17996-12-2Relevant articles and documents
ACRIDIN-9-YL-AMINE, QUINOLIN-9-YL-AMINE, 1 -AMINO-9H-THIOXANTHENE-9-ONE AND BENZO[B][1,5]NAPHTHYRI DIN-10-YL-AMINE DERIVATIVES AS AUTOPHAGY INHIBITORS FOR TREATING CANCER
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Paragraph 0333; 0337; 0354; 0358, (2021/07/17)
This disclosure provides a cridin-9-yl-amine, quinolin-9-yl-amine, 1- amino-9H-thioxanthene-9-one and benzo[b][l,5]naphthyridin-10- yl-amine derivatives and structurally related compounds for use as autophagy inhibitors for treating cancer. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 77 to 155; examples 1 to 22; compound A; compounds 1 to 21; tables 1 to 3).
The breaking beads approach for photocleavage from solid support
Alshanski, Israel,Bakhatan, Yasmeen,Grunhaus, Dana,Hurevich, Mattan
supporting information, p. 4183 - 4188 (2020/06/21)
Photocleavage from polystyrene beads is a pivotal reaction for solid phase synthesis that relies on photolabile linkers. Photocleavage from intact porous polystyrene beads is not optimal because light cannot penetrate into the beads and the surface area exposed to irradiation is limited. Thus, hazardous, technically challenging and expensive setups are used for photocleavage from intact beads. We developed a new concept in which grinding the beads during or prior to irradiation is employed as an essential part of the photocleavage process. By grinding the beads we are exposing more surface area to the light source, hence, photocleavage can be performed even using a simple benchtop LED setup. This approach proved very efficient for photocleavage of various model compounds including fully protected oligosaccharides.
Synthetic method 6-amino-1-hexanol
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Paragraph 0031-0032; 0034-0035, (2019/10/23)
The invention discloses a synthetic method 6-amino-1-hexanol. According to the synthetic method 6-amino-1-hexanol, chlorosulphonyl isocyanate and 1, 6-hexanediol are taken as main raw materials, one-pot method is adopted to synthesize 6-amino-1-hexanol. The synthesis route comprises following steps: 1, under the catalyst effect of a tertiary amine, chlorosulphonyl isocyanate and a primary alcoholare reacted to generate a Burgess reagent, 1, 6-hexanediol is added to generate an intermediate 6-hydroxyhexyl carbamic acid; and 2, the intermediate 6-hydroxyhexyl carbamic acid synthesized in step is subjected to projecting group removing directly without separation so as to obtain target product 6-amino-1-hexanol. The synthetic method is low in cost, simple in reaction conditions, few in reaction steps, short in time, and high in purity and yield of finished product 6-amino-1-hexanol.
ENDOSOMAL CLEAVABLE LINKERS
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Paragraph 00568, (2018/08/20)
The present disclosure relates generally to cleavable linkers and uses thereof.
Toward aplyronine payloads for antibody-drug conjugates: Total synthesis of aplyronines A and D
An?i?ek, Nika,Williams, Simon,Housden, Michael P.,Paterson, Ian
supporting information, p. 1343 - 1350 (2018/03/06)
The aplyronines are a family of antimitotic marine macrolides that disrupt cytoskeletal dynamics by dual targeting of both actin and tubulin. Given their picomolar cytotoxicity profile and unprecedented mode of action, the aplyronines represent an excellent candidate as a novel payload for the development of next-generation antibody-drug conjugates (ADCs) for cancer chemotherapy. Enabled by an improved second-generation synthesis of the macrolactone core 5, we have achieved the first total synthesis of the most potent congener aplyronine D together with a highly stereocontrolled synthesis of aplyronine A. To facilitate step economy, an adventurous site-selective esterification of the C7 hydroxyl group was performed to install the N,N,O-trimethylserine pharmacophore to directly afford aplyronines A and D. Toward the assembly of ADCs incorporating an aplyronine warhead, the C29-ester derivative 4 featuring an Fmoc-amino substituted linker attached to the actin-binding tail region was also prepared by adapting this flexible endgame.
METHOD OF CONJUGATING OLIGOMERIC COMPOUNDS
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Page/Page column 39, (2018/04/21)
Provided herein are solid phase methods for the synthesis of conjugated oligomeric compounds and intermediates used in such methods. In particular, the solid phase methods provide for addition of a phosphoramidite functionalized conjugate group to a solid support bound oligomeric compound. The methods also provide an increase in overall yield and a cost benefit over existing methods.
Method for synthesis of reactive conjugate clusters
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Page/Page column 79-80, (2018/11/10)
Provided herein are improved methods for the synthesis of reactive conjugate clusters and intermediates used in such methods. In particular, improvements are provided that enhance the synthesis of reactive conjugate clusters by reducing the number of synthetic steps required. The reactive conjugate clusters prepared using the improved methods don't include any transacylation impurities that are formed using existing methods. The improved methods also provide an increase in overall yield and a cost benefit over existing methods.
METHOD FOR PREPARING 6-AMINOHEXYL LACTOSIDE-NOTA CONJUGATE
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Paragraph 0046; 0047; 0048; 0049, (2017/07/14)
The present invention provides a method for preparing a 6-aminohexyl lactoside-NOTA conjugate. The preparation method comprises brominating perbenzoylated lactose with hydrobromic acid; glycosylating 6-azidohexanol to obtain 6-azidohexyl perbenzoyl lactoside; and deprotecting this precursor in two steps to obtain 6-aminohexyl lactoside and conjugating 6-aminohexyl lactoside to NCS-benzyl-NODA GA (i.e. 2,2′-(7-(1-carboxy-4-((4-isothiocyanate benzyl) amino)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl) diacetic acid) in triethyl amine as an alkaline solvent, to obtain a 6-aminohexyl lactoside-NCS-benzyl-NODA GA conjugate. In this novel preparation method, no deglycosylated side product is produced, such that the yield is considerably increased to 46%. Therefore, the method is suitable for future massive production since the requirement for repeated preparations for massive production is reduced, and the impurities produced in the previously scaled-up preparation process are not present.
Orthoester in Cyclodehydration of Carbamate-Protected Amino Alcohols under Acidic Conditions
Park, Heemin,Kwon, Yongseok,Shin, Jae Eui,Kim, Woo-Jung,Hwang, Soonho,Lee, Seokwoo,Kim, Sanghee
supporting information, p. 2761 - 2767 (2017/06/13)
The first acid-promoted reaction system to form azaheterocycles from N -carbamate-protected amino alcohols is described. The reaction involves the activation of the hydroxyl group via the use of orthoesters. Despite the reduced nucleophilicity of carbamate nitrogen, this reaction system provides several types of pyrrolidines and piperidines in good to high yields. Using this protocol, prolinol derivatives can also be synthesized from carbamate-protected amino diols with regio- and stereoselectivity.
Metal-free one-pot α-carboxylation of primary alcohols
Van Der Heijden, Gydo,Kraakman, Jasper,Biemolt, Jasper,Ruijter, Eelco,Orru, Romano V. A.
supporting information, p. 9716 - 9719 (2016/10/31)
An efficient metal-free procedure for the formal α-carboxylation of primary alcohols has been developed. The method involves a one-pot oxidation/Passerini/hydrolysis sequence and provides access to α-hydroxy acids bearing a broad range of functional groups. A minor modification to the reaction conditions extends the range of accessible products to α-hydroxy esters.
