Abstract: The presently disclosed subject matter provides compositions that selectively bind cyclooxygenase-2 and comprise a therapeutic and/or diagnostic moiety. Also provided are methods for using the disclosed compositions for diagnosing (i.e., by imaging) a target cell and/or treating a disorder associated with a cyclooxygenase-2 biological activity.

Abstract: The present invention relates to a prodrug, comprising a pharmaceutically and/or diagnostically active compound, and one or more bisphosphonate groups, to a process for producing such a prodrug, and to a pharmaceutical composition comprising said prodrug, to be used for the treatment of bone-related disorders such as bone cancer.

Abstract: The presently disclosed subject matter provides compositions that selectively bind cyclooxygenase-2 and comprise a therapeutic and/or diagnostic moiety. Also provided are methods for using the disclosed compositions for diagnosing (i.e., by imaging) a target cell and/or treating a disorder associated with a cyclooxygenase-2 biological activity.

Abstract: Novel chemical species capable of simultaneously alkylating double-stranded DNA and cleaving the same; methods for alkylating and cleaving DNA by using these species; and anticancer agents with the use of these compounds. Compounds represented by the following general formula (I) which are capable of simultaneously alkylating double-stranded DNA and cleaving the same; a method for alkylating DNA and a method for cleaving double stranded DNA by using these compounds; and medicinal compositions with the use of these compounds: B—L—A(I) wherein B represents a chemical structure capable of recognizing the base sequence of DNA, for example, optionally substituted pyrrole-imidazole polyamide; A represents a chemical structure capable of binding to one base of DNA, for example, the alkylation moiety of duocarmycin A; and L represents a linker capable of binding the chemical structures A and B, for example, vinyl.

Abstract: The current invention discloses hydroxyamidino derivatives useful as nitric oxide synthase inhibitors.

Abstract: It is to provide a cyclic imide derivative which is useful as an active ingredient of a pharmaceutical composition. A pharmaceutical composition which comprises, a cyclic imide derivative represented by the general formula (I): wherein Q1 is a single bond, —CH2—, —O—, —S— or —NH—, each of Q2 and Q3 is —C(O)—, —C(S)— or —CH2—, provided that at least one of Q2 and Q3 is —C(O)— or —C(S)—, Z is a single bond or a lower alkanediyl group, R is an aryl group which may be substituted or a cycloalkyl group which may be substituted, X is a nitro group, an amino group which may be acylated, a cyano group, a trifluoromethyl group, a hydroxyl group, a halogen atom, an alkyl group, an alkoxy group or an alkylthio group, m is an integer of from 0 to 4, and when m is 2 or above, X may be the same or different, or its salt.

Abstract: There is disclosed a chiral molecular magnet having characteristics exhibiting a monocrystal, a magnetic property, an optical activity, a transparent color and a relatively high transition temperature. This chiral molecular magnet is formed of a monocrystal represented by a general formula [Mn(L)]3[Cr(CN)6]2.4H2O (wherein L is optically active (R or S)-1,2-diamines and derivatives thereof or optically active (R or S)-1,3-diamines and derivatives thereof).

Abstract: A prodrug of the formula (I): ##STR1## where R.sup.1 is a group such that the compound R--NH.sub.2 represents actinomycin D, doxorubicin, mitomycin C, or a nitrogen mustard of the formula (IV): ##STR2## a prodrug of the formula (II): ##STR3## where R.sup.1 is a group such that the compound R.sup.2 OH is a phenolic nitrogen mustard; and processes whereby the prodrugs shown above are made in which a prodrug precursor compound is reacted with 4-nitrobenzyl chloroformate under anhydrous conditions.

Abstract: The present invention provides conjugates of mitomycin C or derivatives thereof and oligonucleotides. A conjugate of the present invention corresponds to formula I, below: ##STR1## where R is H, CH.sub.3, or C(O)SCH.sub.3, R' is O or NH, m is an integer from 1 to 10 and Ogn is an oligonucleotide. Pharmaceutical compositions and methods of using such conjugates to inhibit gene product expression are also provided.

Abstract: Substituted lactone compounds are useful in the treatment of precancerous lesions and neoplasms.

Abstract: This invention relates to a stable, easy to constitute, injectable formulation of anticancer agent BMY-25067. More specifically, the present invention concerns a formulation of BMY-25067 obtained from lyophilizing a solution comprising up to 4 mg of BMY-25067 per mL of 65% t-butanol/water, further comprising about 2% PVP (K-12 or K-17), optionally comprising pharmaceutically acceptable carrier(s).

Abstract: This invention is a water-soluble high molecular polymerized drug comprising a water-soluble clock copolymer having a hydrophilic segment and a hydrophobic pharmacological-functioning segment to side chain of which a drug is bonded.The hydrophilic first segments of the present invention include polyethylene glycol, polysaccharides, polyacrylamide, and so on.The hydrophobic segments being attached to a drug include polyaspartic acid, polyglutamic acid, polylysine, or derivatives thereof.Drugs to be attached to the hydrophobic segment include anti-cancer drugs, drugs for central nerve, drugs for circulatory organs, and so on.

Abstract: The present invention relates to analogues of 2,7-diaminomitosene, a mitomycin C metabolite, useful as antitumor, antimicrobial and/or antiviral agents. These analogues involve functionalization of the N-2 nitrogen with organic groups.

Abstract: Provided are drug/ligand compounds of Formula (I): ##STR1## in which D is a drug moiety;n is an integer from 1 to 10;p is an integer from 1 to 6;Y is O or NH.sub.2.sup.+ Cl.sup.- ;z is 0 or 1;q is about 1 to about 10;X is a ligand; and,A is a Michael Addition Adduct.In a preferred embodiment, the ligand is an immunoglobulin, preferably a chimeric antibody or fragment thereof. Also provided are formulations comprising as an active ingredient a compound of Formula (I), intermediates useful for preparing the compounds of Formula (I), processes for preparing the compounds of Formula (I), and methods for using the compounds of the invention.

Abstract: New intermediates, and processes therefor, provide an efficient method for deriving 4-amino-1,2,2a,3,4,5-hexahydrobenz[cd]indoles, which are themselves intermediates to useful CNS agents, from the Kornfeld-Woodward ketone and like compounds. Preferred embodiments provide means for the preparation of substantially pure enantiomers of the desired 4-amino-1,2,2a,3,4,5-hexahydrobenz[cd]indole.

Abstract: The present invention relates to the synthesis of mitomycin and analogs thereof that are useful as anticancer antibiotics. The invention further relates to analogs of mitomycin, which can be prepared according to the methods of synthesis provided. The synthetic method of the invention provides for reacting a derivitized indole with a dialkylvinylsulfonium salt to yield a tricyclic skeleton having the precursors of the fourth ring in one step, followed by an oxidation step or steps to close the fourth ring and prepare mitomycin or a related compound.

Abstract: The present invention provides novel mitomycin analogs containing a cyclic acetal or thioacetal group. These compounds are mitomycin C analogs in which the 7-amino group bears a 5-membered heterocyclic substituent. Mitomycin C is an antitumor agent of established utility, and the 7-N-substituted mitosane analogs thereof have similar utility.

Abstract: 6-heterocyclic-4-amino-1,3,4,5-tetrahydrobenz[cd]indoles are provided which are useful in modifying the function of serotonin in mammals.

Abstract: 7-(Diphenylmethyl)oxy-9a-methoxymitosane is a novel intermediate for conversion into 7-amino and 7-oxy-9a-methoxymitosanes and is also useful for inhibiting mammalian tumor growth. The compound is prepared by reacting 7-hydroxy-9a-methoxymitosane with diazodiphenylmethane. In a preferred reaction, the compound is prepared from mitomycin C via 7-hydroxy-9a-methoxymitosane without drying (water removal). The intermediate is advantageously converted to the very effective anti-tumor agent 7-[2-(4-nitrophenyldithio)ethylamino]-9a-methoxymitosane in unexpectedly high yields using a two step process where the first step constitutes conversion to 7-[2-(2-pyridyldithio)ethylamino]-9a-methoxymitosane or 7-[2-(3-nitro-2-pyridyldithio)ethylamino]-9a-methoxymitosane.

Abstract: Novel mitomycin derivatives represented by the formula (I) are obtained by introducing a substituent at the 6-position. The mitomycin derivatives of the present invention have an antitumor activity.

Abstract: Disclosed are mitomycin derivatives of formula (I): ##STR1## where W represents halogen; X represents methoxy, amino or ethylenimino; Y represents hydrogen or methyl; Z represents hydrogen or methyl; and one of R.sup.1 and R.sup.2 represents carbamoyloxymethyl, and the other represents hydrogen. The derivatives are usable as an antitumor and antibacterial agent.

Abstract: Disclosed in a mitomycin derivative represented by the formula (I): ##STR1## wherein W is a heterocyclic group.

Abstract: A method for purification of mitomycin C comprises;a. a step of treating the culture of a mitomycin C-producing microorganism with reverse phase adsorption resin to adsorb mitomycin C onto the resin;b. a step of eluting mitomycin C with ethyl acetate out of the resin;c. a step of adding phosphate buffer to the eluate and then evaporating ethyl acetate;d. a step of passing, under pressure, the residue remaining after the evaporation through a column packed with a reverse phase adsorbent having a small particle diameter to adsorb mitomycin C onto the resin;e. a step of eluting mitomycin C with aqueous methanol out of the resin under pressure;f. a step of treating the eluate with a reverse phase adsorption resin to adsorb mitomycin C onto the resin;g. a step of eluting mitomycin C with methanol out of the resin; and,h. a step of concentrating the methanol eluate to crystallize mitomycin C.By this method, mitomycin C can be efficiently purified in an industrial scale.

Abstract: 7-(Diphenylmethyl)oxy-9a-methoxymitosane is a novel intermediate for conversion into 7-amino and 7-oxy-9a-methoxymitosanes and is also useful for inhibiting mammalian tumor growth. The compound is prepared by reacting 7-hydroxy-9a-methoxymitosane with diazodiphenylmethane. In a preferred reaction, the compound is prepared from mitomycin C via 7-hydroxy-9a-methoxymitosane without drying (water removal). The intermediate is advantageously converted to the very effective anti-tumor agent 7-[2-(4-nitrophenyldithio) ethylamino]-9a-methoxymitosane in unexpectedly high yields using a two step process where the first step constitutes conversion to 7-[2-(2-pyridyldithio) ethylamino]-9a-methoxymitosane. or 7-[2-(3-nitro-2-pyridyldithio)ethylamino]-9a-methoxymitosane.

Abstract: Mitomycin derivatives containing substituted dithioethylamino groups at the 7th position are provided. The mitomycin derivatives according to the present invention are superior to mitomycin C with respect to their improved anti-tumour activity and toxicity. More particularly, they exhibit a wider tolerance of dosage against Sarcoma 180A solid tumour as well as a better survival time and weaker bone marrow supression against P388.Furthermore, certain compounds exhibit a high water-solubility which is advantageous for pharmaceutical purposes. Excellent anti-tumour agents may readily be prepared by using the derivatives of the present invention.

Abstract: The present invention provides novel mitomycin analogs containing a disulfide group and processes for the preparation thereof. These compounds are mitomycin A analogs in which the 7-alkoxy group bears an organic substituent incorporating a disulfide group. Mitomycin A is an antibiotic of established utility, and the 7-O-substituted mitosane analogs thereof have similar utility.

Abstract: Novel methods for treatment of neoplastic disease states in animals, which methods comprise administering a therapeutically effective amount of a compound of the formula IV, ##STR1## wherein: Y is hydrogen or lower alkyl; and X is a radical of the formula --O--R, wherein R is:a substituted lower alkyl radical selected from the group consisting of mono- and di-hydroxy lower alkyl, cyano lower alkyl, halo lower alkyl, lower alkyl amino lower alkyl, hydroxy lower alkylthio lower alkyl, hydroxy lower alkyldithio lower alkyl, di-lower alkoxy lower alkyl, hydroxy or lower alkoxy substituted lower alkoxy lower alkyl, cyclo lower alkyl substituted lower alkyl; and lower alkyl substituted dioxolanyl lower alkyl ora lower alkenyl radical; ora lower alkynyl radical; ortetrahydro furanyl or a lower alkyl substituted derivative thereof, oxiranyl lower alkyl, tetrahydropyranyl lower alkyl, or furanyl lower alkyl.

Abstract: The present invention provides novel mitomycin analogs containing a disulfide group and processes for the preparation thereof. These compounds are mitomycin A analogs in which the 7-alkoxy group bears an organic substituent incorporating a disulfide group. Mitomycin A is an antibiotic of established utility, and the 7-O-substituted mitosane analogs thereof have similar utility.

Abstract: The invention relates to certain derivatives of mitomycins A and C and the use thereof to treat bacterial infections and to supress the growth of cancer cells. The invention also relates to processes for the preparation of the mitomycin derivatives of the invention.

Abstract: 7-(Diphenylmethyl)oxy-9a-methoxymitosane is a novel intermediate for conversion into 7-amino and 7-oxy-9a-methoxymitosanes and is also useful for inhibiting mammalian tumor growth. The compound is prepared by reacting 7-hydroxy-9a-methoxymitosane with diazodiphenylmethane. In a preferred reaction, the compound is prepared from mitomycin C via 7-hydroxy-9a-methoxymitosane without drying (water removal). The intermediate is advantageously converted to the very effective anti-tumor agent 7-[2-(4-nitrophenyldithio)ethylamino]-9a-methoxymitosane in unexpectedly high yields using a two step process where the first step constitutes conversion to 7-[2-(2-pyridyldithio)ethylamino]-9a-methoxymitosane or 7-[2-(3-nitro-2-pyridyldithio)ethylamino]-9a-methoxymitosane.

Abstract: Novel mitomycin derivatives are characterized by a substituent on the C.sub.6 -methyl group. The mitomycin derivatives exhibit anti-tumor and antibacterial activity and have low toxicity.

Abstract: Novel methods for treatment of neoplastic disease states in animals, which methods comprise administering a therapeutically effective amount of a compound of the formula V, ##STR1## wherein: Y is hydrogen of lower alkyl; and X is a radical of the formula --O--R, wherein R is:N,N-di (hydroxy lower alkyl)amino lower alkyl, or tri-lower alkoxy silyl lower alkyl, or cyclo lower alkyl, or halo substituted lower alkoxy lower alkyl, or tetrahydro pyranyl, or carboethoxy lower alkyl, or 1-lower alkyl pyrrolidinyl lower alkyl, or N-pyrrolidinyl lower alkyl, or 1-lower alkyl pyrrolydinyl, or dioxanyl, or hydroxy lower alkenyl, or hydroxy lower alkyl thio lower alkyl thio lower alkyl, or dioxanyl lower alkyl, or lower alkyl thio lower alkyl, or phenyl thio lower alkyl, or phenoxy lower alkyl, or thiophenyl lower alkyl, or 1-lower alkyl piperidyl, or alkyl carbonyl amino alkyl, or N-piperidyl lower alkyl, or lower alkoxy lower alkyl or lower alkyl thio hydroxy lower alkyl, or 1-lower alkyl N-piperazinyl lower alkyl, or N

Abstract: Mitomycin derivatives having the formula ##STR1## wherein X is acyl, lower alkyl, alkoxycarbonyl aryloxycarbonyl or aralkoxycarbonyl;Y is hydrogen or methyl;Z is hydrogen, methyl, acyl or allyloxycarbonyl;one of R.sub.1 and R.sub.2 represents carbamoyloxymethyl and the other represents hydrogen, or R.sub.1 and R.sub.2 together represent methylene, show antibacterial and antitumor activities.

Abstract: The present invention provides novel mitomycin analogs containing a disulfide group and processes for the preparation thereof. These compounds are mitomycin A analogs in which the 7-alkoxy group bears an organic substituent incorporating a disulfide group. Mitomycin A is an antibiotic of established utility, and the 7-O-substituted mitosane analogs thereof have similar utility.

Abstract: Novel methods for treatment of neoplastic disease states in animals, which methods comprise administering a therapeutically effective amount of a compound of the formula IV, ##STR1## wherein: Y is hydrogen or lower alkyl; and Z is a radical of the formula --O--R, wherein R is:a substituted lower alkyl radical selected from the group consisting of mono- and di-hydroxy lower alkyl, cyano lower alkyl, halo lower alkyl, lower alkyl amino lower alkyl, hydroxy lower alkylthio lower alkyl, hydroxy lower alkyldithio lower alkyl, di-lower alkoxy lower alkyl, hydroxy or lower alkoxy substituted lower alkoxy lower alkyl, and cyclo lower alkyl substituted lower alkyl; ora lower alkenyl radical; ora lower alkynyl radical; ora substituted or unsubstituted oxygen-containing heterocyclic radical selected from the group consisting of tetrahydro furanyl or lower alkyl substituted derivatives thereof, lower alkyl substituted oxiranyl, lower alkyl substituted dioxolanyl, lower alkyl substituted pyranyl, or lower alkyl substitute

Abstract: Mitomycin derivatives having potent anti-tumor activity having the formula: ##STR1## wherein one of R.sub.1 and R.sub.2 represents carbamoyloxymethyl and the other represents hydrogen or R.sub.1 and R.sub.2 are bonded together to form methylene;X is hydrogen or halogen;Y is hydrogen or methyl;Z is hydrogen, methyl or acyl; andn is an integer of 2 or 3.

Abstract: Disclosed herein are N.sup.7 -alkylphosphate derivatives of mitomycin C and porfiromycin showing antitumor activity against transplanted human tumor and reduced toxicity relative to the parent N.sup.7 -alkanol mitomycin compounds.

Abstract: This invention refers to 7-amino mitosane analogs (mitomycin C) in which the 7-amino group bears an organic substituent incorporating a disulfide group and to a novel thiol exchange process for producing these compounds. The compounds are inhibitors of experimental animal tumors.

Abstract: Mitomycin derivatives having potent anti-tumor activity against solid sarcoma 180 tumors and lymphocytic leukemia P-388 tumors.

Abstract: 7-N,8-N-Ethylenemitomycin 8-imines represented by the formula ##STR1## wherein one of the R.sub.1 and R.sub.2 represents carbamoyloxymethyl and another represents hydrogen or both are combined together to form methylene; R.sub.3, R.sub.4, R.sub.5 and R.sub.6 each independently represent hydrogen or C.sub.1-4 alkyl, or R.sub.3 and R.sub.4 may be combined together to represent --(CH.sub.2).sub.n --, wherein n is 3 or 4; and Y and Z represent hydrogen or methyl, provided that when R.sub.1 represents carbamoyloxymethyl and Y represents methyl, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6 and Z are not hydrogen simultaneously, has an excellent antitumor activity.

Abstract: Mitomycin compound having potent antitumour activity having the formula: ##STR1## wherein ##STR2## (wherein Ra, Rb and Rc each independently represent lower alkyl, cycloalkyl having 3-7 carbon atoms or phenyl; or Ra and Rb are bonded together to form a poly-methylene group having 2-5 carbon atoms);one of R.sub.1 and R.sub.2 represents carbamoyloxymethyl and the other represents hydrogen; or R.sub.1 and R.sub.2 may together form an exocyclic methylene group;and Y and Z each independently represents hydrogen or methyl.

Abstract: The present invention provides novel mitomycin analogs containing a disulfide group and processes for the preparation thereof. These compounds are mitomycin A analogs in which the 7-alkoxy group bears an organic substituent incorporating a disulfide group. Mitomycin A is an antibiotic of established utility, and the 7-O-substituted mitosane analogs thereof have similar utility.

Abstract: The present invention refers to mitomycin analogs containing a disulfide group. These compounds are mitromycin C derivatives in which the 7-amino group bears an organic substituent incorporating a disulfide group. The compounds are inhibitors of experimental animal tumors.

Abstract: Mitomycin derivatives having potent antitumor activity having the formula: ##STR1## wherein A is ON--or R.sub.4 N.dbd.N--[wherein R.sub.4 is selected from ##STR2## and optionally substituted heterocyclic groups (wherein R.sub.5 and R.sub.8 are each independently selected from hydrogen, lower alkyl and lower cycloalkyl; R.sub.6 is selected from hydrogen, halogen, hydroxy, lower alkoxy, amino and nitro; R.sub.7 is selected from lower alkyl and lower cycloalkyl; and X is selected from oxygen, sulphur and imino)];R.sub.1 and R.sub.2 are each independently selected from hydrogen, lower alkyl, lower cycloalkyl, optionally substituted aralkyl, optionally substituted alkanoyl, optionally substituted arylcarbonyl, optionally substituted alkanesulfonyl, arylsulfonyl and aralkylsulfonyl;R.sub.3 is hydrogen or carbamoyl;Y is hydrogen or methyl;Z is selected from hydrogen, methyl and acetyl;and is an .alpha. or .beta. bond.

Abstract: Mitomycin derivatives having potent antitumour activity have the formula: ##STR1## wherein R represents lower alkyl, cycloalkyl or unsubstituted or substituted aralkyl;X represents hydrogen or carbamoyl;Y and Z each independently represents hydrogen or methyl;and represents an .alpha. or .beta. bond.

Abstract: Mitomycin derivatives of the formula: ##STR1## wherein X is ##STR2## [wherein R.sub.3 is alkyl, cycloalkyl or optionally substituted phenyl; and R.sub.4 is alkyl or cycloalkyl]; n is an integer of 2 to 8; one of R.sub.1 and R.sub.2 is a hydrogen atom and the other is a carbamoyloxymethyl group, or alternatively R.sub.1 and R.sub.2 may be combined together to form a methylene group (.dbd.CH.sub.2); and Y and Z independently represent hydrogen or methyl;exhibit anti-bacterial and anti-tumor activities.

Abstract: Mitomycin derivatives represented by the formula (I): ##STR1## wherein R.sub.1 and R.sub.2 may be the same or different, and represent a hydrogen atom or a lower alkyl group; R.sub.3 and R.sub.4 mean that when R.sub.3 is a hydrogen atom, R.sub.4 represents --CH.sub.2 OCONH.sub.2 or ##STR2## (wherein R.sub.1 and R.sub.2 have the same significances as defined above), or R.sub.3 and R.sub.4 are combined to form .dbd.CH.sub.2 ; Y and Z may be the same or different, and represent a hydrogen atom or a methyl group; represents .alpha.- or .beta.-bond, provided that Y represents a hydrogen atom when R.sub.4 takes .beta.-configuration, have an excellent anti-tumor activity.

Abstract: Novel methods for treatment of neoplastic disease states in animals, which methods comprise administering a therapeutically effective amount of a compound of the formula IIIa, ##STR1## wherein: Y is hydrogen or lower alkyl; and Z is an hydroxy substitited 1-pyrrolidinyl radical, ora lower alkyl substituted piperidyl radical, ora 1-piperazinyl radical or an acetamino, acetyl, carbamido, cyano, carboxy lower alkylamino, di-lower alkoxy, nitro, sulfamyl, or lower alkyl substituted anilino radical, ora radical of the formula, ##STR2## wherein R is hydrogen or lower alkyl and R.sup.1 is a nitrogen containing heterocyclic radical selected from the group consisting of amino substituted triazolyl, lower alkyl substituted isothiazolyl, benzothiazolyl, and nitro and halo substituted derivatives of benzothiazolyl, or R.sup.

Abstract: This invention discloses 1a- and 7-substituted derivatives of mitosanes containing thiocarbamoyl and glycosyl residues. The compounds possess antibacterial and antitumor activity, with a concomitant reduction in bone marrow toxicity as compared to the parent compounds.

Abstract: The present invention provides new mitomycin derivatives of general formula (I) ##STR1## [wherein Y and Z, which may be the same or different, each represents a hydrogen atom or a methyl group;represents .alpha. or .beta. bonding and X represents a group of formula (II) ##STR2## (wherein R.sub.1 to R.sub.5 are each selected from hydrogen, halogen, hydroxyl, nitro, amino, lower alkyl, lower alkoxy, lower alkylamino or lower alkanoylamino);or an S-yl group of an amino acid having a thiol group, the carboxyl group optionally being protected e.g. in the form of a lower alkyl ester group and the amino group optionally being protected e.g. in the form of a lower alkanoylamino group;or an S-yl group of a di- or tripeptide containing an amino acid residue with a thiol group, the carboxyl group optionally being protected e.g. in the form of a lower alkyl ester and the amino group optionally being protected e.g. in the form of a lower alkanoylamino group]; and salts thereof.