Month: November 2022

On April 1, 2022, Huang, Liye; Li, Hua; Liu, Huabin; Wang, Zhiyuan; Li, Tao; Ouyang, Feiyan; Zhang, Xinmiao published a patent.Quality Control of 5-Methoxy-1H-pyrazole The title of the patent was Preparation of N-(3-(2-((1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-1H-indol-7-yl)pyrrolidine-2-carboxamide derivatives as Jak1 kinase inhibitors. And the patent contained the following:

The invention discloses the preparation of N-(3-(2-((1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-1H-indol-7-yl)pyrrolidine-2-carboxamide derivatives with general formula I as Jak1 kinase inhibitors wherein R1=H, halogen, substituted or unsubstituted C1-C6 linear or branched alkyl, substituted or unsubstituted C3-C6 cycloalkyl or ORa; R2=H, substituted or unsubstituted C1-C6 straight or branched chain alkyl, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted C2-C10 heterocycloalkyl; R3=H, halogen, cyano radical, unsubstituted or halogenated C1-C6 straight or branched chain alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C6 cycloalkyl; R4=SO2Ra2, CORa2, COORa2, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted C2-C10 heterocycloalkyl; R5=F, cyano, C1-C6 straight or branched chain alkyl, C3-C6 cycloalkyl or ORa5; Ra, Ra2, Ra5=H, substituted or unsubstituted C1-C10 straight or branched chain alkyl, substituted or unsubstituted C2-C10 alkenyl, substituted or unsubstituted C2-C10 alkynyl, substituted or unsubstituted C3 -C10 cycloalkyl, substituted or unsubstituted C2-C10 heterocycloalkyl; R6=D, halogen, cyano, hydroxyl, unsubstituted or halogenated C1-C6 straight or branched chain alkyl, C2-C6 alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C2-C6heterocycloalkyl, ORa6, SRa6, NRb6Rc6, CORa6, CONRb6Rc6, COORd6, SO2Ra6, SO2NRb6Rc6, NRb6CORa6, NRd6CONRb6Rc6, NRb6SO2Ra6, NRd6SO2NRb6Rc6 or SORa. For example, (S)-N-(3-(5-fluoro-2-((3-methoxy-1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-1H-indol-7-yl)-1-(methylsulfonyl)pyrrolidine-2-carboxamide was prepared from Me 3-methoxy-1H-pyrazole-4-carboxylate by hydrolysis, nitration, reduction, substitution reaction, amidation and so on. The title compounds have good inhibitory activity against Jak1 kinase and can be used to prepare drugs for the treatment of inflammation, autoimmune diseases or cancer. The experimental process involved the reaction of 5-Methoxy-1H-pyrazole(cas: 215610-30-3).Quality Control of 5-Methoxy-1H-pyrazole

The Article related to amidation preparation pyrimidine treatment human inflammation autoimmune disease cancer, Heterocyclic Compounds (More Than One Hetero Atom): Pyrimidines and Quinazolines and other aspects.Quality Control of 5-Methoxy-1H-pyrazole

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

On September 24, 2021, Zhao, Zhiming; Liu, Lifeng; Liu, Qingyun; Wang, Hailong; Guan, Huiping; Da, Chenxiao; Chen, Xi; Xu, Guiliang published a patent.Safety of Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate The title of the patent was Polyheterocyclic substituted pyrimidine or pyridylamine derivatives, compositions thereof and medical applications thereof. And the patent contained the following:

The invention discloses the polyheterocyclic substituted pyrimidine or pyridylamine derivatives (e.g., I) as adenosine receptor antagonists, which have significant adenosine A2A receptor and/or adenosine A2B receptor antagonistic activities. For example, 3-(2-amino-6-(1-((5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)pyrimidin-4-yl)-2-methylbenzonitrile (I) was prepared via reaction of 3-bromo-2-methylbenzonitrile with bis(pinacolato)diboron, followed by Suzuki coupling reaction with 2-amino-4,6-dichloropyrimidine, followed by Sonogashira coupling with (triisopropylsilyl)acetylene, followed by Click reaction with 2-(azidomethyl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole. The title compounds can be used in medicines for treating diseases mediated by adenosine A2A receptor and/or adenosine A2B receptor. The experimental process involved the reaction of Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate(cas: 153597-59-2).Safety of Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate

The Article related to pyrimidine pyridylamine triazole adenosine receptor antagonist immunomodulator antitumor, Heterocyclic Compounds (More Than One Hetero Atom): Pyrimidines and Quinazolines and other aspects.Safety of Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

On December 7, 2017, Eriksen, Birgitte Langer; Gustafsson, Magnus; Hougaard, Charlotte; Jacobsen, Thomas Amos; Jefson, Martin R.; Klein, Jessica; Larsen, Janus Schreiber; Lowe, John A., III; McCall, John M.; Strooebaek, Dorte; Von Schoubye, Nadia Lyboel; Keaney, Gregg F. published a patent.Safety of 5-Methoxy-1H-pyrazole The title of the patent was Preparation of cycloalkylamino nitrogen heterocycles as potassium channel modulators for the treatment and prevention of disorders. And the patent contained the following:

The invention relates to preparation of cycloalkylamino nitrogen heterocycles of formula I wherein all the variables are as defined in the disclosure, and pharmaceutically acceptable salts thereof, which are useful for treating a variety of diseases, disorders or conditions which can be affected by potassium channel modulation. Also provided are pharmaceutical compositions comprising the compounds I pharmaceutically acceptable salts thereof, and methods for their use in treating one or more diseases, disorders or conditions, associated with potassium channels. The experimental process involved the reaction of 5-Methoxy-1H-pyrazole(cas: 215610-30-3).Safety of 5-Methoxy-1H-pyrazole

The Article related to cycloalkylamino nitrogen heterocycle potassium channel modulator disease treatment prophylaxis, Heterocyclic Compounds (More Than One Hetero Atom): Pyrimidines and Quinazolines and other aspects.Safety of 5-Methoxy-1H-pyrazole

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

On April 20, 2017, Nicolaou, Kyriacos C.; Rhoades, Derek; Wang, Yanping; Totokotsopoulos, Sotirios published a patent.Category: pyrazoles-derivatives The title of the patent was Methods of synthesis, methods of treatment with, and drug conjugates of epothilone analogs. And the patent contained the following:

In one aspect, the present disclosure provides epothilone analogs I [wherein: X1 is absent, O or NRa; Ra is H, C≤8-alkyl, C≤8-cycloalkyl,(C≤6-alkyldiyl)-(C≤8-cycloalkyl), or a substituted version of either of these groups; provided that when X1 is absent, that the atoms to which it is attached are a part of a double bond;]. [X2, X3 and X4 are each independently O or NRb; wherein, Rb is H or C≤8-alkyl, C≤8-cycloalkyl, (C≤6-alkanediyl)-(C≤8-cycloalkyl), C≤b-aralkyl, or a substituted version of either of these groups;]. [Y1 and Y2 are each independently NH2, OH, or C≤8-alkoxy, C≤8-aralkoxy, C≤8-acyloxy, (C≤8-alkyl)amino, di(C≤8-alkyl)amino, C≤8-amido, or a substituted version of any of these groups, or ORc, wherein Rc is a hydroxy protecting group;]. [R1, R3, R4, R5, R6 and R7 are each independently H or C≤12-alkyl, C≤12-cycloalkyl, C≤12-alkenyl, C≤12-alkynyl, C≤12-aryl, or a substituted version of any of these groups; and,]. [R2 is C≤12-heteroaryl, C≤8-heteroarenediyl-Rd, or a substituted version of either of these groups; wherein Rd is C≤12-alkyl, C≤12-aryl, C≤12-aralkyl, C≤12-heteroaryl, C≤12-heteroaralkyl, or a substituted version of either of these groups;]. [Provided that R2 is not 2-methylthiazolyl, 2-(hydroxymethyl)thiazolyl, N-2-methyl-3- (methylthio)pyrazolyl or 2-(methylthio)thiazolyl;], or a pharmaceutically acceptable salt thereof. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein. Addnl., drug conjugates with cell targeting moieties of the compounds are also provided. Thus, epothilone B pyrazole analog II was prepared and tested for pharmacol. activity [EC50 = 19 μM for induction of tubulin assembly; GI50 = 14 nM vs. MCF-7 cell line; GI50 = 38 nM vs. OVCAR-8 cell line]. The experimental process involved the reaction of 5-Bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole(cas: 1187582-58-6).Category: pyrazoles-derivatives

The Article related to epothilone analogs preparation antitumor, antibody epothilone analog conjugate preparation cancer cell targeting, Biomolecules and Their Synthetic Analogs: Other Bacterial and Fungal Metabolites and other aspects.Category: pyrazoles-derivatives

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

On September 10, 2020, Cregg, James Joseph; Buckl, Andreas; Aay, Naing; Tambo-Ong, Arlyn A.; Koltun, Elena S.; Gill, Adrian Liam; Thompson, Severin; Gliedt, Micah J. published a patent.Reference of 1-(Tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylic acid The title of the patent was Preparation of bicyclic heterocyclyl compounds as SOS1 modulators. And the patent contained the following:

The present disclosure is directed to the title compounds I [Q1 = CH or N; Q4 = CH, C, or N; each Q2 = (independently) CR1 or N (wherein one Q2 = N and the other Q2 = CR1); each Q3 and Q5 = (independently) (un)substituted CH2, NH, CO, O, S, or SO2; wherein at least one of Q1-Q5 = N, (un)substituted NH, O, or SO2; m = 0-3; n = 0-3; wherein when m = 0, then n is not 0; R1 = H, alkyl, halo, etc.; L2 = a bond, C(O), C(O)O, etc.; R2 = H, alkyl, cycloalkyl, etc.; R3 and R4 = (independently) H or alkyl optionally substituted with halo or OH; wherein at least one of R3 and R4 = H or wherein R3 and R4 together with the atom to which they are attached combine to form a 3-6 membered cycloalkyl; A = (un)substituted 6-membered aryl or 5-6 membered heteroaryl; with the proviso] or pharmaceutically acceptable salts, solvates, isomers, prodrugs, or tautomers thereof, that are modulators of SOS1 and their use in the treatment of disease. E.g., a multi-step synthesis of (1R)-II, starting from 2,4-dichloro-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine and morpholine-4-carbonyl chloride, was described. Exemplified compounds I were evaluated for their activity as SOS1 modulators (data given for representative compounds I). Also disclosed are pharmaceutical compositions comprising compounds I. The experimental process involved the reaction of 1-(Tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylic acid(cas: 1340372-11-3).Reference of 1-(Tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylic acid

The Article related to bicyclic heterocyclyl compound pyrrolopyrimidinamine cyclopentapyrimidinamine pyrimidoazepinamine preparation sos1 modulator, Heterocyclic Compounds (More Than One Hetero Atom): Pyrimidines and Quinazolines and other aspects.Reference of 1-(Tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylic acid

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

On November 18, 2021, Vu, Binh; Dominique, Romyr; Li, Hongju; Fahr, Bruce; Good, Andrew published a patent.Recommanded Product: 1340372-11-3 The title of the patent was Preparation of heteroaryl-substituted indole derivatives for restoring mutant p53 function. And the patent contained the following:

Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The disclosure provided compounds of formula I capable of binding to mutant p53 and restoring the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. Compounds of formula I [wherein X1 to X4 independently = N, O, S, (un)substituted C, etc.; X5 = CH, N, or (un)substituted NH; wherein at least one of X1 to X4 is a carbon atom connected to Q1; A = (un)substituted ring; Q1 = C=O, C=S, alkylene, etc.; m = 1, 2, 3, or 4; Y = N, O, or absent; R1 = alkyl, halo, (hetero)aryl, etc.; R2 = alkyl, alkenyl, aryl, etc.; R3 and R4 independently = alkyl, aryl, heteroaryl, etc.; R3 and R4 together with the nitrogen atom to which R3 and R4 are bound form a ring] and pharmaceutically acceptable salts thereof, are claimed and exemplified. Example compound II was prepared a multistep procedure (preparation given). Exemplified I were evaluated for DNA binding activity using recombinant His-tag Y220C p53 DBD protein and TR-FRET anal. with some invention candidates demonstrating SC150 results in the range of 0μM to less than 2μM. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation. The experimental process involved the reaction of 1-(Tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylic acid(cas: 1340372-11-3).Recommanded Product: 1340372-11-3

The Article related to heteroaryl indole preparation mutant p53 restoration cancer progression, dna binding oncogene p53 stabilization heteroaryl indole, Heterocyclic Compounds (More Than One Hetero Atom): Pyrimidines and Quinazolines and other aspects.Recommanded Product: 1340372-11-3

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics