68887-65-0

Upstream product

• 72338-58-0 1H-imidazole-1-butanoic acid 
• 14660-52-7 ethyl 5-bromovalerate 
• 72338-50-2 ethyl 5-(1H-imidazol-1-yl)pentanoate 
• 5454-83-1 5-bromovaleric acid methyl ester 
• 1619971-70-8 (5-imidazole-1-yl)pentanoic acid methyl ester 

Relevant academic research and scientific papers

Preparation of tetrazine-containing [2 + 1] complexes of 99mTc and: In vivo targeting using bioorthogonal inverse electron demand Diels-Alder chemistry

The aim of this work was to synthesize and evaluate [2 + 1] 99mTc(i) polypyridine complexes containing tetrazines, which along with the corresponding Re(i) complexes, represent a new class of isostructural nuclear and turn-on luminescent probes that can be derivatized and targeted using bioorthogonal chemistry. To this end, [2 + 1] complexes of 99mTc(i) of the type [99mTc(CO)3(N^N)(L)] (N^N = bathophenanthroline disulfonate (BPS) or 2,2′-bipyridine (bipy)), where the monodentate ligand (L) was a tetrazine linked to the metal through an imidazole derivative, were prepared. The desired products were obtained in nearly quantitative radiochemical yield by adding [99mTc(CO)3(N^N)(OH2)]n to the imidazole-tetrazine ligand and heating at 60 °C for 30 min. Measurement of the reaction kinetics between the tetrazine and (E)-cyclooct-4-enol revealed a second-order rate constant of 8.6 × 103 M-1 s-1 at 37 °C, which is suitable for in vivo applications that require rapid coupling. Stability studies showed that the metal complexes were resistant to ligand challenge and exhibited reasonable protein binding in vitro. Biodistribution studies of the more water-soluble BPS derivative in normal mice, one hour after administration of a bisphosphonate derivative of trans-cyclooctene (TCO-BP), revealed high activity concentrations in the knee (9.3 ± 0.3 %ID g-1) and shoulder (5.3 ± 0.7 %ID g-1). Using the same pretargeting approach, SPECT/CT imaging showed that the [2 + 1] tetrazine complex localized to implanted skeletal tumors. This is the first report of the preparation of 99mTc complexes of BPS and demonstration that their tetrazine derivatives can be used to prepare targeted imaging probes by employing bioorthogonal chemistry.

Dual-Functional Small Molecules for Generating an Efficient Cytochrome P450BM3 Peroxygenase

We report a unique strategy for the development of a H2O2-dependent cytochrome P450BM3 system, which catalyzes the monooxygenation of non-native substrates with the assistance of dual-functional small molecules (DFSMs), such as N-(ω-imidazolyl fatty acyl)-l-amino acids. The acyl amino acid group of DFSM is responsible for bounding to enzyme as an anchoring group, while the imidazolyl group plays the role of general acid–base catalyst in the activation of H2O2. This system affords the best peroxygenase activity for the epoxidation of styrene, sulfoxidation of thioanisole, and hydroxylation of ethylbenzene among those P450–H2O2 system previously reported. This work provides the first example of the activation of the normally H2O2-inert P450s through the introduction of an exogenous small molecule. This approach improves the potential use of P450s in organic synthesis as it avoids the expensive consumption of the reduced nicotinamide cofactor NAD(P)H and its dependent electron transport system. This introduces a promising approach for exploiting enzyme activity and function based on direct chemical intervention in the catalytic process.

Imidazole heterocyclic diphosphonic acid compound as well as preparation method and application thereof

The invention belongs to the field of pharmaceutical chemistry, and in particular relates to an imidazole heterocyclic diphosphonic acid compound as well as a preparation method and application thereof. The imidazole heterocyclic diphosphonic acid compound has a larger non-toxic concentration range for an osteoclast precursor, and can significantly inhibit the formation of osteoclasts at the same time; the imidazole heterocyclic diphosphonic acid compound can damage actin ring to the utmost extent, thus having an obvious inhibiting effect on the osteoclasts and further being used as an osteoclast inhibitor; the imidazole heterocyclic diphosphonic acid compound solves the problems that diphosphonate in the prior art is low in inhibiting effect on the osteoclasts, high in toxicity and large in side effects.

Novel Autotaxin Inhibitors for the Treatment of Osteoarthritis Pain: Lead Optimization via Structure-Based Drug Design

In an effort to develop a novel therapeutic agent aimed at addressing the unmet need of patients with osteoarthritis pain, we set out to develop an inhibitor for autotaxin with excellent potency and physical properties to allow for the clinical investigation of autotaxin-induced nociceptive and neuropathic pain. An initial hit identification campaign led to an aminopyrimidine series with an autotaxin IC50 of 500 nM. X-ray crystallography enabled the optimization to a lead compound that demonstrated favorable potency (IC50 = 2 nM), PK properties, and a robust PK/PD relationship.

Bicyclic Pyrimidine Compounds

The present invention provides compounds of the Formula I: wherein X is a bond or CH2; R is selected from the group consisting of R1 and R2 are each independently selected from the group consisting of CH and N; R3 is H or CH3; R4 is H or CH3; L is selected from the group consisting of —O(CH2)3—, —C(O)NH(CH2)2—, —CH2C(O)NH(CH2)2—, —(CH2)3N(C(O)CH3)CH2—, —(CH2)2N(C(O)CH3)CH2—, —(CH2)3NH—, (CH2)2OCH2—, —(CH2)4—, —(CH2)2NHCH2—, —(CH2)3O—, and —CH2O(CH2)2—; or a pharmaceutically acceptable salt thereof. Compounds of this invention are autotaxin inhibitors.

Development of imidazole alkanoic acids as mGAT3 selective GABA uptake inhibitors

A new series of potential GABA uptake inhibitors starting from of 1H-imidazol-4-ylacetic acid with the carboxylic acid side chain originating from different positions and varying in length have been synthesized and tested for the inhibitory potency at the

Pharmaceutical composition containing quinoline or quinazoline derivatives

The present invention provides a pharmaceutical composition for inhibiting bone resorption or for preventing or treating osteoporosis which comprises a quinoline or quinazoine derivative as an active ingredient.

Quinoline or quinazoline derivatives, their production and use

A compound represented by the general formula: STR1 wherein Y represents a nitrogen atom or C--G (G represents a carboxyl group which may be esterified); ring R is a nitrogen-containing unsaturated heterocyclic group which may be substituted or unsubstituted; each of rings A and B may have a substituent; n represents an integer from 1 to 4; k represents the integer 0 or 1, or a salt thereof, which serves well as an anti-inflammatory agent, particularly a therapeutic agent for arthritis.