- Latent Nucleophilic Carbenes
-
Using DFT and ab initio calculations, we demonstrate that noncyclic formamidines can undergo thermal rearrangement into their isomeric aminocarbenes under rather mild conditions. We synthesized the silylformamidine, for which the lowest activation energy in this process was predicted. Experimental studies proved it to serve as a very reactive nucleophilic carbene. The reactions with acetylenes, benzenes, and trifluoromethane proceeded via insertion into sp, sp2, and spCH bonds. The carbene also reacted with the functional groups, such as CHO, COR, and CN at double or triple bonds, displaying high mobility of the trimethylsilyl group. The obtained silylformamidine can be considered as a latent nucleophilic carbene. It can be prepared in bulk quantities, stored, and used when the need arises. Calculation results predict similar behavior for some other silylated formamidines and related compounds.
- Marchenko, Anatoliy,Koidan, Georgyi,Hurieva, Anastasiya,Shvydenko, Kostiantyn,Rozhenko, Alexander B.,Rusanov, Eduard B.,Kyrylchuk, Andrii A.,Kostyuk, Aleksandr
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p. 373 - 385
(2021/12/27)
-
- Dihydroisocoumarin derivative and preparation method and application thereof
-
The present invention discloses a dihydroisocoumarin derivative and preparation method and application thereof, the dihydroisocoumarin derivative having a structure as shown in formula (I) or (II). The method of preparing dihydroisocoumarin derivatives of
- -
-
Paragraph 0045; 0047-0048
(2022/01/10)
-
- Dihydroisocoumarin derivative and preparation method and application thereof
-
The present invention discloses a dihydroisocoumarin derivative and preparation method and application thereof, the dihydroisocoumarin derivative having a structure as shown in formula (I) or (II). The method of preparing dihydroisocoumarin derivatives of
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Paragraph 0039-0042; 0061-0065
(2022/01/10)
-
- Palladium-catalyzed ortho-C(sp2)[sbnd]H bromination of benzaldehydes via a monodentate transient directing group strategy
-
A facile and efficient monodentate transient directing group strategy was developed to enable the palladium-catalyzed ortho-C(sp2)[sbnd]H bromination of benzaldehydes. A broad scope of benzaldehydes were transformed into the desired products by employing 2-amino-5-chlorobenzotrifluoride as a monodentate transient directing group, demonstrating good functional group tolerance. Mild reaction conditions and no requirement for a silver salt are also features of this strategy.
- Yong, Qiyun,Sun, Bing,Zhang, Fang-Lin
-
supporting information
(2019/11/03)
-
- Variations on the Theme of JohnPhos Gold(I) Catalysts: Arsine and Carbene Complexes with Similar Architectures
-
Arsine and carbene gold(I) complexes with architectures closely related to those of 2-(di-tert-butylphosphino)biphenyl gold(I) complexes have been prepared and structurally characterized. As predicted, 2-(di-tert-butylarsine)biphenyl gold(I) complexes are more electrophilic catalysts in comparison to their phosphine analogues, whereas those based on 4-arylindazole behave similarly to NHC-gold(I) catalysts.
- Carreras, Javier,Pereira, Ana,Zanini, Margherita,Echavarren, Antonio M.
-
supporting information
p. 3588 - 3597
(2018/10/31)
-
- Pd-Catalyzed, ortho C-H Methylation and Fluorination of Benzaldehydes Using Orthanilic Acids as Transient Directing Groups
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The direct, Pd-catalyzed ortho C-H methylation and fluorination of benzaldehydes have been accomplished using commercially available orthanilic acids as transient directing groups. In these reactions, the 1-fluoro-2,4,6-trimethylpyridinium salts can be either a bystanding F+ oxidant or an electrophilic fluorinating reagent. An X-ray crystal structure of a benzaldehyde ortho C-H palladation intermediate was obtained using triphenylphosphine as the stabilizing ligand.
- Chen, Xiao-Yang,Sorensen, Erik J.
-
supporting information
p. 2789 - 2792
(2018/03/08)
-
- HETEROCYCLIC COMPOUNDS, PROCESS FOR PREPARATION OF THE SAME AND USE THEREOF
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The present invention provides a heterocyclic compound represented by the formula (I), its stereoisomers, or a pharmaceutically acceptable salt thereof, pharmaceutical compositions thereof, and their use in preparing a medicament for the prevention and/or treatment of central nervous system disease.
- -
-
Paragraph 0361; 0362; 0363
(2017/07/15)
-
- Process for synthesizing 2-cyanogroup 3-fluorophenylboronic acid
-
The invention relates to a process for synthesizing 2-cyanogroup 3-fluorophenylboronic acid. According to the method, 3-bromofluorobenzene is used as a raw material, and takes a reaction with LDA and dimethylformamide in a tetrahydrofuran solvent to obtain 2-fluorine 6-bromobenzaldehyde; then, the 2-fluorine 6-bromobenzaldehyde and hydroxylamine hydrochloride take a reaction at 100 DEG C to obtain 2-fluorine 6-bromoxynil; finally, triisopropyl borate is added into the intermediate; n-butyllithium is dropwise added at -70 DEG C; reduced pressure distillation is performed to obtain 2-fluorine 6-bromophenylboronic acid. The process provided by the invention has the advantages that the operation is simple and convenient; the raw material can be easily obtained; the yield is high.
- -
-
Paragraph 0025; 0029
(2017/08/29)
-
- Diverse ortho-C(sp2)-H functionalization of benzaldehydes using transient directing groups
-
Pd-catalyzed C-H functionalizations promoted by transient directing groups remain largely limited to C-H arylation only. Herein, we report a diverse set of ortho-C(sp2)-H functionalizations of benzaldehyde substrates using the transient directing group strategy. Without installing any auxiliary directing group, Pd(II)-catalyzed C-H arylation, chlorination, bromination, and Ir(III)-catalyzed amidation, could be achieved on benzaldehyde substrates. The transient directing groups formed in situ via imine linkage can override other coordinating functional groups capable of directing C-H activation or catalyst poisoning, significantly expanding the scope for metal-catalyzed C-H functionalization of benzaldehydes. The utility of this approach is demonstrated through multiple applications, including late-stage diversification of a drug analogue.
- Liu, Xi-Hai,Park, Hojoon,Hu, Jun-Hao,Hu, Yan,Zhang, Qun-Liang,Wang, Bao-Long,Sun, Bing,Yeung, Kap-Sun,Zhang, Fang-Lin,Yu, Jin-Quan
-
supporting information
p. 888 - 896
(2017/05/16)
-
- Tandem Pd-catalyzed C-C coupling/recyclization of 2-(2-bromoaryl)cyclopropane-1,1-dicarboxylates with primary nitro alkanes
-
The first successful synthesis of 1H-2,3-benzoxazine 3-oxides has been described. The efficiency of the approach is provided by the C-C-coupling of 2-(2-bromoaryl)cyclopropane-1,1-dicarboxylates with primary nitroalkanes catalyzed by Pd(dba)2/JohnPhos system followed by in situ recyclization of the intermediates. Several representative transformations allowing selective modification of the nitronate as well as malonate functionalities in the resulting compounds are demonstrated.
- Mikhaylov, Andrey A.,Dilman, Alexander D.,Novikov, Roman A.,Khoroshutina, Yulia A.,Struchkova, Marina I.,Arkhipov, Dmitry E.,Nelyubina, Yulia V.,Tabolin, Andrey A.,Ioffe, Sema L.
-
supporting information
p. 11 - 14
(2015/12/23)
-
- QUINAZOLINES AND AZAQUINAZOLINES AS DUAL INHIBITORS OF RAS/RAF/MEK/ERK AND PI3K/AKT/PTEN/MTOR PATHWAYS
-
The present application provides novel quinazolines and azaquinazolines and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful in for co-regulating RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways by administering a therapeutically effective amount of one or more of the compounds of formula (I), wherein X, Y, T and R4, and R6 to R8' are defined herein, to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways. A variety of conditions can be treated using these compounds and include diseases which are characterized by abnormal cellular proliferation. In one embodiment/ the disease is cancer.
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Page/Page column 57; 58
(2014/10/29)
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- Synthesis of 1,6-, 2,7-, 3,8-, and 4,9-isomers of didodecyl[1] benzothieno[3,2-b][1]benzothiophenes
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The synthesis of 1,6-, 2,7-, 3,8-, and 4,9-isomers of dibromo- and didodecyl[1]benzothieno[3,2-b][1]benzothiophenes, via the stilbene pathway, is described. Starting from the synthesis of bromo-2-(methylthio)benzaldehydes, a series of functionalization, McMurry coupling, and finalising cyclization reactions were explored. The stereochemistry of the cyclization mechanism was investigated. Using this methodology didodecyl[1]benzothieno[3,2-b][1] benzothiophenes were formed in overall yields of 5-32%.
- Ruzie, Christian,Karpinska, Jolanta,Kennedy, Alan R.,Geerts, Yves H.
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p. 7741 - 7748
(2013/09/02)
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- TRPV1 Antagonists
-
Disclosed herein are compounds of formula (I) or pharmaceutically acceptable salts, solvates, or combinations thereof, wherein X1, X2, X3, X4, J, K, L, X5, X6, Rb, G2, and m are defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.
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Page/Page column 35
(2012/10/08)
-
- Selective ortho -bromination of substituted benzaldoximes using Pd-catalyzed C-H activation: Application to the synthesis of substituted 2-bromobenzaldehydes
-
Substituted 2-bromobenzaldehydes were synthesized from benzaldehydes using a three-step sequence involving a selective palladium-catalyzed ortho-bromination as the key step. O-Methyloxime serves as a directing group in this reaction. A rapid deprotection of substituted 2-bromobenzaldoximes afforded substituted 2-bromobenzaldehydes with good overall yields.
- Dubost, Emmanuelle,Fossey, Christine,Cailly, Thomas,Rault, Sylvain,Fabis, Frederic
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experimental part
p. 6414 - 6420
(2011/09/16)
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- TRPV1 ANTAGONISTS
-
Disclosed herein are compounds of Formula (I), or pharmaceutically acceptable salts, solvates, prodrugs, salts of prodrugs, or combinations thereof, wherein R1, R2, R3, R4, and m are defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.
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Page/Page column 37
(2010/04/30)
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- TRPV1 ANTAGONISTS
-
Disclosed herein are compounds of formula (I), or pharmaceutically acceptable salts, solvates, prodrugs, salts of prodrugs, or combinations thereof, wherein R1, R2, R3, R4, and m are defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.
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Page/Page column 35
(2010/04/30)
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- MINERALOCORTICOID RECEPTOR ANTAGONISTS AND METHODS OF USE
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The present invention provides a compound of Formula (I): or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising a compound of Formula (I) in combination with a suitable carrier, diluent, or excipient; and methods for treating physiological disorders, particularly congestive heart failure, hypertension, diabetic nephropathy, or chronic kidney disease, comprising administering a compound of Formula (I), or a pharmaceutically acceptable salt thereof.
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Page/Page column 18
(2009/07/10)
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- TRP-M8 RECEPTOR LIGANDS AND THEIR USE IN TREATMENTS
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Tetrahydroisoquinoline compounds of formula (I), and compositions containing them, for the treatment of acute, inflammatory and neurophatic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neurophatic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintened pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.
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Page/Page column 43
(2009/07/17)
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- INDAZOLE DERIVATIVES THAT INHIBIT TRPV1 AND USES THEREOF
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Compounds of formula (I) wherein R3, R7, R9 and L are defined in the description are TRPV1 antagonists that exhibit low inhibitory activity against CYP3A4. Compositions comprising such compounds and methods for treating co
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Page/Page column 29
(2008/06/13)
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- COMPOUNDS AND METHODS FOR MODULATING FXR
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Compounds of formula. wherein variables are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating dyslipidemia and related diseases.
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Page/Page column 19-20
(2008/06/13)
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- Process for the Preparation of Indazolyl Ureas that Inhibit Vanilloid Subtype1 (VR1) Receptors
-
The present invention relates to a process of preparing indazolyl ureas that are useful as antagonists of the vanilloid receptor subtype 1 (VR1).
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Page/Page column 11
(2008/06/13)
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- 3-ARYL-5,6-DISUBSTITUTED PYRIDAZINES
-
The present invention provides compounds of Formula (I) or (II) salt form or prodrug thereof, wherein variables are defined herein, that are modulators of metalloproteases such as matrix metalloproteases (MMPs) and ADAMs. The compounds or compositions described herein can be used to treat diseases associated with metalloprotease activity including, for example, arthritis, cancer, cardiovascular disorders, skin disorders, inflammation or allergic conditions.
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Page/Page column 55-56
(2010/02/15)
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- FUSED HETEROCYCLE DERIVATIVE, MEDICINAL COMPOSITION CONTAINING THE SAME, AND MEDICINAL USE THEREOF
-
The present invention provides nitrogen-containing fused cyclic derivatives represented by the following general formula or pharmaceutically acceptable salts thereof, or prodrugs thereof, which exhibit an excellent inhibitory activity in human SGLT and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications or obesity, in the formula one of R1 and R4 represents a group represented by the following general formula (S) (in which R5 and R6 represent H, OH, a halogen atom, etc.; Q represents an alkylene group etc.; and ring A represents an aryl group etc.), and the other represents H, OH, an amino group, etc.; R2 and R3 represent H, OH, an amino group, a halogen atom, and an optionally substituted alkyl group, etc.; A1 represents O, S, etc.; A2 represents CH or N; G represents a group represented by the following general formula (G-1) or (G-2) (E1 represents H, F or OH; and E2 represents H, F, a methyl group, etc.), and pharmaceutical compositions comprising the same, and pharmaceutical uses thereof.
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Page/Page column 28
(2010/11/24)
-
- 4-Substituted (benzo[b]thiophene-2-carbonyl)guanidines as novel Na +/H+ exchanger isoform-1 (NHE-1) inhibitors
-
A series of 4-substituted (benzo[b]thiophene-2-carbonyl)guanidines was synthesized and evaluated for the NHE-1 inhibitory activity and cardioprotective efficacy both in vitro and in vivo. Several analogs exhibited a strong inhibition on NHE-1, and which was generally well correlated with their cardioprotective efficacy. Especially the 4-nitro 20 and cyano 50 compounds excellently improved the cardiac function and reduced infarct size against ischemia/reperfusion injury.
- Lee, Sunkyung,Lee, Hyunsuk,Kyu, Yang Yi,Byung, Ho Lee,Yoo, Sung-Eun,Lee, Kyunghee,Nam, Sook Cho
-
p. 2998 - 3001
(2007/10/03)
-
- 4,5-DISUBSTITUTED-2-ARYL PYRIMIDINES
-
4,5-disubstituted-2-arylpyrimidines of Formula (I) and Formula (II) are provided: wherein R1, R2, R3, R8, R9, A and Ar are defined herein. Such compounds are ligands of C5a receptors. Preferred compounds of Formula I and II bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse activity at C5a receptors. The present invention also relates to pharmaceutical compositions comprising such compounds, and to the use of such compounds in treating a variety of inflammatory, cardiovascular, and immune system disorders. In addition, the present invention provides labeled 4,5-disubstituted-2-arylpyrimidines, which are useful as probes for the localization of C5a receptors.
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Page/Page column 59
(2008/06/13)
-
- 1-ARYL-4-SUBSTITUTED ISOQUINOLINES
-
1-Aryl-4-substituted isoquinolines analogues of Formula (I) and Formula (II) are provided, as follows : wherein R1, R2, R3, R8, R9, A and Ar are defined herein. Such compounds are ligands of C5a receptors. Preferred compounds of Formula (I) and (II) bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. The present invention also relates to pharmaceutical compositions compositions comprising such compounds, and to the use of such compounds in treating a variety of inflammatory, cardiovascular, and immune system disorders. In addition, the present invention provides labeled 1-aryl-4-substituted isoquinolines, which are useful as probes for the localization of C5a receptors.
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Page/Page column 52-53
(2010/02/14)
-
- 3-SUBSTITUTED-6-ARYL PYRIDINES
-
3-substituted-6-aryl pyridines of Formula (I) are provided: Formula (I) wherein R1, R2, R3, R8, R9, A and Ar are defined herein. Such compounds are ligands of C5a receptors. Preferred compounds of Formula (I) bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. The present invention also relates to pharmaceutical compositions comprising such compounds, and to the use of such compounds in treating a variety of inflammatory, cardiovascular, and immune system disorders. In addition, the present invention provides labeled 3-substituted-6-aryl pyridines, which are useful as probes for the localization of C5a receptors.
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-
-
- Dihydroimidazo[2,1-b]thiazole and dihydro-5h-thiazolo[3,2-A]pyrimidines as antidepressant agents
-
The present invention relates to certain novel substituted dihydroimidazo[2,1-b]thiazole and dihydro-5H-thiazolo[3,2-a]pyrimidine compounds of Formula (I) including pharmaceutically acceptable salts thereof in which have affinity for 5-HT1A receptors and which inhibits neuronal reuptake of 5-hydroxytryptamine and/or noradrenaline, to processes for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, obesity, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, obsessive-compulsive behaviour, panic attacks, social phobias, eating disorders such as bulimia, anorexia, snacking and binge eating, non-insulin dependent diabetes mellitus, hyperglycaemia, hyperlipidaemia, stress, as an aid to smoking cessation and in the treatment and/or prophylaxis of seizures, neurological disorders such as epilepsy and/or in which there is neurological damage such as stroke, brain trauma, cerebral ischaemia, head injuries and haemorrhage.
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