- Iridium- and rhodium-catalyzed dehydrogenative silylations of C(sp 3) - H bonds adjacent to a nitrogen atom using hydrosilanes
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Now that is just silylated: In the presence of iridium or rhodium catalysts, C(sp3) - H bonds adjacent to a nitrogen atom were silylated by the aid of a pyridine-directing group. In iridium catalysis, a hydrogen-trapping reagent such as norbornene or tert-butylethylene, which is usually required in late transition-metal-catalyzed dehydrogenative coupling reactions, was not required. In rhodium catalysis, however, 1 equivalent of COD (1,5-cyclooctadiene) was necessary to induce higher conversion. Copyright
- Mita, Tsuyoshi,Michigami, Kenichi,Sato, Yoshihiro
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- Synthesis, Crystal Structure and Inhibitory Activities of 2-(N-Tert-Butoxycarbonylamino)Pyridine Derivatives
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Abstract: 2-(N-tert-butoxycarbonylamino) pyridine and 2-(N-tert-butoxycarbonylamino)-3-methylpyridine were synthesized in a one-step method using either 2-aminopyridine or 2-amino-3-methyphyridine with tert-butylcarbonyl anhydride as the starting materials. The products were characterized by single-crystal X-ray diffraction, 1H NMR, 13C NMR, and HRMS. The biological activity of the two compounds against five fungi was determined. 2-(N-tert-butoxycarbonylamino) pyridine has more than 50% inhibitory activity against Pyricularia oryzae, Colletotrichum gloeosporioides, and Alternaria alternate. In addition, the inhibitory activity of 2-(N-tert-butoxycarbonylamino)-3-methylpyridine against Alternaria alternate reached 67.69%. Graphic Abstract: Two 2-BOC aminopyridine derivatives were synthesized and structurally characterized by 1H NMR, 13C NMR, HRMS analysis and X-ray crystal diffraction. The inhibitory activity both compounds was studied. [Figure not available: see fulltext.]
- Shi, Yun-Lian,Nie, Xu-Liang,Huang, Tao,Shi, Ming-Zhu,Peng, Da-Yong,Ren, Xue-Xiang,Shi, Xu-Gen,Zhao, Ming-Yu,Li, Bao-Tong
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Read Online
- Design and synthesis of novel pyrrolo[2,3-b]pyridine derivatives targeting V600EBRAF
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Several pyrrolo[2,3-b]pyridine-based B-RAF inhibitors are well known and some of them are currently FDA approved as anticancer agents. Based on the structure of these FDA approved V600EB-RAF inhibitors, two series of pyrrolo[2,3-b]pyridine scaffold were designed and synthesized in attempt to develop new potent V600EB-RAF inhibitors. The 38 synthesized compounds were biologically evaluated for their V600EB-RAF inhibitory effect at single dose (10 μM). Compounds with high percent inhibition were tested to determine their IC50 over V600EB-RAF. Compounds 34e and 35 showed the highest inhibitory effect with IC50 values of 0.085 μM and 0.080 μM, respectively. Headed for excessive biological evaluation, the synthesized derivatives were tested over sixty diverse human cancer cell lines. Only compound 35 emerged as a potent cytotoxic agent against different panel of human cancer cell lines.
- Abdel-Maksoud, Mohammed S.,Ali, Eslam M. H.,Ammar, Usama M.,Mersal, Karim I.,Oh, Chang-Hyun,Yoo, Kyung Ho
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- PHENYL AND PYRIDINYL SUBSTITUTED IMIDAZOLES AS MODULATORS OF RORyT
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The present invention comprises compounds of Formula I. wherein: R1, R2, R3, R4, R5, Ra, Rb, Q1, and Q2 are defined in the specification. The invention also comprises a method of treating or ameliorating a ROR-γ-t mediated syndrome, disorder or disease, including wherein the syndrome, disorder or disease is selected from the group consisting of rheumatoid arthritis, psoriatic arthritis, and psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula I.
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Paragraph 0516-0517
(2020/01/08)
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- Synthesis method of 5-chloro-7-azaindole
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The invention provides a synthesis method of 5-chloro-7-azaindole. The synthesis method comprises the following steps: (1) reacting a dilithium initiator and trimethylbromosilane to prepare silicon-containing organic lithium; (2) reacting 2-amino-3-methylpyridine and di-tert-butyl dicarbonate to prepare 2-N-BOC-amino-3-methylpyridine; (3) performing lithiation on the 2-N-BOC-amino-3-methylpyridine through the silicon-containing organic lithium, and performing delithiation activation, cyclization and dehydration to prepare 7-azaindole; (4) performing hydrogenation reduction reaction on the 7-azaindole to generate 2,3-dihydro-7-azaindole; (5) performing chlorination reaction on the 2,3-dihydro-7-azaindole through liquid chlorine to generate 5-chloro-2,3-dihydro-7-azaindole; and (6) performing dehydrogenation reaction on the 5-chloro-2,3-dihydro-7-azaindole to obtain 5-chloro-7-azaindole. The synthesis method provided by the invention has the advantages of mild conditions and high yield.
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Paragraph 0027; 0035; 0043; 0051; 0059; 0067
(2017/08/25)
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- Azonia Aromatic Cations by Ring-Closing Metathesis: Synthesis of Azaquinolizinium Cations
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A strategy based on a ring-closing metathesis (RCM) reaction of pyridinium azadienes in the presence of the second generation Grubbs catalyst was employed as a new approach to synthesize the 1-azaquinolizinium (pyrido[1,2-a]pyrimidin-5-ium) heterocycle and some simple derivatives. This method was also successfully applied to the first reported synthesis of the benzo-1-azaquinolizinium (pyrimido[2,1-a]isoquinolinium) cation by using the Hoveyda-Grubbs catalyst in Cl2CHCHCl2 at 130 C.
- Abeng?zar, Alberto,Abarca, Beatriz,Cuadro, Ana M.,Sucunza, David,álvarez-Builla, Julio,Vaquero, Juan J.
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p. 4214 - 4223
(2015/06/30)
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- Aminoazabenzimidazoles, a Novel Class of Orally Active Antimalarial Agents
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Whole-cell high-throughput screening of the AstraZeneca compound library against the asexual blood stage of Plasmodium falciparum (Pf) led to the identification of amino imidazoles, a robust starting point for initiating a hit-to-lead medicinal chemistry effort. Structure-activity relationship studies followed by pharmacokinetics optimization resulted in the identification of 23 as an attractive lead with good oral bioavailability. Compound 23 was found to be efficacious (ED90 of 28.6 mg·kg-1) in the humanized P. falciparum mouse model of malaria (Pf/SCID model). Representative compounds displayed a moderate to fast killing profile that is comparable to that of chloroquine. This series demonstrates no cross-resistance against a panel of Pf strains with mutations to known antimalarial drugs, thereby suggesting a novel mechanism of action for this chemical class.
- Hameed P, Shahul,Chinnapattu, Murugan,Shanbag, Gajanan,Manjrekar, Praveena,Koushik, Krishna,Raichurkar, Anandkumar,Patil, Vikas,Jatheendranath, Sandesh,Rudrapatna, Suresh S.,Barde, Shubhada P.,Rautela, Nikhil,Awasthy, Disha,Morayya, Sapna,Narayan, Chandan,Kavanagh, Stefan,Saralaya, Ramanatha,Bharath, Sowmya,Viswanath, Pavithra,Mukherjee, Kakoli,Bandodkar, Balachandra,Srivastava, Abhishek,Panduga, Vijender,Reddy, Jitender,Prabhakar,Sinha, Achyut,Jiménez-Díaz, María Belén,Martínez, María Santos,Angulo-Barturen, I?igo,Ferrer, Santiago,Sanz, Laura María,Gamo, Francisco Javier,Duffy, Sandra,Avery, Vicky M.,Magistrado, Pamela A.,Lukens, Amanda K.,Wirth, Dyann F.,Waterson, David,Balasubramanian,Iyer, Pravin S.,Narayanan, Shridhar,Hosagrahara, Vinayak,Sambandamurthy, Vasan K.,Ramachandran, Sreekanth
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supporting information
p. 5702 - 5713
(2014/08/05)
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- Discovery and characterization of NVP-QAV680, a potent and selective CRTh2 receptor antagonist suitable for clinical testing in allergic diseases
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Optimization of a 7-azaindole-3-acetic acid CRTh2 receptor antagonist chemotype derived from high throughput screening furnished a highly selective compound NVP-QAV680 with low nM functional potency for inhibition of CRTh2 driven human eosinophil and Th2 lymphocyte activation in vitro. The molecule exhibited good oral bioavailability in the rat, combined with efficacy in rodent CRTh2-dependent mechanistic and allergic disease models and was suitable for clinical development.
- Sandham, David A.,Arnold, Nicola,Aschauer, Heinrich,Bala, Kamlesh,Barker, Lucy,Brown, Lyndon,Brown, Zarin,Budd, David,Cox, Brian,Docx, Cerys,Dubois, Gerald,Duggan, Nicholas,England, Karen,Everatt, Brian,Furegati, Marcus,Hall, Edward,Kalthoff, Frank,King, Anna,Leblanc, Catherine J.,Manini, Jodie,Meingassner, Josef,Profit, Rachael,Schmidt, Alfred,Simmons, Jennifer,Sohal, Bindi,Stringer, Rowan,Thomas, Matthew,Turner, Katharine L.,Walker, Christoph,Watson, Simon J.,Westwick, John,Willis, Jennifer,Williams, Gareth,Wilson, Caroline
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supporting information
p. 6582 - 6591
(2013/10/22)
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- PYRIDAZINE AMIDE COMPOUNDS
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The present invention relates to the use of novel triazolopyridine derivatives of formula I: wherein all variable substituents are defined as described herein, which are SYK inhibitors and are useful for the treatment of auto-immune and inflammatory diseases.
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Paragraph 0252
(2013/07/19)
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- Novel Heterocyclic Compounds and Uses Thereof
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New substituted heterocyclic compounds, compositions containing them, and methods of using them for the inhibition of Raf kinase activity are provided. The new compounds and compositions may be used either alone or in combination with at least one additional agent for the treatment of a Raf kinase mediated disorder, such as cancer.
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Paragraph 0395
(2013/08/28)
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- A metal-free tandem demethylenation/C(sp2)-H cycloamination process of N -Benzyl-2-aminopyridines via C-C and C-N bond cleavage
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A mild, metal-free synthesis of pyrido[1,2-a]benzimidazoles starting with N-benzyl-2-aminopyridines, which employs PhI(OPiv)2 as a stoichiometric oxidant, has been developed. The process is initiated by an unusual PhI(OPiv)2-mediated ipso SEAr reaction, followed by solvent-assisted C-C and C-N bond cleavage.
- Liang, Dongdong,He, Yimiao,Liu, Lanying,Zhu, Qiang
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supporting information
p. 3476 - 3479
(2013/07/26)
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- NOVEL ANTIVIRAL COMPOUNDS
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The present invention relates to a compound of formula I: or a pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same, a method for treating or preventing a viral infection such as HIV using the same.
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Page/Page column 125-126
(2012/05/31)
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- TRICYCLIC COMPOUNDS, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM.
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Compounds of formula (I): wherein: A represents a 5, 6 or 7-membered (hetero)aromatic or non-aromatic ring,Z1, Z2 and Z3 each independently of the others represents a CH group or a nitrogen atom, it being understood that at least one of these three groups is a nitrogen atom,X represents an alkylene chain as defined in the description,R2 represents an aryl or heteroaryl group,the group R1 represents a group of formula (II) as defined in the description Medicinal products containing the same which are useful in treating conditions involving a defect in apoptosis.
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Page/Page column 5
(2011/05/16)
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- Improved synthesis of the selective rho-kinase inhibitor 6-chloro-n4-{3,5-difluoro-4-[(3-methyl-1h-pyrrolo[2,3-b]pyridin-4-yl)oxy]phenyl} pyrimidin-2,4-diamine
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A highly potent and selective Rho-kinase inhibitor containing a 7-azaindole moiety has been developed at Bayer Schering Pharma. Herein we disclose details of a significantly improved synthesis of the compound in 8.2% overall yield. Key aspects include cost and safety considerations and the uncommon use of a trifluoromethyl group with controllable reactivity as a masked methyl group.
- Schirok, Hartmut,Paulsen, Holger,Kroh, Walter,Chen, Gang,Gao, Ping
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scheme or table
p. 168 - 173
(2010/04/29)
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- Application of fragment-based NMR screening, X-ray crystallography, structure-based design, and focused chemical library design to identify novel μM leads for the development of nM BACE-1 (β-site APP cleaving enzyme 1) inhibitors
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Fragment-based NMR screening, X-ray crystallography, structure-based design, and focused chemical library design were used to identify novel inhibitors for BACE-1. A rapid optimization of an initial NMR hit was achieved by a combination of NMR and a funct
- Wang, Yu-Sen,Strickland, Corey,Voigt, Johannes H.,Kennedy, Matthew E.,Beyer, Brian M.,Senior, Mary M.,Smith, Elizabeth M.,Nechuta, Terry L.,Madison, Vincent S.,Czarniecki, Michael,McKittrick, Brian A.,Stamford, Andrew W.,Parker, Eric M.,Hunter, John C.,Greenlee, William J.,Wyss, Daniel F.
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experimental part
p. 942 - 950
(2010/07/16)
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- Site-selective azaindole arylation at the azine and azole rings via N-oxide activation
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Subjection of N-methyl 6-and 7-azaindole N-oxides to a Pd(OAc) 2/DavePhos catalyst system enables regioselective direct arylation of the azine ring. Following deoxygenation, 7-azaindole substrates undergo an additional regioselective azole direct arylation event in good yield.
- Huestis, Malcolm P.,Fagnou, Keith
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supporting information; scheme or table
p. 1357 - 1360
(2009/09/05)
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- Derivatives of pyrrolopyridine-2-carboxamides, preparation thereof and therapeutic application thereof
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The invention relates to compounds of formula (I): Wherein n, the pyrrolopyridine core, X, Y and W are as described herein. The invention also relates to a preparation method and to a therapeutic application.
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Page/Page column 6-7
(2009/12/23)
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- COMPOUNDS AND METHODS FOR TREATING INFLAMMATORY AND FIBROTIC DISORDERS
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Disclosed are compounds and methods for treating inflammatory and fibrotic disorders, including methods of modulating a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits low potency for inhibition of the p38 MAPK; and wherein the contacting is conducted at a SAPK-modulating concentration that is at a low percentage inhibitory concentration for inhibition of the p38 MAPK by the compound. Also disclosed are derivatives and analogs of pirfenidone, useful for modulating a stress activated protein kinase (SAPK) system.
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Page/Page column 68-69; 93
(2009/12/28)
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- NOVEL HETEROCYCLIC COMPOUNDS AND USES THEROF
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New substituted heterocyclic compounds, compositions containing them, and methods of using them for the inhibition of Raf kinase activity are provided. The new compounds and compositions may be used either alone or in combination with at least one additional agent for the treatment of a Raf kinase mediated disorder, such as cancer.
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Page/Page column 119
(2009/10/22)
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- Synthesis of 2-substituted-7-azaindoles from 2-amino-3-picolin
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An easy route to the synthesis of 2-substituted-7-azaindole derivatives has been developed. The carbinol intermediate dissolved in DMF undergoes cyclization upon treatment with sodium hydride, trifluoroacetic anhydride, and trifluoroacetic acid at 120 °C
- Parcerisa, Javier,Romero, Manel,Pujol, Maria Dolors
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p. 500 - 507
(2008/03/27)
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- N-(ARYLALKYL)-1H-PYRROLOPYRIDINE-2-CARBOXAMIDE DERIVATIVES, PREPARATION AND THERAPEUTIC USE THEREOF
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The invention concerns compounds of general formula (I), wherein n, the pyrrolopyridine ring, X, Z1, Z2, Z3, Z4, Z5 and W are as defined herein. The invention also concerns a method for preparing said compounds and their therapeutic use.
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Page/Page column 10
(2008/12/05)
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- NOVEL HETEROARYL DERIVATIVE
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A compound of the following formula (1), or its prodrug or pharmaceutically acceptable salt thereof, being useful as a diabetic medicine or preventive, or blood sugar regulator, or therapeutic agent for hyperlipemia, etc. wherein the ring Z is an optionally substituted heteroaryl, W4 is a single bond, lower alkylene, etc., Ar2 is an optionally substituted aryl, etc., W3 is a single bond, lower alkylene, etc., Ar1 is an optionally substituted arylene, etc., each of W1 and W2 is an optionally substituted lower alkylene, etc., and R1 is carboxyl, an alkoxycarbonyl.
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- UREA DERIVATIVE
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The present invention relates to a urea derivative or a pharmacologically acceptable salt thereof having an excellent DGAT inhibitory effect. A urea derivative having the formula: [wherein R 1 is a C 6 -C 10 aryl group which may be independently mono- to pentasubstituted by a group selected from Substituent Group a or others; R 2 is a C 6 -C 10 aryl group which may be independently mono- to pentasubstituted by a group selected from Substituent Group a or others; E is a group having the formula (II) or the formula (III) (wherein R 3 is a hydrogen atom or others; R 4 and R 5 , which are the same or different, are a hydrogen atom or others; X and U, which are the same or different, are a group represented by the formula CH or others; m and n, which are the same or different, are 1 or another number) or others; and A is a group represented by the formula -NH-C(=O)- or others], or a pharmacologically acceptable salt thereof.
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Page/Page column 195
(2010/11/26)
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- NOVEL HETEROARYL DERIVATIVE
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A compound of the following formula (1), or its prodrug or pharmaceutically acceptable salt thereof, being useful as a diabetic medicine or preventive, or blood sugar regulator, or therapeutic agent for hyperlipemia, etc. (1) wherein: the ring Z is an optionally substituted heteroaryl, W4 is a single bond, lower alkylene, etc., Ar2 is an optionally substituted aryl, etc., W3 is a single bond, lower alkylene, etc., Ar1 is an optionally substituted arylene, etc., each of W1 and W2 is an optionally substituted lower alkylene, etc., and R1 is carboxyl, an alkoxycarbonyl, etc.
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Page/Page column 69-70
(2008/06/13)
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- Chemical synthesis of azaindoles
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The present invention relates to a process for the preparation of azaindole derivatives of the formula STR1 wherein Q is hydrogen, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, hydroxy, aryl or arylC1-4 alkyl; one of X, Y and Z is --N= and the others are --CH=; R1 is hydrogen, C1-6 alkyl, C2-6 alkenyl or C1-6 alkyl substituted by a group selected from aryl or --NR2 R3 where R2 and R3 each independently represent C1-4 alkyl, or R2 and R3, together with the nitrogen atom to which they are attached, form a 4-7 membered saturated heterocyclic ring, optionally containing in the ring an oxygen or sulphur atom or a group NR4 where R4 is C1-4 alkyl, aryl or arylC1-4 alkyl; and R5 is a hydrogen atom or a group selected from C1-6 alkyl or aryl.
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- A convenient method for the preparation of 5-, 6- and 7-azaindoles and their derivatives
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The directed ortho lithiation of 2-tert-butoxycarbonylamino-3-methylpyridine (6a) has provided a convenient method for the preparation of 1H-pyrrolo[2,3-b]pyridine (4a, 7-azaindole). This procedure has been used to prepare a range of 3-substituted 2-tert-butoxycarbonylaminopyridines 6, 2- and 3-substituted and 2,3-disubstituted 1H-pyrrolo[2,3-b]pyridines 4 and shown to be of value in the preparation of 1H-pyrrolo[3,2-c]pyridine (15, 5-azaindole) and 1H-pyrrolo[2,3-c]pyridine (18, 6-azaindole) and derivatives.
- Hands, David,Bishop, Brian,Cameron, Mark,Edwards, John S.,Cottrell, Ian F.,Wright, Stanley H. B.
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p. 877 - 882
(2007/10/03)
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- Sulfonamide herbicides
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Herbicidal sulfonamides of the formula: STR1 and salts thereof, where: A represents a substituted or unsubstituted benzene ring, or a 5- or 6-membered substituted or unsubstituted heteroaromatic ring; Q is --O--, --S-- or a group --CXX'--; X and X', which may be the same or different, are each hydrogen, halogen, cyano, an optionally-substituted alkyl group, or a group --ORa, --SRa, or --CORb ; or one of X and X' represents hydroxy and the other is as defined above; or X and X' together represent =O or =S; Ra is an optionally-substituted alkyl, aryl or acyl group; Rb is an optionally-substituted alkyl or aryl group, or a group --ORc or --NRc Rd ; Rc and Rd, which may be the same or different, are each hydrogen, or an optionally-substituted alkyl or aryl group; Y is nitrogen or a group CR9 ; R1 is an optionally-substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, benzoheterocyclyl or amino group; R2 is hydrogen, an optionally-substituted alkyl or carboxylic acyl group, or a group --SO2 R1 ; R3 and R4, which may be the same or different, are each hydrogen, halo, an optionally substituted alkyl, alkoxy, cycloalkyl or amino group, or an optionally-substituted heterocyclyl group; and R9 represents hydrogen or an optionally-substituted alkyl group.
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- Substituted indole derivatives
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Compounds of the Formula (I), (II), or (III): STR1 wherein the variables are as defined in the specification and the pharmaceutically acceptable salts thereof, exhibit useful pharmacological properties, and are particularly useful as angiotensin II antago
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- Substituted indole antagonists derivatives which are angiotensin II
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Compound of the Formula (I), (II), or (III): STR1 wherein: R 1 is lower alkyl or 2""-(1H-tetrazol-5-yl)biphenyl-4''-ylmethyl;R 2 is lower alkyl when R 1 is 2""-(1H-tetrazol-5-yl)biphenyl-4''-ylmethyl; or R 2 is 2""-(1H-tetrazol-5-yl)biphenyl-4''-ylmethyl
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- Preparation of indoles and oxindoles from N-(tert-butoxycarbonyl)-2-alkylanilines
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Treatment of dilithiated N-(tert-butoxycarbonyl)anilines 1 with dimethylformamide or carbon dioxide furnishes intermediates 3, 5, that are easily converted to N-(tert-butoxycarbonyl)indoles 4 and oxindoles (indol-2(3H)-ones, 7), respectively. Condensation of dilithiated 1 with N-methoxy-N-methylamides provides ketones 9 which are cyclized upon trifluoroacetic acid treatment to either 2-substituted 1-(tert-butoxycarbonyl)indoles 10 or 2-substituted indoles 11 depending on the reaction time. This general methodology has been applied to efficient synthesis of 1,2-alkyl-bridged indoles 12, 1,3,4,5-tetrahydrobenz[c,d]indole (16), 2a,3,4,5-tetrahydrobenz[c,d]indol-2(1H)-one (18), and 1-(tert-butoxycarbonyl)1H-pyrrolo[2,3-b]pyridine (21).
- Clark,Muchowski,Fisher,Flippin,Repke,Souchet
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p. 871 - 878
(2007/10/02)
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