- Synthesis of New 1,3-Thiazolecarbaldehydes
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H-Lithiation and Br-lithiation reactions of 1,3-thiazole were studied in order to obtain new thiazole derivatives. Four isomeric chloromethyl derivatives of 1,3-thiazole containing a protected aldehyde group like 2-(1,3-dioxolan-2-yl)-5-(chloromethyl)-1,3-thiazole, 5-(1,3-dioxolan-2-yl)-2-(chloromethyl)-1,3-thiazole, 4-(1,3-dioxolan-2-yl)-2-(chloromethyl)-1,3-thiazole, and 2-(1,3-dioxolan-2-yl)-4-(chloromethyl)-1,3-thiazole were synthesized. Their nucleophilic substitution reactions with dimethylamine and sodium methylthiolate were studied. New aldehydes of 1,3-thiazole series of low-molecular weight were obtained.
- Sinenko,Slivchuk,Mityukhin,Brovarets
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Read Online
- Asymmetric synthesis of (1R,2S,3R)-2-acetyl-4-(1,2,3,4- tetrahydroxybutyl)thiazole
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Two different methods for preparing the thiazole analogue 3 of the biologically active compound (1R,2S,3R)-2-acetyl-4(5)-(1,2,3,4- tetrahydroxybutyl)imidazole 1 are reported.
- Ung, Alison T.,Pyne, Stephen G.
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- Reductive Alkylation of 2-Bromoazoles via Photoinduced Electron Transfer: A Versatile Strategy to Csp2-Csp3 Coupled Products
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Access to Csp2-Csp3-coupled products is a challenging goal at the forefront of catalysis. The photocatalytic reductive coupling of aryl bromides with unactivated alkenes is introduced as a convenient method that circumvents any need for synthesis of sp3-hybridized coupling partners. The reaction takes place via photoinduced electron transfer from a tertiary amine to an aryl bromide that fragments to provide an aryl radical and subsequently reacts with an alkene to form a C-C bond. Conveniently, the amine also serves as the final reductant. The method is operationally simple, functional group tolerant, and takes place with selectivities that will allow it to be used in the context of complex molecule synthesis.
- Arora, Amandeep,Teegardin, Kip A.,Weaver, Jimmie D.
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- The Development and Scale-Up of an Antibody Drug Conjugate Tubulysin Payload
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Significant development and scale-up work was completed on the synthesis of an antibody drug conjugate payload based on the tubulysin natural products. This work included the development of new routes to the tubuvaline and tubuphenylaniline portions of the molecules, as well as extensive optimization of the solid phase peptide synthesis used to assemble the molecule. The initial route (21 steps longest linear sequence, 0.01% overall yield) was improved to a new, more robust route (19 steps longest linear sequence, 2.4% overall yield) affording a 240-fold increase in overall yield and allowing delivery of over 86 g of the required molecule.
- Parker, Jeremy S.,McCormick, Marc,Anderson, David W.,Maltman, Beatrice A.,Gingipalli, Lakshmaiah,Toader, Dorin
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- Design, Synthesis, and Cytotoxic Activity of New Tubulysin Analogues
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Synthesis of tubulysin analogues, containing an N-methyl substituent on tubuvaline-amide together with the replacement of either the hydrophobic N-terminal N-methyl pipecolic acid (Mep) or at both N- and C- terminal peptides with available heteroaromatic
- Le, Hai Van,Tran, Loc Van,Tran, Anh Tuan,Tran, Thao Thi Phuong,Tran, Sung Van,Tran, Chien Van
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p. 187 - 195
(2021/12/03)
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- 1-(4-(4-(5-PHENYL-4,5-DIHYDROISOXAZOL-3-YL)THIAZOL-2-YL)PIPERIDIN-1-YL)-ETHAN-1-ONE DERIVATIVES AND RELATED COMPOUNDS AS FUNGICIDES FOR CROP PROTECTION
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The present invention relates to 1-(4-(4-(5-phenyl-4,5- dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-l-yl)-ethan-l-one derivatives and related compounds as fungicides for crop protection. The present description discloses the synthesis and characterisation of exemplary compounds as well as biological data thereof (e.g. pages 47 to 69; examples 1 to 4; compounds 1 to 81; table 1). An exemplary compound is e.g. 1-(4-(4-(5-(2,6-dichlorophenyl) -4,5-dihydroisoxazol-3-yl)thiazol-2-yl) piperidin-1-yl)-2-((3- methoxypyridin-2-yl)oxy)ethan-1-on ( example 1 ).
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Page/Page column 47; 48
(2021/05/21)
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- 1 -(4-(4-(5-PHENYL-4,5-DIHYDROISOXAZOL-3-YL)THIAZOL-2-YL)PIPERIDIN-1 -YL)-ETHAN-1 -ONE DERIVATIVES AND RELATED COMPOUNDS AS FUNGICIDES FOR CROP PROTECTION
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The present invention relates to 1-(4-(4-(5-phenyl-4,5- dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-1-yl)-ethan-1-one derivatives and related compounds for use as fungicides for crop protection, as well as to a process for preparing the same. The present description discloses the synthesis and characterisation of exemplary compounds as well as biological data thereof (e.g. pages 55 to 94; examples 1 to 4; compounds 1 to 194; table 1).
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Page/Page column 55
(2021/05/21)
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- NOVEL SULFILIMINES OR SULFOXIMINES CONTAINING FUNGICIDAL HETEROCYCLIC COMPOUNDS
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The present invention relates to a compound formula (I) and a process for preparing the same, wherein, R2, A, E, Hy, Ra, n, Q and W1 are each as defined in the description. The invention also relates to the combination and composition comprising the compound of formula (I).
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Page/Page column 65-66
(2021/05/21)
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- Synthesis process of thiazole medical intermediate
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The invention discloses a synthesis process of thiazole medical intermediate.The synthesis process comprises the following steps: step 1, mixing ethyl pyruvate and dichloromethane of which the volume is 2 times that of the ethyl pyruvate at room temperature, adding an obtained mixture into a reactor, starting stirring, and keeping the temperature of a system at about 20 DEG C; step 2, starting to dropwise add a dichloromethane solution of bromine, controlling the temperature to enable the system to be about 20-30 DEG C, sealing the reactor, and introducing a strong alkali solution to absorb acid gas HBr; and step 3, after dropwise adding is completed, closing a cold well, performing stirring at normal temperature for about 2 hours until the color of the reaction liquid gradually becomes light yellow to light brown, monitoring that no raw material exists through TLC, and concentrating the obtained reaction liquid. According to the synthesis process of the thiazole medical intermediate, by introducing the defoaming agent n-hexane, generated gas foam can be quickly dissolved out and released from the solvent, and the phenomenon of one-time flushing is avoided; and by introducing the n-hexane solvent, solids can be effectively separated out at low temperature, the impurity content can be controlled to be about 1%, the purification difficulty is greatly reduced, and crystallization is facilitated.
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Paragraph 0013-0014; 0016
(2021/06/09)
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- SUBSTITUTED BICYCLIC HETEROARYL COMPOUNDS
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Disclosed are compounds of Formula (I) N-oxides, or salts thereof, wherein X, Y, A, G, R1, and R5 are defined herein. Also disclosed are methods of using such compounds as inhibitors of signaling through Toll-like receptor 7, or 8, or 9, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating inflammatory and autoimmune diseases.
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Page/Page column 212-213
(2021/04/10)
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- HTS-based discovery and optimization of novel positive allosteric modulators of the α7 nicotinic acetylcholine receptor
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HTS campaign of the corporate compound collection resulted in a novel, oxalic acid diamide scaffold of α7 nACh receptor positive allosteric modulators. During the hit expansion, several derivatives, such as 4, 11, 17 demonstrated not only high in vitro potency, but also in vivo efficacy in the mouse place recognition test. The advanced hit molecule 11 was further optimized by the elimination of the putatively mutagenic aromatic-amine building block that resulted in a novel, aminomethylindole compound family. The most balanced physico-chemical and pharmacological profile was found in case of compound 55. Docking study revealed an intersubunit binding site to be the most probable for our compounds. 55 demonstrated favorable cognitive enhancing profile not only in scopolamine-induced amnesia (place recognition test in mice) but also in natural forgetting (novel object recognition test in rats). Compound 55 was, furthermore, active in a cognitive paradigm of high translational value, namely in the rat touch screen visual discrimination test. Therefore, 55 was selected as a lead compound for further optimization. Based on the obtained favorable results, the invented aminomethylindole cluster may provide a viable approach for cognitive enhancement through positive allosteric modulation of α7 nAChRs.
- Holm, Patrik,éles, János,Balázs, Ottilia,Fodor, László,Greiner, István,Horváth, Anita,Kóti, János,Kiss, László,Kolok, Sándor,Kostyalik, Diána,Krámos, Balázs,Lévay, Gy?rgy,Ledneczki, István,Lendvai, Balázs,Mahó, Sándor,Molnár, Katalin Dudás,Némethy, Zsolt,Szigetvári, áron,Tapolcsányi, Pál,Thán, Márta,Vágó, István,Vastag, Mónika,Visegrády, András
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- NOVEL FUNGICIDAL HETEROCYCLIC COMPOUNDS
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The present invention relates to a compound selected from Formula I and a process for preparing same, wherein R2, T, L1, A, G, J, n, W, Z and Z1 are each as defined in the description. The invention also relates to the combination and composition comprising the compound of Formula I.
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(2019/04/10)
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- NOVEL FUNGIDAL HETEROCYCLIC COMPOUNDS
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The present invention relates to a compound selected from Formula (I) and its salts, metal complexes, N-oxides, isomers, and polymorphs: Formula (I) wherein E, Z, R3, n, G, J & Q have the meaning as defined in the description.
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Page/Page column 60
(2019/04/10)
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- HETEROCYCLIC COMPOUNDS WITH MICROBIOCIDAL PROPERTIES
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The present disclosure relates to a compound of Formula I, wherein the substituents T, A, W, R2, n, Z, G, Z1 and J are as defined in the description.
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(2018/11/22)
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- 6,5-BICYCLIC OCTAHYDROPYRROLOPYRIDINE OREXIN RECEPTOR ANTAGONISTS
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The present invention is directed to 6,5-bicyclic octahydropyrrolopyridine compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.
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- Thiazole-4-formyl-piperazine derivatives and its preparation method and application
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The invention relates to thiazole-4-formyl piperazine derivative and a preparing method and application thereof. The thiazole-4-formyl piperazine derivative is compound of the structure shown in a general formula I. The invention further provides the prep
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- THERAPEUTIC COMPOUNDS
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Compounds of formula (I): or salts thereof are disclosed. Also disclosed are pharmaceutical compositions comprising a compound of formula (I), processes for preparing compounds of formula (I), intermediates useful for preparing compounds of formula (I) an
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- TUBULYSIN DERIVATIVES
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Novel tubulysin derivatives which may be useful as cytotoxic agents to provide therapeutic benefits in the treatment of various types of cancers, alone or as drug conjugates with antibodies are provided. The tubulysin derivatives consist of a tetrapeptide scaffold comprising methyl and ethyl substituted piperidines. The tubulysin conjugates further comprise monoclonal antibody via succinimide linkers.
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(2015/11/17)
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- THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
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Provided are compounds useful for treating cancer and methods of treating cancer comprising administering to a subject in need thereof a compound described herein.
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Paragraph 1232
(2015/02/18)
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- THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
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Provided are compounds useful for treating cancer and methods of treating cancer comprising administering to a subject in need thereof a compound described herein.
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Page/Page column 270
(2015/02/02)
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- Concise synthesis and X-ray crystal structure of N -benzyl-2-(pyrimidin-4'- ylamino)-thiazole-4-carboxamide (Thiazovivin), a small-molecule tool for stem cell research
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Stem cell research is one of the most promising fields of modern biomedical research and regenerative medicine. Limited availability and ethical concerns suggest the renouncement of embryonic stem cells (ESCs), thus raising the need for more efficient pro
- Ries, Oliver,Granitzka, Markus,Stalke, Dietmar,Ducho, Christian
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supporting information
p. 2876 - 2882
(2013/09/02)
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- NUCLEAR TRANSPORT MODULATIORS AND USES THEREOF
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The invention generally relates to the field of nuclear transport modulators, e.g., CRM1 inhibitors, and more particularly to new substituted-heterocyclic azole compounds, the synthesis and use of these compounds and their pharmaceutical compositions, e.g
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Page/Page column 224-225
(2011/10/03)
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- QUINOLONES USEFUL AS INDUCIBLE NITRIC OXIDE SYNTHASE INHIBITORS
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The present invention relates to novel quinolones of Formula I that inhibit inducible NOS synthase together with methods of synthesizing and using the compounds including methods for inhibiting or modulating nitric oxide synthesis and/or lowering nitric oxide levels in a patient by administering the compounds for the treatment of disease.
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- Concise total synthesis of the thiazolyl peptide antibiotic GE2270 A
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The potent antibiotic thiazolylpeptide GE2270 A was synthesized starting from N-tert-butyloxycarbonyl protected valine in a longest linear sequence of 20 steps and with an overall yield of 4.8 %. Key strategy was the assembly of the 2,3,6-trisubstituted p
- Delgado, Oscar,Martin Mueller,Bach, Thorsten
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experimental part
p. 2322 - 2339
(2009/04/10)
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- Thiazoles as inhibitors of 11B-hydroxysteroid dehydrogenase
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Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, type II diabetes mellitus and metabolic syndrome.
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(2008/06/13)
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- Total synthesis of N14-desacetoxytubulysin H
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Equation presented The N14-desacetoxy analogue of tubulysin H was prepared in 20 steps and 2.1% overall yield. Our strategy features a thiazole anion addition to assemble the tubuvaline residue at the C(10)-C(11) bond, as well as acylations at
- Wipf, Peter,Wang, Zhiyong
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p. 1605 - 1607
(2008/02/03)
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- INHIBITORS OF HCV NS5B POLYMERASE
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The present invention porivdes compounds of Formula I, compositons and methods that are useful for treating viral infections and associated diseases, particularly HCV infections and associated diseases.
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- 4-[(4-(CARBOXYETHYL) PIPERIDINYL) METHYL] PYRROLIDINES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
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3-Substituted pyrrolidines having a 4-carboxypiperidinylmethyl substituent on the 4-position of the ring are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-3 and/or CCR-5.
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(2010/02/07)
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- Viral polymerase inhibitors
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An isomer, enantiomer, diastereoisomer, or tautomer of a compound, represented by formula I: wherein R1 is selected from: H, haloalkyl, (C1-6)alkyl, (C2-6)alkenyl, (C3-7)cycloalkyl, (C2-6)alkynyl, (C5-7)cycloalkenyl, 6 or 10-membered aryl, Het all optionally substituted; R2 is selected from (C1-6)alkyl, (C3-7)cycloalkyl, (C6-10)bicycloalkyl, 6- or 10-membered aryl, or Het all optionally substituted; B is N or CR5, wherein R5 is H, halogen, haloalkyl, (C1-6)alkyl, (C3-7)cycloalkyl or (C1-6)alkyl-(C3-7)cycloalkyl; X is N or CR5; D is N or CR5; each of Y1 and Y2 is independently O or S; Z is O, N, or NRz wherein Rz is H, (C1-6)alkyl, (C3-7)cycloalkyl or (C1-6)alkyl-(C3-7)cycloalkyl; R3 and R4 are each independently H, (C1-6)alkyl, first (C3-7)cycloalkyl or 6- or 10-membered aryl, Het (C1-6)alkyl-6- or 10-membered aryl, (C1-6)alkyl-Het; or each R3 and R4 are independently covalently bonded together to form second (C3-7)cycloalkyl, or heterocycle, all optionally substituted; or when Z is N, either R3 or R4 are independently covalently bonded thereto to form a nitrogen-containing heterocycle; R7 is H, (C1-6 alkyl), (C3-7)cycloalkyl or (C1-6)alkyl-(C3-7)cycloalkyl; or R7 is covalently bonded to either of R3 or R4 to form a heterocycle; A is (C1-6) alkyl-CONHR8 wherein R8 is-6- or 10-membered aryl, or Het; or A is a 6- or 10-membered aryl, or Het said aryl or Het being optionally substituted; or a salt or a derivative thereof; such compounds being potent inhibitors of HCV NS5B polymerase.
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- Cyclic diamine compound with 5-membered ring groups
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A compound of formula (1): wherein A is a single bond, C≡C, CONH or NHCO; W is a carbon atom or a nitrogen atom; X is CH, a nitrogen atom, an oxygen atom or a sulfur atom; Y is CH, CHR1, in which R1is a hydrogen atom, or a lower alkyl, hydroxy lower alkyl, lower alkoxy-lower-alkyl, aryl, aryl-lower-alkyl or heteroaryl-lower-alkyl group, a nitrogen atom, an oxygen atom, a sulfur atom or NR2, in which R2is a hydrogen atom, or a lower alkyl, hydroxy lower alkyl, lower alkoxy-lower-alkyl, aryl, aryl-lower-alkyl or heteroaryl-lower-alkyl group; Z is a nitrogen atom, an oxygen atom, a sulfur atom, CH or NR3, in which R3is a hydrogen atom, or a lower alkyl, hydroxy lower alkyl, lower alkoxy-lower-alkyl, aryl, aryl-lower-alkyl or heteroaryl-lower-alkyl group; m is 1 or 2; and n is a number of 1 to 5, with the proviso that one or two of W, X, Y and Z are heteroatoms; an acid-addition salt thereof, or a hydrate thereof. The compounds have inhibitory effects on cell adhesion and are useful for prevention or treatment of diseases such as allergy, asthma, rheumatism, arteriosclerosis and inflammation.
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- EP4 receptor selective agonists in the treatment of osteoporosis
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This invention is directed to EP4 receptor selective prostaglandin agonists of the Formula I, wherein R2, X, Z and Q are as defined in the specification. This invention is also directed to pharmaceutical compositions containing those compounds. This invention is also directed to methods of treating conditions which present with low bone mass, particularly osteoporosis, frailty, an osteoporotic fracture, a bone defect, childhood idiopathic bone loss, alveolar bone loss, mandibular bone loss, bone fracture, osteotomy, bone loss associated with periodontitis, or prosthetic ingrowth in a mammal comprising administering those compounds.
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- Treatment of parasitic diseases by inhibition of cysteine proteases of the papain superfamily
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The present invention relates to compounds and pharmaceutical compositions which inhibit proteases, such as cysteine proteases. In particular, the present invention relates to compounds and pharmaceutical compositions which inhibit cysteine proteases of the papain superfamily. The compounds and pharmaceutical compositions of the present invention are useful for treating diseases, particularly parasitic diseases, which are mediated by such proteases. In particular, the present invention relates to a method of treating malaria by inhibiting the cysteine protease falcipain.
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- Protease inhibitors
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The present invention provides compounds of formula (I) which inhibit proteases, including cathepsin K, pharmaceutical compositions of such compounds, and methods for treating diseases of excessive bone loss or cartilage or matrix degradation, including osteoporosis; gingival disease including gingivitis and periodontitis; arthritis, more specifically, osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia or malignancy; and metabolic bone disease therewith.
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- Design, synthesis, and pharmacological evaluation of new farnesyl protein transferase inhibitors
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New CA1A2X peptidomimetics are described as Ras farnesyl transferase inhibitors (FTIs). They include cysteine and methionine as mimetics of the C-terminus sequence of farnesylated proteins. Furthermore, cysteine was replaced by heter
- Houssin, Raymond,Pommery, Jean,Salaün, Marie-Catherine,Deweer, Sophie,Goossens, Jean-Fran?ois,Chavatte, Philippe,Hénichart, Jean-Pierre
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p. 533 - 536
(2007/10/03)
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- Erythromycin derivatives with antibiotic activity
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Erythromycin derivatives with antibiotic activity and pharmaceutically acceptable salts thereof. A process for preparing such erythromycin derivatives and pharmaceutical compositions containing them as the active principle.
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- PROTEASE INHIBITORS
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Disclosed herein is a compound of the formula STR1 known as 2-[N-(N-benzyloxycarbonyl-L-leucinyl)]-2'-[N'-[4-(N,N-dimethylaminomethyl) benzyloxy]carbonyl-L-leucinyl]carbohydrazide; and pharmaceutically acceptable salts, hydrates and solvates thereof.
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- Total synthesis of dimethyl sulfomycinamate
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Dimethyl sulfomycinamate (1), a methanolysis product from the natural antibiotic sulfomycin I, is synthesized in 11 steps. The chemistry of various pyridine, thiazole, and oxazole heterocycles and their coupling reactions under palladium catalysis are examined. The key transformations in the synthesis are the selective palladium-catalyzed coupling reactions on doubly activated pyridine 62 and the condensation reaction between bromo ketone 69 and amide 28 to form the oxazole moiety 76. The first preparation of oxazole triflates is described, as are some of their chemical properties.
- Kelly, T. Ross,Lang, Fengrui
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p. 4623 - 4633
(2007/10/03)
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- Pyrethrinoid esters of thiazole alcohols
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In all possible stereoisomer forms and mixtures thereof of the formula STR1 wherein one of R1, R2 or R3 is: STR2
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- Total synthesis of dimethyl sulfomycinamate
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The first total synthesis of dimethyl sulfomycinamate (1) is described. Highlights of the synthesis include a selective palladium-catalyzed coupling reaction on the bromotriflate 21, and a condensation reaction to form the oxazole ring.
- Ross Kelly,Lang, Fengrui
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p. 5319 - 5322
(2007/10/02)
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