849928-22-9

Usage

Uses

Used in Medicinal Chemistry:
4-OXO-2-SPIRO(N-BOC-PIPERIDINE-4-YL)-BENZOPYRAN is used as a key intermediate in the synthesis of pharmaceutical compounds due to its unique structural features and potential biological activities. Its BOC-protected piperidine ring allows for selective reactions and subsequent deprotection to yield diverse bioactive molecules.
Used in Drug Development:
In the pharmaceutical industry, 4-OXO-2-SPIRO(N-BOC-PIPERIDINE-4-YL)-BENZOPYRAN serves as a precursor for the development of new drugs. Its spirocyclic structure and BOC protection facilitate the creation of novel molecular entities with potential therapeutic applications.
Used in Chemical Synthesis:
4-OXO-2-SPIRO(N-BOC-PIPERIDINE-4-YL)-BENZOPYRAN is utilized as a building block in the synthesis of complex organic molecules. Its unique structural elements and reactivity make it a valuable component in the construction of advanced chemical entities for various applications, including materials science and specialty chemicals.

Upstream product

• 118-93-4 o-hydroxyacetophenone 
• 490-78-8 2,5-Dihydroxyacetophenone 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 582-24-1 1-phenyl-2-hydroxyethanone 
• 119-61-9 benzophenone 

Downstream Products

• 136081-84-0 spiro[chroman-2,4'-piperidin]-4-one 
• 1024604-94-1 tert-butyl 4-hydroxy-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxylate 
• 911228-63-2 tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[chromene-2,4'-piperidine]-1'-carboxylate 
• 1160247-75-5 1'-(tert-butoxycarbonyl)spiro[chromene-2,4'-piperidine]-4-carboxylic acid 
• 1394028-93-3 (3,4-dimethoxyphenyl)-(4-phenylspiro[chromane-2,4'-piperidine]-1'-yl)methanone 
• 1394031-01-6 (3,4-dimethoxyphenyl)-(4-phenylspiro[chromene-2,4'-piperidine]-1'-yl)methanone 
• 1394031-00-5 4-phenylspiro[chromene-2,4'-piperidine] hydrochloride 
• 1013335-23-3 tert-butyl 4-phenylspiro[chromene-2,4'-piperidine]-1'-carboxylate 
• 1207163-67-4 tert-butyl 1'H-spiro[chromene-2,4'-piperidine]-1'-carboxylate 

Relevant academic research and scientific papers

Spirocyclic sulfonamides with carbonic anhydrase inhibitory and anti-neuropathic pain activity

A novel series of 4-oxo-spirochromane bearing primary sulfonamide group were synthetized as Carbonic Anhydrase inhibitors (CAIs) and tested for their management of neuropathic pain. Indeed, CAs have been recently validated as novel therapeutic targets in neuropathic pain. All compounds, here reported, showed strong activity against hCA II and hCA VII with KI values in the low or sub-nanomolar range. Two compounds (6d and 6l) showed good neuropathic pain attenuating effects and longer duration than drug reference acetazolamide in an animal model of oxaliplatin induced neuropathy.

DNA-Encoded Library Technology-Based Discovery, Lead Optimization, and Prodrug Strategy toward Structurally Unique Indoleamine 2,3-Dioxygenase-1 (IDO1) Inhibitors

We report the discovery of a novel indoleamine 2,3-dioxygenase-1 (IDO1) inhibitor class through the affinity selection of a previously unreported indole-based DNA-encoded library (DEL). The DEL exemplar, spiro-chromane 1, had moderate IDO1 potency but high in vivo clearance. Series optimization quickly afforded a potent, low in vivo clearance lead 11. Although amorphous 11 was highly bio-available, crystalline 11 was poorly soluble and suffered disappointingly low bio-availability because of solubility-limited absorption. A prodrug approach was deployed and proved effective in discovering the highly bio-available phosphonooxymethyl 31, which rapidly converted to 11 in vivo. Obtaining crystalline 31 proved problematic, however; thus salt screening was performed in an attempt to circumvent this obstacle and successfully delivered greatly soluble and bio-available crystalline tris-salt 32. IDO1 inhibitor 32 is characterized by a low calculated human dose, best-in-class potential, and an unusual inhibition mode by binding the IDO1 heme-free (apo) form.

Spirocyclic compound containing pyrimidine and application thereof

The invention discloses a pyrimidine-containing spiro compound, structure as shown in a general formula I : The compound of the invention has a broad-spectrum bactericidal activity . and has an excellent control effect, on cucumber downy mildew, wheat powdery mildew, corn rust, rice blast, cucumber anthracnose and the like.

Design, Synthesis, and Structure-Activity Relationship of Novel Spiropyrimidinamines as Fungicides against Pseudoperonospora cubensis

Harmful fungus and the developed resistance to available fungicides seriously threaten the yield and quality of crops; thus, the search for new, highly efficient, and resistance-overcoming fungicides remains a quite urgent goal of agricultural scientists. In this study, a series of novel spiropyrimidinamine derivatives were designed and synthesized by employing the intermediate derivatization method (IDM). Their structures were identified by 1H NMR, elemental analyses, and MS spectra. The structure of compound 5 was further confirmed by X-ray diffraction. Bioassays indicated that a number of the title compounds exhibited some fungicidal activities against Pseudoperonospora cubensis. Especially, compound 5 displayed excellent activity (EC50 = 0.422 mg/L), significantly higher than those of the commercialized fungicides cyazofamid, flumorph, and diflumetorim. The structure-activity relationship was also discussed. It was concluded that compound 5 with super fungicidal potency and a novel structure is a promising agrochemical fungicide candidate for further development.

From PARP1 to TNKS2 inhibition: A structure-based approach

Tankyrases (TNKSs) have recently gained great consideration as potential targets in Wnt/β-catenin pathway-dependent solid tumors. Previously, we reported the 2-mercaptoquinazolin-4-one MC2050 as a micromolar PARP1 inhibitor. Here we show how the resolution of the X-ray structure of PARP1 in complex with MC2050, combined with the computational investigation of the structural differences between TNKSs and PARP1/2 active sites, provided the rationale for a structure-based drug design campaign that with a limited synthetic effort led to the discovery of the bis-quinazolinone 5 as a picomolar and selective TNKS2 inhibitor, endowed with antiproliferative effects in a colorectal cancer cell line (DLD-1) where the Wnt pathway is constitutively activated.

Whole cell screen based identification of spiropiperidines with potent antitubercular properties

Abstract Whole cell based screens to identify hits against Mycobacterium tuberculosis (Mtb), carried out under replicating and non-replicating (NRP) conditions, resulted in the identification of multiple, novel but structurally related spiropiperidines with potent antitubercular properties. These compounds could be further classified into three classes namely 3-(3-aryl-1,2,4-oxadiazol-5-yl)-1′-alkylspiro[indene-1,4′-piperidine] (abbr. spiroindenes), 4-(3-aryl-1,2,4-oxadiazol-5-yl)-1′-alkylspiro[chromene-2,4′-piperidine] (abbr. spirochromenes) and 1′-benzylspiro[indole-1,4′-piperidin]-2(1H)-one (abbr. spiroindolones). Spiroindenes showed ≥4 log10 kill (at 2-12 μM) on replicating Mtb, but were moderately active under non replicating conditions. Whole genome sequencing efforts of spiroindene resistant mutants resulted in the identification of I292L mutation in MmpL3 (Mycobacterial membrane protein Large), required for the assembly of mycolic acid into the cell wall core of Mtb. MIC modulation studies demonstrated that the mutants were cross-resistant to spirochromenes but not to spiroindolones. This Letter describes lead identification efforts to improve potency while reducing the lipophilicity and hERG liabilities of spiroindenes. Additionally, as deduced from the SAR studies, we provide insights regarding the new chemical opportunities that the spiroindolones can offer to the TB drug discovery initiatives.

Synthesis, biological evaluation and molecular docking studies of piperidinylpiperidines and spirochromanones possessing quinoline moieties as Acetyl-CoA carboxylase inhibitors

Acetyl-coenzyme A carboxylases (ACCs) play critical roles in the regulation of fatty acid metabolism and have been targeted for the development of drugs against obesity, diabetes and other metabolic diseases. Two series of compounds possessing quinoline moieties were designed, synthesized and evaluated for their potential to inhibit acetyl-CoA carboxylases. Most compounds showed moderate to good ACC inhibitory activities and compound 7a possessed the most potent biological activities against ACC1 and ACC2, with IC50 values of 189 nM and 172 nM, respectively, comparable to the positive control. Docking simulation was performed to position compound 7a into the active site of ACC to determine a probable binding model.

Synthesis and pharmacological evaluation of novel N-aryl-3,4-dihydro- 1′H-spiro[chromene-2,4′-piperidine]-1′-carboxamides as TRPM8 antagonists

A novel series of N-aryl-3,4-dihydro-1′H-spiro[chromene-2,4′- piperidine]-1′-carboxamides was identified as transient receptor potential melastatin 8 (TRPM8) channel blockers through analogue-based rational design, synthesis and screening. Details of the synthesis, effect of aryl groups and their substituents on in-vitro potency were studied. The effects of selected functional groups on the 4-position of the chromene ring were also studied, which showed interesting results. The 4-hydroxy derivatives showed excellent potency and selectivity. Optical resolution and screening of alcohols revealed that (R)-(-)-isomers were in general more potent than the corresponding (S)-(+)-isomers. The isomer (R)-(-)-10e (IC50: 8.9 nM) showed a good pharmacokinetic profile upon oral dosing at 10 mg/kg in Sprague-Dawley (SD) rats. The compound (R)-(-)-10e also showed excellent efficacy in relevant rodent models of neuropathic pain.

CHROMAN - SPIROCYCLIC PIPERIDINE AMIDES AS MODULATORS OF ION CHANNELS

The invention relates to chroman spirocyclic piperidine amide derivatives useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

NOVEL SPIRO COMPOUNDS USEFUL AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE

Heteroaromatic compounds of structural formula (I) are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and