- Design, Synthesis, and Fungicidal Activities of Novel Piperidyl Thiazole Derivatives Containing Oxime Ether or Oxime Ester Moieties
-
To explore the influence of the positions of the two nitrogen atoms on the thiazole ring and the isoxazoline ring on the activity, a series of novel piperidyl thiazole derivatives containing oxime ether and oxime ester moieties with two nitrogen atoms on the same or opposite sides have been designed, synthesized, and first evaluated for their fungicidal activities against Phytophthora capsici in vitro. The bioassay results showed that the target compounds possessed moderate to good fungicidal activities against P. capsici, among which oxime ether compound 11b shows the highest fungicidal activity in vitro (EC50 = 0.0104 μg/mL) which is higher than dimethomorph (EC50 = 0.1148 μg/mL) and diacetylenyl amide (EC50 = 0.040 μg/mL). Compared with oxime ether compounds (the two nitrogen atoms are on the opposite sides), the activities of oxime ester compounds were significantly reduced. It is different from the commercial fungicide fluoxapiprolin, and the activities of the compounds with the two nitrogen atoms on the same side were significantly reduced compared to the compounds with the two nitrogen atoms on the opposite sides. Moreover, compounds 11b, 11d, 11e, and 11g showed moderate to good antifungal activities in vivo against Phytophthora capsici, Pseudoperonospora cubensis, and Phytophthora infestans. Scanning electron microscopy of compound 11b on the hyphae morphology showed that compound 11b might cause mycelial abnormalities of P. capsici.
- Bian, Qiang,Zhao, Rui-Qi,Peng, Xing-Jie,Gao, Li-Jie,Zhou, Guo-Na,Yu, Shu-Jing,Zhao, Wei-Guang
-
p. 3848 - 3858
(2021/05/04)
-
- Piperidyl tetrahydrobenzothiazole oxime ether derivative and application thereof
-
The invention relates to a piperidyl tetrahydrobenzothiazole oxime ether derivative as shown in a general formula (I) and application of the piperidyl tetrahydrobenzothiazole oxime ether derivative asa bactericide. The compound represents a novel bactericide structure type, has excellent sterilization activity and can be used for preventing and treating diseases such as downy mildew, late blightand downy mildew generated by oomycetes pathogenic bacteria, particularly cucumber downy mildew, grape downy mildew, cabbage downy mildew, tomato late blight, potato late blight, pepper late blight, litchi downy blight and soybean phytophthora root rot. The compound is also suitable for sclerotinia sclerotiorum, ring rot, gray mold, banded sclerotial blight and the like. The compound disclosed bythe invention can be directly used, can also be used together with an agriculturally acceptable carrier, and can also be compounded with other bactericides for use.
- -
-
Paragraph 0033; 0062-0063
(2020/09/23)
-
- Design and biological evaluation of tetrahydropyridine derivatives as novel human GPR119 agonists
-
A series of novel tetrahydropyridine derivatives were prepared and evaluated using cell-based measurements. Systematic optimization of general structure G-1 led to the identification of compound 35 (EC50 = 4.9 nM) and 37 (EC50 = 8.8 nM) with high GPR119 agonism activity and moderate clog P. Through single and long-term pharmacodynamic experiments, we found that compound 35 showed a hypoglycemic effect and may have an effect on improving basal metabolic rate in DIO mice. Both in vitro and in vivo tests indicated that compound 35 was a potential potent GPR119 agonist in allusion to T2DM treatment.
- Zuo, Zeping,Chen, Miaomiao,Shao, Xiaoni,Qian, Xinying,Liu, Xiaocong,Zhou, Xia,Xiang, Jiawei,Deng, Pengchi,Li, Yan,Jie, Hui,Liu, Chunqi,Cen, Xiaobo,Xie, Yongmei,Zhao, Yinglan
-
supporting information
(2020/01/08)
-
- Synthetic method and application of piperidyl thiazole formamide compound
-
The invention relates to a 2-(4-piperidyl)-thiazole-4-formamide compound and a synthetic method and medicinal evaluation thereof. The synthetic method comprises the following steps: carrying out a substitution reaction between N-Boc-4-piperidine-carboxylic acid and ammonium chloride to prepare an intermediate 2; carrying out a thiolation reaction between the compound 2 and a Lawesson reagent to obtain an intermediate 3; carrying out a reaction between the compound 3 and ethyl bromopyruvate to obtain an intermediate 4; carrying out esterolysis on the compound 4 to obtain a compound 5; carryingout a reaction between the compound 5 and ammonia to obtain an intermediate 6; deprotecting the Boc protected compound 6 to obtain a compound 7; performing acid condensation on the compound 7 to obtain an intermediate 8; deprotecting the Boc protected intermediate 8 to obtain a compound 9; and carrying out a reaction between the compound 9 and different isocyanates to obtain a final product. An MTT method is adopted for tests, and it shows that part of the 2-(4-piperidyl)-thiazole-4-formamide compounds have certain anti-tumor activity, wherein the antitumor activity of a compound 10f-10m is superior to that of a compound 10a-10d.
- -
-
Paragraph 0012
(2020/06/09)
-
- Synthesis and biological evaluation of thiazole derivatives as GPR119 agonists
-
A series of 4-(phenoxymethyl)thiazole derivatives was synthesized and evaluated for their GPR119 agonistic effect. Several 4-(phenoxymethyl)thiazoles with pyrrolidine-2,5-dione moieties showed potent GPR119 agonistic activities. Among them, compound 27 and 32d showed good in vitro activity with an EC50 value of 49 nM and 18 nM, respectively with improved human and rat liver microsomal stability compare with MBX-2982. Compound 27 & 32d did not exhibit significant CYP inhibition, hERG binding, and cytotoxicity. Moreover, these compounds lowered the glucose excursion in mice in an oral glucose-tolerance test.
- Kim, Hyojin,Cho, Suk Joon,Yoo, Minjin,Kang, Seung Kyu,Kim, Kwang Rok,Lee, Hwan Hee,Song, Jin Sook,Rhee, Sang Dal,Jung, Won Hoon,Ahn, Jin Hee,Jung, Jae-Kyung,Jung, Kwan-Young
-
supporting information
p. 5213 - 5220
(2017/11/21)
-
- Sterilization compound and preparation method and application thereof
-
The invention relates to the field of agricultural plant protection, and particularly relates to a sterilization compound and a preparation method and an application thereof. The compound has the structure represented by a formula defined in the specification, wherein R is selected from one of components defined in the specification; the compound has excellent bacteriostatic activity on potato phytophthora infestans, phytophthora capsici, phytophthora nicotianae, peronophthora litchii, pseudoperonospora cubensis and other plant pathogenic oomycetes, and has broad application prospects in prevention and control of oomycete diseases.
- -
-
Paragraph 0022; 0056; 0057; 0058
(2016/10/27)
-
- GLYCOSIDASE INHIBITORS
-
Compounds of formula (I) wherein A, R, W, Q, n and m have the meaning according to the claims can be employed, inter alia, for the treatment of tauopathies and Alzheimer's disease.
- -
-
-
- Hofmann Rearrangement of Carboxamides Mediated by N-Bromoacetamide
-
An efficient, one-pot procedure for the Hofmann rearrangement of aromatic and aliphatic amides has been developed. Methyl and benzyl carbamates are produced with N-bromoacetamide in the presence of lithium hydroxide or lithium methoxide, in high yields. β-Phenylamino amides gave five-membered cyclic ureas stereospecifically. Side products of aryl or benzyl bromination were minimized. This procedure offers an easy access to various protected amines or diamines, which represent important synthetic precursors.
- Jevti?, Ivana I.,Do?en-Mi?ovi?, Ljiljana,Ivanovi?, Evica R.,Ivanovi?, Milovan D.
-
p. 1550 - 1560
(2016/06/01)
-
- HETEROAROMATIC DERIVATIVES AND PHARMACEUTICAL APPLICATIONS THEREOF
-
Disclosed are heteroaryl derivatives, pharmaceutical composition and uses in the manufacture of a medicine for treating respiratory diseases, especially for chronic obstructive pulmonary disease (COPD).
- -
-
-
- Aromatic heterocyclic derivatives and applications of aromatic heterocyclic derivatives in medicines
-
The present invention discloses aromatic heterocyclic derivatives and applications of the aromatic heterocyclic derivatives in medicines, and specifically provides a class of aromatic heterocyclic compounds or stereoisomers, geometric isomers, tautomers, racemic bodies, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof, and pharmaceutical compositions containing the compounds. The present invention further discloses uses of the compounds or pharmaceutical compositions in drug preparation, wherein the drug is used for treatment of respiratory diseases, particularly chronic obstructive pulmonary disease (COPD).
- -
-
-
- General Ser/Thr Kinases Pharmacophore Approach for Selective Kinase Inhibitors Search as Exemplified by Design of Potent and Selective Aurora A Inhibitors
-
A general pharmachophore model for various types of Ser/Thr kinases was developed. Search for the molecules fitting to this pharmacophore among ASINEX proprietary library revealed a number of compounds, which were tested and appeared to possess some activity against several Ser/Thr kinases such as Aurora A, Aurora B and Haspin. The possibility of performing the fine-tuning of the general Ser/Thr pharmacophore to desired types of kinase to get active and selective inhibitors was exemplified by Aurora A kinase. As a result, several hits in 3–5?nm range of activity against Aurora A kinase with rather good selectivity and ADME properties were obtained.
- Vasilevich, Natalya I.,Aksenova, Elena A.,Kazyulkin, Denis N.,Afanasyev, Ilya I.
-
-
- Trisubstituted thieno[3,2-b]pyrrole 5-carboxamides as potent inhibitors of alphaviruses
-
Chikungunya virus (CHIKV) is a re-emerging vector-borne alphavirus and is transmitted to humans by Aedes mosquitoes. Despite the re-emergence of CHIKV as an epidemic threat, there is no approved effective antiviral treatment currently available for CHIKV. Herein, we report the synthesis and structure-activity relationship studies of a class of thieno[3,2-b]pyrroles and the discovery of a trisubstituted thieno[3,2-b]pyrrole 5-carboxamide 15c that exhibits potent inhibitory activity against in vitro CHIKV infection. Compound 15c displayed low micromolar activity (EC50 value of ca. 2 μM) and limited cytotoxic liability (CC50 > 100 μM) therefore furnishing a selectivity index of greater than 32. Notably, 15c not only controlled viral RNA production, but efficiently inhibited the expression of CHIKV nsP1, nsP3, capsid, and E2 proteins at a concentration as low as 2.5 μM. More importantly, 15c also demonstrated broad spectrum antiviral activity against other clinically important alphaviruses such as O'nyong-nyong virus and Sindbis virus.
- Ching, Kuan-Chieh,Kam, Yiu-Wing,Merits, Andres,Ng, Lisa F. P.,Chai, Christina L. L.
-
p. 9196 - 9213
(2015/12/23)
-
- Synthesis of Nitriles from Aldoximes and Primary Amides Using XtalFluor-E
-
The dehydration reaction of aldoximes and amides for the synthesis of nitriles using [Et2NSF2]BF4 (XtalFluor-E) is described. Overall, the reaction proceeds rapidly (normally 1 h) at room temperature in an environmentally benign solvent (EtOAc) with only a slight excess of the dehydrating agent (1.1 equiv). A broad scope of nitriles can be prepared, including chiral nonracemic ones. In addition, in a number of cases, further purification of the nitrile after the workup was not required.
- Keita, Massaba,Vandamme, Mathilde,Paquin, Jean-Fran?ois
-
p. 3758 - 3766
(2015/11/28)
-
- SUBSTITUTED NICOTINIMIDE INHIBITORS OF BTK AND THEIR PREPARATION AND USE IN THE TREATMENT OF CANCER, INFLAMMATION AND AUTOIMMUNE DISEASE
-
Compounds of Formula I, as shown below and defined herein: and pharmaceutically acceptable salts, syntheses, intermediates, formulations, and methods of treating diseases including cancer, inflammation, and autoimmune disease mediated at least in part by Bruton's Tyrosine Kinase (BTK).
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-
Page/Page column 114
(2015/04/15)
-
- Palladium-Catalyzed α,β-Dehydrogenation of Esters and Nitriles
-
A highly practical and general palladium-catalyzed methodology for the α,β-dehydrogenation of esters and nitriles is reported. Generation of a zinc enolate or (cyanoalkyl)zinc species followed by the addition of an allyl oxidant and a palladium catalyst results in synthetically useful yields of α,β-unsaturated esters, lactones, and nitriles. Preliminary mechanistic investigations are consistent with reversible β-hydride elimination and turnover-limiting, propene-forming reductive elimination.
- Chen, Yifeng,Romaire, Justin P.,Newhouse, Timothy R.
-
supporting information
p. 5875 - 5878
(2015/05/27)
-
- Diarylthiazole: An antimycobacterial scaffold potentially targeting PrrB-PrrA two-component system
-
Diarylthiazole (DAT), a hit from diversity screening, was found to have potent antimycobacterial activity against Mycobacterium tuberculosis (Mtb). In a systematic medicinal chemistry exploration, we demonstrated chemical opportunities to optimize the potency and physicochemical properties. The effort led to more than 10 compounds with submicromolar MICs and desirable physicochemical properties. The potent antimycobacterial activity, in conjunction with low molecular weight, made the series an attractive lead (antibacterial ligand efficiency (ALE) >0.4). The series exhibited excellent bactericidal activity and was active against drug-sensitive and resistant Mtb. Mutational analysis showed that mutations in prrB impart resistance to DAT compounds but not to reference drugs tested. The sensor kinase PrrB belongs to the PrrBA two component system and is potentially the target for DAT. PrrBA is a conserved, essential regulatory mechanism in Mtb and has been shown to have a role in virulence and metabolic adaptation to stress. Hence, DATs provide an opportunity to understand a completely new target system for antimycobacterial drug discovery.
- Bellale, Eknath,Naik, Maruti,Vb, Varun,Ambady, Anisha,Narayan, Ashwini,Ravishankar, Sudha,Ramachandran, Vasanthi,Kaur, Parvinder,McLaughlin, Robert,Whiteaker, James,Morayya, Sapna,Guptha, Supreeth,Sharma, Sreevalli,Raichurkar, Anandkumar,Awasthy, Disha,Achar, Vijayshree,Vachaspati, Prakash,Bandodkar, Balachandra,Panda, Manoranjan,Chatterji, Monalisa
-
supporting information
p. 6572 - 6582
(2014/10/15)
-
- THIAZOLYLPHENYL-BENZENESULFONAMIDO DERIVATIVES AS KINASE INHIBITORS
-
Thiazolylphenyl-benzenesulfonamido derivatives of formula (I) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.
- -
-
Paragraph 0308; 0309; 0310
(2014/01/07)
-
- Conversion of aldoximes into nitriles and amides under mild conditions
-
A series of Pd(en)X2 salts were used as catalysts for the conversion of aldoximes into nitriles and amides. Highlights of this protocol include the use of inexpensive polar solvents, including water, and moderate reaction temperatures. A high degree of selectivity in the reaction outcome was observed when using aliphatic vs. aromatic/conjugated aldoximes. The Royal Society of Chemistry 2013.
- Tambara, Koujiro,Pantos, G. Dan
-
p. 2466 - 2472
(2013/06/05)
-
- THIAZOLYLPHENYL-BENZENESULFONAMIDO DERIVATIVES AS KINASE INHIBITORS
-
Thiazolylphenyl-benzenesulfonamido derivatives of formula (I) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.
- -
-
Page/Page column 40
(2012/09/11)
-
- PREPARATION OF 5-ETHYL-2-{4-[4-(4-TETRAZOL-1-YL-PHENOXYMETHYL)-THIAZOL-2-YL]-PIPERIDIN-1-YL}-PYRIMIDINE
-
Processes and intermediates for the synthesis of 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine are provided.
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-
Page/Page column 12-13
(2011/12/14)
-
- COMPOSITIONS OF 5-ETHYL-2--PYRIMIDINE
-
This invention relates to the field of pharmaceutical chemistry and, more specifically, to pharmaceutical formulations as well as to intermediates used to prepare such formulations and to methods for manufacturing such formulations.
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-
Page/Page column 11
(2012/01/13)
-
- Inhibitors of protein kinases
-
Compounds of general Formula (I): wherein R1, R2, R3, Ra, A, B and x are as defined herein are inhibitors of protein kinases in particular members of the cyclin-dependent kinase family and/or the glycogen synthase kinase 3 family and are useful in preventing and/or treating any type of pain, inflammatory disorders, cancer, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases, metabolic disorders, renal diseases, neurologic and neuropsychiatric diseases and neurodegenerative diseases.
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-
Page/Page column 20
(2011/10/04)
-
- COMPOUNDS HAVING A POTENTIATING EFFECT ON THE ACTIVITY OF ETHIONAMIDE AND USES THEREOF
-
The present invention relates to the use of compounds with a potentiating effect on the activity of antibiotics that are activatable via the EthA enzymatic pathway, for the preparation of a medicament for preventing and/or treating mycobacterial infections such as tuberculosis and leprosy, to pharmaceutical compositions comprising them in combination with an antibiotic that is activatable via the EthA pathway, to compounds having a potentiating effect on the activity of antibiotics that are activatable via the EthA enzymatic pathway, to pharmaceutical compositions comprising them and to their use as medicaments, especially medicaments for preventing and/or treating mycobacterial infections such as tuberculosis and leprosy.
- -
-
Page/Page column 35
(2011/06/24)
-
- Synthesis of 7-(4-piperidyl)- [1,6]naphthyridin-5-one and 3-(4-piperidyl)isoqunolin-1-one
-
7-(4-Piperidyl)[1,6]napththiridin-5-one was synthesized on the basis of 2-methylnicotinic acid. 3-(4-Piperidyl)isoquinolin-1-one was synthesized from the diethylamide of o-toluic acid and Weinreb′s amide of N-Boc-isonipecotic acid.
- Kovalskiy,Perevalov
-
experimental part
p. 1503 - 1507
(2010/07/04)
-
- Dihydroxypyrimidine-4-carboxamides as novel potent and selective HIV integrase inhibitors
-
Human immunodeficiency virus type-1 (HIV-1) integrase, one of the three constitutive viral enzymes required for replication, is a rational target for chemotherapeutic intervention in the treatment of AIDS that has also recently been confirmed in the clinical setting. We report here on the design and synthesis of N-benzyl-5,6-dihydroxypyrimidine-4-carboxamides as a class of agents which exhibits potent inhibition of the HIV-integrase-catalyzed strand transfer process. In the current study, structural modifications on these molecules were made in order to examine effects on HIV-integrase inhibitory potencies. One of the most interesting compounds for this series is 2-[1-(dimethylamino)-1-methylethyl]-N-(4-fluorobenzyl)-5,6-dihydroxypyrimidine- 4-carboxamide 38, with a CIC95 of 78 nM in the cell-based assay in the presence of serum proteins. The compound has favorable pharmacokinetic properties in preclinical species (rats, dogs, and monkeys) and shows no liabilities in several counterscreening assays, highlighting its potential as a clinically useful antiviral agent.
- Pace, Paola,Di Francesco, M. Emilia,Gardelli, Cristina,Harper, Steven,Muraglia, Ester,Nizi, Emanuela,Orvieto, Federica,Petrocchi, Alessia,Poma, Marco,Rowley, Michael,Scarpelli, Rita,Laufer, Ralph,Paz, Odalys Gonzalez,Monteagudo, Edith,Bonelli, Fabio,Hazuda, Daria,Stillmock, Kara A.,Summa, Vincenzo
-
p. 2225 - 2239
(2007/10/03)
-
- Design and synthesis of tri-ring P3 benzamide-containing aminonitriles as potent, selective, orally effective inhibitors of cathepsin K
-
We have prepared a series of achiral aminoacetonitriles, bearing tri-ring benzamide moieties and an aminocyclohexanecarboxylate residue at P2. This combination of binding elements resulted in sub-250 pM, reversible, selective, and orally bioavailable cathepsin K inhibitors. Lead compounds displayed single digit nanomolar inhibition in vitro (of rabbit osteoclast-mediated degradation of bovine bone). The best compound in this series, 39n (CRA-013783/L-006235), was orally bioavailable in rats, with a terminal half-life of over 3 h. 39n was dosed orally in ovariectomized rhesus monkeys once per day for 7 days. Collagen breakdown products were reduced by up to 76% dose-dependently. Plasma concentrations of 39n above the bone resorption IC50 after 24 h indicated a correlation between functional cellular and in vivo assays. Inhibition of collagen breakdown by cathepsin K inhibitors suggests this mechanism of action may be useful in osteoporosis and other indications involving bone resorption.
- Palmer, James T.,Bryant, Clifford,Wang, Dan-Xiong,Davis, Dana E.,Setti, Eduardo L.,Rydzewski, Robert M.,Venkatraman, Shankar,Tian, Zong-Qiang,Burrill, Leland C.,Mendonca, Rohan V.,Springman, Eric,McCarter, John,Chung, Tobee,Cheung, Harry,Janc, James W.,McGrath, Mary,Somoza, John R.,Enriquez, Philip,Yu, Z. Walter,Strickley, Robert M.,Liu, Liang,Venuti, Michael C.,Percival, M. David,Falgueyret, Jean-Pierre,Prasit, Peppi,Oballa, Renata,Riendeau, Denis,Young, Robert N.,Wesolowski, Gregg,Rodan, Sevgi B.,Johnson, Colena,Kimmel, Donald B.,Rodan, Gideon
-
p. 7520 - 7534
(2007/10/03)
-
- SUBSTITUTED 3- AND 4- AMINOMETHYLPIPERIDINES FOR USE AS BETA-SECRETASE IN THE TREATMENT OF ALZHEIMER’S DISEASE
-
The invention relates to novel compounds, which are substituted chiral or achiral derivatives of 3- or 4- aminomethylpiperidine of the general formula (I). The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more compounds of general formula (I) and especially their use as inhibitors of beta-secretases for the treatment of Alzheimer’s disease.
- -
-
Page/Page column 21-22
(2008/06/13)
-
- N-H Insertion reactions of rhodium carbenoids. Part 5: A convenient route to 1,3-azoles
-
Dirhodium(II) carboxylate catalysed reaction of diazocarbonyl compounds 2 in the presence of primary amides 1 results in the formation of α-acylaminoketones 3 (12 examples) by N-H insertion reaction of the intermediate rhodium carbene. The 1,4-dicarbonyl
- Davies, James R.,Kane, Peter D.,Moody, Christopher J.
-
p. 3967 - 3977
(2007/10/03)
-
- PIPERIDINYL-THIAZOLE CARBOXYLIC ACID DERIVATIVES AS ANGIOGENESIS INHIBITORS
-
This invention relates to compounds of formula (I) and (II) that are useful in treating vascular endothelial growth factor (VEGF)-mediated disorders, particularly endometriosis and acute macular degenerative disorder. The invention also relates to a topical system for the treatment of acute macular degenerative disorder comprising a VEGF inhibitor.
- -
-
-
- MEDICINAL COMPOSITIONS
-
The present invention relates to an agent for the prophylaxis or treatment of pain, an agent for suppressing activation of osteoclast, and an inhibitor of osteoclast formation, which contains a p38 MAP kinase inhibitor and/or a TNF-α production inhibitor.
- -
-
-
- Substituted 1,3-thiazole compounds, their production and use
-
(1) A 1,3-thiazole compound of which the 5-position is substituted with a 4-pyridyl group having a substituent including no aromatic group or (2) a 1,3-thiazole compound of which the 5-position is substituted with a pyridyl group having at the position adjacent to a nitrogen atom of the pyridyl group a substituent including no aromatic group has an excellent p38 MAP kinase inhibitory activity.
- -
-
-
- 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
- -
-
-
- Antithrombotic amides
-
This application relates to a compound of formula (I) (or a pharmaceutically acceptable salt thereof) as defined herein, pharmaceutical compositions thereof, and its use as an inhibitor of factor Xa, as well as a process for its preparation and intermidates thereof.
- -
-
-
- 4-Aminothiazole derivatives, their preparation and their use as inhibitors of cyclin-dependent kinases
-
This invention is directed to aminothiazole compounds of formula (I) wherein R1 is a substituted or unsubstituted group selected from : C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; C1-6-alkoxyl; C1-6-alcohol; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; carbonyl; ether; (C1-6-alkyl)-carbonyl; (C1-6-alkyl)-aryl; (C1-6-alkyl)-cycloalkyl; (C1-6-alkyl)-(C1-6-alkoxyl); aryl-(C1-6-alkoxyl); thioether; thiol; and sulfonyl; wherein when R1 is substituted, each substituent independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; amino; nitro; thiol, thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; ester; oxygen; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; or carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; and R2 is a carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, ring structure having a substituent at the position adjacent to the point of attachment, which ring structure is optionally further substituted, where each substituent of R2 independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; amino; nitro; thiol; thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; ester; oxygen; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; or carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; or a pharmaceutically acceptable salt of a compound of formula (I), or a prodrug or pharmaceutically active metabolite of a compound of formula (I) or pharmaceutically acceptable salt thereof, for inhibiting cyclin-dependent kinases (CDKs), such as CDK1, CDK2, CDK4, and CDK6. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds and to methods of treating malignancies and other disorders by administering effective amounts of such compounds.
- -
-
Example J(4)
(2010/11/29)
-
- LTA4 Hydrolase inhibitors
-
The present invention provides compounds of the formula Ar1-Q-Ar2-Y-R-Z and pharmaceutically acceptable salts thereof wherein Ar1 and Ar2 are optionally substituted aryl moieties, Z is an optionally substituted nitrogen-containing moiety which may be an acyclic, cyclic or bicyclic amine or an optionally substituted monocyclic or bicyclic nitrogen-containing heteroaromatic moiety; Q is a linking group capable of linking two aryl groups; R is an alkylene moiety; Y is a linking moiety capable of linking an aryl group to an alkylene moiety and wherein Z is bonded to R through a nitrogen atom. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of inflammatory diseases which are mediated by LTB4 production, such as proriasis, ulcerative colitis, IBD and asthma.
- -
-
-
- Novel potent antagonists of human neuropeptide Y Y5 receptors. Part 2: Substituted benzo[a]cycloheptene derivatives
-
Novel benzo[a]cycloheptene derivatives were prepared for the purpose of searching new neuropeptide Y-Y5 (NPY-Y5) receptor antagonists. The structure-activity relationships are described and compound 2o (FR226928) showed the most potent affinity for Y5 receptor of all we prepared and was found to have higher potency and better selectivity for Y5 over Y1 receptor affinities when compared with the known lead compound 1.
- Itani, Hiromichi,Ito, Harunobu,Sakata, Yoshihiko,Hatakeyama, Yoshifumi,Oohashi, Hiroko,Satoh, Yoshinari
-
p. 757 - 761
(2007/10/03)
-
- Studies on new platelet aggregation inhibitors 1. Synthesis of 7-nitro-3,4-dihydroquinoline-2(1H)-one derivatives
-
A series of 6-cyclic aliphatic amino-7-nitro-3,4-dihydroquinoline-2(1H)-ones were prepared and tested for platelet aggregation inhibitory effect, cardiotonic activity and chronotropic activity. These compounds appeared to show selective inhibitory activity against platelet aggregation. Among them, 6-(4-ethoxycarbonylpiperidino)-7-nitro-3,4-dihydroquinoline-2(1H)-one (22f) showed the most potent inhibitory activity and high selectivity. A divergent synthetic route to 6-cyclic aliphatic amino-7-nitro-3,4-dihydroquinoline-2(1H)-one derivatives has also been investigated.
- Iyobe,Uchida,Kamata,Hotel,Kusama,Harada
-
p. 822 - 829
(2007/10/03)
-
- Tetrazole analogues of GABA-mimetic agents
-
Six tetrazole analogues of GABA-mimetic compounds were synthesized. In vitro only two compounds, analogues of GABA and isoguvacine, showed a weak affinity for GABA-A and GABA-B receptors. In vivo compounds were inactive in a psychopharmacological screening in mice. The results were interpreted in terms of intercharge distance, electronic delocalisation and ability of membrane crossing.
- Schlewer,Wermuth,Chambon
-
p. 181 - 186
(2007/10/02)
-
