260417-93-4

Upstream product

• 18162-48-6 tert-butyldimethylsilyl chloride 
• 95687-41-5 (2S,4R)-N1-(benzyloxycarbonyl)-4-hydroxy-2-(hydroxymethyl)-pyrrolidine 
• 13504-85-3 (2S,4R)-1-(benzyloxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid 
• 6674-22-2 1,8-diazabicyclo[5.4.0]undec-7-ene 
• 51-35-4 4R-4-hydroxyproline 
• 501-53-1 benzyl chloroformate 
• 64187-48-0 methyl (2S,4R)-1-benzyloxycarbonyl-4-hydroxypyrrolidine-2-carboxylate 

Downstream Products

• 232931-63-4 1,1'-[[(propane-1,3-diyl)dioxy]-bis[(2-amino-N-allyloxycarbonyl-5-methoxy-1,4-phenylene)carbonyl]]-bis[(2S)-2-hydroxymethyl-4-methylidene-2,3-dihydropyrrole] 
• 260417-96-7 1,1'-[[(propane-1,3-diyl)dioxy]-bis[(2-amino-5-methoxy-1,4-phenylene)carbonyl]]-bis[(2S,4R)-2-t-butyldimethylsilyloxymethyl-4-hydroxypyrrolidine] 
• 260417-95-6 1,1'-[[(propane-1,3-diyl)dioxy]-bis[(2-nitro-5-methoxy-1,4-phenylene)carbonyl]]-bis[(2S,4R)-2-t-butyldimethylsilyloxymethyl-4-hydroxypyrrolidine] 
• 260417-98-9 1,1'-[[(propane-1,3-diyl)dioxy]-bis[(2-amino-N-allyloxycarbonyl-5-methoxy-1,4-phenylene)carbonyl]]-bis[(2S)-2-t-butyldimethylsilyloxymethyl-4-oxo-pyrrolidine] 
• 260417-97-8 1,1'-[[(propane-1,3-diyl)dioxy]-bis[(2-amino-N-allyloxycarbonyl-5-methoxy-1,4-phenylene)carbonyl]]-bis[(2S,4R)-2-t-butyldimethylsilyloxymethyl-4-hydroxypyrrolidine] 
• 260418-24-4 1,1'-[[(propane-1,3-diyl)dioxy]-bis[(2-amino-N-allyloxycarbonyl-5-methoxy-1,4-phenylene)carbonyl]]-bis[(2S)-2-t-butyldimethylsilyloxymethyl-4-methylidene-2,3-dihydropyrrole] 
• 260418-26-6 1,1'-[[(pentane-1,5-diyl)dioxy]-bis[(2-amino-5-methoxy-1,4-phenylene)carbonyl]]-bis[(2S,4R)-2-t-butyldimethylsilyloxymethyl-4-hydroxypyrrolidine] 
• 260418-30-2 1,1'-[[(pentane-1,5-diyl)dioxy]-bis[(2-amino-N-allyloxycarbonyl-5-methoxy-1,4-phenylene)carbonyl]]-bis[(2S)-2-hydroxymethyl-4-methylidene-2,3-dihydropyrrole] 
• 260418-25-5 (S,R)-((pentane-1,5-diylbis(oxy))bis(5-methoxy-2-nitro-4,1-phenylene))bis(((2S,4R)-2-(((tert-butyldimethylsllyl)oxy)methyl)-4-hydroxypyrrolidin-1-yl) methanone) 
• 260418-28-8 1,1'-[[(pentane-1,5-diyl)dioxy]-bis[(2-amino-N-allyloxycarbonyl-5-methoxy-1,4-phenylene)carbonyl]]-bis[(2S)-2-t-butyldimethylsilyloxymethyl-4-oxo-pyrrolidine] 
• 260418-27-7 1,1'-[[(pentane-1,5-diyl)dioxy]-bis[(2-amino-N-allyloxycarbonyl-5-methoxy-1,4-phenylene)carbonyl]]-bis[(2S,4R)-2-t-butyldimethylsilyloxymethyl-4-hydroxypyrrolidine] 
• 260418-29-9 1,1'-[[(pentane-1,5-diyl)dioxy]-bis[(2-amino-N-allyloxycarbonyl-5-methoxy-1,4-phenylene)carbonyl]]-bis[(2S)-2-t-butyldimethylsilyloxymethyl-4-methylidene-2,3-dihydropyrrole] 
• 260417-87-6 (2S,4R)-N-(2-amino-4,5-dimethoxybenzoyl)-2-(tert-butyldimethylsilyloxymethyl)-4-hydroxypyrrolidine 
• 301838-62-0 {2-[(S)-4-Eth-(E)-ylidene-2-hydroxymethyl-pyrrolidine-1-carbonyl]-4,5-dimethoxy-phenyl}-carbamic acid allyl ester 

Relevant academic research and scientific papers

Practical Gram-Scale Synthesis of Iboxamycin, a Potent Antibiotic Candidate

A gram-scale synthesis of iboxamycin, an antibiotic candidate bearing a fused bicyclic amino acid residue, is presented. A pivotal transformation in the route involves an intramolecular hydrosilylation-oxidation sequence to set the ring-fusion stereocenters of the bicyclic scaffold. Other notable features of the synthesis include a high-yielding, highly diastereoselective alkylation of a pseudoephenamine amide, a convergent sp3-sp2 Negishi coupling, and a one-pot transacetalization-reduction reaction to form the target compound's oxepane ring. Implementation of this synthetic strategy has provided ample quantities of iboxamycin to allow for its in vivo profiling in murine models of infection.

LINCOSAMIDE ANTIBIOTICS AND USES THEREOF

Provided are compounds of Formula (I) for the treatment of infectious and inflammatory diseases. The compounds described herein are lincosamides modified at the amino acid (southern) region. The compounds may have further modification at the C-7 position of the aminooctose (northern) region, thus distinguishing them from lincomycin and clindamycin. Also provided are methods for preparing the compounds, pharmaceutical compositions comprising the compounds, and methods of treating infectious diseases using the disclosed compounds.

FUSED HETEROCYCLIC BENZODIAZEPINE DERIVATIVES AND USES THEREOF

The present disclosure provides compounds and compositions capable of extending lifespan, and methods of use thereof.

NOVEL BENZODIAZEPINE DERIVATIVES AND USES THEREOF

The present disclosure provides compounds and compositions capable of extending lifespan, and methods of use thereof.

Scale-up Synthesis of Tesirine

This work describes the enabling synthesis of tesirine, a pyrrolobenzodiazepine antibody-drug conjugate drug-linker. Over the course of four synthetic campaigns, the discovery route was developed and scaled up to provide a robust manufacturing process. Early intermediates were produced on a kilogram scale and at high purity, without chromatography. Midstage reactions were optimized to minimize impurity formation. Late stage material was produced and purified using a small number of key high-pressure chromatography steps, ultimately resulting in a 169 g batch after 34 steps. At the time of writing, tesirine is the drug-linker component of eight antibody-drug conjugates in multiple clinical trials, four of them pivotal.

PYRROLOBENZODIAZEPINE DERIVATIVES, COMPOSITIONS COMPRISING THE SAME AND METHODS RELATED THERETO

Disclosed are compounds of Formula (I) wherein X, Y, R1-R7, T1, T2, Z, and p are as described herein; a pharmaceutical composition comprising a compound of Formula (I) and a carrier; a method of inhibiting growth of a cell, which method comprises administering in an amount effective to inhibit growth a compound of Formula (I); a method of treating cancer in a mammal, which method comprises administering in an amount effective to treat cancer a compound of Formula (I); a method of treating a viral, parasitic, or bacterial infection of a cell, which method comprises administering in an amount effective to treat a viral, parasitic, or bacterial infection a compound of Formula (I); and a method of preparing a compound of Formula (I) as described herein.

11-HYDROXY-5H-PYRROLO[2,1-C][1,4]BENZODIAZEPIN-5-ONE DERIVATIVES AS KEY INTERMEDIATES FOR THE PREPARATION OF C2 SUBSTITUTED PYRROLOBENZODIAZEPINES

The present inventors have developed a key intermediate for the production of C2 substituted PBDs, which has a leaving group at the C2 position, a carbamate protecting group at the N10 position and a protected hydroxy group at the C11 position. In a first

Linker Length Modulates DNA Cross-Linking Reactivity and Cytotoxic Potency of C8/C8′ Ether-Linked C2-exo-Unsaturated Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) Dimers

A C2/C2′-exo-unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer 4b (DRG-16) with a C8-O(CH2)nO-C8′ diether linkage (n = 5) has been synthesized that shows markedly superior in vitro cytotoxic potency (e.g., > 3400-fold in IGRO

Pyrrolobenzodiazepines

Compounds of the formulae Ia and Ib: wherein: A is CH2, or a single bond; R2 is selected from: R, OH, OR, CO2H, CO2R, COH, COR, SO2R, CN; R6, R7 and R9 are independently selected from H, R, OH, OR, halo, amino, NHR, nitro, Me3Sn; and R8 is selected from H, R, OH, OR, halo, amino, NHR, nitro, Me3Sn, where R is as defined above, or the compound is a dimer with each monomer being the same or different and being of formula Ia or Ib, where the R8 groups of the monomers form together a bridge having the formula —X—R′—X— linking the monomers, where R′ is an alkylene chain containing from 3 to 12 carbon atoms, which chain may be interrupted by one or more hetero-atoms and/or aromatic rings and may contain one or more carbon-carbon double or triple bonds, and each X is independently selected from O, S, or N; except that in a compound of formula Ia when A is a single bond, then R2 is not CH═CH(CONH2) or CH═CH(CONMe2). Other related compounds are also disclosed.

Pyrrolobenzodiazepines

Compounds of the formulae Ia and Ib: wherein:A is CH2, or a single bond;R2 is selected from: R, OH, OR, CO2H, CO2R, COH, COR, SO2R, CN;R6, R7 and R9 are independently selected from H, R, OH, OR, halo, amino, NHR, nitro, Me3Sn;and R8 is selected from H, R, OH, OR, halo, amino, NHR, nitro, Me3Sn, where R is as defined above, or the compound is a dimer with each monomer being the same or different and being of formula Ia or Ib, where the R8 groups of the monomers form together a bridge having the formula -X-R'-X- linking the monomers, where R' is an alkylene chain containing from 3 to 12 carbon atoms, which chain may be interrupted by one or more hetero-atoms and/or aromatic rings and may contain one or more carbon-carbon double or triple bonds, and each X is independently selected from O, S, or N; except that in a compound of formula Ia when A is a single bond, then R2 is not CH=CH(CONH2) or CH=CH(CONMe2). Other related compounds are also disclosed.