions of which are incorporated in this document by reference. The antibody can be a chimeric antibody. Chimeric animal-human monoclonal antibodies can be prepared by conventional recombinant DNA and gene transfection techniques well known in the art. Variable region genes from a myeloma cell line that produces mouse antibody of known antigen-binding specificity were linked to the human immunoglobulin constant region genes. When such gene constructs were transfected into mouse myeloma cells, antibodies were produced which are largely human, but contain antigen binding specificities generated in mice. As demonstrated by Morrison et al., Proc. Nati Acad. Sci. USA 81, 6851-6855, 1984, both genes of the human C heavy chain (VH) region of the exon of the chimeric heavy chain region V and constructs of the human light chain gene * (V *) of the exon of the light chain V region of chimeric mouse can be expressed when transfected into mouse myeloma cell lines. When both chimeric heavy and light chain genes are transfected into the same myeloma cell, an intact H2L2 chimeric antibody is produced. The methodology for producing such chimeric antibodies by combining genomic clones of the V and C region genes is described in the aforementioned document by Morrison et al., And by Boulianne et al., Nature 312, 642-646, 1984. see, Tan et al., J. Immunol. 135, 3564-3567, 1985, for a description of high level expression of a human heavy chain promoter of a human-mouse chimeric chain after transfection of mouse myeloma cells. As an alternative for combining genomic DNA, cDNA clones from relevant regions V and C can be combined for production of chimeric antibodies, as described by Whitle et al., Protein Eng. 1, 499-505, 1987 and Liu et al. al., Proc.

Nati Acad. Sci. USA 84, 3439-3443, 1987. For examples of the preparation of chimeric antibodies, see the following United States Patents: 5,292,867; 5,091, 313; 5,204,244; 5,202,238; and 5,169,939. The complete description of these patents and the publications mentioned in the preceding paragraph are incorporated in this document by reference. The invention is not constructed as limited in scope by any particular method of producing an antibody whether bifunctional, chimeric, bifunctional-chimeric, humanized or an antigen recognition fragment or derivative thereof. To further reduce the immunogenicity of the murine antibodies, "humanized" antibodies have been constructed in which only the minimum necessary parts of a mouse antibody, the regions that determine complementarity (CDRs), are combined with the structures of the region. Human V and human C regions (Jones et al., Nature 321, 522-525, 1986; Verhoeyen et al., Science 239, 1534-1536, 1988; Reichmann et al., 322, 323-327, 1988; Hale et al., Lancet 2, 1394-1399, 1988; Queen ei al., Proc. Nati Acad. Sci. USA 86, 10029-10033, 1989). The full descriptions of the aforementioned documents are incorporated herein by reference. This technique results in the reduction of the xenogeneic elements in the humanized antibody to a minimum. The rodent antigen binding sites are constructed directly on human antibodies, transplanting only the antigen binding site, instead of the full variable domain, of a rodent antibody. This technique is available for the production of chimeric rodent / human antibodies of reduced human immunogenicity. Antigen binding fragments and antibodies representative thereof, which target tumor antigens or associated antigens, and are commercially available include: Pendeide Satumomab (by Cytogen, a murine Mab directed conira TAG-72); Igovomab (by CIS Bio, a fragment Mab murine Fab2 directed coníra the aníígeno associate to lumor CA 125); Arcitumomab (by Immunomedics, a Fab Murine Fragment Fab directed against the human carcinoembryonic antigen CEA); Capromab Pentetate (by Cytogen, a murine Mab directed against the antigen on the surface of the PSMA tumor); Tecnemab Kl (by Sorin, murine Mab fragments (Fab / Fab2 mixture) directed against HMW-MAA); Nofetumomab (by Boehringer Ingelheim / NeoRx, murine fragments Mab (Fab) directed coníra the antigen associated with carcinoma); Rituximab (by Geneníech / IDEC Pharmaceuticals, a chimeric Mab directed against the CD20 antigen on the surface of B lymphocytes); Trastuzumab (by Genintech, a humanized antibody directed against the human epidermal growth factor receptor 2 (HER 2)); Votumumab (by Organon Teknika, a human Mab directed against the antigen associated with the cytokeratin tumor); Ontak (by Seragen / Ligand Pharmaceuticals, a fusion protein of the IL-2-diphtheria toxin, which directs cells that exhibit a surface IL-2 receptor); IMC-C225 (by Imclone, a chimerized monoclonal antibody that binds to EGFR); LCG-Mab (by Cytoclonal Pharmaceutics Monoclonal, an antibody targeting the lung cancer gene LCG); ABX-EGF (by Abgenix, a fully human monoclonal antibody against the epidermal growth factor receptor (EGFRr)); and Epratuzumab (by Immunomedics, a humanized anti-CD22 monoclonal antibody). In accordance with one embodiment of the invention, the antibody comprises a tumor-specific antibody, preferably, a monoclonal antibody specific for the tumor or a monospecific polyclonal antibody specific for the tumor. Particularly preferred monoclonal antibodies for use in the present invention, which recognize tumor-associated antigens, include, for example, those listed in Table 1. All references listed in Table 5 are incorporated herein in their entirety by reference.

TABLE 5 TABLE 5 (continued) TABLE 5 (continued) B. Linkage of a Compound of Formula I to an Antibody (Ab) An antibody can be covalently linked to a compound of Formula I, via a covalenle linker (L) to form a conjugate of Formula I-L-Ab. The structural components of substituents on the phenyl or Q rings of the compounds of Formula I (for example, -OH, -SH, and substituents comprising amino acid or peptidyl moieties), provide the binding sites, by which a host can to be linked to a compound of Formula through a linker portion L.

The compounds of Formula I can be easily covalently linked to antibodies via a suitable bifunctional linker (-L) to provide a conjugate of general Formula l-L-Ab. In addition, the compounds of Formulas NA, HB, IIIA, IIIB, IVA, IVB, VA, VB, VIA and VIB, can be covalently linked to antibodies (Ab) via a suitable functional linker (-L-) to provide conjugates of Formula general, IIA-L-Ab, IIB-L-Ab, IIIA-L-Ab, IIIB-L-Ab, IVA-L-Ab, IVB-L-Ab, VA-L-Ab, VB-L-Ab, VIA-L-Ab, and VIB-L-Ab. The covalent linker (L) provided between a compound according to Formula I and an antibody (Ab) to form a conjugate of Formula I-Ab can, in its simplest form, comprise a single covalent bond connecting the according to Formula I to the antibody. An example of a covalent bond formed as a linker between a compound according to Formula I and an antibody is a disulfide bond. A disulfide bond can be formed by the oxidation of an antibody and a compound according to Formula I, wherein a substituent on the phenyl ring or ring Q of Formula I, comprises a peptidyl portion containing one or more amino acids of cysteine. The cysteine residues can be oxidized to form disulfide bonds by dissolving 1 mg of the suitable compound according to Formula I and 0.5 equivalents of the desired antibody in 1.5 ml of 0.1% (v / v) of 17.5 mM acetic acid, pH 8.4, followed by nitrogen discharge and then 0.01 M K2Fe (CN) 6.

After incubation for one hour at room temperature, the adduct peptide is purified, for example, by HPLC. Another example of a suitable covalent bond formed as a linker between a compound according to Formula I and an antibody is an amide bond. An amide bond can be formed by reacting an amino group in a compound of the invention with a carboxylic acid group which forms part of the primary structure of the antibody (Ab) (eg, for example, a residue of glutamic or amino acid). aspartic). Alternatively, an amide bond can be formed if the reacted portions are inverted, that is, the compound according to Formula I contains a carboxylic acid functionality and reacts with an amino functionality with the Ab structure. Most commonly, the compound according to Formula I is attached to the antibody using a suitable bifunctional linking reagent. The term "bifunctional linking reagent" refers to a molecule comprising two reactive portions which are contacted by a spacer element. The term "reactive portions" in this context refers to chemical functional groups capable of coupling with an antibody or a compound according to Formula I, causing it to react with functional groups on the antibody and the compound according to Formula I. Therefore, in accordance with one embodiment of the invention, a compound according to Formula I, wherein a substituent on the phenyl ring or ring Q of Formula I, comprises a portion -OH, -NH2, or -SH , is coupled to an antibody using a bifunctional binding reagent. The procedures for the preparation of immunoconjugates using these linkers are detailed in Toxln-Targeted Design for Anticancer Therapy. II: Preparation and Biological Comparison of Different Chemically Linked Gelonin- Antibody Conjugates (Cattel, eí al, J. Pharm. Sci., 82: 7, p699-704, 1993), (full description which is incorporated herein by reference). The conjugates according to the invention can be prepared using homo-bifunctional linking reagent (wherein the two reactive portions in the bi-functional linking reagent are the same), such as, for example, disuccinimidyl tartrate, disuccinimidyl suberate, ethylene glycol bis (succinyl succinate), 1,5-difluoro-2,4-dinitrobenzene ("DFNB"), 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene ("DIDS"), and bis -maleimldohexane ("BMH"). The binding reaction occurs randomly between the Ab and a compound according to Formula I having a peptidyl moiety as part of at least one substituent on the phenyl ring or the Q ring of Formula I. The hetero-bifunctional linking reagents (wherein the two reactive portions in the bifunctional bond reactant are different) may also be employed in the preparation of conjugates in accordance with the invention. For hetero-bifunctional linkage, a compound according to Formula I is derivatized with, for example, the N-hydroxysuccinimidyl portion of the bifunctional reagent, and the resultant derivatized Formula I compound, is purified by chromatography. Then, a suitable antibody is reacted with the second functional group of the bifunctional linking reagent, ensuring a directed sequence of reaction between the compound of Formula I, the linker and the antibody (Ab). Typical hetero-bifunctional bonding agents for forming conjugates between a compound and anannibody, have an amino-reactive N-hydroxysuccinimide ester (NHS ester), as a functional group and a sulfhydryl reactive group as the other functional group. First, the amino groups of the compound of Formula I are acylated with the NHS ester group of the crosslinking agent. The antibody possessing the free sulfhydryl groups is reacted with the sulfhydryl reactive group of the crosslinking agent to form a covalently cross-linked dimer. Common thiol reactive groups include, for example, maleimides, pyridyl disulfides and active halogens. For example, MBS contains an NHS ester as the amino reactive group, and a maleimide portion as the sulfhydryl reactive group. There are numerous bifunctional linkers, used as linkers (-L-), which have been used specifically to couple small molecules to monoclonal anficuerpos. Many of these linkers are commercially available. Examples include n-succinyl-methyl-3- (2-pyridyl) -propionic acid (SPDP), 2-iminophiolane (2-IT), 3- (4-carboxamidophenyldityl) propionthioimidate (CDPT). ), N-succinimidyl-acetylthioacetate (SATA), ethyl-S-acetyl-propionthioimidate (AMPT) and N-succinimidyl-3- (4-carboxamidiphenyldithio) propionate (SCDP), sulfo-succinimidyl-2- (p-azidosalicylamido) ) ethyl-1-3'-dithiopropionate ("SASD", Pierce Chemical Company, Rockford, IL), N-maleimidobenzoyl-N-hydroxy-succinimidyl ester ("MBS"), m-maleimidobenzoylsulfosuccinimide ester ("sulfo-MBS") "), N-succinimidyl (4-iodoacetyl) aminobenzoate (" SlAB "), 4- (N-maleimidomethyl) -cyclohexan-1-succinimidylcarboxylate (" SMCC "), succinimidyl-4- (p-maleimidophenyl) butyrate ( "SMPB"), sulfosuccinimide (4-iodo-acetyl) aminobenzoate ("sulfo-SlAB"), 4- (N-maleimido-methyl) cyclohexan-1-carboxylate sulfosuccinimidyl ("sulfo-SMCC"), 4- (p-malemidophene) -sulfosuccinimidylbutyrate ("sulfo-SMPB"), bromoacetyl-p-aminobenzoyl-N-hydroxysuccinimidyl ester , and iodoacetyl-N-hydroxysuccinimidyl ester. Photoactive hetero-bifunctional linking reagents, for example, photoreactive phenyl azides, may also be employed. One such reagent, SASD, can be linked, via its NHS-ester group, to either an antibody or a compound of Formula I, wherein at least one substituent in Q or the phenyl ring of Formula I, comprises a peptidyl moiety. . The conjugation reaction is carried out at pH 7 at room temperature for approximately 10 minutes. The molar ratios between about 1 and about 20 of the crosslinking agents to the compounds to be bound, can be used. Exemplary synthetic routes for preparing conjugates of the present invention of the general Formula l-Ab are shown in Reaction Scheme 14. In accordance with Reaction Scheme 14, a Mab monoclonal antibody, wherein A is -NH- or - S-, is derivatized by reaction with the linker reagent CDPT or SCDP. A compound according to Formula I, wherein A is -NH- or -S-, is derivatized by reaction with the linker reagent CDPT, SATA or AMPT. The coupling of the derivatized compound of Formula I with the derivatized monoclonal antibody produces a conjugate of conformity with the Formula l-L-Ab. Vile. Compound salts of the invention The compounds of the present invention may take the form of salts. The term "salts" embraces salts commonly used to form alkali metal salts and form addition salts of free acids or free bases. The term "pharmaceutically acceptable salt" refers to salts which have toxicity profiles within a range to have utility in pharmaceutical preparations. The pharmaceutically unacceptable salts may, however, possess properties such as high crystallinity, which have utility in the practice of the present invention, such as, for example, utility in a synthetic process. Suitable pharmaceutically acceptable acid addition salts can be prepared from inorganic acid or from an organic acid. Examples of such inorganic acids are hydrochloric, hydrobromic, yodhydric, nitric, carbonic, sulfuric and phosphoric acids. Suitable organic acids may be selected from aliphatic, cycloaliphatic, aromatic, arallhalic, heterocyclic, carboxylic and sulphonic organic acids, examples of organic acids examples of which are formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric acid , ascorbic, glucuronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, mesylic, 4-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic), measulfonic, easulfonic, benzenesulfonic, panyotenic, 2-hydroxyethane sulfonic, toluene sulfonic, sulphanilic, cyclohexylaminosulfonic, stearic, alginic, B-hydroxybuiric, salicylic, galacíaric and galacturonic. Examples of pharmaceutically unacceptable acid addition salts include, for example, perchlorates and tetrafiuoroborates. Suitable pharmaceutically-based addition salts of compounds of the invention include, for example, metal salts made from calcium, magnesium, potassium, sodium and zinc, or organic salts made from? /./ V-dibenzylethylenediamine, chloroprocaine, choline, diethylamine , ethylenediamine, meglumine (? / - methylglucamine) and procaine. Examples of pharmaceutically acceptable salts include lithium salts and cyanate salts. All these salts can be prepared by conventional means from the corresponding compound according to Formula I, by reacting for example, the appropriate acid or base with the compound according to Formula I.

V l. Administration of compounds and conjugates of the invention The compounds and conjugates of the invention can be administered by any route, including oral and parenteral administration. Parenteral administration includes, for example, intravenous, intramuscular, intraarterial, intraperitoneal, intranasal, rectal intravaginal, intravesical (e.g., to the bladder), intradermal, topical or subcutaneous administration. Also contemplated within the scope of the invention is the instillation of the drug in the patient's body in a controlled formulation, with systemic or local release of the drug occurring at a later time. For example, the drug can be located in a container for controlled release to the circulation, or for release to a local tumor growth site. One or more compounds or conjugates, used in the practice of the present invention, can be administered simultaneously, by the same or different routes, or at different times during the treatment. For parenteral administration, the active agent can be mixed with a suitable carrier or diluent, such as water, an oil (particularly a vegetable oil), ethanol, saline, aqueous dexory (glucose) and related sugar solutions, glycerol or a glycol such as propylene glycol or polyethylene glycol. Solutions for parenteral administration preferably contain a water soluble salt of the active agent. Stabilizing agents, anti-oxidizing agents and preservatives, they can also be added. Suitable antioxidant agents include sulfite, ascorbic acid, citric acid and its salts, and sodium EDTA. Suitable preservatives include benzalkonium chloride, methyl or propyl paraben and chlorobutanol. The composition for parenteral administration can take the form of an aqueous or non-aqueous solution, dispersion, suspension or emulsion. For oral administration, the active agent can be combined with one or more solid inactive ingredients, for the preparation of tablets, capsules, pills, powders, granules or other suitable oral dosage forms. For example, the active agent can be combined with at least one excipient such as fillers, binders, wetting agents, disintegrating agents, solution retarders, absorption accelerators, wetting agents, absorbents or lubricant agents. According to a tablet embodiment, the active agent can be combined with calcium carboxymethylcellulose, magnesium stearate, mannitol and starch, and then formed into tablets by conventional tableting methods. The specific dose of a compound in accordance with the invention, to obtain therapeutic benefit for the treatment of a proliferative disorder, will, of course, be determined by the particular circumstances of the individual patient which include size, weight, age, and sex of the patient, the nature and stage of the proliferative disorder, the aggressiveness of the proliferative disorder, and the route of administration of the compound. For example, a daily dosage from about 0.05 to about 50 mg / kg / day can be used. Higher or lower doses are also contemplated.

A. Radioprotection The specific dose of the compound according to the invention, to obtain therapeutic benefit for radioprotection will be, determined by the particular circumstances of the individual patient that includes, the size, weight, age and sex of the patient, the type, dose and synchronization of the ionizing radiation, and the route of administration of the compound of the invention.

For example, a daily dosage from about 0.05 to about 50 mg / kg / day can be used. Higher or lower doses are also contemplated. Exposure to radiation by an individual, may comprise therapeutic radiation administered to the individual or in some indications, to the bone marrow removed from the individual. An individual may also be exposed to ionizing radiation from environmental or occupational sources, as discussed in the Background of the Invention, above. For purposes of the invention, the source of the radiation is not as important as the type (ie, acute or chronic) and level of dose absorbed by the individual. It is understood that the following discussion encompasses ionizing radiation exposures from both occupational and environmental sources. Individuals suffering from effects of acute or chronic exposure to ionizing radiation, which are not immediately fatal, are said to have remediable radiation damage. Such remediable radiation damage can be reduced or eliminated by the compounds and methods of the present invention. An acute dose of ionizing radiation which can cause remediable radiation damage, includes a full or localized body dose, for example, between approximately 10,000 millirem (0.1 Gy) and approximately 1,000,000 millirem (10 Gy) in 24 hours or less , preferably between about 25,000 millirem (0.25 Gy) and about 200,000 (2 Gy) in 24 hours or less, and more preferably, between about 100,000 millirem (1 Gy) and about 150,000 millirem (1.5 Gy) in 24 hours or less. A chronic dose of ionizing radiation which can cause remediable radiation damage, includes a full-body dose of approximately 100 millirem (.001 Gy) to approximately 10,000 millirem (0.1 Gy), preferably, a dose between approximately 1000 millirem (0.01 Gy). ) and approximately 5000 (.05 Gy), for a period greater than 24 hours, or a localized dose of 15,000 millire (0.15 Gy) to 50,000 millirem (0.5 Gy) for a period greater than 24 hours.

() Rad oppression: Therapeutic radiation radiation For radioprotective administration to individuals receiving therapeutic ionizing radiation, the compounds of the invention should be administered sufficiently in advance of the therapeutic radiation, such that the compound is capable of reaching the normal cells of the therapeutic radiation. individual in sufficient concentration, to exert a radioprotective effect on normal cells. The pharmacokinetics of specific compounds can be determined by means known in the art and the tissue levels of a compound in a particular individual can be determined by conventional analyzes. The compound can be administered for about 24 hours, preferably no more than about 18 hours, before the administration of the radiation. In one embodiment, the therapy is administered at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 hours before the administration of therapeutic radiation. More preferably, the compound is administered once to about 18 hours and again to about 6 hours before exposure to radiation. One or more compounds of Formula I can be administered simultaneously, or different compounds of Formula I can be administered at different times during treatment. Where therapeutic radiation is administered serially, it is preferable to intercalate the administration of one or more radioprotective compounds within the radiation treatment program. As previously, the different radioprotective compounds of the invention, can be administered either simultaneously or at different times during the treatment. Preferably, a period of about 24 hours separates the administration of the radioprotective compound and the therapeutic radiation. More preferably, the administration of the radioprotective compound and the therapeutic radiation are separated for about 6 to 18 hours. This strategy will provide a significant reduction of the side effects induced by radiation, without affecting the anti-cancer activity of therapeutic radiation. For example, therapeutic radiation at a dose of 0.1 Gy may be given daily for five consecutive days, within a two-day break, for a total period of 6-8 weeks. One or more compounds of Formula I can be administered to the individual 18 hours before reaching the radiation round. It should be noted however, that more aggressive breeding programs, ie, provision of a higher dosage, are contemplated in accordance with the present invention, due to the protection of the normal cells provided by the radioprotective compounds. Thus, the radiopropactive effect of the compound increases the therapeutic index of the therapeutic radiation, and may allow the specialist to safely increase the dosage of the therapeutic radiation above the currently recommended levels, without risking the increased damage to the cells and normal surrounding tissues. (ii) Radiation protection: Bone marrow treated by radiation The radioprotective compounds of the invention are also useful in the protection of normal cells of the bone marrow, from radiological treatments designed to destroy hematological neoplastic cells or tumor cells, which have undergone metastasis in the bone marrow. Such cells include, for example, myeloid leukemia cells. The appearance of these cells in the bone marrow and elsewhere in the body is associated with various disease conditions, such as the French-American-British (FAB) subtypes of acute myelogenous leukemia (AML), chronic myeloid leukemia (CML). ), and acute lymphocytic leukemia (ALL): CML, in particular, is characterized by abnormal proliferation of immature granulocytes (eg, neutrophils, eosinophils, and basophils) in blood, bone marrow, spleen, liver and other tissues and accumulation of granulocytic precursors in esio tissues. Individuals who present with such symptoms will typically have more than 20,000 white blood cells per microliter of blood, and the count may exceed 400,000. Virtually all patients with CML will develop "blasts crisis", the terminal stage of the disease during which immature blasts cells will rapidly proliferate, leading to death. Other individuals suffer from metastatic tumors and require treatment with total body irradiation (TBI). Because BITs will also kill individual hematopoietic cells, a portion of the individual's bone marrow is removed prior to irradiation for subsequent reimplantation. However, metastatic tumor cells are probably present in the bone marrow, and reimplantation often results in a relapse of the cancer within a short time. Individuals who have neoplastic disease of the bone marrow or metastatic tumors can be treated by removing a portion of the bone marrow (also called "collecting"), purging the bone marrow collected from the malignant stem cells, and reimplanting the purged bone marrow. Preferably, the individual is irradiated with radiation or some other anti-cancer therapy until the purged bone marrow is reimplanted. Thus, the invention provides a method for reducing the number of malignant cells in the bone marrow, comprising the steps of removing a portion of the individual's bone marrow, administering an effective amount of at least one radioprotechlor compound in accordance with present invention and irradiate the bone marrow brought with a sufficient dose of ionizing radiation, such that the malignant cells in the bone marrow are eliminated. As used in this document, "malignant cell" means any uncontrollably proliferating cells, such as a tumor cell or neoplastic cell. The radioprotective compounds protect the normal haematopoietic cells present in the bone marrow from the damaging effects of ionizing radiation. The compounds also have a direct elimination effect on malignant cells. The number of malignant cells in the bone marrow is significantly reduced before rellaning, thus minimizing the incidence of a relapse. Preferably, each compound according to the Formula I, is administered to the bone marrow in a concentration from about 0.25 to about 100 micromolar; more preferably, from about 1.0 to about 50 micromolar; in particular, from approximately 2.0 to approximately 25 micromolar. Particularly preferred concentrations are 0.5, 1.0 and 2.5 micromolar and 5, 10 and 20 micromolar. The radioprotective compounds can be added directly to the collected bone marrow, but are preferably dissolved in an organic solvent such as DMSO. Pharmaceutical formulations of the compounds of formula I can also be used, as such are described in more detail below. Preferably, the radioprotective compound is added to the bone marrow collected approximately 20 hours before exposure to radiation, preferably no more than about 24 hours before exposure to radiation. In one embodiment, the radioprochloride compound is administered to the collected bone marrow, at least about 6 hours before exposure to radiation. One or more compounds can be administered simultaneously, or different compounds can be administered at different times. Other dosing regimens are also contemplated. If the individual is to be treated with ionizing radiation before the reimplantation of the purged bone marrow, the individual may be treated with one or more radioprotective compounds before receiving the dose of ionizing radiation, as described above. (ii) Radioprotection: Exposure to Environmental or Occupational Radiation The invention also provides a method for tracing individuals who have incurred remediable damage by radiation from a water or chronic exposure to ionizing radiation, which comprises reducing or eliminating the cytotoxic effects of radiation. exposure to radiation in normal cells and tissues, administering an effective amount of at least one radioprotective compound. The compound is preferably administered in a short time as possible, after exposure to radiation for example, between 0-6 hours after exposure. Remediable radiation damage can occur in the form of cytotoxic and genotoxic effects (ie, adverse genetics) in the individual. In another embodiment, there is thus provided a method for reducing or eliminating the cytotoxic and genotoxic effects of exposure to radiation in normal cells and tissues, comprising, administering an effective amount of at least one radioactive compound before exposure to radiation. acute or chronic The compound can be administered, for example, approximately 24 hours before exposure to radiation, preferably no more than about 18 hours before exposure to radiation. In one embodiment, the compound is administered at least about 6 hours before exposure to radiation. More preferably, the compound is administered at about 18 and again at about 6 hours before exposure to radiation. One or more radioprotective compounds can be administered simultaneously, or different radioprotective compounds can be administered at different times. When multiple acute exposures are anticipated, the radioprotective compounds of the invention can be administered multiple times. For example, if fire or rescue personnel must enter contaminated areas multiple times, the radloprotective compounds of the invention may be administered before each exposure. Preferably, a period of about 24 hours separates the administration of the compound and exposure to radiation. More preferably, the administration of radio-generating compounds and exposure to radiation is separated by approximately 6 to 18 hours. It is also contemplated that a worker in a nuclear power plant may be administered with an effective amount of a radioprotective compound of the invention, upon beginning each change to reduce or eliminate the effects of exposure to ionizing radiation. If an individual is anticipating chronic exposure to ionizing radiation, the radloprotective compound may be administered periodically through the duration of the anticipated exposure. For example, to a worker or soldier of a nuclear power plant operating in a front area contaminated with radioactive dust, the radioprotective compound can be given every 24 hours, preferably every 6-18 hours, to mitigate the effects of radiation damage. . Similarly, the radioproteclor compound can be periodically administered to civilians living in areas contaminated with radioactive dust until the area is decontaminated or civilians are removed to a safer environment.

B. Chemoprotection The specific dose of a compound according to the invention to obtain therapeutic benefit for chemoprotection, will be determined by the particular circumstances of the individual patient that include, the size, weight, age and sex of the patient, the type and dose of chemotherapy. administered, the nature and stage and cell damage, and the route of administration of the compound of the invention. For example, a daily dose from about 0.05 up to about 50 mg / kg / day can be used. Higher or lower doses are also contemplated. To provide cytoprophylation of the cytoxic effects of chemo-therapeutic agents, the program of administration of the cytotoxic drug, ie, the mitotic phase cell inhibitor or topoisomerase inhibitor, can be any program with the stipulation that the compound according to Formula I is administering anis of the cytotoxic drug. The cytoprotective compound must be administered sufficiently in advance of the cytotoxic drug, so that the former is able to reach the normal cells of the patient in a sufficient concentration to exert a cytoprotective effect on normal cells. Again, individual drug pharmacokinetics and blood levels of a specific drug in a specific patient are factors that can be determined by methods known in the art. The cytoprotective compound is administered at least about 1 hour, preferably, at least about 2 hours, and more preferably, at least about 4 hours, before the administration of the cltotoxic drug. The compound can be administered for about 48 hours, preferably no more than about 36 hours, prior to administration of the cytotoxic drug. More preferably, the compound is administered approximately 24 hours before the cytotoxic drug. The compound can be administered more or less 24 hours before the chloroiotoxic effect, but the pro-active effect of the compound is greater when it is administered approximately 24 hours before the cytotoxic drug. One or more cytotoxic drugs can be administered. Similarly, one or more compounds of Formula I may be combined. Where the cytotoxic drug or drugs are administered serially, they can provide practice for interspersing clone-protective compounds of the invention, within the program with the warning that a period of 4-48 hours, preferably a period of 12-36 hours, more preferably , a period of 24 hours, separates the administration of the two types of drugs. This technique will provide partial to complete irradiation of the side effects of cytoxic drugs without affecting the anticancer activity. For example, the myxoid inhibitor can be given daily, or even every four days or every twenty-one days. The compound according to Formula I; it can be given 24 hours before each round of inhibitor administration, both as a cytoprotective agent and as an anti-tumor agent. The compounds of the invention can be administered by therapeutic effect by any route, for example, enteric administration (e.g. oral, rectal, inlranasal, etc.) and parenteral. Parenteral administration includes, for example, intravenous, intramuscular, intraarterial, intraperitoneal, intravaginal, intravesical (e.g., in the bladder), intradermal, topical, subcutaneous or sublingual administration. Also contemplated within the scope of the invention is the insipilation of the drug in the body of the patient in a conirrolated formulation, with a local or symlotic release of the drug occurring at a later time. For anticancer use, the drug can be located in a container for controlled release to the circulation, or local site of tumor growth. When more than one compound according to Formula I is administered, or when one or more compounds of Formula I are administered, in addition to one or more cytoxic drugs, the different compounds may be administered by the same or differentials.

IX. Pharmaceutical Compositions The compounds and conjugates of the invention can be administered in the form of a pharmaceutical composition, in combination with a pharmaceutically acceptable carrier. The active ingredient in such formulations, may comprise from 0.1 to 99.99 percent by weight. By "pharmaceutically acceptable carrier", it means any carrier, diluent or excipient, which is comparable to the other ingredients of the formulation and deleterious to the container.

The active agent is preferably administered with a pharmaceutically acceptable carrier selected on the basis of the selected route of administration and standard pharmaceutical practice. The active agent can be formulated into dosage forms in accordance with standard practices in the field of pharmaceutical preparations. See, Alphonso Gennaro, ed., Remington's Pharmaceutical Sciences, 18th Ed., (1990) Mack Publishing Co., Easton, PA. Suitable dosage forms may comprise, for example, tablets, capsules, solutions, parenteral solutions, troches, suppositories or suspensions. For parenteral administration, the active agent can be mixed with a suitable carrier or diluent, such as water, an oil (particularly a vegetable oil), ethanol, saline, aqueous dextrose (glucose) and related sugar solutions, glycerol, or a glycol such as propylene glycol or polyethylene glycol. Solutions for parenteral administration preferably contain a water soluble salt of the active agent. Slavic agents, antioxidants and preservatives can also be added. Suitable antioxidant agents include sulfite, ascorbic acid, citric acid, and their salts, and sodium EDTA. Suitable preservatives include benzalkonyl chloride, mephyl or propyl paraben, and chlorbranol. The composition for parenteral administration may take the form of an aqueous or non-aqueous solution, dispersion, suspension or emulsion. For oral administration, the active agent can be combined with one or more solid inactive ingredients, for the preparation of tablets, capsules, pills, powders, granules or other suitable oral dosage forms. For example, the active agent can be combined with at least one excipient, such as fillers, binders, wetting agents, disintegrating agents, solution rearers, absorption accelerators, wetting agent absorbers or lubricating agents. According to a tablet method, the active agent can be combined with calcium carboxymethylcellulose, magnesium stearate, mannitol and starch, and then formed into tablets by conventional tableting methods. The practice of the invention is illustrated by the following non-limiting examples.

EXAMPLES EXAMPLE 1 Synthesis of (E) -5 - ((2,4,6-trimethoxystirylsulfonyl) methyl) -2-methoxyphenol A. Benzaldehyde of 3-O-urea-butylmethylamido-4-meloxy To a cooled solution (0 ° C) of benzaldehyde of 3-hydroxy-4-methoxy (10 g, 65.7 mmol, 1 eq. ), in dry DMF (75 ml), DIPEA was added (16.99 g, 131.4 mmol, 2 eq.). The mixture was stirred under nihorogen for 10 minutes. A 1.0 M solution of t-BDMS-CI in THF (78.9 ml, 1.2 eq.) Was added dropwise for 30 minutes. The resulting mixture was stirred 12-16 hours and monitored by thin layer chromatography (TLC). When the reaction was complete, water (75 ml) was added to the reaction mixture. The resulting mixture was extracted with DCM (3 x 75 ml). The combined organic layer was washed with saturated aqueous sodium bicarbonate (75 ml) and water (75 ml) and dried (Na 2 SO). The volatile components were removed in vacuo to provide the crude product. The crude product was purified by column chromatography on silica eluted with CHCl3 to give the product (Yield, 26.75 g), 3-0-ee / -c-butyl dimethyl-silyloxy-4-methoxy benzaldehyde, as a yellow oil.

B. Benzyl alcohol of 3-O-ér-butylmethylsilyloxy-4-methoxy To a cooled (0 ° C) solution of benzaldehyde of 3-O-ér-butyl-dimethylsilyloxy-4-methoxy (13 g), 48.8 mmol, 1 eq.), In sodium (100 ml), under nilrogen, sodium borohydride (1 eq.) Was added. The resulting mixture was allowed to warm to room temperature and was stirred (30 min) and monitored by TLC. When the reduction was complete, ice water was added to the reaction mixture. The resulting mixture was extracted with ethyl acetate (3 x 50 ml). The combined organic extract was washed with water (50 ml) and dried (Na 2 SO 4). The volatile components were removed in vacuo to provide a yield of 73.5% of the desired product, benzyl alcohol of 3-O-ér-butylmethylmethyloxy-4-methoxy.

C. 3-0-Ierc-Butyldimethylsilyloxy-4-methoxybenzyl Chloride To a cooled (0 ° C) solution of 3-0-ert-butyldimethyl-silyloxy-4-meloxybenzyl alcohol (9.5 g, 35.4 mmol, 1 eq.), In benzene (50 ml), under nitrogen, thionyl chloride (6.32 g, 1.5 eq.) dissolved in benzene (5 ml) was added dropwise for 10 minutes. The resulting mixture was stirred at 0 ° C and monitored by TLC. When the reaction was completed, ice water was added (50 g) and the resulting mixture was extracted with ethyl acetate (3 x 50 ml). The combined organic extract was washed with saturated bicarbonate solution (50 ml) and water (50 ml) and dried (Na S0). The volatile components were removed in vacuo to provide a quantitative yield of the product of 3-O-ferro-butylmethylmethyloxy-4-methoxybenzyl chloride, as a yellow oil.

O 2 - ((3-0-tert-buyldimethylsily! Oxy-4-methoxybenzyl) sulfanyl) acetic acid To a solution of sodium hydroxide (2.79 g, 69J mmol, 2 eq.) In methanol (30 ml) was added mercaptoacetic acid (3.21 g, 34.9 mmol, 1 eq.) by dripping for 10 minutes. 3-0-Yerc-butyldimethylsilyloxy-4-methoxybenzyl ester was added in portions to the mixture of mercaptoacetic acid and the resulting mixture was stirred at room temperature and monitored by TLC. When the reaction was complete, the reaction mixture was poured onto ice (100 ml) containing concentrated HCl (excess based on sodium hydroxide). The resulting mixture was extracted with ethyl acetate (3 x 50 ml). The combined organic extract was washed with water (30 ml) and dried (Na 2 SO 4). The volatile components were removed in vacuo to give a yield of 75% of the desired product of 2 - ((3-0-iron-dimethylsilyloxy-4-meioxybenzyl) sulfanyl) acetic acid as a solid having a fusion of 57-59 ° C.

E. 2 - ((3-Hydroxy-4-methoxybenzyl) sulfanyl) acetic acid To a cooled (0 ° C) solution of 2 - ((3-0-Ier-butyldimethylsilyloxy-4-methoxybenzyl) sulfanyl) acetic acid (8J5) g, 25.5 mmol, 1 eq.) in THF (40 ml), TBFA (1 eq., 1 M in THF) was added dropwise. The resulting mixture was stirred under nilrogen at room temperature and monitored by TLC. When the reaction was complete, water (40 ml) was added to the reaction mixture. The resulting mixture was exfoliated with ethyl acetate (3 x 40 ml). The combined organic extractions were washed with water (40 ml) and dried (Na 2 SO 4). The volatile components were removed in vacuo to provide the crude product, which was purified by column chromatography to give a yield of 50% of the purified product of 2 - ((3-hydroxy-4-methoxybenzyl) sulfanil) acidic acid.

F. 3-Hydroxy-4-methoxy-benzyl-sulfonacetic acid To a solution of 2 - ((3-hydroxy-4-meloxybenzyl) -siphenyl) -acetic acid (2.9 g) in glacial acetic acid (15 ml), peroxide was added. hydrogen (6 ml, 30% solution). The resulting mixture was stirred overnight at room temperature and monitored by TLC. When the reaction was complete, the reaction mixture was poured into ice water (10 ml) and extracted with ethyl acetate (3 x 10 ml). The combined organic extract was washed with water (10 ml) and dried (Na 2 SO 4). The volatile components were removed in vacuo, to give a yield of 60% of the pure product of 3-hydroxy-4-methoxy benzyl sulfonacetic acid, having a melting point of 164-165 ° C.

G. (E) -5 - ((2,4,6-Trme-oxy-xyryl-sulfonyl) -methyl) -2-methoxy-phenol A mixture of 3-hydroxy-4-methoxy-benzyl-sulfonacetic acid (1.9 g, 7.3 mmol, 1 eq. .), 2,4,6-trimethoxybenzaldehyde (1.58 g, 8.0 mmol, 1.1 eq.), Benzoic acid (134 mg, 0.15 eq.) And piperidine (81 mg, 0.13 eq.) In toluene (50 ml), was heated at reflux temperature for 2-3 hours with continuous water removal using a Dean-Stark trap. When the reaction was complete by TLC analysis, the reaction mixture was cooled to room temperature. Water was added and the resulting mixture was extracted with ethyl acetate (3 x 50 ml). The combined organic extracts were washed with saturated sodium bicarbonate solution (50 ml), dilute hydrochloric acid (50 ml) and water (50 ml) and dried (Na 2 SO 4). The volatile components were removed in vacuo to provide the crude product, which was purified by recrystallization of isopropanol to provide (1.8 g, 62.5%) of the (E) -5- ((2,4,6-trimethoxystir 1-sulfonyl) methyl) -2-methoxyphenol.

EXAMPLE 2 (E) -5 - ((2,4,6-trimethoxystyrylsulfinyl) metii) -2-methoxyphenol A. 2 - ((3-Hydroxy-4-methoxy-benzyl) sulfinyl) acetic acid To a cooled solution (-5 ° C) of 2 - ((3-hydroxy-4-methoxybenzyl) ) sulfanyl) acetic acid (2.9 g) in anhydrous DCM (15 ml), MCPBA (20 mmol, 50% base concentration, Lancaster) was added. The reaction mixture was stirred at -5 ° C for 6 hours. The precipitated 3-chloroperbenzoic acid was removed by filtration. The filtrate was washed with water, dried over magnesium sulfate and concentrated. After removal of the solvent, the product of 2 - ((3-hydroxy-4-methoxy-benzyl) sulfinyl) acid was purified either by crystallization or by chromatography on silica gel.

B. (E) -5 - ((2,4,6-trimethoxystiryl-sulfinyl) methyl) -2-methoxy-phenol To a mixture of 3-hydroxy-4-methoxy-benzyl-sulfonacetic acid (7 mmol, 1 eq.), 2 , 4,6-trimethoxybenzaldehyde (8.0 mmol, 1.1 eq.), Benzoic acid (0.15 eq.) And piperidine (0.1 eq.) In íoluene (50 ml), was heated to reflux temperature for 2-3 hours with continuous removal of water using a Dean-Stark trap. When the reaction was complete by TLC analysis, the reaction mixture was cooled to room temperature, water was added and the resulting mixture was extracted with ethyl acetate (3 x 50 ml). The combined organic extract was washed with saturated sodium bicarbonate solution (50 ml), dilute hydrochloric acid (50 ml) and water (50 ml) and dried (Na 2 SO 4). The volatile components were removed in vacuo to provide the crude product, (E) -5- (2,4,6-tirmethoxystyrilsulfinyl) methy1) -2-methoxy-phenol, which was purified by recrystallization from isopropanol EXAMPLE 3 (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenyl dibenzyl phosphate To a stirred solution of 5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl-2-methoxy-phenol (1.9 g, 4.8 mmol) in acetonylyl (24 mL) at room temperature, carbon tetrahydride (1.94) was added. g, 1.22 eq.) and triethylamine (0.728 g, 1.5 eq.) The resulting mixture was stirred for 10 minutes and then cooled to 0 ° C in an ice water bath Dibencll phosphite (1.51 g, 1.2 eq.) dissolved in acetonitrile (16 ml), added dropwise to the cooled reaction mixture, the reaction mixture was stirred for 2 hours and monotreated by TLC.The reaction was terminated by dropwise addition of aqueous potassium dihydrogen phosphate. (10 ml, 0.5 M) The resulting mixture was extracted with ethyl acetate (3 x 30 ml) The combined organic extract was dried (Na 2 SO) and concentrated in vacuo to provide the desired product.

EXAMPLE 4 (E) -5 - ((2A6-Trimethoxystyrylsulfonyl) methyl) -2-methoxyphenol dihydrogen phosphate To a stirred solution of 5- (2,4,6-trimethoxy-styphsulfonyl) methyl) -2-meioxy-phenyl-dibenzyl phosphate (4.36 g, 6.7 mmol) in anhydrous DCM (40 mL) under nihorogen at 0 ° C, bromotrimethylsilane was added. (2.14 g, 2.1 eq.). The resulting mixture was stirred for 45 minutes and moniiored by TLC. sodium. When the reaction was complete, aqueous sodium thiosulfate (1%, 50 ml) was added and the resulting mixture was stirred for an additional 5 minutes. The organic phase was separated and the aqueous phase was extracted with acetyl ether (3 x 25 ml). The combined organic extract was concentrated in vacuo to give the crude 5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenyl dihydrogen phosphate. The product was purified in column chromatography on silica eluted with a gradient of methanol / chloroform to provide 1.4 g of the purified product having a melting point of 202-205 ° C.

EXAMPLE 5 Disodium salt of (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenyl dihydrogen phosphate To a stirred solution of 5 - ((2,4,6-trimethoxysilylsulfonyl) methyl) -2-meloxyphenyl dihydrogen phosphate (1.35 g) in ethylene glycol dimethyl ether (125 ml), 2N sodium hydroxide (2.4 eq.) Was added. . The resulting mixture was stirred for 3 hours, filtered, washed with acetone (2 x 25 ml) and dried under vacuum to provide 1.45 g of the disodium salt having a melting point of 152-154 ° C.

EXAMPLE 6 (E) -5 - ((2,4,6-Trimethoxystyrylsulfonyl) methyl) -2-methoxyphenyl diethyl phosphate To a stirred solution of 5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenyl dihydrogen phosphate (1.9 g, 4.8 mmol) in acetonitrile (24 ml) at room temperature, tetrabromide carbon (1.94 g, 1.22 eq.) and triethylamine (0.728 g, 1.5 eq.). The resulting mixture was stirred for 10 minutes and then cooled to 0 ° C in an ice water bath. Diethyl phosphite (1.51 g, 1.2 eq.) Dissolved in acetononiyl (16 ml) was added to the cooled reaction mixture. The reaction mixture was stirred for 2 hours and monitored by TLC. The reaction was terminated by dropwise addition of aqueous potassium dihydrogen phosphate (10 mL, 0.5 M). The resulting mixture was extracted with ethyl acetate (3 x 30 ml). The combined organic extract was dried (Na2SO4) and concentrated in vacuo to provide the desired product.

EXAMPLE 7 Effect of Compounds of Formula I on Tumor Cell Lines The effect of compounds of Formula I on tumor cells of prostate, colon, lung, pancreatic, brain, renal, gastrointestinal, epidermal, lymphocyte, ovarian and breast origin was examined using a variety of cancer cell lines (listed in Table 1). 6). Cells were plated at density levels of 1.0 x 10 5 cells per cavity in six-well plates. Cell cultures were maintained at 37 ° C in a humidified atmosphere of 5% CO2. Cells from 36 different cell lines were treated with (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenol (Example 1) or sodium salt of (E) -5- ( (2,4,6-trimethyloxystyiriisulphonyl) methy1) -2-methoxy-phenol dihydrogen phosphate (Example 5), at doses ranging from 2 nM to 10 nM concentration, and cell viability was determined after 96 hours by the exclusion method of blue Trypan. In addition, DU-145 cells were spiked with additional compounds of the invention: (E9-4- (3- (5 - ((2,4,6-ylmeyoxy-styrene-sulfonyl) methyl) -2 -methoxyphenoxy) propyl) morpholine; 2- (dimethylamino) acetal of (E) -5 - ((2,4,6-trimethoxystirylsulfonyl) methy1) -2-methoxyphenyl and 4-methyl-benzenesulfonation of (E) - 5 - ((2,4,6-Tr! Methoxystyrylsulphonyl) dimethyl) -2-methoxyphenyl, structures of which are shown in Table 7. The results are shown in Table 6 and Table 7. The values are reported as the GI50, that is, the concentration (μM) required for inhibition of 50% growth, compared with vehicle-treated cells (DMSO) .The notations "ER +" and "ER-", designate breast cancer lines They are sensitive and not sensitive to estrogen, respectively The notations "AR +" and "AR-" designate prostate cancer lines that are sensitive and not sensitive to androgens, respectively The "NT" rotation indicates that the compound was not tested on the line Particular cellular By cell lines designated by "*", the dose response curve for the compound (E) -5 - ((2,4,6-trimethoxysilylsulfonyl) meily) -2-mefoxphhenol (Example 1 ), is shown in Figure 1.

TABLE 6 TABLE 6 (continued) TABLE 7 EXAMPLE 8 Radioprotective Effect of Compounds of Formula I on Normal Human Cultured Cells The radioprotective effect of the compounds of Formula I on normal cultured cells was evaluated as follows. HFL-1 cells were plated in 24-well discs at a cell density of 3000 cells per 10 mm2 in DMEM supplemented with 10% fetal bovine serum and antibiotics. A test compound according to Formula I was added to the cells, 24 hours later at the concentrations of 0.25, 0.5, 1.0 and 2.0 micromolar, using DMSO as a solvent. The control cells were irradiated with DMSO alone. The cells were exposed to the test compound or DMSO for 24 hours. The cells are then irradiated with either 10 Gy or 15 Gy of ionizing radiation (IR) using a Model 30-I Shepherd Mark I Radiator, equipped with cesium-137 as a source. After irradiation, the medium in the test and the control cells were removed and replaced again with fresh growth medium without the test compounds or DMSO. The irradiated cells are incubated for 96 hours and the duplicated cavities were trypsinized and plated again on 100 mm2 tissue culture dishes. The cells plated again were grown under normal conditions with a change of fresh medium for 3 weeks. The number of colonies of each culture dish of 100 mm2, which represents the number of surviving cells, is determined by dyeing the discs as described below. To visualize and count colons derived from the clonal growth of individual radioprobe cells, the medium is removed and the plates are washed once with phosphate buffered saline at room temperature. The cells were stained with a modified Giemsa staining solution diluted 1: 10 (Sigma), for 20 minutes. The dyeing was removed and the plates washed with running water. The plates are dried by air, the number of colonies of each plate is counted and the average of the duplicate plates is determined.

EXAMPLE 9 Effect of Ionizing Radiation Exposure on Normal and Malignant Hematopoietic Progenitor Cell Growth after Pretreatment with Compounds of the Invention The effect of ionizing radiation on normal and malignant haematopoietic progenitor cells, which are pretreated with compounds of the invention, is determined by assessing the cloning efficiency and development of the pretreated cells after irradiation. To obtain hematopoietic progenitor cells, cells from human bone marrow (BMC) or peripheral blood cells (PB), from normal healthy volunteers or from acute or chronic myelogenous leukemia (AML, CML), are obtained by Ficoll density gradient centrifugation. -Hypaque, and are partially enriched by hematopoietic progenitor cells by positively selected CD34 + cells with immunomagnetic beads (Dynal AS, Oslo, Norwegian). CD34 + cells are suspended in supplemented alpha medium and incubated with anti-HPCA-I antibody in a dilution 1: 20, 45 minutes at 4 ° C, with soft inversion of the tubes. The cells are washed x3 in a supplemented alpha medium, and then incubated with perlillas coated with the goat anti-mouse IgGi Fc fragment (75 μl of immunobeads / CD34 + cells 107). After 45 minutes of incubation (4 ° C), the cells adhering to the perlillas are positively selected using a magnetic particle concentrator directed by the manufacturer. 2 × 10 4 CD34 + cells were incubated in 5 ml polypropylene tubes (Fisher Scientific, Pittsburgh, PA), in a total volume of 0.4 ml of Iscove's modified Dulbecco's medium (IMDM) containing 2% human AB serum and regulator of 10 mM Hepes pH. The test compounds of Formula I are added to the cells, in four different concentrations (0.25 μM, 0.5 μM and 2.0 μM). The control cells receive DMSO alone. The cells are incubated for 20-24 hours and irradiated by 5 Gy and 10 Gy of ionizing radiation. Immediately after irradiation, the medium is removed and replaced with the fresh medium without the test compound or DMSO.

Twenty-four hours after irradiation, the tray and conírol cells are prepared by plating methylcellulose cultures or blood clots. The cells (1 x 104 CD34 + cells per disk) are not washed before plating them. The assessment of the cloning efficiency and development of the treated hematopoietic progenitor cells is carried out essentially as reported in Gewirtz et al., Science 242, 1303-1306 (1988), a description of which is incorporated by reference in This is documenlo.

EXAMPLE 10 Bone Marrow Purged With Ionizing Radiation After Pretreatment With Compounds of the Invention The bone marrow was collected from iliac bones of an individual under general anesthesia in an operating room using standard techniques. Multiple aspirations were taken in heparinized syringes. Sufficient marrow was extracted so that the individual will be able to receive approximately 4 x 108 to approximately 8 x 10 8 marrow cells processed per kg of body weight. In this way, approximately 750 to 1000 ml of marrow are extracted. The aspirated marrow is transferred immediately into a transport medium (TC-199, Gibco, Grand Island, New York), which contains 10,000 units of preservative-free heparin per 100 ml of medium. The aspirated marrow is filtered through three progressively finer meshes to obtain a cellular suspension devoid of cellular aggregates, debris and bone particles. The filtered marrow is then further processed, in a self-priming cell separator (e.g., Cobe Cell Processor 2991), which prepares a "mononuclear cell culture" product, (i.e., leukocytes devoid of red cells and platelets). The culinary mononuclear cell preparation is then placed in a transfer packet for further processing and storage. It can be stored until purging in liquid nitrogen using standard procedures. Alternatively, the purge can be carried out immediately, then the bone marrow can be stored frozen in liquid nitrogen until it is ready to transplanle. The purging procedure is carried out as follows. Cells in the preparation of culture mononuclear cells are set at a cell concentration of approximately 2 x 10 7 / ml in TC-199 containing approximately 20% auiologous plasma. The compounds of the invention, for example, at concentrations from 0.25 μM to 2.0 μM, are added to the transfer packages containing the cell suspension and incubated in a water bath at 37 ° C for 20-24 hours with gentle agitation. The transfer packets are then exposed to ionizing radiation of 5-10 Gy. Recombinant human hematopoietic growth factors, for example, rH IL-4 or rH GM-CSF, can be added to the suspension to stimulate the growth of hematopoietic neoplasms and thereby increase their sensitivity to ionizing radiation. The cells can then either be frozen in liquid nitrogen, or washed once at 4 ° C in TC-199 containing approximately 20% autologous plasma. The washed cells are then infused into the individual. Care should be taken to work under sterile conditions whenever possible and to maintain scrupulous aseptic techniques at all times.

EXAMPLE 11 Protection of Normal Human Fibroblasts of Paclitaxel Cytotoxicity by Compounds of Formula I HFL-1 cells were plated at a cell density of 1.0 x 105 per well, 24 hours before the drug addition. The cells are pretreated with a compound according to Formula I (2.0 μM) for 8 hours and then exposed to paclitaxel (250 μM). Other cells are then irradiated with paclitaxel alone, or both agents simultaneously. Cells are enumerated by exclusion of blue Trypan, using a hematocytometer 96 hours after exposure to paclitaxel. The cytoprotein activity can be compared by comparing the number of viable cells after irradiation with a compound according to Formula I and paclitaxel, divided by the number of viable cells remaining after treatment with paclitaxel alone.

EXAMPLE 12 Protection of Normal Human Fibroblasts from Anticancer Agent Cytotoxicity HF-1 cells are plated at a cell density of 1.0 x 105 in 1 ml of medium. Twenty-four hours after plating, 2.0 μM of a compound according to Formula I is added to the medium. After a pre-incubation of 24 hours with the compound according to Formula I, the various cilotoxic agents selected from the list in Table 8 are added to the cells. The number of viable cells is determined by exclusion of blue Trypan using a hematocymeter 96 hours after exposure to a cytoxy agent. The "Protection Ratio" is the number of viable cells after irradiation with a compound according to Formula I and the selected cytotoxic agent, divided by the number of viable cells remaining after treatment with cytotoxic agent alone. A protection ratio of 2 or more is considered highly significant, while a projection ratio of 1.5-2 is considered less significant.

TABLE 8 EXAMPLE 13 Protection of Normal Human Fibroblasts of Vincristine Cytotoxicity by Compounds of Formula I HFL-1 cells were treated with 0-250 μM vincristine and, optionally, a 2.0 μM preparation of a compound according to Formula I, either 24 hours before or after treatment with vincristine, or simultaneously with the treatment of vincristine. Cell viability was assessed 96 hours after the addition of vincrisine.

EXAMPLE 14 Protection of Mice from the Toxicity of Paclitaxel using Compounds of Formula I Female ICR mice of 10-12 weeks of age (Taconlc), were divided into the following groups of trawl and received iniralperitoneal injections of 50 mg / kg, a compound according to Formula I, dissolved in DMSO and / or 50 mg / kg of pacliaxel (Taxol, Sigma Chemical Co.), dissolved in DMSO. The compound according to Formula I is given 24 hours before paclitaxel, 4 hours before paclitaxel, or simultaneously with paclitaxel. The conirol animals received paclilaxel alone or a compound according to Formula I alone. Mortality is assessed 48 and 144 hours after the injection of paclltaxel. All references cited in this document are incorporated by reference. The present invention can be included in other specific forms without departing from the spirit or essential attributes thereof, and, therefore, reference should be made to the appended claims, preferably to the aforementioned specification, as an indication of the scope of the invention.

Claims (94)

1. NOVELTY OF THE INVENTION CLAIMS 1. A compound according to the Formula wherein, A is -S- or -O-; R1 is selected from the group consisting of -H; alkyl halo of (C C6), -C (= 0) Rw; -S (= 0) Rw; -S02Rw; - (hydrocarbylene C C6) Rz, -P (= 0) (ORv) 2, -C (Ra) (Rv) -C (= 0) -Rn, unsubstituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, -Si [alkyl] of (C? -C6)] 3, and -CH2CH2Si [(d-C6) alkyl] 3; each Rv is independently selected from the group consisting of -H and -hydrocarbyl of (CrC7); Rw is selected from the group consisting of -hydrocarbyl of (d-C7), -NRV2; -ORv; halo (d-C3 alkyl), -NRvCRvRa-C (= 0) -Rn; -CRvRa-N (Rv) -Rc; substituted and unsubstituted aryl, substituted and unsubstituted aryl (CrC3), substituted and unsubstituted heteroaryl, substituted and unsubstituted (C-1-C3) heteroaryl, substituted and unsubstituted heterocyclyl, substituted and unsubstituted heterocyclylalkyl (C C3), - (alkylene) of C1-C3) P (= 0) (ORv) 2; -perfluoroalkylene of (C C3) -N (CH3) 2; -alkylene (d-C3) -N ((C3) alkyl) 2; - ((C C 3) alkylene-N + (CrC 3) alkyl); -alkylene (C1-C3) -N + (CH2CH2OH) 3; - (alkylene of d-C4) -C (= 0) -halogen; - perfluoroalkylene of (C C4) -C02Rv; - (alkylene of d-C3) C (= 0) ORv; and - (C C3 alkylene) OC (= 0) - (C C3 alkylene) C (= 0) Ry; Ry is selected from the group consisting of -OR, -NRV2 and -alkyl of (dC6); Rz is selected from the group consisting of -C (= 0) Ry; -NRvCRvRa-C (= 0) -Rn; -NRV2; -ORv; substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, substituted and unsubstituted (C1-C3) heteroarylkyloxy, and -C (= 0) (C1-C3) alkyl; each Ra is independently selected from the group consisting of -H; -alkyl of (C? -C6), -heteroalkyl of (d-C6), - (CH2) 3-NH-C (NH2) (= NH), -CH2C (= 0) NH2, -CH2COOH, - (CH2) 2COOH, unsubstituted and unsubstituted aryl, substituted and unsubstituted (C C 3) aryl, substituted and unsubstituted heterocyclyl, and unsubstituted and substituted (C 1 -C 3) heterocyclic alkyl; each Rn is independently selected from the group consisting of -ORv, -NRV2, and an N-terminally linked peptidyl residue containing from 1 to 3 amino acids in which the terminal carboxyl group of the peptidyl residue is present as a functional group, selected from group consisting of -C0 R and -C (= 0) NRv2; each Rc is independently selected from the group consisting of -H and a terminally linked peptidyl carboxy residue containing from 1 to 3 amino acids in which the terminal amino group of the peptidyl residue is present as a functional group selected from the group consisting of -NH2 , -NHC (= 0) alkyl of (C C6); -NHalkyl of (C C6), -NH (C1-C6 alkyl) 2, and -NHC (= 0) Ohridrocarbyl of (C C7); Q is aryl or heteroaryl; each R2 and R3 is independently selected from the group consisting of halogen; -hydrocarbyl of (d-C7), -C (= 0) Rv, -NRV2, -NHC (= 0) Rv, -NHS02Rv, -NHRa, -NHCRvRaC (= 0) Rn, -NHS02Rv, -C (= 0 ) ORv, -C (= 0) NHRv, -N02, -CN, -ORv, -P (= 0) (ORv) 2, -C (= NH) NH2l dimethylamino (C2-C6 alkoxy), -NHC (= NRV) NHRV, -haloalkyl of (d-C6), and -haloalkoxy of (d-C6); the two Rv groups in -P (= 0) (ORv) 2 and -NRV2 may optionally form a heterocyclic ring of five or six elements, which may optionally also be fused to an aryl or carbocyclic ring; a is 0, 2, 2 or 3; b is 0, 1, 2 or 3; the conformation of the substituents on the exocyclic carbon-carbon double bond is either E- or Z-; X is -C * H (RX) Y- or -NRX-Z-; Y is -S (= 0) - or -S02-; Z is -C (= 0) - or -S02-; Rx is selected from the group consisting of -H; -alkyl of (d-C6), and -C (= 0) alkyl of (C C3); and * indicates that, when Rx is different from H, the conformation of the substitutes in the designated carbon atom is (R) -, (S) - or any mixture of (R) - and (S) -; or a compound salt; provided that: (a) when A is -O- and R1 is -H: b is greater than 0; and R3 is different from alkyl of (d-C6), -OH and -N02, (b) when X is -NRX-Z- and A is -O-; Rz is different from -C (= 0) Ry, -NRV2 and unsubstituted aryl; and Rw is different from -alkyl of (d-C6); and (c) when X is -C * H (RX) Y- and A is -O-; R1 is different from haloalkyl of (d-d); Rz is different from -NRV2 and insoluble aryl; and Rw is different from -hydrocarbyl of (d-C).
2. 2. The compound according to claim 1, further characterized in that: Rw is selected from the group consisting of -hydrocarbyl of (C C7), -NRV2; -ORv; halo (C Cs alkyl), -NRvCRvRa-C (= 0) -Rn; -CRvRa-N (Rv) -Rc, unsubstituted and unsubstituted aryl, substituted and unsubstituted (C1-C3) arylalkyl, unsubstituted and substituted heteroaryl, unsubstituted substituted (C1-C3) heteroarylalkyl, unsubstituted substituted heteroaryclic, heterocyclylalkyl of (d-C3) n-substituted substitution, - (alkylene of d-C3) P (= 0) (ORv) 2, -perfluoroalkullene of (C1-C3) -N (CHs) 2, - (alkylene of (C C3) -N + (C C3) alkyl 3); -alkylene of (CrC3) -N + (CH2CH2OH) 3, - (C? -C4 alkylene) -C (= 0) -halogen, -perfluoroalkylene of (CrC4) -C02Rv, - (C-C3 alkylene) C ( = 0) OR; and - (alkylene of C d) OC (= 0) - (alkylene of d-C3) C (= 0) Ry; and Rz is selected from the group consisting of -C (= 0) Ry; -NRvCRvRa-C (= 0) -Rn; -NRV2; -ORv; substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, and -C (= 0) alkyl of (C d); provided that (c) when X is -C * H (RX) Y- and A is -O-; R1 is differentiated to haloalkyl of (C? -C6) and aryl insusiiuuido; Rz is different from -NRV2 and n-substituted aryl; and Rw is different from -hydrocarbyl of (d-d).
3. 3. The compound according to claim 1, further characterized in that Q is aryl.
4. 4. The compound according to claim 1, further characterized in that Q is heteroaryl.
5. 5. The compound according to claim 1, further characterized in that it is of Formula IE: wherein the exocyclic carbon-carbon double bond is in (E) - conformation; and R1, R2, R3, A, a, b, A and Q are as defined in claim 1.
6. 6. The compound according to claim 1, further characterized in that it is of Formula IZ: where the exocyclic carbon-carbon double bond is in the (Z) -formation; and R1, R2, R3, A, a, b, A and Q are as defined in claim 1.
7. 7. The compound according to claim 1, further characterized in that the sum of a and b is at least 1.
8. 8. The compound according to claim 1, further characterized in that the sum of a and b is at least 2. The compound according to claim 1, further characterized in that it is of Formula II: wherein R 32, D R 3, A, a, b, A and Q are as defined in claim 1, or a salt thereof. 10. The compound according to claim 9, further characterized in that it is of the Formula HA: wherein R2, R3, A, a, b, and Q are as defined in claim 9; And it is -S (= O) - or -SO2-; * indicates that, when Rx is different from H, the conformation of the substituents at the designated carbon atom is (R) -, (S) - or any mixture of (R) - and (S) -; and Rx is selected from the group consisting of -H, -alkyl of (d-C6) and -C (= 0) (alkyl d-C6), a salt of such a compound. 11. The compound according to claim 10, further characterized in that Rx is -H. The compound according to claim 11, further characterized in that it is selected from the group consisting of (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenol; (E) -5 - ((2,4,6-trimethoxystolysulfonyl) meityl) -2-methoxybenzentiol; (E) -5 - ((2,4,6-trimethoxy-styrylsulfinyl) methyl) -2-methoxyphenol; (E) -5 - ((2,4,6-Trimethioxy-styrylsulfonyl) methyl) -2-methoxybenzothiol; and you come out of them. The compound according to claim 9, further characterized in that it is of Formula IIB: wherein R2, R3, A, a, b, and Q are as defined in claim 9; Z is -C (= 0) - or -S02-; and Rx is selected from the group consisting of -H, -alkyl of (C Ce) and -C (= 0) (alkyl d-d), a compound salt. 14. The compound according to claim 13, further characterized in that Rx is -H. 15. The compound according to claim 14, further characterized in that it is selected from the group consisting of: (E) -5 - ((2,4,6-trimethoxystyryl) sulfonamido) -2-methoxyphenol; (E) -5 - ((2,4,6-trimethoxystyryl) suphonamido) -2-methoxybenzothiol; (E) -N- (3-hydroxy-4-methoxy-phenyl) -3- (2,4,6-trimethoxyphenyl) acrylamide; (E) -N- (3-mercapto-4-methoxyphenyl) -3- (2,4,6-trimethoxyphenyl) -acrylamide; and you come out of them. 16. The compound according to claim 1, further characterized in that R1 is different from H. 17. The compound according to claim 1, further characterized in that it is of formula III: wherein R2, R3, R, X, A, Q, a and b are as defined in claim 1, or a salt thereof. 18. The compound according to claim 17, further characterized in that it is of Formula IIIA: wherein R2, R3, A, a, b and Q are as defined in claim 9; Y is -S (= 0) - or -S02-; * indicates that, when Rx is different from H, the conformation of the sustiluyenles at the designated carbon atom is (R) -, (S) - or any of the mixtures of (R) - and (S) -; and Rx is selected from the group consisting of -H, -alkyl of (d-d), and -C (= 0) alkyl of (Crd), or a salt of such a compound. 19. The compound according to claim 18, further characterized in that Rx is -H. The compound according to claim 19, further characterized in that it is selected from the group consisting of: (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenyl; dimethyl phosphate of (E) -5 - ((2,4,6-methoxystiryl) sulfonyl) methyl) -2-methoxyphenyl; diethyl phosphate of (E) -5 - ((2,4,6-trimethioxysilylsulfonyl) methyl) -2-methoxyphenyl; Dibenzium phosphate of (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) -methyl) -2-methoxyphenyl; phosphorothioate of (E) -S-5 - ((2,4,6-lyrimidoxysaryl-sulfonyl) -methyl) -2-methioxyphenyl-0,0-dihydrogen; phosphorousium of (E) -S-5 - ((2,4,6-trimethoxystylsulfonyl) meily) -2-methoxyphenyl-0,0-dimethyl; phosphorothioaio of (E) -S-5 - ((2,4,6-frimetoxy-pyridyl) -methyl) -2-methoxy-phenyl-O, O-diethyl; phosphoroaioaio of (E) -S-5 - ((2,4,6-lrimethoxystiryl-sulfonyl) methyl) -2-methoxyphenyl-0, 0-dibenzyl; dihydrogen phosphate of (E) -5 - ((2,4,6-trimethoxystyrylsulfinyl) methyl) -2-methoxyphenyl; dimethyl phosphate of (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenyl; diethyl phosphate of (E) -5 - ((2,4,6-trimethoxystyrylsulfinyl) methy1) -2-methoxy-phenol; phosphatic dibenzyl of (E) -5 - ((2,4,6-urimoxystyilsyryl) -methyl) -2-methoxyphenyl; phosphorothioate of (E) -S-5 - ((2,4,6-trimethoxystyryl-sulfinyl) methyl) -2-methoxyphenyl-0,0-dihydrogen; phosphorothioalo of (E) -S-5 - ((2,4,6-trimethoxystirylsulfinyl) methyl) -2-methoxy-phenyl-0,0-dlmethyl; phosphorothioate of (E) -S-5 - ((2,4,6-trimethoxy-styrylsulfinyl) methy1) -2-methoxy-phenyl-0,0-diethyl; phosphoroalloy of (E) -S-5 - ((2,4,6-ynedimoxy-styryl-sulfinyl) methyl) -2-methoxyphenyl-O.O-dibenzyl; and you come out of them. 21. The compound according to claim 17, further characterized in that it is of Formula IIIB: wherein R2, R3, Rx, Rv, a, b, A, Z and Q are as defined in accordance with claim 17; Z is -C (= 0) - or -S02-; and Rx is selected from the group consisting of -H, -alkyl of (C | -C6), and -C (= 0) alkyl of (C | -C6), or a salt thereof. 22. The compound according to claim 21, further characterized in that Rx is -H. 23. The compound according to claim 22, further characterized in that it is selected from the group of dihydrogen phosphate of (E) -5- (2,4,6-trimethoxystyrylsulfonamido.) -2-methoxy-phenyl; dimethylsilyl phosphate of (E) -5- (2,4,6-lrimethoxystyrylsulfonamido) -2-meloxophenyl; diethyl phosphate of (E) -5- (2,4,6-trimethoxystirylsulfonamido) -2-methoxyphenyl; (E) -5- (2,4,6-trimethoxystyrylsulfonamido) -2-methoxyphenyl di-benzylphosphate; phosphorothioaio of (E) -S- (5- (2,4,6-trimethoxy-styrene-sulfonamido) -2-meioxy-phenyl) -0,0-dihydrogen; phosphorothioate of (E) -S- (5- (2,4,6-trimethoxystyrylsulfonamido) -2-methoxyphenyl) -O.O-dimethyl; phosphorothioate of (E) -S- (5- (2,4,6-trimethoxy-styrylsulfonamido) -2-methoxyphenyl) -O, 0-diethyl; phosphorothioate of (E) -S- (5- (2,4,6-trimethoxystyrylsulfonamido) -2-methoxyphenyl) -0,0-dibenzyl; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxyphenium phosphate dihydrogen; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) -acylamide) -2-methoxy-phenyl dimethyl phosphate; 5 - ((E) -3- (2,4,6-trimethoxy-phenyl) -acrylamide) -2-methoxy-phenol diethyl phosphate; 5 - ((E) -3- (2,4,6-Trimethyloxy-phenyl) acrylamide) -2-methoxyphenyl dibenzyl phosphate; phosphorothioate of S-5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxyphenyl-0,0-dlhydrogen; phosphorothioate of S-5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamide) -2-meloxyphenyl-0,0-dimethyl; phosphorothioate of S-5 - ((E) -3- (2,4,6-trimethoxy-phenyl) acrylamido) -2-methoxyphenyl-O.O-d-ethyl; phosphorothioate of S-5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxyphenyl-0, O-dibenzyl; and you come out of them. 24. The compound according to claim 1, further characterized in that it is of Formula IV: wherein R, R, R, X, A and Q are as defined in accordance with claim 1, or a salt thereof. 25. The compound according to claim 24, further characterized in that it is of the Formula IVA: wherein R2, R3, Rw, A, a, b, and Q are as defined in accordance with claim 24; Y is -S (= 0) - or -S02-; * indicates that, when Rx is other than -H, the conformation of the substituents at the designated carbon atom is (R) - (S) - or any mixture of (R) and (S) -; and Rx is selected from the group consisting of -H, alkyl of (CrC6), and -C (= 0) alkyl of (C | -C6), or a salt of the compound. 26. The compound according to claim 25, further characterized in that Rx is -H. 27. The compound according to claim 26, further characterized in that it is selected from the group consisting of: (E) -2 - ((5 - ((2,4,6-trimethoxystiryl) sulfonyl) methyl) -2- methoxyphenoxy) -carbonyl) acetic acid; (E) -5 - ((2,4,6-trimethoxy-styrylsulfonyl) methyl) -2-methoxyphenyl-3,5-dinitrobenzoate; (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) -methyl) -2-methoxyphenyl-3,5-diaminobenzoate; (E) -5 - ((2,4,6-lyr-methoxy-ylsulfonyl) -methyl) -2-methoxyphenyl-2-chloroacetate; (E) -5 - ((2,4,6-trimethoxy-styrylsulfonyl) mephyl) -2-methoxy-phenyl-2- (4-methyl-piperazin-1-yl) -acetate; benzoate of (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenyl; (E) -5 - ((2,4,6-trimethoxystiryl sulfonyl) methyl) -2-methoxyphenyl-4-nitrobenzoate; (E) -5 - ((2,4,6-Trimethioxysilylsulfonyl) methyl) -2-methoxyphenyl-4-aminobenzoate; (E) - (R) -5 - ((2,4,6-trimethoxystirylsulfonyl) methy1) -2-methoxyphenyl-2,6-diaminohexanoate; (E) - (R) -5 - ((2,4,6-trimethoxy-styrylsulfonyl) methy1) -2-methoxyphenyl-2-amino-3-hydroxypropanoane; (E) - (5) -5 - ((2,4,6-trimethoxy-styrylsulfonyl) methyl) -2-methoxyphenyl-2-amino-3-hydroxypropanoate; carbamate of (E) -5 - ((2,4,6-tr ~ methoxystyrylsulfonyl) methyl) -2-methoxy-phenyl; (E) -5 - ((2,4,6-trimethoxystirylsulfonyl) -methyl) -2-meioxy-phenyl-2- (di-meitylammon) -acetate; (E) -5- ((2,4,6-Trimethyloxystyrylsulfonyl) meily) -2-mexoxyphenyl-4- (4-methylpiperazin-1-yl) benzoate; (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenyl-2-hydroxyacetate; (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) -methyl) -2-methoxyphenyl-2- (pyridinium-1-yl) acetyl; (E) -5 - ((2,4,6-trimethoxy-styrylsulfonyl) methyl) -2-methoxyphenyl-2-acetoxyacetate; (E) -5 - ((2,4,6-tri-methoxystyiri-sulphonyl) methyl) -2-methoxy-phenyl-2-hydroxypropanoate; (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) meily) -2-mexoxyphenyl-2- (ioethyl-ammonium) -acetate; (E) -5 - ((2,4,6-trimethyloxystyrylsulfonyl) methyl) -2-methoxyphenyl-2- (tris (2-hydroxyethyl) ammonium) acetyl; (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methy1) -2-methoxyphenyl-2-hydroxy-2-methylpropanoate; (E) -5 - ((2,4,6-trimethioxy-ylsilylsulfonyl) -methyl) -2-methoxyphenyl-2-acetoxy-2-methylpropanoate; (E) -5 - ((2,4,6-trimethoxystiryl sulfonyl) methyl) -2-methoxy-phenyl-2,2,2-trifluoroacetate; (E) -3 - ((5 - ((2,4,6-trimethoxy-siliconyl-sulfonyl) -methyl) -2-methoxyphenoxy) -carbonyl) propanoic acid; (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenyl-3- (chlorocarbonyl) -propanoate; 2- (3-carboxypropanoic) acetylate of (E) -5 - ((2,4,6-trimethoxy-styrylsulfonyl) methyl) -2-methoxy-phenyl; (E) -4 - ((5 - ((2,4,6-trimethoxy-styrylsulfonyl) -methyl) -2-methoxyphenoxy) -carbonyl) butanoic acid; dihydrogen phosphate of (E) - ((5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenoxy) -carbonyl) methyl; Methyl carbonate of (E) -5 - ((2,4,6-trimethoxystiryl sulfonyl) methyl) -2-methoxyphenyl; (E) -5 - ((2,4,6-trimethoxy-slylylsulfonyl) -methyl) -2-methoxyphenyl-2-acetoxypropanoane; methylyl succinalo of (E) -5 - ((2,4,6-trimethoxy-styrylsulfonyl) methyl) -2-meloxyphenyl; ethyl ester of (E) -5 - ((2,4,6-lyrimethylsilyl-sulfonyl) -methyl) -2-methoxyphenyl; (E) -5 - ((2,4,6-trimethoxy-syrylsulfonyl) methyl) -2-methoxyphenyl-2,2,3,3,3-penta-fluoropropanoate; (E) -1- (5 - ((2,4,6-trimethoxy-syrylsulphonyl) me'l) -2-methoxy-phenyl) -3-methyl-2,2-difluoromalonate; (E) -3 - ((5 - ((2,4,6-trimethoxy-styrylsulfonyl) methyl) -2-meioxyphenoxy) -carbonyl) -2,2,3,3-tetrafluoro-propanoic acid; 2-Aminoacetal of (E) -5 - ((2,4,6-dimethoxystyrylsulfonyl) methyl) -2-methoxy-phenyl; (E) -2 - ((5 - ((2,4,6-trimethoxystylsulphonyl) -methyl) -2-methoxyphenoxy) carbonyl) -2,2-d-fluoroacetic acid; (E) -5 - ((2,4,6-trimethoxy-styrylsulfonyl) methyl) -2-methoxyphenyl-2- (dimethylammonyl) -2,2-difluoroacetal; 5 - ((2,4,6-trimethoxystyrylsulfonyl) meily) -2-methoxyphenyl-2- (dimethylamino) acetate; (E) -2 - ((5 - ((2,4,6-trimethoxylysilyrilsulfinyl) methyl) -2-methoxyphenoxy) carbonyl) acetic acid; (E) -5 - ((2,4,6-trimethoxy-sphyrylsulfinyl) -methyl) -2-mexoxyphenyl-3,5-dinoxybenzoal; (E) -5 - ((2,4,6-fr'methoxysaryl-sulfinyl) methyl) -2-methoxyphenyl-3,5-diaminobenzoate; (E) -5 - ((2,4,6-trimethoxy-ylsilyl-sulfinyl) methyl) -2-meloxyphenyl-2-chloroacety; (E) -5 - ((2,4,6-trimethoxystyrisulfinyl) methyl) -2-meioxy-phenyl-2- (4-methyl-piperazin-1-yl) acetate; benzoaio of (E) -5 - ((2,4,6-dimethoxystyrylsulfinyl) meily) -2-methoxyphenyl; (E) -5 - ((2,4,6-trimeloxiestirilsulfinil) methyl) -2-methoxyphenyl-4-nitrobenzoate; (E) -5 - ((2,4,6-Trimethoxysphyrylsulfinyl) methy1) -2-methoxyphenyl-4-aminobenzoate; 2,6-diamlnohexanoate of (E) - (R) -5 - ((2,4,6-trimethoxystirylsulfinyl) -methyl) -2-mexoxyphenyl; 2-amino-3-hydroxypropanole of (E) - (R) -5 - ((2,4,6-trimethoxy-styrylsulfinyl) methyl) -2-methoxyphenyl; (E) - (S) -5 - ((2,4,6-uro-dimethylsulfinyl) -sulfinyl) -methyl) -2-methoxyphenyl-2-amino-3-hydroxypropanoate; carbamate of (E) -5 - ((2,4,6-ylmethylsilyl-sulfinyl) methyl) -2-methoxy-phenyl; 2- (di-methyl-amino) -acetyl of (E) -5 - ((2,4,6-dimethoxystyrylsulfinyl) methyl) -2-methoxy-phenyl; 4- (4-Methylpiperazin-1-yl) benzoate of (E) -5 - ((2,4,6-trimethoxystiryl-sulfonyl) -methyl) -2-methoxyphenyl; (E) -5 - ((2,4,6-Trimethioxy-ylsilyl-sulfinyl) methyl) -2-mexoxyphenyl-2-hydroxyacety; (E) -5 - ((2,4,6-γ-methoxystyrylsulfinyl) -methyl) -2-methoxyphenyl-2- (pyridinium-1-yl) -acetate; (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenyl-2-acetoxyacetate; (E) -5 - ((2,4,6-Tri- methoxystyrylsulfinyl) meily) -2-methoxy-phenyl-2-hydroxypropanoate; (E) -5 - ((2,4,6-trimelloxiestirilsulfinyl) -metl) -2-methoxy-phenyl-2- (triethylammonium) acetate; 2- ((E) -5 - ((2,4,6-Trimethoxystyryl-sulfinyl) methyl) -2-methoxy-phenyl (tris (2-hydroxyethyl) -ammonium) acetate; 2-Hldroxy-2-methylpropanoate of (E) -5 - ((2,4,6-dimethoxystyrrylsulfinyl) meily) -2-methoxy-phenyl; (E) -5 - ((2,4,6-N-methoxystyrylsulfinyl) -methyl) -2-methoxy-phenyl-2-acetoxy-2-methylpropanoate; (E) -5 - ((2,4,6-ylmethylsilylsulfinyl) -methyl) -2-meloxyphenyl-2,2,2-и fluoroacety; (E) -3 - ((5 - ((2,4,6-Trimethyloxy-styrylsulfinyl) methyl) -2-methoxyphenoxy) -carbonyl) -propanoic acid; (E) -5 - ((2,4,6-Trylmethystyrylsulfinyl) methyl) -2-methoxy-phenyl-3- (chlorocarbonyl) -propanoate; (E) -5 - ((2,4,6-trimethoxystiryl-sulfinyl) -methyl) -2-methoxyphenyl-2- (3-carboxypropanoic) acetate; (E) -4 - ((5 - ((2,4,6-trimethoxystyilsylsulfinyl) -methyl) -2-methoxyphenoxy) -carbonyl) butanoic acid; dihydrogen phosphate of (E) - ((5 - ((2,4,6-trimoxysphyrylsulfinyl) methyl) -2-methoxyphenoxy) -carbonyl) -methyl; Methyl Carbonate of (E) -5 - ((2,4,6-trimethoxystirylsulfinyl) methyl) -2-methoxyphenyl; (E) -5 - ((2,4,6-Trimethioxysilyl-sulfinyl) -methyl) -2-mexoxyphenyl-2-acetoxypropanoate; Methyl succinate (E) -5 - ((2,4,6-trimethoxy-1-ylsulfonyl) -methyl) -2-methoxyphenyl; ethyl ester of (E) -5 - ((2,4,6-trimethoxystyrylsulfinyl) methyl) -2-methoxyphenyl; (E) -5 - ((2,4,6-trimethoxy-sulphurysulfinyl) methyl) -2-methoxy-phenyl-2,2,3,3,3-penta-fluoropropanoate; (E) -1- (5 - ((2,4,6-lime-mexylsilyl-sulfinyl) -methyl) -2-methoxyphenyl) -3-methyl-2,2-difluoromalonade; (E) -3 - ((5 - ((2,4,6-Frimethoxy-styrylsulfinyl) methyl) -2-methoxyphenoxy) -carbonyl) -2,2,3,3-terafluoro-propanoic acid; (E) -5 - ((2,4,6-trimethoxystyilsylsulfinyl) methy1) -2-methoxy-phenyl-2-aminoacetate; (E) -2 - ((5 - ((2,4,6-trimethoxystiryl-sulfinyl) -methyl) -2-methoxyphenoxy) -carbonyl) -2,2-difluoroacetic acid; (E) -5 - ((2,4,6-trimethoxy-styrylsulfinyl) methyl) -2-methoxy-phenyl-2- (dimethylamino) -2,2-difluoroacetamide; 5 - ((2,4,6-trimethoxy-styrylsulfunyl) methyl) -2-methoxyphenyl-2- (dimethylamino) acetamide; and you come out of them. 28. The compound according to claim 24, further characterized in that it is of Formula IVB: wherein R2, R3, Rw, a, b, A, and Q are as defined in accordance with claim 24; Z is -C (= 0) - or -S02-; and Rx is selected from the group consisting of -H, -alkyl of (C | -C6), and -C (= 0) alkyl of (CrC6), or a salt thereof. 29. The compound according to claim 28, further characterized in that Rx is -H. 30. The compound according to claim 29, further characterized in that it is selected from the group consisting of: 2- acid. { [5- ( { [(1 E) -2- (2,4,6-l-methoxyphenyl) vinyl] sulfonyl] amino) -2-methoxy-phenyl] oxycarbonyl} acéíico; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) -vinyl] sulfonyl}. Amino) -2-methoxy-phenyl-3,5-dinitrobenzoate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl.} Amino) -2-methoxyphenyl-3,5-diaminobenzoate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl.] Amino) -2-methoxyphenyl-2-cyoroacetamide; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) -vinyl] -sulfonyl} -amino) -2-meioxypropyl 2- (4-methylpiperazinyl) -acetate; benzoaio of 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl.] amino) -2-methoxyphenyl; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl}. Amino) -2-methoxyphenyl 4-nitrobenzoal; 5- ( { [(1 E) -2- (2,4,6-ynedioxyphenyl) vinyl] -sulfonyl] amino) -2-methoxyphenyl-4-aminobenzoate; 5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl) vinyl] -sulfonyl] amino) -2-methoxyphenyl- (2R) -2,6-diamino -hexanoate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) viny] sulphonyl] amino) -2-methioxyphenyl- (2R) -2-amino- 3-hydroxypropanoate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] -sulfonyl}. Amino) -2-methoxyphenyl- (2S) -2-amino-3-hydroxypropanoate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl} -amino) -2-methoxyphenyl carbamate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl.] Amino) -2-mexoxyphenyl-2- (dimethylamino) -acetate; 5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl) vinyl] sulfonyl] amino) -2-methoxy-phenyl-4- (4-methyl-piperazinyl) - benzoaio; 5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl) -v-n-1] sulfonyl} -amino) -2-methoxy-phenyl-2-hydroxy-acetate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] -sulfonyl}. Amino) -2-methoxyphenyl-2-pyrid-1-ylacetate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl] amino] -2-methoxy-phenyl-2-acetyloxyacetate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl] -amino) -2-methoxyphenyl-2-hydroxypropanoate; 5- ( { [(1 E) -2- (2,4,6-uroxy-phenyl) -vinyl] -sulfonyl} -amino) -2-methoxy-phenyl-2- (γ-ethyl-ammonium) -acetate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl.] Amino) -2-methoxyphenyl-2- [tris (2-hydroxyethyl) ammonium Or] acetate; 2-Hydroxy-2-methylpropanoate of 5- ( { [(1 E) -2- (2,4,6-Rlymethio-phenyl) -vinyl] -sulfonyl] -amino) -2- methoxyphenol; 5- ( { [(1 E) -2- (2,4,6-ynedioxyphenyl) vinyl] sulfonyl] amino] -2-methoxyphenyl-2-acetyloxy-2-methylpropanoane; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl] -amino) -2-methoxyphenyl-2,2,2-trifluoroacetate; acid 3-. { [5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl] -amino) -2-methoxyphenyl] oxycarbonyl} -propanoic; 5- ( { [(1 E) -2- (2,4,6-trimelloxyphenyl) vinyl] sulfonyl] amino) -2-methoxyphenyl-3- (chlorocarbonyl) -propanoate; 3 - [( { [5- ( { [(1 E) -2- (2,4,6-uroxy-phenyl) -vinyl] -sulfonyl} -amino) -2-methoxy L] oxycarbonyl, ylmethyl) oxycarbonyl] propanoic acid; 4- acid. { [5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl) -vinyl] sulfonyl] amino] -2-methoxyphenyl] -oxocarbonyl } butanoic; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) viny] -sulfonii.} Amino) -2-methoxyphenyl-2- (phosphonooxy) acetate; methoxyformate of 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) viny] sulphonyl] -amino) -2-methoxyphenyl; 5- ( { [(1 E) -2- (2,4,6-ynedioxyphenyl) vinyl] sulfonyl}. Amino) -2-methoxyphenyl-2-acetyloxypropanoate; butane-1,4-dioate methyl 5- ( { [(1 E) -2- (2,4,6-lrimethoxyphenyl) -vinyl] sulfonyl}. amino) -2-methoxy-phenyl; Propan-1,3-dioate ethyl of 5- (. {[[(1 E) -2- (2,4,6-trimethoxyphenyl) viny] -sulfonyl}. amino) -2-methoxy-phenyl; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl.} - amino) -2-methoxy-phenyl-2,2,3,3,3 -pentafluoropropanoate; 2,2-difluoropropan-1,3-dioate methyl from 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl} -amino) -2- methoxy phenyl; acid 3-. { [5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] -sulfonyl}. Amino) -2-methoxyphenyl] -oxocarbonyl} -2,2,3,3-telrafluoropropanoic; 5- ( { [(1 E) -2- (2,4,6-ylmeoxyl-phenyl) vinyl] sulfonyl] amino] -2-methoxy-phenyl-2-aminoacetic acid; 2- acid. { [5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) viny] -sulfonyl.] Amino) -2-methoxyphenyl] -oxocarbonyl} -2,2-difluoroacetic; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) -vinyl] sulfonyl.}. Amino) -2-methoxy-phenyl-2- (dimethylmethane) -2,2-difluoro-acetate; 5 - ((E) -3- (2,4,6-trimethoxy) phenyl) -acrylamide) -2-methoxyphenyl-2- (carboxy) acetate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamide) -2-methoxy-phenyl-3,5-dinitrobenzoate; 5 - ((E) -3- (2,4,6-trimethoxyfenii) acrylamido) -2-methoxyphenyl-3,5-dinhydrobenzoate; 5 - ((E) -3- (2,4,6-tr.methoxyphenyl) acryl-amido) -2-methoxyphenyl-2-chloroacetate; 5 - ((E) -3- (2,4,6-trlmethoxyphenyl) -acrylamido) -2-methoxyphenyl-2- (4-methyl-piperazin-1-yl) acetyl; 5 - ((E) -3- (2,4,6-trylperoxyphenyl) acrylamido) -2-methoxyphenyl benzoate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-meloxophenyl-4-nitrobenzoate; 5 - ((E) -3- (2,4,6-trimethoxy-phenyl) -acrylamide) -2-methoxyphenyl-4-aminobenzoate; (R) -5 - ((E) -3- (2,4,6-Trimethioxyphenyl) acrylamide) -2-methoxy-phenyl-2,6-di-aminohexanoate; (R) -5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxy-phenyl-2-amino-3-hydroxypropanoate; (S) -5 - ((E) -v3- (2,4,6-trimethoxyphenyl) -acrylamido) -2-mexoxyphenyl-2-amino-3-hydroxypropanole; carbamado of 5 - ((E) -3- (2,4,6-lyrimethoxyphenyl) acrylamido) -2-methoxyphenyl; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamide) -2-methoxyphenyl-2- (dimethylamino) acetate; 5 - ((E) -3- (2,4,6-trimellidoxyphenyl) acrylamido) -2-mexoxyphenyl-4- (4-methyl-plperazin-1-yl) benzoate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxyphenyl-2-hydroxyacetate; 5- ((E) -3- (2,4,6-dimidoxyphenyl) -acyl-amido) -2-methoxyphenyl 2- (pyridin-1-yl) acetal; 5 - ((E) -3- (2,4,6-trimethoxy-phenyl) acrylamido) -2-methoxyphenyl-2-acetyloxyacetate; 5 - ((E) -3- (2,4,6-tr'-methoxy-phenyl) -acrylamido) -2-methoxy-phenyl-2-hydroxypropanoate; 5 - ((E) -3- (2,4,6-Trimethioxyphenyl) acrylamido) -2-methoxyphenyl-2- (N, N, N-triethyl-amino) acetate; 5 - ((E) -3- (2) 4,6-trimethoxyphenyl) acrylamido) -2-methoxy-phenyl-2- (N, N, N-tri- (2-hydroxyethyl) amino) acetate; 5 - ((E) -3- (2,4,6-trimethoxy-fenii) acrylamido) -2-methoxyphenyl-2-hydroxy-2-methylpropanoate; 5 - ((E) -3- (2,4,6-tr.methoxyphenyl) acrylamido) -2-methoxyphenyl-2-acetoxy-2-methylpropanoate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxyphenyl-2,2,2-trifluoroacetate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) -acylamido) -2-methoxyphenyl-3-carboxypropanoate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamide) -2-methoxy-phenyl-3- (chlorocarbonyl) propanoate; 5 - ((E) -3- (2,4,6-tri-methoxyphenyl) acrylamido) -2-methoxyphenyl-2- (3-carboxypropanoic) acetate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxyphenyl- (4-carboxy-butyrate); 5 - ((E) -3- (2,4,6-Frimethoxy-phenyl) -acrylamido) -2-methoxyphenoxy) -carbonyl) -methyl dihydrogen phosphate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) -acrylamido) -2-methoxyphenyl methylated carbonate; 5 - ((E) -3- (2,4,6-Rlymethoxy-phenyl) -acrylamido) -2-methoxyphenyl-2-acetoxypropanoate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) -acylamide) -2-methoxyphenyl methylsuccinate; 5- ((E) -3- (2,4,6-trimelloxophenyl) acrylamido) -2-methoxyphenyl ethyl malonate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxyphenyl-2,2,3,3,3-penne-fluoropropanoate; 3-melyyl-2,2-difluoromalonalo from 1 - (5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxy-phenyl); 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acryl-amido) -2-methoxyphenyl- (3-carboxy-2,2,3,3-tetraf) uorobutyrate); 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxyphenyl-2-amino-acetate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-mexoxyphenyl- (2-carboxy-2,2-difluoroacety); 5 - ((E) -3- (2,4,6-trimethoxy) phenyl) acrylamido) -2-methoxy-phenyl-2- (dimethylamino) -2,2-difluoroacetate; 5 - ((E) -3- (2,4,6-trimethoxy-phenyl) acrylamido) -2-methoxyphenyl acetate; 5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl) vinyl] sulfonyl] amino] -2-methoxyphenyl-2- (dimethylamino) -acetate; 5 - ((2,4,6-trimethoxystyrylsulfonyl) amino) -2-methoxyphenyl-2- (dimethylamino) acetate; and you come out of them. 31. The compound according to claim 1, further characterized in that it is of Formula V: wherein R, R, R, X, A and Q are as defined in accordance with claim 1, or a salt thereof. 32. The compound according to claim 31, further characterized in that it is of the Formula VA: wherein R2, R3, Rw, A, a, b, and Q, are as defined in accordance with claim 31; Y is -S (= 0) - or -S02-; * indicates that, when Rx is other than -H, the conformation of the substituents at the designated carbon atom is (R) -, (S) -, or any mixture of (R) and (S); and Rx is selected from the group consisting of -H, -alkyl of (d-d), and -C (= 0) alkyl of (Q-d), or a salt of such a compound. 33. The composite according to claim 32, further characterized in that Rx is -H. 34. The compound according to claim 33, further characterized in that it is selected from the group consisting of: (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-meloxyphenyl carboxy-methanesulfonate.; (E) -5 - ((2,4,6-lrimethoxystyrylsulfonyl) methyl) -2-methoxy-phenyl-2,4-dinitrobenzenesulfonate; (E) -5 - ((2,4,6-trimethoxystyryl-sulfonyl) -methyl) -2-methoxyphenyl-2,4-diaminobenzenesulfonate; trifluoromethanesulfonalo of (E) S - ((2,4,6-trimethoxy-sys-lysulfonyl) methyl) -2-methoxyphenyl, (E) -5 - ((2,4,6-tr'methoxystyrylsulfonyl) methyl) -2 -methoxy-phenyl-4-methoxy-benzenesulfonate; carboxymethanesulfonate of (E) -5 - ((2,4,6-trimethoxystirylsulfinyl) methyl) -2-methoxy-phenyl; (E) -5 - ((2,4,6-trimethoxystiryl-sulfinyl) -methyl) -2-methoxyphenyl-2,4-dinitrobenzenesulfonate; (E) -5 - ((2,4,6-trimethoxystirylsulfinyl) methy1) -2-methoxyphenyl-2,4-diaminobenzenesulphonate; trifluoromethanesulfonate of (E) -5 - ((2,4,6-trimethoxystyrylsulfonyl) methyl) -2-methoxyphenyl; (E) -5 - ((2,4,6-trimelloxysilyl-sulfinyl) -methyl) -2-methoxyphenyl-4-methoxy-benzenesulfonate; (E) -5- ((2,4,6-trimethoxystyryl-sulfonyl) methyl) -2-methoxyphenyl-4-meitylbenzenesulfonate; (E) -5 - ((2,4,6-Tr'methoxystyrylsulfonyl) methyl) -2-mexoxyphenyl-4-meityl-benzenesulphone; and you come out of them. 35. The compound according to claim 31, further characterized in that it is of Formula VB: wherein R2, R3, Rw, A, a, b, and Q are as defined in accordance with claim 31; Z is -C (= 0) -, or -S02-; Rx is selected from the group consisting of -H, -alkyl of (C? -C6), and -C (= 0) alkyl of (C? -C6), or a salt of such a compound. 36. The compound according to claim 35, further characterized in that Rx is -H. 37. The compound according to claim 36, further characterized in that it is selected from the group consisting of: 2- acid. { [5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl}. Amino) -2-methoxy-phenyl] oxysulfonyl} acetic; 5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl) vinyl] -sulfonyl}. Amino) -2-methoxyphenyl-2,4-diniienbensulfonate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyi] sulfonyl}. Amino) -2-methoxyphenyl-2,4-diamino-benzenesulfonate; 5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] -sulfonyl}. Amino) -2-methoxyphenyl- (trifluoromethyl) sulfonate; 5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl) vinyl] sulfonyl.] Amino) -2-methoxyphenyl-4-methoxy-benzenesulphone; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxy-phenylcarboxymenesulfonate; 5 - ((E) -3- (2,4,6-trimethioxyphenyl) -acrylamido) -2-methoxy-phenyltrifluoromethanesulfonate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acryl-amydo) -2-methoxyphenyl-2,4-dinitrobenzenesulfonate; 5 - ((E) -3- (2,4,6-trimethoxyphenyl) acrylamido) -2-methoxy-phenyl-2,4-diaminobenzenesulfonate; 5 - ((E) -3- (2,4,6-trimethoxy-phenyl) -acrylamido) -2-methoxyphenyl-4-methoxy-benzenesulfonate; 5 - ((E) -3- (2,4,6-trimethoxy-phenyl) acrylamido) -2-methoxy-phenyl-4-methylbenzenesulfonate; (E) -5 - ((2,4,6-trimethoxy-styrylsulfonyl) -amino) -2-methoxy-phenyl-4-methylbenzenesulfonate; and you come out of them. 38. The compound according to claim 1, further characterized in that it is of Formula VI: wherein R, 2, D R3, n Rz, X, A, Q, a and b, are as defined in accordance with formula 1, or a salt thereof. 39. The compound according to claim 38, further characterized in that it is of the Formula VIA: wherein R2, R3, Rz, A, a, b, and Q, are as defined in accordance with claim 38; Y is -S (= 0) - or -S02-; * indicates that, when Rx is other than -H, the conformation of the substituents on the designated carbon atom is (R), (S) -, or any mixture of (R) - and (S); and Rx is selected from the group consisting of -H, alkyl of (C | -C6), and -C (= 0) alkole of (C? -C6), or a salt of the compound. 40. The compound according to claim 39, further characterized in that Rx is -H. 41. The compound according to claim 40, further characterized in that it is selected from the group consisting of: (E) -2- (5 - ((2,4,6-trimethoxystyrylsulfonyl) meily) -2-methoxyphenoxy) - acetic; (E) -2- (5 - ((2,4,6-trimethoxystirlylsulfonyl) methy1) -2-methoxy-phenoxy) -propanoic acid; (E) -4- (5 - ((2,4,6-Trimethioxy-ylsilyl-sulfonyl) -methyl) -2-methoxy-phenoxy) -butanoic acid; (E) -3- (5 - ((2,4,6-Trimethoxystyryl-sulfinyl) methy1) -2-methoxyphenoxy) -propanoic acid; (E) -2- (5 - ((2,4,6-trimethoxystirylsulfinyl) -methyl) -2-methoxyphenoxy) -acetic acid; (E) -2- (5 - ((2,4,6-trimethoxystyryl-sulfonyl) methyl) -2-methoxyphenoxy) -propanoic acid; (E) -4- (5 - ((2,4,6-trimethoxystyrylsulfinyl) meily) -2-methoxyphenoxy) -butanoic acid; (E) -3- (5 - ((2,4,6-trimethoxylysilyrilsulfinyl) methyl) -2-methoxyphenoxy) -propanoic acid; (E) -4- (2- (5 - ((2,4,6-iryoxystyrylsulfonyl) methyl) -2-methoxyphenoxy) ethyl) -morpholine; (E) -4- (2- (5 - ((2,4,6-trimethoxystiryl-sulfinyl) -methyl) -2-methoxy-phenoxy) -ethyl) -morpholine; and you come out of them. 42. The compound according to claim 38, further characterized in that it is of Formula V1B: wherein R2, R3, Rz, a, b, and Q are as defined in accordance with claim 38; and Z is -C (= 0) - or -S02-; and Rx is selected from the group consisting of -H, -alkyl of (C | -C6), and -C (= 0) alkyl of (C | -C6), or a salt thereof. 43. The compound according to claim 42, further characterized in that Rx is H. 44. The compound according to claim 43, further characterized in that it is selected from the group consisting of: 2- [5- (. [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl.] Amino) -2-methoxy-phenoxy] -acetic acid; 2- [5- ( { [(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl] -amino) -2-mexoxyphenoxypropanol; 4- [5- ( { [(1 E) -2- (2,4,6-trimethoxy-phenyl) vinyl] -sulfoniyl} -amino) -2-methoxy-phenoxy] butanoic acid; 3- [5 - (([(1 E) -2- (2,4,6-trimethoxyphenyl) vinyl] sulfonyl}. amino) -2-methoxy-phenoxy] -propanoic acid; (E) -N- ( 3- (carboxymethioxy) -4-methoxyphenyl) -3- (2,4,6-trimethoxyphenyl) acrylamide; (E) -N- (3- (1-carboxyethoxy) -4-methoxyphenyl) - 3- (2,4,6-ylmethoxyphenyl) -acrylamide; (E) -N- (3- (3-carboxypropoxy) -4-meioxyphenyl) -3- (2,4,6-trimethoxyphenyl) acrylamide; (E) -N- (3- (2-carboxy-ethoxy) -4-methoxyphenyl) -3- (2,4,6-trimethoxyphenyl) acrylamide; (E) -N- (3- (2-morpholinoethoxy) 4-methoxyphenyl) -3- (2,4,6-trimethoxy-phenyl) acrylamide; (E) -4- (2- (5 - ((2,4,6-trimethoxy-styrylsulfonyl) amino) ) -2-meioxyphenoxy) ethyl) -morpholine, and salts thereof 45. A compound according to Formula Vll further characterized in that: n is 0, 1 or 2; R is -H or -alkyl of (C | -C6); A is -S- or -O-; R1 is selected from the group consisting of -H; alkyl halo of (CrC6), -C (= 0) Rw; -S (= 0) Rw; -S02Rw; - (hydrocarbylene dC6) Rz, -P (= 0) (ORv) 2, -C (Ra) (Rv) -C (= 0) -Rn, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, -Si [ alkyl of (CrC6)] 3, and -CH2CH2Si [(CrC6) alkyl] 3; each Rv is independently selected from the group consisting of -H and -hydrocarbyl of (d-d); Rw is selected from the group consisting of -hydrocarbyl of (d-d), -NRV2; -ORv; halo (d-d alkyl), -NRvCRvRa-C (= 0) -Rn; -CRvRa-N (Rv) -Rc; substituted and unsubstituted aryl, substituted and unsubstituted (C, -C3) alkyl substituted, unsubstituted heteroaryl, substituted and unsubstituted (C1-C3) heteroarylalkyl, substituted and unsubstituted heterocyclyl, substituted and unsubstituted heterocyclylalkyl (dd), - ( alkylene of d-C3) P (= 0) (ORv) 2; -perfluoroalkylene of (C C3) -N (CH3) 2; - ((C C 3) alkylene-N + (CrC 3) alkyl); -alkylene of (CrC3) -N + (CH2CH2OH) 3; - (C 4 C alkylene) -C (= 0) -halogen; -perfluoroalkylene of (C C4) -C02Rv; - (alkylene of d-C3) C (= 0) ORv; and - (C1-C3 alkylene) OC (= 0) - (C C3 alkylene) C (= 0) Ry; Ry is selected from the group consisting of -ORv, -NRV2 and -alkyl of (Cr d); Rz is selected from the group consisting of -C (= 0) Ry; -NRvCRvRa-C (= 0) -Rn; -NRV2; -ORv; substituted and unsubstituted aryl, substituted and unsusiluted heteroaryl, and -C (= 0) (C3) alkyl; each Ra is independently selected from the group consisting of -H; -alkyl of (dd), -heteroalkyl of (dd), - (CH2) 3-NH-C (NH2) (= NH), -CH2C (= 0) NH2, -CH2COOH, - (CH2) 2COOH, sushiluted aryl and unsubstituted, substituted and unsubstituted (dd) arylalkyl, substituted and unsubstituted heterocyclyl, and substituted and unsubstituted heterocyclic (C1-C3) alkyl; each Rn is independently selected from the group consisting of -ORv, -NRV2, and an N-terminally linked peptidyl residue containing from 1 to 3 amino acids in which the terminal carboxyl group of the peptidyl residue is present as a functional group, selected from the group consisting of group consisting of -C02Rv and -C (= 0) NRv2; each Rc is independently selected from the group consisting of -H and a terminally linked peptidyl carboxy residue containing from 1 to 3 amino acids in which the terminal amino group of the peptidyl residue is present as a functional group selected from the group consisting of -NH2 , -NHC (= 0) alkyl of (C C6); -NHalkyl of (C Cß), - NH (Crd) alkyl 2, and -NHC (= 0) Ohdrocarbyl of (d-d); each R2 is independently selected from the group consisting of halogen; -hydrocarbyl of (dd), -C (= 0) Rv, -NRV2, -NHC (= 0) Rv, -NHS02Rv, -NHRa, -NHCRvRaC (= 0) Rn, -NHS02Rv, -C (= 0) ORv , -C (= 0) NHRv, -N02, -CN, -ORv, -P (= 0) (ORv) 2, -C (= NH) NH2, dimethylamino (C2-C6 alkoxy), -NHC (= NRV ) NHRV, -haloalkyl of (CrC6), and -haloalkoxy of (dd); the two Rv groups in -P (= 0) (ORv) 2 and -NRV2 may optionally form a five or six element heterocyclic ring, which may optionally also be fused to an aryl or carbocyclic ring; a is 0, 1, 2 or 3; Rx is selected from the group consisting of -H; -alkyl of (d-d), and -C (= 0) alkyl of (d-C6); and * indicates that, when Rx is different from H, the conformation of the substitutes in the designated carbon atom is (R) -, (S) - or any mixture of (R) - and (S) -; or a salt of compose; provided that: R1 is different from haloalkyl of (d-d); Rz is different from -NRV2 and unsubstituted aryl; and Rw is different from -hydrocarbyl of (d-d). 46. The compound according to claim 45, further characterized in that n is 1. 47. The compound according to claim 46, further characterized in that it is selected from the group consisting of: 2- (3-hydroxy-4-) methoxybenzylsulfinyl) acetic; 2- (3-mercapto-4-methoxybenzisulfinyl) acetic acid; 2- (3-tert-butyldimethylsilyi-oxy-4-methoxybenzylsulfinyl) acetic acid; 2- (3 - ((tert-Butyldimethylsilyl) sulfanyl) -4-methoxybenzylsulfinyl) acrylic acid; phosphate dihydrogen 0-2-methoxy-5- (carboxymethylsulfinylmethyl) phenyl; dimethyl 0-2-meloxy-5- (carboxymethyl-sulfinylmetyl) phenol; diethyl phosphate 0-2-methoxy-5- (carboxymethylsulfinylmethyl) phenol; Dibenzyl 0-2-methoxy-5- (carboxymethylsulfinylmethyl) phenyl phosphate; phosphorothioaio S-2-methoxy-5- (carboxymethylsulfinylmethyl) phenyl-0,0-dihydrogen; phosphorus thioate S-2-mephoxy-5- (carboxymethylsufinylmethylphenyl-0,0-dimethyl; phosphorothioate S-2-methoxy-5- (carboxymethylsulfinylmethyl) phenyl-0,0-dieryl; phosphorothioate S-2-methoxy-5- (carboxymethylsulfinylmethyl) phenyl-0.0-dibenzyl, and salts thereof 48. The compound according to claim 45, further characterized in that n is 2. 49. The compound according to claim 48, further characterized because it is selected from the group consisting of: 2- (3-hydroxy-4-methoxybenzylsulfonyl) acetic acid 2- (3-mercapto-4-methoxybenzylsulfonyl) acetic acid 2- (3-tert-butyldimethyl) L-llyoxy-4-methoxy-benzylsulfonyl) acetic acid 2- (3 - ((tert-butyldimethylsilyl) sulfanyl) -4-methoxy-benzylsulfonyl) -acetic acid-dihydrogen phosphate 0-2-methoxy-5- ( carboxymethylsulfonyl-methyl) -phenyl, dimethyl phosphate 0-2-methoxy-5- (carboxymethyl-sulfonyl-methyl) phenyl; diethyl phosphate 0-2-methoxy-5- (carboxymethylsulfonyl-methyl) phenyl; dibenzyl phosphate 0-2-methoxy -5- (carboxymethylsulfoni) l-methyl) phenyl; phosphorothioate S-2-methoxy-5- (carboxymethylsulfonyl-methyl) phenyl-0,0-dihydrogen; phosphoro-thioate S-2-methoxy-5- (carboxymethyl-sulfonyl-methyl) phenyl-0.0-dimethyl; phosphorothioate S-2-methoxy-5- (carboxymethylsulfonylmethyl) phenyl-0,0-diethyl; phosphorothioate S-2-methoxy-5- (carboxymethylsulfonylmethyl) phenyl-0,0-dibenchol; and you come out of them. 50. The compound according to claim 45, further characterized in that n is 0. 51. The compound according to claim 50, further characterized in that it is selected from the group consisting of: 2- (3-hydroxy-4-) methoxybenzylsulfanyl) acetic; 2- (3-tert-Butyldimethylsilyloxy-4-methoxybenzylsulfanyl) acetic acid; dihydrogen phosphate 0-2-methoxy-5- (carboxymethylsulfanylmethyl) phenyl; dimethyl 0-2-methoxy-5- (carboxymethylsulfanylmethyl) phenyl phosphate; diethyl phosphate 0-2-methoxy-5- (carboxymethylsulfanylmethyl) phenyl; dibenzyl phosphate 0-2-methoxy-5- (carboxymethylsulfanylmethyl) phenol; and you come out of them. 52. A compound according to Formula XI: characterized in that: A is -O-; R1 is selected from! group consisting of -H; alkyl halo of (d-d), -C (= 0) R; -S (= 0) Rw; -S02Rw; - (hydrocarbylene dC6) RZ, -P (= 0) (ORv) 2, -C (Ra) (Rv) -C (= 0) -Rn, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, -Si [ alkyl (CrC6)] 3, and -CH2CH2Si [(CrC6) alkyl] 3; each Rv is independently selected from the group consisting of -H and -hydrocarbyl of (C C7); R is selected from the group consisting of -hydrocarbyl of (d-d), -NRV2; -ORv; halo (d-C3 alkyl), -NRvCRvRa-C (= 0) -Rn; -CRvRa-N (Rv) -Rc; substituted and unsubstituted aryl, substituted and unsubstituted arylalkyl (Q-C3), unsubstituted substituted heteroaryl, substituted and unsubstituted (dd) heteroarylalkyl, unsubstituted substituted heterocyclic, substituted and unsubstituted (d-C3) heyerocyclylalkyl, - ( alkylene of d-C3) P (= 0) (OR) 2; -perfluoroalkylene of (C C3) -N (CH3) 2; - ((d-C3) alkylene-N + (d-C3) alkyl); -alkylene of (d-d) -N + (CH2CH2OH) 3; - (C 4 C alkylene) -C (= 0) -halogen; -perfluoroalkylene of (C C4) -C02Rv; - (C C3 alkylene) C (= 0) ORv; and - (C C3 alkylene) OC (= 0) - (alkylene of dC3) C (= 0) Ry; Ry is selected from the group consisting of -ORv, -NRV2 and -alkyl of (C d); Rz is selected from the group consisting of -C (= 0) Ry; -NRvCRvRa-C (= 0) -Rn; -NRV2; -ORv; substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, and -C (= 0) alkyl of (d-d); each Ra is independently selected from the group consisting of -H; -alkyl of (d-C6), -heteroalkyl of (dd), - (CH2) 3-NH-C (NH2) (= NH), -CH2C (= 0) NH2, -CH2COOH, - (CH2) 2COOH, substituted and unsubstituted aryloxy, unsubstituted and unsubstituted (dd) arylalkyl, unsubstituted and substituted heterocyclic, and unsubstituted and unsubstituted (dd) heterocyclylalkyl; each Rn is independently selected from the group consisting of -ORv, -NRV2, and an N-terminally linked peptidyl residue containing from 1 to 3 amino acids in which the terminal carboxyl group of the peptidyl residue is present as a functional group, selected from group consisting of -C02Rv and -C (= 0) NRv2; each Rc is independently selected from the group consisting of -H and a terminally linked peptidyl carboxy residue containing from 1 to 3 amino acids in which the terminal amino group of the peptidyl residue is present as a functional group selected from the group consisting of -NH2 , -NHC (= 0) alkyl of (dd); -NHalkyl of (d-C6), -NH (d-C6 alkyl) 2, and -NHC (= 0) Ohydrocarbyl of (C C7); Q is aryl or heteroaryl; each R2 and R3 is independently selected from the group consisting of halogen; -hydrocarbyl of (dd), -C (= 0) Rv, -NRV2, -NHC (= 0) Rv, -NHS02Rv, -NHRa, -NHCRvRaC (= 0) Rn, -NHS02Rv, -C (= 0) ORv , -C (= 0) NHRv, -N02, -CN, -ORv, -P (= 0) (ORv) 2, -C (= NH) NH2, dimethylamino (C2-C6 alkoxy), -NHC (= NRV ) NHRV, -haloalkyl of (C C6), and -haloalkoxy of (C C6); wherein the two Rv groups in -P (= 0) (ORv) 2 and -NRV2 may optionally together form a five or six element helerocylic ring, which may optionally also be fused to an aryl or carbocyclic ring; a is 0, 1, 2 or 3; b is 0, 2, or 3; the conformation of the exocyclic carbon-carbon double bond is -Z; Rx is selected from the group consisting of -H; -alkyl of (d-d), and -C (= 0) alkyl of (d-d); and * indicates that, when Rx is different from H, the conformation of the substituents on the designated carbon atom is (R) -, (S) - or any mixture of (R) - and (S) -; or a salt of such compound 53. A compound according to Formula Xlll: characterized in that: R is -H or -alkyl of (Crd); A is -S- or -O-; R1 is selected from the group consisting of -H; alkyl halo of (d-d), -C (= 0) R; -S (= 0) Rw; -S02Rw; - (hydrocarbylene C C6) Rz, -P (= 0) (ORv) 2, -C (Ra) (Rv) -C (= 0) -Rn, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, -Si [ C (C6) alkyl] 3, and -CH2CH2Si [(CrC6) alkyl] 3; each Rv is independently selected from the group consisting of -H and -hydrocarbyl of (d-d); Rw is selected from the group consisting of -hydrocarbyl of (d-d), -NRV2; -ORv; halo (d-d alkyl), -NRvCRvRa-C (= 0) -Rp; -CRvRa-N (Rv) -Rc; substituted and unsubstituted aryl, substituted and unsubstituted aryl (CrC3), unsubstituted and unsubstituted heteroaryl, substituted and unsubstituted (dd) heteroaryl, unsubstituted and unsubstituted heterocyclyl, substituted and unsubstituted (dd) heterocyclyl, - (alkylene Crd) P ( = 0) (ORv) 2; -perfluoroalkylene of (CrCs) -N (CHs) 2; - ((d-C3) alkenyl) -N + (d-C3) alkyl 3); -alkylene of (CrC3) -N + (CH2CH2OH) 3; - (alkylene of d-C4) -C (= 0) -halogen; perfluoroalkylene of (C C4) -C02Rv; - (C C3 alkylene) C (= 0) ORv; and - (alkylene of d-C3) OC (= 0) - (alkylene of d-C3) C (= 0) Ry; Ry is selected from the group consisting of -ORv, -NRV2 and -alkyl of (d- C6); Rz is selected from the group consisting of -C (= 0) Ry; -NRvCRvRa-C (= 0) -Rn; -NRV2; -ORv; unsubstituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, and -C (= 0) alkyl of (CrC3); each Ra is independently selected from the group consisting of -H; -alkyl (dd), -heteroalkyl of (dd), - (CH2) 3-NH-C (NH2) (= NH), -CH2C (= 0) NH2, -CH2COOH, - (CH2) 2COOH, substituted aryl and unsubstituted, substituted and unsubstituted (dd) arylalkyl, substituted and unsubstituted heterocyclyl, and substituted and unsubstituted he- (dd) -heterocyclylalkyl; each Rn is independently selected from the group consisting of -ORv, -NRV2, and a N-terminally linked peptidyl residue containing from 1 to 3 amino acids in which the terminal carboxyl group of the peptidyl residue is present as a functional group, selected from group consisting of -C02Rv and -C (= 0) NRv2; each Rc is independently selected from the group consisting of -H and a terminally linked peptidyl carboxy residue containing from 1 to 3 amino acids in which the terminal amino group of the peptidyl residue is present as a functional group selected from the group consisting of -NH2 , -NHC (= 0) alkyl of (dd); -NHalkyl of (d-d), -NH (alkyoule of d-C6) 2, and -NHC (= 0) Ohydrocarbyl of (C C7); each R2 is independently selected from the group consisting of halogen; -hydrocarbyl of (dd), -C (= 0) Rv, -NRV2, -NHC (= 0) Rv, -NHS02Rv, -NHRa, -NHCRvRaC (= 0) Rn, -NHS02Rv, -C (= 0) ORv , -C (= 0) NHRv, -N02, -CN, -ORv, -P (= 0) (ORv) 2, -C (= NH) NH2, d-methylamino (C2-C6 alkoxy), NHC (= NRV) NHRV, -haloalkyl of (d-d), and -haloalkoxy of (C C6); the two Rv groups in -P (= 0) (ORv) and -NRV2 may optionally together form a five or six element heterocyclic ring, which may optionally also be fused to an aryl or carbocyclic ring; a is 0, 1, 2 or 3; X is -S02- or -C (= 0) -; Rx is selected from the group consisting of -H; -alkyl of (d-d), and -C (= 0) alkyl of (d-d); or a salt of the compose. 54. A process for preparing a compound according to claim 5, of the Formula IE: or a salt of the compound; which comprises the steps of: (a) reacting a compound according to Formula Vll: where: n is 1 or 2; R is -H; A is -S- or -O-; R1 is selected from the group consisting of -H; alkyl halo of (d-d), -C (= 0) Rw; -S (= 0) Rw; -S02Rw; - (hydrocarbylene C Ce) Rz, -P (= 0) (ORv) 2, -C (Ra) (Rv) -C (= 0) -Rn, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, -Si [alkyl] of (d-dXb, and -CH2CH2Si [alkyl of (dd)] 3; ca Rv is independently selected from the group consisting of -H and -hydrocarbyl of (dd); Rw is selected from the group consisting of -hydrocarbyl of (dd); dd), -NRV2; -ORv; halo (C1-Cyl of CrC3), -NRvCRvRa-C (= 0) -Rn; -CRvRa-N (Rv) -Rc; substituted and unsubstituted aryl, arylalkyl of (C | C3) substituted and unsubstituted, substituted and unsubstituted heteroarylalkyl substituted and unsubstituted (C C3) alkyl, substituted and unsubstituted heterocyclyl, unsubstituted and substituted (dd) heterocyclylalkyl, - (CrC3 alkylene) P (= 0) (ORv) 2; -perfluoroalkylene of (CrC3) -N (CH3) 2; - (alkylene of (C C3) -N + alkyl of (C Cs) 3); -alkylene of (C C3) -N + (CH2CH2OH) 3; - (alkylene) of CC) -C (= 0) -halogen; -perfluoroalkylene of (dd) -C02Rv; - (alkylene of d-C3) C (= 0) ORv; and - (alkylene of d-C3) OC (= 0) - (alqullen of d-d) C (= 0) Ry; Ry is selected from the group consisting of -OR, -NRV2 and -alkyl of (dC6); Rz is selected from the group consisting of -C (= 0) Ry; -NRvCRvRa-C (= 0) -Rn; -NRV2; -ORv; substituted and unsubstituted aryl, unsubstituted and unsubstituted heteroaryl, and -C (= 0) alkyl of (d-d); each Ra is independently selected from the group consisting of -H; -alkyl (dd), -haloalkyl of (C C6), - (CH2) 3-NH-C (NH2) (= NH), -CH2C (= O) NH2, -CH2COOH, - (CH2) 2COOH, aryl unsubstituted and unsubstituted, substituted and unsubstituted (Crd) arylalkyl, substituted and unsubstituted heterocyclyl, and unsubstituted and unsubstituted (dd) unsubstituted heterocyclylalkyl; each Rn is independently selected from the group consisting of -ORv, -NRV2, and a N-terminally linked peptidyl residue containing from 1 to 3 amino acids in which the terminal carboxyl group of the peptidyl residue is present as a functional group, selected from the group consisting of group consisting of -C02Rv and -C (= 0) NRv2; each Rc is independently selected from the group consisting of -H and a terminally linked peptidyl carboxy residue containing from 1 to 3 amino acids in which the terminal amino group of the peptidyl residue is present as a functional group selected from the group consisting of -NH2 , -NHC (= 0) alkyl of (C C6); -NHalkyl of (d-C6), -NH (C6-C6 alkyl) 2, and -NHC (= 0) Oh-hydrocarbyl of (d-d); each R2 is independently selected from the group consisting of halogen; - hydrocarbyl of (dd), -C (= 0) Rv, -NRV2, -NHC (= 0) Rv, -NHS02Rv, -NHRa, -NHCRvRaC (= 0) Rn, -NHS02Rv, -C (= 0) ORv , -C (= 0) NHRv, -N02, -CN, -ORv, -P (= 0) (ORv) 2, -C (= NH) NH2, dimethylamino (C2-C6 alkoxy), -NHC (= NRV ) NHRV, -haloalkyl of (dd), and -haloalcoxl of (dd); the two Rv groups in -P (= 0) (ORv) 2 and -NRV2 may optionally together form a five or six element heterocyclic ring, which may optionally also be fused to an aryl or carbocyclic ring; a is 0, 1, 2 or 3; R is selected from the group consisting of -H; -alkyl of (d-d), and -C (= 0) alkyl of (d-d); and * indicates that, when Rx is different from H, the conformation of the substituents at the designated carbon atom is R-, S- or any mixture of R- and S-; or a salt of such compound; provided that: R1 is distinct from haloalkyl of (CrC6); Rz is different from -NRV2 and unsubstituted aryl; and Rw is other than hydrocarbyl of - (CrC); with a compound according to Formula XVI: wherein: Q is aryl or heteroaryl; each R3 is independently selected from the group consisting of halogen; -hydrocarbyl of (d-d), -C (= 0) Rv; -NRV2; -NHC (= 0) Rv; -NHS02Rv; -NHRa; -NHCRvRaC (= 0) Rn; -NHS02Rv; -C (= 0) ORv; -C (= 0) NHRv; -N02; -CN; -ORv; -P (= 0) (ORv) 2; -C (= NH) NH2, dimethylamino (C2-C6 alkoxy); -NHC (= NRV) NHRV; -haloalkyl of (CrC6), and haloalkoxy of (-C6); and b is 0, 1, 2 or 3; and (b) isolating a compound according to Formula IE, or a salt thereof, from the reaction products. 55. A process for preparing a compound according to claim 6, of Formula IZ: or a salt of such compound; where A is -O-; which comprises the steps of: (a) reacting a compound in accordance with Formula XI: where: A is -O-; R1 is selected from the group consisting of -H; alkyl halo of (C C6), -C (= 0) Rw; -S (= 0) Rw; -S02Rw; - (hydrocarbylene dC6) Rz, -P (= 0) (ORv) 2, -C (Ra) (Rv) -C (= 0) -Rn, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, -Si [ C (C6) alkyl] 3, and -CH2CH2Si [(C6) alkyl] 3; each Rv is independently selected from the group consisting of -H and -hydrocarbyl of (d-d); Rw is selected from the group consisting of -hydrocarbyl of (d-d), -NRV2; -ORv; halo (alkyoule of d-d), -NRvCRvRa-C (= 0) -Rn; -CRvRa-N (Rv) -Rc; substituted and unsubstituted aryl, substituted and unsubstituted (CrC3) arylalkyl, unsubstituted and substituted heteroaryl, and unsubstituted and unsubstituted (dd) heterocyclyl, unsubstituted and unsubstituted heterocyclyl, unsubstituted and unsubstituted (dd) heterocyclylalkyl, - (d-C3 alkylene) ) P (= 0) (ORv) 2; -perfluoroalkylene of (CrC3) -N (CH3) 2; - ((C C 3) alkylene-N + (CrC 3) alkyl); -alkylene of (CrC3) -N + (CH2CH2OH) s; - (alkylene of d-C4) -C (= 0) -halogen; -perfluoroalkylene of (C C) -C02Rv; - (alqullen of d-C3) C (= 0) ORv; and - (alkylene of dC3) OC (= 0) - (C3 alkylene) C (= 0) Ry; Ry is selected from the group consisting of -0RV, -NRV2 and -alkyl of (d ~ d); Rz is selected from the group consisting of -C (= 0) Ry; -NRvCRvRa-C (= 0) -Rn; -NRV2; -ORv; substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, and -C (= O) (Crd) alkyl; each Ra is independently selected from the group consisting of -H; -alkyl of (d-C6), -heteroalkyl of (dd), - (CH2) 3-NH-C (NH2) (= NH), -CH2C (= 0) NH2, -CH2COOH, - (CH2) 2COOH, substituted and unsubstituted aryl, substituted and unsubstituted (dd) arylalkyl, unsubstituted and unsusiluted heterocyclyl, and unsubstituted and unsusilined (dd) heterocyclylalkyl; each Rp is independently selected from the group consisting of -ORv, -NRV2, and an N-terminally linked peptidyl residue containing from 1 to 3 amino acids in which the terminal carboxyl group of the peptidyl residue is present as a functional group, selected from group consisting of -C02Rv and -C (= 0) NRv2; each Rc is independently selected from the group consisting of -H and a terminally linked peptidyl carboxy residue containing from 1 to 3 amino acids in which the terminal amino group of the peptidyl residue is present as a functional group selected from the group consisting of -NH2 , -NHC (= 0) alkyl of (dd); -NHalkyl of (d-d), -NH (d-C6 alkyl) 2, and -NHC (= 0) Ohydrocarbyl of (C C7); Q is aryl or heteroaryl; each R2 and R3 is independently selected from the group consisting of halogen; -hydrocarbyl of (C C7), -C (= 0) Rv, -NRV2, -NHC (= 0) Rv, -NHS02Rv, -NHRa, -NHCRvRaC (= 0) Rn, -NHS02Rv, -C (= 0) ORv, -C (= 0) NHRv, -N02, -CN, -ORv, -P (= 0) (ORv) 2, -C (= NH) NH2, dimethylamino (C2-C6 alkoxy), -NHC (= NRV) NHRV, -haloalkyl of (dd), and -haloalkoxy of (dd); the two Rv groups in -P (= 0) (ORv) 2 and -NR 2 may optionally together form a heterocyclic ring of five or six elements, which may optionally also be fused to an aryl or carbocyclic ring; a is 0, 1, 2 or 3; b is 0, 1, 2 or 3; the conformation of the exocyclic carbon-carbon double bond is -Z; Rx is selected from the group consisting of -H; -alkyl of (d-d), and -C (= 0) alkyl of (d-d); and * indicates that, when Rx is different from H, the conformation of the substitutes at the designated carbon atom is (R) -, (S) - or any mixture of (R) - and (S) -; or a salt of such compound; when an oxidizing agent is capable of oxidizing a sulphide for a sulfoxide; and (b) isolating a compound according to Formula IZ, or a salt thereof, from the reaction products. 56. A process for preparing a compound according to claim 5, of the Formula IE: or a salt of such a compound; comprising the steps of: (a) reacting a compound according to Formula XIV: where: A is ~ S- u -O-; R1 is selected from the group consisting of -H; alkyl halo of (d-d), -C (= 0) Rw; -S (= 0) Rw; -S02Rw; - (hydrocarbylene dC6) Rz, -P (= 0) (ORv) 2, -C (Ra) (Rv) -C (= 0) -Rn, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, -Si [ alkyl (CrC6)] 3, and -CH2CH2Si [(d-C6) alkyl] 3; each Rv is independently selected from the group consisting of -H and -hydrocarbyl of (d-d); Rw is selected from the group consisting of -hydrocarbyl of (d-d), -NRV2; -ORv; halo (CrC3 alkyl), -NRvCRvRa-C (= 0) -Rn; -CRvRa-N (Rv) -Rc; substituted and unsubstituted aryl, unsubstituted and unsubstituted (CrC3) arylalkyl, substituted and unsubstituted heteroaryl, substituted and unsubstituted (dd) heteroaryl, substituted and unsubstituted heterocyclyl, substituted and unsubstituted (dd) heterocyclyl, - (d-C3 alkylene) ) P (= O) (ORv) 2; -perfluoroalkylene of (d-C3) -N (CH3) 2; - (alkylene of (Cr C3) -N + alkyl of (C C3) 3); -alkullen of (C C3) -N + (CH2CH2OH) 3; - (Crd alkylene) -C (= 0) -halogen; -perfluoroalkylene of (CrC) -C0 Rv; - (C C3 alkylene) C (= 0) ORv; and - (CrC3 alkylene) OC (= 0) - (C C3 alkylene) C (= 0) Ry; Ry is selected from the group consisting of -ORv, -NRV2 and -alkyl of (C d); Rz is selected from the group consisting of -C (= 0) Ry; -NRvCRvRa-C (= 0) -Rn; -NR 2; -ORv; substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, and -C (= 0) (C3) alkyl; each Ra is independently selected from the group consisting of -H; -alkyl (C C6), -heteroalkyl of (dd), - (CH2) 3-NH-C (NH2) (= NH), -CH2C (= 0) NH2, -CH2COOH, - (CH2) 2COOH, aryl substituted and unsubstituted, substituted and unsubstituted (dd) arylalkyl, substituted and unsubstituted heterocyclyl, and unsubstituted and substituted (dd) heterocyclylalkyl; each Rn is independently selected from the group consisting of -ORv, -NRV2, and a N-terminally linked peptidyl residue containing from 1 to 3 amino acids in which the terminal carboxyl group of the peptidyl residue is present as a functional group, selected from group consisting of -C02Rv and -C (= 0) NRv2; each Rc is independently selected from the group consisting of -H and a terminally linked peptidyl carboxy residue containing from 1 to 3 amino acids in which the terminal amino group of the peptidyl residue is present as a functional group selected from the group consisting of -NH2 , -NHC (= 0) alkyl of (C C6); -NHalkyl of (d-d), -NH (C-Ce alkyl) 2, and -NHC (= 0) Oh-hydrocarbyl of (d-d); each R2 is independently selected from the group consisting of halogen; - hydrocarbyl of (C C7), -C (= 0) Rv, -NRV2, -NHC (= 0) Rv, -NHS02Rv, -NHRa, - NHCRvRaC (= 0) Rn, -NHS02Rv, -C (= 0) ORv, -C (= 0) NHRv, -N02, -CN, -ORv, - P (= 0) (ORv) 2, -C (= NH) NH2, dimethylamino (C2-C6 alkoxy), -NHC (= NRV) NHRV, -haloalkyl of (dd), and -haloalkoxy of (dd); the two R groups in P (= 0) (ORv) 2 and -NRV2 may optionally together form a five or six element heterocyclic ring, which may optionally also be fused to an aryl or carbocyclic ring; a is 0, 1, 2 or 3; and Rx is selected from the group consisting of -H; -alkyl of (d-d), and -C (= 0) alkyl of (d-d); or a salt thereof; with a compound of formula XV: wherein R is alkyl of (dd); L is a halogen; and Z is -S02- or -C (= 0) -; to provide a compound according to Formula III, or a salt thereof: wherein R is alkyl of (d-d); (b) hydrolyzing the compound according to Formula III formed in step (a), to form a compound according to Formula Xlll, wherein R is -H; (c) optionally, if R1 is a protecting group comprising, -Si [(CrC6) alkyl] 3, or -CH2CH2Si [(CrC6)] s, remove said protecting group to form a compound in accordance with the Formula XIIIA: (d) coupling either the compound according to Formula Xlll of step (a), or the compound according to Formula XI HA of step (c), with an aromatic aldehyde of Formula XVI: where: Q is aryl or heeroaryl; each R3 is independently selected from the group consisting of halogen; -hydrocarbyl of (Crd), -C (= O) Rv; -NRV2; -NHC (= 0) Rv; -NHS02Rv; -NHRa; -NHCRvRaC (= 0) Rn; -NHS02Rv; -C (= 0) ORv; -C (= 0) NHRv; -N02; -CN; -ORv; -P (= 0) (ORv) 2; -C (= NH) NH2, dimethylamino (C2-C6 alkoxy); -NHC (= NRV) NHRV; haloalkyl of (CrCß), and haloalkoxy of (C | -C6); and b is 0, 1, 2 or 3; and (5) isolating a compound according to Formula IE, or a salt thereof, wherein Z is -NRX-Z-, or a salt of such a compound. 57. A process for preparing a compound according to claim 6 is of the Formula IZ: a compound according to claim 5 of the Formula IE: or a salt of said compound, further characterized comprising the steps of: (a) reacting a compound in accordance with Formula XVIIIA: wherein: each Rv each Rv is independently selected from the group consisting of -H and -hydrocarbyl of (C C7); each Ra is independently selected from the group consisting of -H; -alkyl of (dd), -heteroalkyl of (d-Ce), - (CH2) 3-NH-C (NH2) (= NH), -CH2C (= 0) NH2, -CH2COOH, - (CH2) COOH, substituted and unsubstituted aryl, substituted and unsubstituted arylalkyl (CrCs), substituted and unsubstituted heterocyclyl, and unsubstituted and substituted (dd) heterocyclylalkyl; each Rn is independently selected from the group consisting of -ORv, -NRV2, and an N-terminally linked peptidyl residue containing from 1 to 3 amino acids in which the terminal carboxyl group of the peptidyl residue is present as a functional group, selected from the group consisting of group consisting of -C0 Rv and -C (= 0) NRv2; Q is aryl or heteroaryl; each R3 is independently selected from the group consisting of halogen; -hydrocarbyl of (dd), -C (= 0) Rv, -NRV2, -NHC (= 0) Rv, -NHS02Rv, -NHRa, -NHCRvRaC (= 0) Rn, -NHS02Rv, -C (= 0) ORv , -C (= 0) NHRv, -NO2, -CN, -ORv, -P (= 0) (ORv) 2, -C (= NH) NH2, dimethylamino (C2-C6 alkoxy), -NHC (= NRV) NHRV, -haloalkyl of (d-C6), and -haloalcoxl of (CrC6); b is 0, 1, 2 or 3; L1 is a leaving group selected from halogen and -OC (= 0) alkyl (d-d); and the exocyclic carbon-carbon double bond can be either (E) - or (Z) -formation, with a compound according to Formula XIV: wherein: A is -S- or -O-; R1 is selected from the group consisting of -H; haloalkyl of (d-d), -C (= 0) Rw; -S (= 0) Rw; -S02Rw; - (hydrocarbylene C d) Rz, -P (= 0) (ORv) 2; -C (Ra) (Rv) -C (= 0) -Rn; substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, -Sifalkyl of (CrC6)] 3, -CH2CH2Si [(d-d) alkyl] 3; Rw is selected from the group consisting of -hydrocarbyl of (dd), -NRV2, -0RV, halo (dd alkyl), -NRvCRvRa-C (= 0) -Rn, -CRvRa-N (R) -RC, aryl substituted and unsubstituted, substituted and unsubstituted (dd) arylalkyl, unsubstituted and unsubstituted heteroaryl, substituted and unsubstituted (dd) heteroarylalkyl, unsubstituted and substituted heterocyclyl, unsubstituted and substituted (dd) -alkyl, - (alkylene dd) P (= 0) ) (ORv) 2; -perfluoroalkylene (C C3) -N (CHs) 2; -alkylene of (d-d) -N + ((d-C3) alkyl) 3); -alkylene of (d-C3) -N + (CH2CH2OH) 3; - (C C alkylene) -C (= 0) -halogen; -perfluoroalkylene of (d-d) -C02Rv; - (alkylene of d-C3) C (= 0) ORv; and - (C C3 alkylene) OC (= 0) - (C C3 alkylene) C (= 0) Ry; Ry is selected from the group consisting of -ORv, -NRV2 and -alkyl of (Cr d); Rz is selected from the group consisting of -C (= 0) Ry; -NRvCRvRa-C (= 0) -Rn; -NRV2; -ORv; substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, and -C (= 0) alkyl of (d-d); each Rc is independently selected from the group consisting of -H and a terminally linked peptidyl carboxyl residue containing from 1 to 3 amino acids in which the terminal amino group of the peptidyl residue is present as a functional group selected from the group consisting of -NH2; -NHC (= 0) alkyl of (d-d); -NHalkyl of (Cr d); -NH (C 6 alkyl) 2; and -NHC (= 0) Ohridrocarbil of (C C7); each R2 is independently selected from the group consisting of halogen; -hydrocarbyl of (d-d), -C (= 0) Rv; -NRV2; -NHC (= 0) Rv; -NHS02Rv; -NHRa; -NHCRvRaC (= 0) Rn; -NHS02Rv; -C (= 0) ORv; -C (= 0) NHRv; -N02; -CN; -ORv; -P (= 0) (ORv) 2; -C (= NH) NH2, dimethylamino (C2-C6 alkoxy); -NHC (= NRV) NHRV; haloalkyl of (d-d), -haloalkoxy of (C d); the two Rv groups in -P (= 0) (ORv) 2 and -NRV2 can optionally form a heterocyclic ring of five or six elements, which may optionally also be fused with an aryl or carbocyclic ring; a is 0, 2, 2 or 3; Rx is selected from the group consisting of -H; -alkyl of (d-d), and -C (= 0) alkyl of (d-C6); and Rv, Ra and Rn are as defined above for the compounds according to Formula XVIIIA; and (b) isolating from the reaction products either (i) a compound in accordance with Formula IE, whether in the exocyclic carbon-carbon double bond of Formula (XVlll is in the (E) -formation, or (ii) a compound according to Formula IZ, if the exocyclic carbon-carbon double bond of Formula XVlll is in the (Z) -configuration, or a salt of such a compound 58. A process for preparing a compound according to claim 17, of the Formula lll: or a salt thereof, wherein R2, R3, A, A, Q, a and b are as defined in claim 17 and Rv is -hydrocarbyl of (d-d); characterized in that it comprises the steps of: (a) reacting a compound according to Formula II: wherein, A is -S- or -O-; each R is independently selected from the group consisting of -H and -hydrocarbyl of (C C7); each Ra is independently selected from the group consisting of -H; -alkyl of (d-Ce), -heteroalkyl of (dd), - (CH2) 3-NH-C (NH2) (= NH), -CH2C (= 0) NH2, -CH2COOH, - (CH2) 2COOH, substituted and unsubstituted aryl, substituted and unsubstituted (C C 3) arylalkyl, unsubstituted and unsubstituted heterocyclyl, and unsubstituted and substituted (dd) heterocyclylalkyl; each Rn is independently selected from the group consisting of -ORv, -NRV2, and an N-terminally linked peptidyl residue containing from 1 to 3 amino acids in which the terminal carboxyl group of the peptidyl residue is present as a functional group, selected from group consisting of -C02Rv and -C (= 0) NRv2; Q is aryl or heteroaryl; each R2 and R3 is independently selected from the group consisting of halogen; -hydrocarbyl of (dd), -C (= 0) Rv, -NRV2, -NHC (= 0) Rv, -NHS02Rv, -NHRa, -NHCRvRaC (= 0) Rp, -NHS02Rv, -C (= 0) ORv , -C (= 0) NHRv, -N02, -CN, -ORv, -P (= 0) (ORv) 2, -C (= NH) NH2, dimethylamino (C2-C6 alkoxy), -NHC (= NRV ) NHRV, -haloalkyl of (dd), and -haloalkoxy of (dd); the two Rv groups in -NR 2 may optionally form a five or six element heterocyclic ring, which may optionally also be fused to an aryl or carbocyclic ring; a is O, 1, 2, or 3; b is 0, 1, 2 or 3; the conformation of the substituyeníes in the carbon-carbon exocyclic double bond is either E- or Z-; X is -C * H (Rx) Y- or -NRX-Z-; Y is -S (= 0) - or -S02-; Z is -C (= 0) - or -S02-; Rx is selected from group consisting of -H; -alkyl of (d-d), and -C (= 0) alkyl of (C C3); Y * indicates that, when Rx is different from -H, the conformation of substituents in the designated carbon atom is (R) -, (S) - or any mixture of (R) - and (S) -; or a salt of compose; provided that: (a) when A is -O- and R1 is -H: b is greater than 0; and R3 is different from alkyl of (d-d), -OH and -N02, (b) when X is -NRX-Z- and A is -O-; Rz is differentiated to -C (= 0) Ry, -NRV2 and unsubstituted aryl; (c) when X is -C * H (RX) Y- and A is -O-; R1 is different from haloalkyl of (d-d); Rz is different from -NRV2 and insoluble aryl; with a hydrocarbylphosphyl halide of the formula Halogen P O hydrocarbyl of (C C7) hydrocarbyl of (c c7); Y (b) isolating from the reaction products, a Formula III compound, or a salt of the same, wherein R2, R3, X, A, Q, a and b are as defined in claim 17; and Rv is -hydrocarbyl of (d-C7). 59. The process for preparing a compound according to claim 17, of Formula III: or a salt thereof, wherein R2, R3, X, A, Q, a and b are as described in claim 17; and Rv is -H; characterized in that it comprises the steps of (a) reacting a compound according to Formula III, wherein Rv is hydrocarbyl of (C C7), with a halotryalkyl silane of the Formula: (C 6) alkyl halogen - Si alkyl of (C | -C6) alkyl of (Ci-Cß) • and (b) isolating from the reaction products, a compound of Formula III, or a salt thereof, wherein R2, R3, X, A, Q, a and b are as defined in claim 17; and Rv is -H. 60. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a compound, or pharmaceutically acceptable salt thereof, according to claim 1. 61. A conjugate according to Formula l-L-Ab; wherein: I is a compound according to claim 1; Ab is an antibody; and -L- is a single covalenle linkage or a linking group covalently linked to said antibody compound. 62. The conjugate according to claim 61, further characterized in that the Ab antibody is a monoclonal antibody or a monospecific polyclonal antibody. 63. The conjugate according to claim 62, further characterized in that the Ab antibody is a tumor-specific antibody. 64. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and at least one conjugate according to claim 61. 65. The use of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for treating a proliferative disorder. 66. The use claimed in claim 65, wherein the proliferative disorder is cancer. 67. The use of a compound in accordance with the claim 1, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the administration before or after an effective amount of therapeutic ionizing radiation for the cancer release. 68. The use of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for inducing apoptosis of tumor cells in an individual suffering from cancer. 69. The use of a conjugate according to claim 61, for the manufacture of a medicament for the treatment of cancer. 70. The use of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for reducing or eliminating the effects of ionizing radiation on normal cells in an individual who has incurred or is at risk of incurring exposure by ionizing radiation. 71. The use claimed in claim 70, wherein the medicament is for administration before the individual is exposed to ionizing radiation. 72. The use claimed in claim 71, wherein the medicament is for administration at least about one hour before the individual is exposed to ionizing radiation. 73. The use claimed in claim 72, wherein the medicament is for administration no more than about twenty-four hours before the individual is exposed to ionizing radiation. 74. The use claimed in claim 73, wherein the medicament is for adsorption approximately eighteen and approximately six hours before the individual is exposed to ionizing radiation. 75. The use claimed in claim 70, wherein the medicament is for administration after the individual is exposed to ionizing radiation. 76. The use claimed in claim 75, wherein the radioprotective compound is administered between zero and six hours after the individual is exposed to ionizing radiation. 77. The use of a compound in accordance with the claim 1 for the preparation of a medicament for the administration together with the administration of an effective amount of therapeutic ionizing radiation for the treatment of a proliferative monomer. 78. The use claimed in claim 77, wherein the proliferative monomer is cancer. 79. The use of a compound for the preparation of a drug for administration to the bone marrow after the removal of the bone marrow of an individual, and before irradiating the bone marrow with an effective amount of ionizing radiation to reduce the number of malignant cells to protect bone marrow cells from the effect of radiation. 80. The use claimed in claim 79, wherein, after treatment, the bone marrow cells will be implanted in the individual. 81. The use claimed in claim 79, wherein the medicament is also for administration to the individual where he receives therapeutic ionizing radiation before re-implantation of the bone marrow, before receiving the therapeutic ionizing radiation. 82. The use claimed in claim 79, wherein the radioprotective compound is for administration at least about 6 hours after exposure of the bone marrow to ionizing radiation. 83. The use claimed in claim 79, wherein the radioprochloride compound is for administration about 20 hours prior to exposure of the bone marrow to ionizing radiation. 84. The use claimed in claim 79, wherein the radioprotechlor compound is for administration approximately 24 hours before exposure to ionizing radiation. 85. Use of a compound according to claim 1 for the preparation of a medicament for protecting an individual from the cytotoxic side effects of the administration of a mitotic phase cell cycle inhibitor or a topoisomerase inhibitor for the forward administration of administration of said inhibitor, an effective amount of at least one cytoprotective compound according to claim 1, wherein the mitotic phase or topoisomerase inhibitor cell cycle inhibitor is not a composite according to claim 1. 86. The The use claimed in claim 85, wherein the medicament is for administration at least about 1 hour prior to administration of the mltototic phase cell inhibitor or iopoisomerase inhibitor. 87. The use claimed in claim 85, wherein the medicament is for administration at least about 4 hours prior to the administration of the mitotic phase cell cycle inhibitor or topoisomerase inhibitor. 88. The use claimed in claim 85, wherein the medicament is for administration approximately 48 hours prior to administration of the mitotic phase cell or topoisomerase inhibitor. 89. The use of a compound according to claim 1 for the preparation of a medicament for administration prior to the administration of at least one mitotic phase or topoisomerase inhibitor of the cell cycle for the treatment of cancer or other proliferative disorders. . 90. The use claimed in claim 87, wherein the medicament is for administration at least about 1 hour prior to the administration of the mitotic phase cell cycle inhibitor or topoisomerase inhibitor. 91. The use claimed in claim 90, wherein the medicament is for administration at least about 12 hours prior to administration of the mitotic phase or topoisomerase inhibitor cell cycle inhibitor. 92. The use claimed in claim 90, wherein the medicament is for administration at least about 24 hours prior to the administration of the miic phase or mipoisomerase inhibitor cell cycle inhibitor. 93. An isolated isopic isomer of a compound of conformance ication 1, or a salt thereof. 94. The compilation in accordance with claim 1 for your edicamenio