1450754-40-1

Usage

Uses

Used in Organic Synthesis:
1-hydroxyhept-6-yn-3-one is used as a building block in organic synthesis for creating more complex molecules. Its unique structure allows for a wide range of chemical reactions, making it a valuable intermediate in the synthesis of pharmaceuticals, agrochemicals, and other specialty chemicals.
Used in Pharmaceutical and Medicinal Applications:
1-hydroxyhept-6-yn-3-one is used as a potential pharmaceutical and medicinal agent due to its antibacterial and antifungal properties. Its ability to inhibit the growth of harmful microorganisms makes it a promising candidate for the development of new antimicrobial drugs and treatments.
Used in Fragrance and Flavor Production:
1-hydroxyhept-6-yn-3-one is used in the production of fragrances and flavors due to its unique chemical structure and aromatic properties. Its distinctive scent and taste characteristics make it a valuable ingredient in the creation of various consumer products, including perfumes, cosmetics, and food products.

Upstream product

• 100330-50-5 3-oxo-hept-6-ynoic acid methyl ester 
• 91798-92-4 2-(2-(but-3-yn-1-yl)-1,3-dioxolan-2-yl)ethan-1-ol 
• 91798-91-3 ethyl 2-<2-(3-butynyl)-1,3-dioxolan-2-yl>acetate 
• 35116-07-5 ethyl 3-oxo-6-heptyneoate 

Downstream Products

• 1450754-52-5 1-(4-(3-(2-(3-(but-3-ynyl)-3H-diazirin-3-yl)ethylcarbamoyl)phenoxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea 
• 1450754-51-4 C₂₇H₂₈N₈O₂ 
• 1450754-47-8 N-(4-(4-(2-(3-(but-3-ynyl)-3H-diazirin-3-yl)ethylamino)-6-(3-methyl-1H-pyrazol-5-ylamino)pyrimidin-2-ylthio)phenyl)cyclopropanecarboxamide 
• 1450754-44-5 2-(6-(2-(3-(but-3-ynyl)-3H-diazirin-3-yl)ethylamino)-2-methylpyrimidin-4-ylamino)-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide 
• 1450754-39-8 C₁₄H₁₅N₃O 
• 1450754-37-6 3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)propanoic acid 
• 1450752-97-2 2-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)ethan-1-amine 
• 1450754-60-5 4-(2-(4-(2-(3-(but-3-ynyl)-3H-diazirin-3-yl)ethoxy)phenyl)-5-(4-fluorophenyl)-1H-imidazol-4-yl)pyridine 
• 1450754-58-1 6-(4-(2-(3-(but-3-ynyl)-3H-diazirin-3-yl)ethoxy)phenyl)-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidine 
• 1450754-57-0 6-(2-(3-(but-3-ynyl)-3H-diazirin-3-yl)ethoxy)-N-(3-chloro-4-fluorophenyl)-7-methoxyquinazolin-4-amine 
• 1450754-41-2 2-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)ethan-1-ol 
• 1450754-55-8 2-(2-fluoro-4-iodophenylamino)-N-(2-(3-(but-3-ynyl)-3H-diazirin-3-yl)ethyl)-3,4-difluorobenzamide 
• 1450754-54-7 C₂₇H₃₄ClN₉O₂ 

Relevant academic research and scientific papers

Design and synthesis of cysteine-specific labels for photo-crosslinking studies

Chemical cross-linking mass-spectrometry (XL-MS) represents a powerful methodology to map ligand/biomacromolecule interactions, particularly where conventional methods such as X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy or cryo-electron microscopy (EM) are not feasible. In this manuscript, we describe the design and synthesis of two new photo-crosslinking reagents that can be used to specifically label free thiols through either maleimido or methanethiosulfonate groups and facilitate PXL-MS workflows. Both crosslinkers are based on light sensitive diazirines-precursors of highly reactive carbenes which offer additional advantages over alternative crosslinking groups such as benzophenones and aryl nitrenes given the controlled rapid and more indiscriminate reactivity.

Exploring the potential intracellular targets of vascular normalization based on active candidates

We previously developed two candidates with potency of inducing vascular normalization, BD7 and B14. However, the definite intracellular molecular target(s) responsible for their activity remains unknown. Herein, we report the discovery and functional assessment of several multifunctional photoaffinity probes for determining the potential biological targets of active compounds. The probes bear a photoaffinity moiety and a bioorthogonal unit attached to B7 or B14 and maintained the bioactivity of the parent active molecules. Using in vitro biological assays, we preliminarily identified VEGFR-2 as a potential intracellular target for the active candidates. Our results demonstrate the utility of these multifunctional photoaffinity probes for analyzing the biological activity and subcellular localization of the intracellular target proteins of active candidates.

Photochemical Probe Identification of a Small-Molecule Inhibitor Binding Site in Hedgehog Acyltransferase (HHAT)**

The mammalian membrane-bound O-acyltransferase (MBOAT) superfamily is involved in biological processes including growth, development and appetite sensing. MBOATs are attractive drug targets in cancer and obesity; however, information on the binding site and molecular mechanisms underlying small-molecule inhibition is elusive. This study reports rational development of a photochemical probe to interrogate a novel small-molecule inhibitor binding site in the human MBOAT Hedgehog acyltransferase (HHAT). Structure-activity relationship investigation identified single enantiomer IMP-1575, the most potent HHAT inhibitor reported to-date, and guided design of photocrosslinking probes that maintained HHAT-inhibitory potency. Photocrosslinking and proteomic sequencing of HHAT delivered identification of the first small-molecule binding site in a mammalian MBOAT. Topology and homology data suggested a potential mechanism for HHAT inhibition which was confirmed by kinetic analysis. Our results provide an optimal HHAT tool inhibitor IMP-1575 (Ki=38 nM) and a strategy for mapping small molecule interaction sites in MBOATs.

COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH NLRP ACTIVITY

In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured.The variables shown in Formula AA are as defined in the claims. The compounds of formula AA are NLRP3 activity modulators and, as such, can be used in the treatment of metabolic disorders (e.g. Type 2 diabetes, atherosclerosis, obesity or gout), a disease of the central nervous system (e.g. Alzheimer's disease, multiple sclerosis, Amyotrophic Lateral Sclerosis or Parkinson's disease), lung disease (e.g. asthma, COPD or pulmonary idiopathic fibrosis), liver disease (e.g. NASH syndrome, viral hepatitis or cirrhosis), pancreatic disease (e.g. acute pancreatitis or chronic pancreatitis), kidney disease (e.g. acute kidney injury or chronic kidney injury), intestinal disease (e.g. Crohn's disease or Ulcerative Colitis), skin disease (e.g. psoriasis), musculoskeletal disease (e.g. scleroderma), a vessel disorder (e.g. giant cell arteritis), a disorder of the bones (e.g. osteoarthritis, osteoporosis or osteopetrosis disorders), eye disease (e.g. glaucoma or macular degeneration), a disease caused by viral infection (e.g. HIV or AIDS), an autoimmune disease (e.g. Rheumatoid Arthritis, Systemic Lupus Erythematosus or Autoimmune Thyroiditis), cancer or aging.

Baicalein active probe and synthetic method and application thereof

The invention discloses a baicalein active probe, and provides a synthetic method and application of the baicalein active probe. The active probe uses baicalein as a reaction group, uses diethyleneimine as a photocrosslinking group, and uses alkynyl as a biologically orthogonal group. A structural formula is as follows: (Please see the specification for the formula). The baicalein active probe hasthe beneficial effects that (1) an anticancer mechanism based on a cell oxidative phosphorylation pathway is a novel anticancer mechanism, and is possible to achieve the effect of selectively killingcancer cells; (2) baicalein is the first discovered activator of the cell oxidative phosphorylation pathway; and (3) key proteins ATP4A(P20648), ATP5A1(P25705), ATP5F1(P24539), ATP5L(O75964), ATP6V1A(P38606), ATP6V1H(Q9UI12), ATP12A(P54707) and NDUFA13(Q9P0J0) in the cell oxidative phosphorylation pathway are targets for the development of novel anticancer drugs.

NOVEL NUCLEIC ACID MODIFIERS

The present inventions generally relate to site-specific delivery of nucleic acid modifiers and includes novel DNA-binding proteins and effectors that can be rapidly programmed to make site-specific DNA modifications. The present inventions also provide a synthetic all-in-one genome editor (SAGE) systems comprising designer DNA sequence readers and a set of small molecules that induce double-strand breaks, enhance cellular permeability, inhibit NHEJ and activate HDR, as well as methods of using and delivering such systems.

Chemical Probes Reveal Sirt2's New Function as a Robust "eraser" of Lysine Lipoylation

Lysine lipoylation, a highly conserved lysine post-translational modification, plays a critical role in regulating cell metabolism. The catalytic activity of a number of vital metabolic proteins, such as pyruvate dehydrogenase (PDH), depends on lysine lipoylation. Despite its important roles, the detailed biological regulatory mechanism of lysine lipoylation remains largely unexplored. Herein we designed a powerful affinity-based probe, KPlip, to interrogate the interactions of lipoylated peptide/proteins under native cellular environment. Large-scale chemical proteomics analysis revealed a number of binding proteins of KPlip, including sirtuin 2 (Sirt2), an NAD+-dependent protein deacylase. To explore the potential activity of Sirt2 toward lysine lipoylation, we designed a single-step fluorogenic probe, KTlip, which reports delipoylation activity in a continuous manner. The results showed that Sirt2 led to significant delipoylation of KTlip, displaying up to a 60-fold fluorescence increase in the assay. Further kinetic experiments with different peptide substrates revealed that Sirt2 can catalyze the delipoylation of peptide (DLAT-PDH, K259) with a remarkable catalytic efficiency (kcat/Km) of 3.26 × 103 s-1 M-1. The activity is about 400-fold higher than that of Sirt4, the only mammalian enzyme with known delipoylation activity. Furthermore, overexpression and silencing experiments demonstrated that Sirt2 regulates the lipoylation level and the activity of endogenous PDH, thus unequivocally confirming that PDH is a genuine physiological substrate of Sirt2. Using our chemical probes, we have successfully established the relationship between Sirt2 and lysine lipoylation in living cells for the first time. We envision that such chemical probes will serve as useful tools for delineating the roles of lysine lipoylation in biology and diseases.

Cortex pseudolaricis acetic acid photoaffinity probe halogen midbody and preparation method thereof

The invention relates to a cortex pseudolaricis acetic acid photoaffinity probe halogen midbody and a preparation method thereof. The general formula of the chemical structure of the cortex pseudolaricis acetic acid photoaffinity probe halogen midbody is as shown in specifications. By designing a new synthetic route, the compound 6 with high yield and high purity can be obtained; and the compoundcan be used to continue reacting with other materials for the preparation of a cortex pseudolaricis acetic acid photoaffinity probe.

Pseudolaric acid photoaffinity probe carbonyl intermediate and preparation method thereof

The invention relates to a pseudolaric acid photoaffinity probe carbonyl intermediate and a preparation method thereof. The chemical structural formula of the pseudolaric acid photoaffinity probe carbonyl intermediate is shown as follows. The compound 4, namely the pseudolaric acid photoaffinity probe carbonyl intermediate, can be prepared at a high yield and high purity by designing new syntheticroutes, and further, can be applied to continuing to react with other raw materials for preparing a pseudolaric acid photoaffinity probe.

Cortex pseudolaricis acetic acid photoaffinity probe and preparation method thereof

The invention relates to a cortex pseudolaricis acetic acid photoaffinity probe and a preparation method thereof. A chemical structure general formula of the cortex pseudolaricis acetic acid photoaffinity probe is as follows: the formula is shown in the description, wherein a group Ac is an acetyl group. By adopting the design, a cortex pseudolaricis acetic acid group is connected to an acylaminocompound containing an alkynyl group to form a special chemical structure; the cortex pseudolaricis acetic acid photoaffinity probe can be used for capturing and identifying corresponding binding protein and specifically binding the binding protein to determine a PAB bacteriostasis target spot.