Abstract: A PEG linker as represented by formula (I), wherein n and m are respectively an integer from 1 to 7, providing the PEG linker with 1 to 49 linking sites. A ligand drug conjugate as represented by formula (II). The conjugate uses the PEG linker to increase a drug loading capacity and drug loading diversity, thereby improving pharmaceutical efficacy.

Abstract: The subject matter described herein is directed to methods of preparing certain antibody-drug conjugates (ADCs) wherein the antibody is linked to the drug through a linker, wherein the drug contains a heteroaryl group having a secondary nitrogen, and the linker is attached to the drug via the secondary nitrogen. The resulting conjugates are useful in treating various diseases and conditions.

Abstract: The invention relates to a compound of formula (I) or formula (II) or pharmaceutically acceptable salts, solvates, tautomers, stereoisomers or mixtures thereof; which are useful as medicaments, in particular as anti-proliferative agents and for use as a drug in an antibody-drug conjugate and in the treatment of proliferative diseases.

Abstract: Provided herein are compounds of formula (I):

Abstract: Pyrrolobenzodiazepine (PBDs) having a (1-methyl-1H-pyrrol-3-yl)phenyl based amino residue were found to be highly effective compounds having improved cytotoxicity ad DNA binding properties.

Abstract: A compound of formula (I) or a salt or solvate thereof, wherein the dotted double bond indicates the presence of a single or double bond between C2 and C3; R2 is selected from —H, —OH, ?O, ?CH2, —CN, —R, OR, halo, dihalo, ?CHR, ?CHRR?, —O—SO2—R, CO2R and COR; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo; where R and R? are independently selected from optionally substituted C1-7 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R10 and R11 either together form a double bond, or are selected from H and QRQ respectively, where Q is selected from O, S and NH and RQ is H or C1-7 alkyl or H and SOxM, where x is 2 or 3, and M is a monovalent pharmaceutically acceptable cation; A is selected from (A1), (A2), (A3), (A4) or (A5) where X1 and Y1 are selected from: CH and NH; CH and NMe; N and NMe; CH and S; N and S; N and O; and CH and O, respectively; X2 and Y2 are selected from: CH and NH; CH and NMe; N and NMe; CH and S; N and S; N and O; and CH and O, respectively; Z1 is selected fr

Abstract: Disclosed are compounds of the following formula: in which R1, R2, R3, R4, R5, R6, R7, X, and t are defined in the specification. Also disclosed are pharmaceutical compositions, kits, and articles of manufacture, which contain the compounds, methods and intermediates useful for making the compounds, and methods of using the compounds to treat diseases, disorders, and conditions related to PARP activity.

Abstract: Disclosed is the synthesis of [18F]flumazenil that is useful in imaging epileptic lesions by PET (positron emission tomography). A method for preparing [18F]flumazenil by reacting a diaryliodonium salt precursor with the positron-emitting radionuclide fluorine-18. [18F]flumazenil can be prepared from the diaryliodonium salt precursor in the presence of kryptofix2.2.2./potassium carbonate(K2.2.2./K2CO3) and TEMPO in dimethylformamide (DMF) at a high yield.

Abstract: This invention relates to pyrrolobenzodiazepines (PBDs), in particular pyrrolobenzodiazepine dimers having a C2-C3 double bond and an aryl group at the C2 position in each monomer unit, and their inclusion in targeted conjugates. The differing substituent groups may offer advantages in the preparation and use of the compounds, particularly in their biological properties and the synthesis of conjugates, and the biological properties of these conjugates.

Abstract: The invention relates to compound of the formula I or a salt thereof, wherein the substituents are as defined in the specification; to its preparation, to its use as medicament and to medicaments comprising it.

Abstract: Conjugate compounds of formula (A): wherein: R2 is where R36a and R36b are independently selected from H, F, C1-4 saturated alkyl, C2-3 alkenyl, which alkyl and alkenyl groups are optionally substituted by a group selected from C1-4 alkyl amido and C1-4 alkyl ester or, when one of R36a and R36b is H, the other is selected from nitrile and a C1-4 alkyl ester; R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, NO2, Me3Sn and halo; R7 is independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, NO2, Me3Sn and halo; Y is selected from formulae A1, A2, A3, A4, A5 and A6: L is a linker connected to a cell binding agent; CBA is the cell binding agent; n is an integer selected in the range of 0 to 48; RA4 is a C1-6 alkylene group; either (a) R10 is H, and R11 is OH, ORA, where RA is C1-4 alkyl; or (b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or (c) R10 is H and R11 is OSOzM, where

Abstract: The invention relates to compounds that are diazahomoadamantane derivatives, compositions comprising such compounds, and methods of using such compounds and compositions.

Abstract: A compound, or a pharmaceutically acceptable salt or solvate thereof, or conjugates thereof, selected from the group consisting of formula wherein: (a) R10 is H, and R11 is OH, ORA, where RA is saturated C1-4 alkyl; (b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or (c) R10 is H and R11 is S02M, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation, or both M together are a divalent pharmaceutically acceptable cation.

Abstract: The present invention relates to tetrahydropyridine derivatives of formula (1) which may be therapeutically useful as anti-bacterial agents, more particularly FabI inhibitors. in which X, Y, Z and “n” have the same meanings given in the specification, and pharmaceutically acceptable salts and pharmaceutically acceptable stereoisomers thereof that are useful in the treatment and prevention in diseases or disorder, in particular their use in diseases or disorder where there is an advantage in inhibiting Enoyl-ACP reductase enzyme (FabI) activity. The present invention also provides methods for synthesizing and administering the FabI inhibitory compounds. The present invention also provides pharmaceutical formulations comprising at least one of the FabI inhibitory compounds together with a pharmaceutically acceptable carrier, diluent or excipient therefor.

Abstract: A compound with the formula (I), wherein: R2 is of formula (II), where X is selected from the group comprising: OH, SH, CO2H, COH, N?C?O, NHNH2, CONHNH2, formula (A), formula (B), NHRN, wherein RN is selected from the group comprising H and C1-4 alkyl; RC1, RC2 and RC3 are independently selected from H and unsubstituted C1-2 alkyl; and either: R12 is selected from the group consisting of: (ia) C5-10 aryl group, optionally substituted by one or more substituents selected from the group comprising: halo, nitro, cyano, ether, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene; (ib) C1-5 saturated aliphatic alkyl; (ic) C3-6 saturated cycloalkyl; (id) formula (C), wherein each of R21, R22 and R23 are independently selected from H, C1-3 saturated alkyl, C2-3 alkenyl, C2-3 alkynyl and cyclopropyl, where the total number of carbon atoms in the R12 group is no more than 5; (ie) formula (D), wherein one of R25a and R25b is H and the other is selected from: phenyl, which phenyl is optionally substituted by a group

Abstract: The present invention provides a compounds of general formula (8), (11) and (14), useful as potential antitumour agents against human cancer cell lines. The present invention further provides a process for the preparation of pyrrolo[2,1-c][1,4]benzodiazepine hybrids of general formula (8), (11) and (14).

Abstract: A compound of formula (I): which is substantially free of any of the corresponding compound of formula (IB): methods of making such compounds, and the further transformation of such compounds.

Abstract: A compound with the formula I: wherein: R2 is of formula II: where A is a C5-7 aryl group, X is selected from the group comprising: NHNH2, CONHNH2, formula III, formula IV, and either: (i) Q1 is a single bond, and Q2 is selected from a single bond and —Z—(CH2)n—, where Z is selected from a single bond, O, S and NH and n is from 1 to 3; or (ii) Q1 is —CH?CH—, and Q2 is a single bond; R12 is a C5-10 aryl group, optionally substituted by one or more substituents selected from the group comprising: halo, nitro, cyano, ether, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene; R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo; where R and R? are independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NHRR?, nitro, Me3Sn and halo; either: (a) R10 is H, and R11 is OH, ORA, where RA is C1-4 alkyl; (b) R10 and R11 form a nitrogen-carbon double bond between the n

Abstract: The present invention provides a compound of general formula A, useful as potential anticancer agents against eleven human cancer cell lines. The present invention further provides a process for the preparation of diaryl ether linked pyrrolo[2,1-c][1,4]benzodi azepine conjugates attached through different alkane spacers of general formula A.

Abstract: The present invention relates to pyrrolo[1,4]benzodiazepine (PBD) dimer conjugates, to the compositions comprising them and to their therapeutic application, in particular as anticancer agents. The invention also relates to the process for the preparation of the conjugates, to their application as anticancer agents and to the dimers themselves.

Abstract: Compounds of formulae I, II or III, and pharmaceutically acceptable salts thereof, are useful as CDK inhibitors.

Abstract: The present invention provides a compound of general formulae (8a-i), (11a-i), (14a-i), and (17a-i), useful as potential antitumour agents against human cancer cell lines. The present invention further provides a process for the preparation of Cinnamido-pyrrolo[2,1-c][1,4]benzodiazepines of general formulae (8a-i), (11a-i), (14a-i), and (17a-i).

Abstract: A compound which is selected from A: B: and C: and salts and solvates thereof, as well as conjugates thereof with cell binding agent.

Abstract: Novel 5-HT3 receptor modulators are disclosed. These compounds are used in the treatment of various disorders, including chemotherapy-induced nausea and vomiting, post-operative nausea and vomiting, and irritable bowel syndrome. Methods of making these compounds are also described in the present invention.

Abstract: Pyrrolobenzodiazepine dimers I having a C2-C3 double bond and an aryl group at the C2 position on one monomer unit, and a C2-C3 double bond and either a conjugated double or triple bond at the C2 position or an alkyl group at the C2 position on the other monomer unit, and conjugates of these compounds.

Abstract: The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds, such as those in formulas (V)-(VII). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The present invention is further directed to methods of preparing a conjugate of a cell-binding agent and a cytotoxic compound. The methods comprise the use of an imine reactive compound to enable efficient conjugations of cytotoxic compounds with cell binding agents.

Abstract: The present invention relates to tricyclic quinoline and quinoxaline derivatives, to a pharmaceutical composition containing such compounds, to their use as modulators, especially agonists or partial agonists, of the 5-HT2C receptor, their use for preparing a medicament for the prevention or treatment of conditions and disorders which respond to the modulation of 5-HT2C receptor, and to a method for preventing or treating conditions and disorders which respond to the modulation of 5-HT2C receptor.

Abstract: Pyrrolobenzodiazepine dimers having a C2-C3 double bond and an aryl group at the C2 position on one monomer unit, and a C2-C3 double bond and either a conjugated double or triple bond at the C2 position or an alkyl group at the C2 position on the other monomer unit, and conjugates of these compounds.

Abstract: The invention relates to compound of the formula I or a salt thereof, wherein the substituents are as defined in the specification; to its preparation, to its use as medicament and to medicaments comprising it.

Abstract: A compound of general formula 9, useful as potential antitumor agents against human cancer cell line and a process for the preparation of Pyrrolo[2,1-c] [1,4]benzodiazepine-benzothiazole or benzoxazole conjugates linked through piperazine of general formula 9 wherein: R, R1=H, F, OCF3, Cl, OMe; R2=OCH3 or H; n1 n2=3, 4; x=S or O.

Abstract: Compounds of the formula I: or solvate thereof, wherein: R2 is an optionally substituted C5-20 aryl group; R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo; where R and R? are independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NHRR?, nitro, Me3Sn and halo; R? is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms and/or aromatic rings; X is selected from O, S, or NH; z is 2 or 3; M is a monovalent pharmaceutically acceptable cation; R2?, R6?, R7?, R9?, X? and M? are selected from the same groups as R2, R6, R7, R9, X and M respectively, or M and M? may together represent a divalent pharmaceutically acceptable cation.

Abstract: The present invention provides a compound of general formula A, useful as potential anticancer agents against eleven human cancer cell lines. The present invention further provides a process for the preparation of diaryl ether linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates attached through different alkane spacers of general formula A.

Abstract: The present invention provides synthesis and in vitro anticancer activity of novel pyrrolo[2,1-c][1,4]benzodiazepine derivatives with dithiocarbamate side chains. The present invention also relates to a process for the preparation of new pyrrolo[2,1-c][1,4]benzodiazepine derivatives with dithiocarbamate side chains of general formula (A) and a process for the preparation thereof.

Abstract: Claimed are unsymmetrical Pyrrolobenzodiazepine-dimers (PBD-dimers) of formula (I), that are unsymmetrical due at least to the values that the variables R12 and R2 represent. Formula (I), wherein: R2 is of formula (II), where A is a C5-7 aryl group, X is selected from the group comprising: OH, SH, CO2H, COH, N?C?O, NHRN, wherein RN is selected from the group comprising H and C1-4 alkyl, and (OC2H4)mOCH3, where m is 1 to 3, and either: (i) Q1 is a single bond, and Q2 is selected from a single bond and —Z—(CH2)n—, where Z is selected from a single bond, O, S and NH and n is from 1 to 3; or (ii) Q1 is —CH?CH—, and Q2 is a single bond; R12 is a C5-10 aryl group, optionally substituted by one or more substituents selected from the group comprising: halo, nitro, cyano, ether, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene. The other variables are as defined in the claims. The compounds are useful for the treatment of proliferative diseases.

Abstract: A conjugate of formula (A): where Y is selected from a single bond, and a group of formulae A1 or A2: where N shows where the group binds to the N10 of the PBD moiety; RL1 and RL2 are independently selected from H and methyl, or together with the carbon atom to which they are bound form a cyclopropylene group; CBA represents a cell binding agent; Q is independently selected from O, S and NH; R11 is either H, or R or, where Q is O, SO3M, where M is a metal cation.

Abstract: The present invention provides a compound of general formula 7, useful as potential antitumour agents against five human cancer cell lines. The present invention further provides a process for the preparation of pyrrolo[2,1-c][1,4]benzodiazepine linked imidazo[1,5-a]pyridine conjugates attached through a piperazine moiety and different alkane spacers of general formula 7 wherein R represents H, OCH3, CF3, CN, F or Cl; n=3, 4, 5 or 6.

Abstract: The present invention is directed to tricyclic compounds which are positive allosteric modulators of metabotropic glutamate receptors, particularly the mGluR5 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.

Abstract: Methods of preparing ZC-423 (I) which result in varying enantiomeric ratios.

Abstract: The invention relates to certain pyrrolobenzodiazepines (PBDs), and in particular pyrrolobenzodiazepine dimers bearing C2 substitutions, including compounds of formula (T): wherein: R2 is CHR2A, and R2A is independently selected from H, R, CO2R, COR, CHO, CO2H, and halo; R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, NO2, Me3Sn and halo; R7 is independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, NO2, Me3Sn and halo; R8 is independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, NO2, Me3Sn and halo; R is independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; or the compound is a dimer with each monomer being of formula (M), where the R7 groups or R8 groups of each monomer form together a dimer bridge having the formula —X—R?—X— linking the monomers; wherein R? is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms, e.g. O, S, N(H), and/or aromatic rings, e.g.

Abstract: The present invention relates to pyrrolo[1,4]benzodiazepine (PBD) dimer conjugates, to the compositions comprising them and to their therapeutic application, in particular as anticancer agents. The invention also relates to the process for the preparation of the conjugates, to their application as anticancer agents and to the dimers themselves.

Abstract: The present invention relates to chalcone linked pyrrolo[2,1-c][1,4]benzodiazepine hybrids and a process for the preparation there of. More particularly it relates to 7-Methoxy-8-{n[4-1-(2 or 4-substituted phenyl)-3-(4-hydroxy-3-methoxyphenyl)-2-propen-1-one]alkyl}-oxy}-(11aS)-1,2,3,11a-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one and 7-Methoxy-8-{n-[-3-(4-hydroxy-3-methoxyphenyl)-1-(2,4-alkyl-3-quinolyl)-2-propen-1-one]alkyl}-oxy-(11aS)-1,2,3,11a-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one with aliphatic chain length variations useful as anticancer (antitumor) agent. The general structural formula of these chalcone linked pyrrolo[2,1-c][1,4]benzodiazepines hybrids is given below. wherein R1=OH, methyl, ethyl or phenyl; R2=H, OH or F; R=H or methyl; x=c or N; n=1-4.

Abstract: The present invention provides a compound of general formulae A useful as potential antitumour agents against human cancer cell lines. The present invention further provides a process for the preparation of pyrrolo[2,1-c][1,4]benzodiazepine hybrids of general formulae 6a-g, 10a-o, 14a-g and 18a-o.

Abstract: Disclosed are novel compounds which inhibit RSK, methods of making such compounds and pharmaceutical compositions comprising such compounds. Also disclosed are methods of treating RSK2 regulated disorders using compounds of the invention.

Abstract: A process for transforming a group >C?O (I) in a compound into a group >C?S (II) or into a tautomeric form of group (II) in a reaction giving a thionated reaction product, by use of crystalline P2S5.2 C5H5N as a thionating agent. A thionating agent which is crystalline P2S5.2 C5H5N.

Abstract: The invention relates to novel tomaymicine derivatives comprising a linker. It also relates to the conjugate molecules that comprise one or more of said tomaymicine derivatives covalently linked to a cell binding agent through a linking group that is present on the linker of the tomaymycin derivative. It also relates to the preparation of the tomaymicine derivatives and of the conjugate molecules.

Abstract: Pyrrolobenzodiazepine dimers I having a C2-C3 double bond and an aryl group at the C2 position on one monomer unit, and a C2-C3 double bond and either a conjugated double or triple bond at the C2 position or an alkyl group at the C2 position on the other monomer unit, and conjugates of these compounds.

Abstract: The present invention provides a compounds of general formula IXa-d, useful as potential antitumour agents and pharmaceutical composition comprising these compounds exhibits binding affinity with calf thymus (CT) DNA at a molar ratio of 1:5 in aqueous sodium phosphate buffer at pH of 7.00. The present invention further provides a process for the preparation of C2-Fluoro substituted piperazine linked pyrrolo[2,1c][1-4], benzodiazepine of formula (IX).

Abstract: The present invention provides compounds of general formula (5a-d) and (9a-h) useful as potential antitumour agents against human cancer cell lines. The present invention also provides a process for the preparation of pyrrolo [2,1-c][1,4]benzodiazepine hybrids of general formula (5a-d) and (9a-h).

Abstract: A compound of formula (I): which is substantially free of any of the corresponding compound of formula (IB): methods of making such compounds, and the further transformation of such compounds.

Abstract: A compound of general formula 9, useful as potential antitumour agents against human cancer cell line and a process for the preparation of Pyrrolo[2,1-c] [1,4]benzodiazepine-benzothiazole or benzoxazole conjugates linked through piperazine of general formula 9 wherein: R, R1=H, F, OCF3, Cl, OMe; R2=OCH3 or H; n1 n2=3, 4; x=S or O.