- An improved procedure for the cyanation of aryl triflates: A convenient synthesis of 6-cyano-1,2,3,4-tetrahydroisoquinoline
-
A short synthesis of 6-cyano-1,2,3,4-tetrahydroisoquinoline is presented. The key step is an improved method of aryl triflate cyanation employing zinc(II)cyanide as the cyanide source.
- Selnick,Smith,Tebben
-
-
Read Online
- Benzimidazole compound, preparation method thereof and application of the benzimidazole compound in preparation of ferroptosis inhibitor
-
The invention discloses a benzimidazole compound, a preparation method thereof and application of the benzimidazole compound in preparation of a ferroptosis inhibitor. The benzimidazole compound has a structure as shown in a formula (I) or a formula (II)
- -
-
Paragraph 0135-0139
(2021/06/13)
-
- MONOCYCLIC B-LACTAM COMPOUND FOR TREATING BACTERIAL INFECTION
-
Disclosed are a class of new monocyclic β-lactam compounds, an isomer thereof or pharmaceutically acceptable salts thereof, and a pharmaceutical composition comprising the compounds, and the use of same in preparing drugs for treating diseases associated
- -
-
Paragraph 0110
(2020/12/16)
-
- CuII/TEMPO-Catalyzed Enantioselective C(sp3)–H Alkynylation of Tertiary Cyclic Amines through Shono-Type Oxidation
-
A novel strategy for asymmetric Shono-type oxidative cross-coupling has been developed by merging copper catalysis and electrochemistry, affording C1-alkynylated tetrahydroisoquinolines with good to excellent enantioselectivity. The use of TEMPO as a co-catalytic redox mediator is crucial not only for oxidizing a tetrahydroisoquinoline to an iminium ion species but also for decreasing the oxidation potential of the reaction. A novel bisoxazoline ligand is also reported.
- Chen, Zhi-Hao,Gao, Pei-Sen,Mei, Tian-Sheng,Sun, Bing,Wang, Zhen-Hua,Weng, Xin-Jun,You, Shu-Li,Zheng, Chao
-
supporting information
p. 15254 - 15259
(2020/06/23)
-
- Azacyclic derivative as well as preparation method and medical use thereof
-
The invention relates to an azacyclic derivative as well as a preparation method and medical use thereof and particularly relates to an azacyclic derivative represented by a general formula (I) (shownin the description), a preparation method thereof, a pharmaceutical composition containing the derivative and use of the derivative as an SMO antagonist, particularly in the treatment of diseases such as cancer related to Hedgehog signal channels. The definitions of groups in the general formula (I) are same as the definitions in the description.
- -
-
Paragraph 0398; 0399; 0400; 0401
(2019/02/04)
-
- Electrochemical Approach for Direct C-H Phosphonylation of Unprotected Secondary Amine
-
Direct α-phosphonylation of an unprotected secondary amine in a single step is of practical importance to amino phophophates. However, this protocol is limited due to the high redox barrier of unprotected amine. In this paper, we report C-H phosphonylation of an unprotected secondary amine via an electrochemical approach in the presence of catalytic carboxylate salt. This metal-free and exogenous oxidant-free method furnishes diverse target molecules with satisfactory yield under mild reaction conditions. Successful application of the protocol in a gram-scale experiment demonstrates the potential utility for further functionalization.
- Huang, Min,Dai, Jie,Cheng, Xu,Ding, Mengning
-
supporting information
p. 7759 - 7762
(2019/10/11)
-
- SUBSTITUTED TETRAHYDROISOQUINOLINE COMPOUNDS USEFUL AS GPR120 AGONISTS
-
The present invention relates to a compound represented by formula (I) and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing diabetes, hyperlipidemia, obesity, NASH, inflammation related disorders, and related di
- -
-
Page/Page column 95
(2017/12/29)
-
- Design and synthesis of novel androgen receptor antagonists via molecular modeling
-
Several androgen receptor (AR) antagonists are clinically prescribed to treat prostate cancer. Unfortunately, many patients become resistant to the existing AR antagonists. To overcome this, a novel AR antagonist candidate called DIMN was discovered by our research group in 2013. In order to develop compounds with improved potency, we designed novel DIMN derivatives based on a docking study and substituted carbons with heteroatom moieties. Encouraging in vitro results for compounds 1b, 1c, 1e, 3c, and 4c proved that the new design was successful. Among the newly synthesized compounds, 1e exhibited the strongest inhibitory effect on LNCaP cell growth (IC50= 0.35 μM) and also acted as a competitive AR antagonist with selectivity over the estrogen receptor (ER) and the glucocorticoid receptor (GR). A docking study of compound 1e fully supported these biological results. Compound 1e is considered to be a novel, potent and AR-specific antagonist for treating prostate cancer. Thus, our study successfully applied molecular modeling and bioisosteric replacement for hit optimization. The methods here provide a guide for future development of drug candidates through structure-based drug discovery and chemical modifications.
- Zhao, Chao,Choi, You Hee,Khadka, Daulat Bikram,Jin, Yifeng,Lee, Kwang-Youl,Cho, Won-Jea
-
supporting information
p. 789 - 801
(2016/05/24)
-
- CYCLOHEXEN-1-YL-PYRIDIN-2-YL-1H-PYRAZOLE-4-CARBOXYLIC ACID DERIVATIVES AND THE USE THEREOF AS SOLUBLE GUANYLATE CYCLASE ACTIVATORS
-
The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacolo
- -
-
Page/Page column 49
(2016/02/28)
-
- As opioid receptor antagonists or inverse agonists of the novel compounds
-
Novel compounds which are antagonists or inverse agonists at one or more of the opioid receptors, pharmaceutical compositions containing them, to processes for their preparation.
- -
-
Paragraph 0488; 0489
(2016/10/08)
-
- COMPOUNDS USEFUL AS IMMUNOMODULATORS
-
Disclosed are compounds of Formula (I): (I). Also disclosed are methods of using such compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of virological diseases or disorders and cancer.
- -
-
Page/Page column 44
(2015/03/28)
-
- 1-(2-hydroxy-2-methyl-3-phenoxypropanoyl)indoline-4-carbonitrile derivatives as potent and tissue selective androgen receptor modulators
-
We present a novel series of selective androgen receptor modulators (SARMs) which shows excellent biological activity and physical properties. 1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)-indoline-4-carbonitriles showed potent binding to the androgen receptor (AR) and activated AR-mediated transcription in vitro. Representative compounds demonstrated diminished activity in promoting the intramolecular interaction between the AR carboxyl (C) and amino (N) termini. This N/C-termini interaction is a biomarker assay for the undesired androgenic responses in vivo. In orchidectomized rats, daily administration of a lead compound from this series showed anabolic activity by increasing levator ani muscle weight. Importantly, minimal androgenic effects (increased tissue weights) were observed in the prostate and seminal vesicles, along with minimal repression of circulating luteinizing hormone (LH) levels and no change in the lipid and triglyceride levels. This lead compound completed a two week rat toxicology study, and was well tolerated at doses up to 100 mg/kg/day, the highest dose tested, for 14 consecutive days.
- Chekler, Eugene L. Piatnitski,Unwalla, Rayomond,Khan, Taukeer A.,Tangirala, Raghuram S.,Johnson, Mark,St. Andre, Michael,Anderson, James T.,Kenney, Thomas,Chiparri, Sue,McNally, Chris,Kilbourne, Edward,Thompson, Catherine,Nagpal, Sunil,Weber, Gregory,Schelling, Scott,Owens, Jane,Morris, Carl A.,Powell, Dennis,Verhoest, Patrick R.,Gilbert, Adam M.
-
supporting information
p. 2462 - 2471
(2014/04/17)
-
- SAR based design of nicotinamides as a novel class of androgen receptor antagonists for prostate cancer
-
Molecular knowledge of pure antagonism and systematic SAR study offered a direction for structural optimization of DIMN to provide nicotinamides as a novel series of AR antagonists. Nicotinamides with extended linear scaffold bearing sterically bulky alkoxy groups on isoquinoline end were synthesized for H12 displacement. AR binding affinity and molecular basis of antiandrogenic effect establish the optimized derivatives, 7au and 7bb, as promising candidates of second generation AR antagonists for advanced prostate cancer.
- Yang, Su Hui,Song, Chin-Hee,Van, Hue Thi My,Park, Eunsook,Khadka, Daulat Bikram,Gong, Eun-Yeung,Lee, Keesook,Cho, Won-Jea
-
supporting information
p. 3414 - 3418
(2013/06/05)
-
- NOVEL COMPOUNDS AS ANTAGONISTS OR INVERSE AGONISTS AT OPIOID RECEPTORS
-
Novel compounds which are antagonists or inverse agonists at one or more of the opioid receptors, pharmaceutical compositions containing them, to processes for their preparation.
- -
-
-
- BICYCLIC ARYL SPHINGOSINE 1-PHOSPHATE ANALOGS
-
Compounds that have agonist activity at one or more of the SlP receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at SlP receptors.
- -
-
Page/Page column 147-148
(2011/02/24)
-
- METHOD OF TREATMENT USING NOVEL ANTAGONISTS OR INVERSE AGONISTS AT OPIOID RECEPTORS
-
A method of treatment using pharmaceutical compositions containing novel antagonists or inverse agonists at opioid receptors for the treatment of binge eating disorder, anorexia nervosa, bulimia nervosa, excess drug or alcohol use, or eating disorder not otherwise specified.
- -
-
-
- INHIBITORS OF ACETYL-COA CARBOXYLASE
-
The present invention relates to compounds that act as acetyl-CoA carboxylase (ACC) inhibitors. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.
- -
-
Page/Page column 31
(2010/11/17)
-
- NOVEL COMPOUNDS AS ANTAGONISTS OR INVERSE AGONISTS FOR OPIOID RECEPTORS
-
This invention relates to novel compounds which are antagonists or inverse agonists at one or more of the opioid receptors, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy.
- -
-
Page/Page column 85
(2010/09/07)
-
- Expeditious one-pot, four-step preparation of 2-t-butoxycarbonyl-6-hydroxy- 1,2,3,4-tetrahydroisoquinoline and an improved conversion to its 6-cyano derivative
-
3-Methoxy-phenethylamine was subjected to a sequential imination/Pictet- Spengler/demethylation/Boc protection sequence that allowed a one-pot preparation of N-Boc-6-hydroxy-1,2,3,4-tetrahydroisoquinoline 1. This intermediate was elaborated almost quantit
- Gordon, David W.,Bains, Carol A.
-
experimental part
p. 1399 - 1404
(2010/07/08)
-
- Discovery of tetrahydroisoquinoline (THIQ) derivatives as potent and orally bioavailable LFA-1/ICAM-1 antagonists
-
This letter describes the discovery of a novel series of tetrahydroisoquinoline (THIQ)-derived small molecules that potently inhibit both human T-cell migration and super-antigen induced T-cell activation through disruption of the binding of integrin LFA-1 to its receptor, ICAM-1. In addition to excellent in vitro potency, 6q shows good pharmacokinetic properties and its ethyl ester (6t) demonstrates good oral bioavailability in both mouse and rat. Either intravenous administration of 6q or oral administration of its ethyl ester (6t) produced a significant reduction of neutrophil migration in a thioglycollate-induced murine peritonitis model.
- Zhong, Min,Shen, Wang,Barr, Kenneth J.,Arbitrario, Jennifer P.,Arkin, Michelle R.,Bui, Minna,Chen, Teresa,Cunningham, Brian C.,Evanchik, Marc J.,Hanan, Emily J.,Hoch, Ute,Huen, Karen,Hyde, Jennifer,Kumer, Jeffery L.,Lac, Teresa,Lawrence, Chris E.,Martell, Jose R.,Oslob, Johan D.,Paulvannan, Kumar,Prabhu, Saileta,Silverman, Jeffrey A.,Wright, Jasmin,Yu, Chul H.,Zhu, Jiang,Flanagan, W. Mike
-
scheme or table
p. 5269 - 5273
(2010/10/18)
-
- Discovery of novel thieno[2,3-d]pyrimidin-4-yl hydrazone-based inhibitors of Cyclin D1-CDK4: Synthesis, biological evaluation and structure-activity relationships. Part 2
-
The design, synthesis and evaluation of novel thieno[2,3-d]pyrimidin-4-yl hydrazone analogues as cyclin-dependent kinase 4 (CDK4) inhibitor are described. Focusing on the optimization of the heteroaryl moiety at the hydrazone with substituted phenyl group
- Horiuchi, Takao,Nagata, Motoko,Kitagawa, Mayumi,Akahane, Kouichi,Uoto, Kouichi
-
experimental part
p. 7850 - 7860
(2010/04/02)
-
- COMPOUNDS AND COMPOSITIONS AS MODULATORS OF GPR119 ACTIVITY
-
The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of GPR119.
- -
-
Page/Page column 133
(2008/12/08)
-
- Structure activity relationship studies of carboxamido-biaryl ethers as opioid receptor antagonists (OpRAs). Part 2
-
A series of 6-bicycloaryloxynicotinamides were identified as opioid receptor antagonists at mu, kappa, and delta receptors. Compounds in the 6-(2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide scaffold exhibited potent in vitro functional antagonism at all three receptors.
- Takeuchi, Kumiko,Holloway, William G.,Mitch, Charles H.,Quimby, Steven J.,McKinzie, Jamie H.,Suter, Todd M.,Statnick, Michael A.,Surface, Peggy L.,Emmerson, Paul J.,Thomas, Elizabeth M.,Siegel, Miles G.
-
p. 6841 - 6846
(2008/09/17)
-
- TETRAHYDROPYRIDO[3,4-D]PYRIMIDINES AND RELATED ANALOGUES
-
Tetrahydropyrido[3,4-d]pyrimidines and related analogues are provided, of the formula (I) in which variables are as described herein, as are methods for their preparation and use. Such compounds may generally be used to modulate ligand binding to histamin
- -
-
Page/Page column 42
(2008/06/13)
-
- PIPERAZINYL OXOALKYL TETRAHYDROISOQUINOLINES AND RELATED ANALOGUES
-
Piperazinyl oxoalkyl tetrahydroisoquinolines and related analogues of the Formula: are provided, in which variables are as described herein. Such compounds may be used to modulate ligand binding to histamine H3 receptors in vivo or in vitro, and are parti
- -
-
Page/Page column 64
(2008/06/13)
-
- COMPOUND HAVING S1P RECEPTOR BINDING POTENCY AND USE THEREOF
-
Provided are: a compound represented by formula (I): (wherein ring A and ring D each represent a cyclic group which may have a substituent(s); E and G each represent a bond or a spacer having 1 to 8 atoms in its main chain; L represents a hydrogen atom or a substituent; X represents amino which may have a substituent(s), or a heterocylcic group which contains at least one nitrogen atom and which may have a substituent(s); n represents 0 to 3, in which when n is 2 or more, a plurality of ring A's may be the same or different from one another); a salt thereof; an N-oxide form thereof; a solvate thereof; a prodrug thereof; and a medicament which includes those. The compound represented by formula (I) is capable of binding S1P receptors (in particular, EDG-1 and/or EDG-6), and useful for preventing and/or treating rejection in transplantation, autoimmune diseases, allergic diseases, etc.
- -
-
Page/Page column 64
(2010/11/26)
-
- Synthesis and structure-activity relationships of novel selective factor Xa inhibitors with a tetrahydroisoquinoline ring
-
A series of novel 2,7-disubstituted tetrahydroisoquinoline derivatives were designed and synthesized. Among these derivatives, compounds 1 and 2 exhibited potent inhibitory activity against factor Xa (FXa) and good selectivity with respect to other serine
- Ueno, Hiroshi,Yokota, Katsuyuki,Hoshi, Jun-Ichi,Yasue, Katsutaka,Hayashi, Mikio,Hase, Yasunori,Uchida, Itsuo,Aisaka, Kazuo,Katoh, Susumu,Cho, Hidetsura
-
p. 3586 - 3604
(2007/10/03)
-
- Synthesis and conformational analysis of a non-amidine factor Xa inhibitor that incorporates 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine as S4 binding element
-
Our exploratory study was based on the concept that a non-amidine factor Xa (fXa) inhibitor is suitable for an orally available anticoagulant. We synthesized and evaluated a series of N-(6-chloronaphthalen-2-yl) sulfonylpiperazine derivatives incorporating various fused-bicyclic rings containing an aliphatic amine expected to be S4 binding element. Among this series, 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine type 61 displayed orally potent anti-fXa activity and evident prolongation of prothrombin time (PT) with the moderate bioavailability in rats. The X-ray crystal analysis afforded an obvious binding mode that 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c] pyridine and 6-chloronaphthalene respectively bound to S4 and S1 subsites. In this X-ray study, we discovered a novel intramolecular S-O close contact. Ab initio energy calculations of model compounds deduced that conformers with the most close S-O proximity were most stable. The Mulliken population analysis proposed that this energy profile was caused by both of electrostatic S-O affinity and N-O repulsion. The results of these calculations and X-ray analysis suggested a possibility that the restricted conformation effected the affinity to S4 subsite of fXa.
- Haginoya, Noriyasu,Kobayashi, Syozo,Komoriya, Satoshi,Yoshino, Toshiharu,Suzuki, Makoto,Shimada, Takashi,Watanabe, Kengo,Hirokawa, Yumiko,Furugori, Taketoshi,Nagahara, Takayasu
-
p. 5167 - 5182
(2007/10/03)
-
- Amidine compounds
-
A compound of the formula [I] wherein R1, R2and R3are the same or different and each is hydrogen atom, wherein each symbol is as defined in the specification, a salt thereof or a prodrug thereof. The compound of the presen
- -
-
-
- Naphthamidine urokinase inhibitors
-
Compounds having the formula: are inhibitors of urokinase and are useful in the treatment of diseases in which urokinase plays a role. Also disclosed are urokinase-inhibiting compositions, methods for the preparation of urokinase-inhibitors, and a method of inhibiting urokinase in a mammal.
- -
-
-
- Sulfonyl derivatives
-
Sulfonyl derivatives represented by general formula (I), salts of the same, and solvates of both: and application of them as drugs: [wherein R1is hydrogen, hydroxyl, nitro or the like; R2and R3are each independently hydrogen, halogeno or the like; R4and R5are each dependently hydrogen, halogeno or the like; Q1is an optionally substituted saturated or unsaturated 5- or 6-membered cyclic hydrocarbon group or the like; Q2is a single bond, oxygen or the like; Q3is, e.g., a group represented by formula (a): T1is carbonyl or the like; and X1and X2are each independently methylidyne or nitrogen]. These compounds exhibit potent Fxa inhibiting activities and serve as excellent anticoagulants which speedily exert satisfactory and persistent anti-thrombotic effects through oral administration and little cause adverse effects.
- -
-
-
- Naphthamidine urokinase inhibitors
-
Compounds having the formula are inhibitors of urokinase and are useful in the treatment of diseases in which urokinase plays a role. Also disclosed are urokinase-inhibiting compositions, methods for the preparation of urokinase-inhibitors, and a method of inhibiting urokinase in a mammal.
- -
-
-
- NOVEL COMPOUNDS USEFUL AS NEURO-PROTECTIVE AGENTS
-
This invention relates to novel phenyl oxazoles, thiazoles, oxazolines, oxadiazoles and benzoxazoles useful as neuro-protective agents.
- -
-
-
- Compounds useful as neuro-protective agents
-
This invention relates to novel phenyl oxazoles, thiazoles, oxazolines, oxadiazoles and benzoxazoles useful as neuro-protective agents.
- -
-
-
- Dipeptides which promote release of growth hormone
-
Compounds of formula (I) are growth hormone releasing peptide mimetics which are useful for the treatment and prevention of osteoporosis. STR1
- -
-
-
- Method for treating pain
-
The present invention provides a method for treating pain using a composition comprising certain phenyl oxazoles or phenyl thiazoles in combination with a Drug Useful in the Treatment of Pain.
- -
-
-
- Method for treating neuropathic pain
-
The present invention provides a method for treating neuropathic pain comprising administering an analgesic dosage of a compound of formula I to an animal in need of such treatment certain phenyl oxazoles or phenyl thiazoles.
- -
-
-
- Use of phenyl oxazole or phenyl thiazole derivatives for treating neuropathic pain
-
The present invention provides a method for treating neuropathic pain comprising administering an analgesic dosage of a compound of formula I to an animal in need of such treatment certain phenyl oxazoles or phenyl thiazoles.
- -
-
-
- Use of phenyl oxazole or phenyl thiazole derivatives for treating pain
-
The present invention provides a method for treating pain comprising administering to an animal in need of such treatment, an analgesic dosage of certain phenyl oxazoles or phenyl thiazoles.
- -
-
-
- Method for treating pain
-
The present invention provides a method for treating pain using a composition comprising certain phenyl oxazoles or phenyl thiazoles in combination with a Drug Useful in the Treatment of Pain.
- -
-
-
- Acetic acid derivatives
-
Acetic acid derivatives of the formula STR1 wherein L, M, T and Q have the significance given in the description, can be used for the treatment or prophylaxis of illnesses which are caused by the binding of adhesive proteins to blood platelets and by blood platelet aggregation and cell-cell adhesion, and are manufactured by cleaving protecting groups in the corresponding protected compounds or by converting the cyano group into the amidino group in corresponding nitriles.
- -
-
-
- PYRROLO-PYRIDINE DERIVATIVES
-
Compounds of formula I are ligands for dopamine receptor subtypes within the body and are therefore useful in the treatment and/or prevention of disorders of the dopamine system, in particular schizophrenia. STR1 wherein Q is STR2
- -
-
-
- Spirocycles
-
Compounds of the general formula: STR1 or a pharmaceutically acceptable salt, hydrate or crystal form enantiomer, diastereomer or mixtures thereof are Class III antiarrhythmic agents.
- -
-
-