35848-90-9

Upstream product

• 4220-66-0 methyl 4,4-dimethoxybutanoate 
• 13865-19-5 4-oxobutanoic acid methyl ester 
• 149-73-5 trimethyl orthoformate 
• 13013-02-0 methyl 4-nitrobutyrate 
• 124-41-4 sodium methylate 

Downstream Products

• 365212-84-6 4,4-Dimethoxy-butyric acid (2R,3S,4aR,6S,8S,8aR)-2-allyl-6-(3-benzyloxy-propyl)-2,8a-dimethyl-8-trimethylsilanyloxy-octahydro-pyrano[3,2-b]pyran-3-yl ester 
• 884004-70-0 C₃₂H₄₄O₇ 
• 1093240-31-3 (2R,3R,4S,5S,6S)-2,6-diallyl-4-(benzyloxy)-5-(4,4-dimethoxybutanoyloxy)-tetrahydro-2H-pyran-3-yl 5,5-dimethoxypentanoate 
• 1092964-63-0 (4S,5R)-4-allyl-5-methyl-2-phenyl-1,3-dioxan-5-yl 4,4-dimethoxybutanoate 

Relevant academic research and scientific papers

Carboxylate isosteres for caspase inhibitors: The acylsulfonamide case revisited

As part of an ongoing effort to discover inhibitors of caspase-1 with an optimized selectivity and biopharmaceutical profile, acylsulfonamides were explored as carboxylate isosteres for caspase inhibitors. Acylsulfonamide analogues of the clinically investigated caspase-1 inhibitor VRT-043198 and of the pan-caspase inhibitor Z-VAD-CHO were synthesized. The isostere-containing analogues with an aldehyde warhead had inhibitory potencies comparable to the carboxylate references. In addition, the conformational and tautomeric characteristics of these molecules were determined using 1H- and 13C-based NMR. The propensity of acylsulfonamides with an aldehyde warhead to occur in a ring-closed conformation at physiological pH significantly increases the sensitivity to hydrolysis of the acylsulfonamide moiety, yielding the parent carboxylate containing inhibitors. These results indicate that the acylsulfonamide analogues of the aldehyde-based inhibitor VRT-043198 might have potential as a novel type of prodrug for the latter. Finally, inhibition of caspase 1 and 11 mediated inflammation in mouse macrophages was found to correlate with the potencies of the compounds in enzymatic assays.

Synthesis of functionalized γ-lactone via Sakurai exo -cyclization/rearrangement of 3,3-bis(silyl) enol ester with a tethered acetal

An efficient synthesis of functionalized γ-lactones has been developed involving Sakurai exo-cyclization/rearrangement of 3,3-bis(silyl) enol esters with a tethered acetal. While the steric and electronic effects of geminal bis(silane) favor the desired Sakurai pathway, the methoxy species formed in the deprotection step also facilitates both cyclization and rearrangement. The synthetic value of this approach has been demonstrated by efficiently transforming the E-vinylsilane into enyne and the γ-lactone moiety into multisubstituted THF.

Synthesis of Azabicycles via Cascade Aza-Prins Reactions: Accessing the Indolizidine and Quinolizidine Cores

The first detailed studies of intramolecular aza-Prins and aza-silyl-Prins reactions, starting from acyclic materials, are reported. The methods allow rapid and flexible access toward an array of [6,5] and [6,6] aza-bicycles, which form the core skeletons of various alkaloids. On the basis of our findings on the aza-Prins and aza-silyl-Prins cyclizations, herein we present simple protocols for the intramolecular preparation of the azabicyclic cores of the indolizidines and quinolizidines using a one-pot cascade process of N-acyliminium ion formation followed by aza-Prins cyclization and either elimination or carbocation trapping. It is possible to introduce a range of different substituents into the heterocycles through a judicial choice of Lewis acid and solvent(s), with halo-, phenyl-, and amido-substituted azabicyclic products all being accessed through these highly diastereoselective processes.

AMIDE DERIVATIVE

The present invention relates to a compound or a pharmacologically acceptable salt thereof that has an excellent antagonistic effect on a neurokinin NK1 receptor, a neurokinin NK2 receptor, and a muscarine M3 receptor and is useful as a therapeutic agent for bronchial asthma, chronic obstructive pulmonary disease, or the like. A compound represented by general formula (I): [wherein R1 represents a hydrogen atom, a C1-C6 alkyl group, or the like; R2 represents a hydrogen atom, a C1-C6 alkyl group, or the like; R3 represents a phenyl group that may be substituted with 1 to 5 group(s) independently selected from Substituent Group A, or the like; R4 represents a phenyl group that may be substituted with 1 to 5 group(s) independently selected from Substituent Group A, or the like; L1 represents a C1-C10 alkylene group or the like; L2 represents a carbonyl group, a group represneted by the formula -N(R5)-C(=O)-, a group represented by the formula -C(=O)-N(R5)-, or the like; R5 represents a hydrogen atom, a C1-C6 alkyl group, or the like; E represents a phenylene group that may be substituted with 1 to 4 group(s) independently selected from Substituent Group A, or the like; m is an integer of 1 to 4; n is an integer of 0 to 4; p is an integer of 0 to 2; q is an integer of 1 to 10; r is 1 or 2; s is 0 or 1; and Substituent Group A represents the group consisting of a halogen atom, a C1-C6 alkyl group, C1-C6 halogenated alkyl group, or the like] or a pharmacologically acceptable salt thereof.