Day: October 26, 2022

On October 15, 2009, Chen, Bei; Jiang, Tao; Marsilje, Thomas H.; Michellys, Pierre-Yves; Nguyen, Truc Ngoc; Pei, Wei; Wu, Baogen; Gao, Zhaobo; Ge, Yonghui; Huang, Chen; Li, Yuncheng published a patent.Computed Properties of 85426-79-5 The title of the patent was Preparation of pyrimidine derivatives as protein kinase inhibitors for treating proliferative disorders, immune disorders, and infections. And the patent contained the following:

The invention relates to pyrimidine derivatives having Formula I or II (wherein R1 and R2 are H, C1-6 alkyl or halo-substituted C1-6 alkyl; R3 is halo, C1-6 alkyl, or a halo-substituted C1-6 alkyl; R4 is H; alternatively, R3 and R4 together form part of a ring; R5, R6 and R8 are independently C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl or C2-6 alkynyl, each optionally substituted; R7 is sulfamoyl, carbamoyl, etc.; R9 is -L-S(O)2R18, -L-S(O)2NRR17, etc.; R is H or C1-6alkyl; R17 and R18 are independently C1-6 alkyl, halo-substituted C1-6 alkyl, etc.; L is (CR2)1-4 or a bond; n = 1-2) and methods for using such compounds as kinase inhibitors for disease treatment. For example, the compounds of the invention may be used to treat, ameliorate or prevent a condition which responds to inhibition of anaplastic lymphoma kinase (ALK) activity, c-ros oncogene (ROS), insulin-like growth factor (IGF-IR), and/or insulin receptor (InsR) kinase activity or a combination thereof. Synthetic procedures for preparing the pyrimidines of the invention are claimed as are compositions containing them. Example compound III, prepared in a multistep synthesis that culminated in the reaction of corresponding pipieridine intermediate with dimethylamino acetyl halide, had an IC50 of 0.026 μM in an ALK assay. The experimental process involved the reaction of 4-Chloro-6-(methylthio)-1H-pyrazolo[3,4-d]pyrimidine(cas: 85426-79-5).Computed Properties of 85426-79-5

The Article related to preparation pyrimidine derivative therapeutic kinase inhibitor, pyrimidine derivative treatment proliferative disorder immune disorder infection, Heterocyclic Compounds (More Than One Hetero Atom): Pyrimidines and Quinazolines and other aspects.Computed Properties of 85426-79-5

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

On October 14, 2013, Jung, Chan Seong; Kim, Dong Jin; Park, Gi Deok; Kim, Yun Gyeong; Pyo, Jeong In; Kim, Hyeon Tae; Hwang, On Yu; Azam, Sharif Mohammed Shafioul; Song, Chi Man; Kim, Yeong Su published a patent.Application of 85426-79-5 The title of the patent was Preparation of pyrazolopyrimidine derivatives for inhibiting nitric oxide generation. And the patent contained the following:

Disclosed are pyrazolopyrimidine derivatives, e.g., I [R1 = H, (un)substituted alkyl, (un)substituted aryl, etc.; R2 = H, halo, (un)substituted alkoxy, etc.; X1 = H, halo or (un)substituted aryl; or pharmaceutically acceptable salts thereof]. For example, compound II was prepared by following general procedure: reaction of 4-chloro-6-(methylthio)-1H-pyrazolo[3,4-d]pyrimidine with an amine (1.1 equiv) [dioxane, reflux temperature, 8 h]. Compound II [NR2 = piperidn-1-ylethylamino] showed 102±6% inhibition at 20 μM for NO generation. Title compounds are claimed useful for the treatment of Parkinson disease, Alzheimer disease, Hungtinton disease, etc. The experimental process involved the reaction of 4-Chloro-6-(methylthio)-1H-pyrazolo[3,4-d]pyrimidine(cas: 85426-79-5).Application of 85426-79-5

The Article related to pyrazolopyrimidine preparation nitric oxide generation inhibition, cerebral nerve disease treatment pyrazolopyrimidine nitric oxide generation inhibition, Heterocyclic Compounds (More Than One Hetero Atom): Pyrimidines and Quinazolines and other aspects.Application of 85426-79-5

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

On August 31, 2017, Chappie, Thomas Allen; Patel, Nandini Chaturbhai; Verhoest, Patrick Robert; Helal, Christopher John; Sciabola, Simone; Lachapelle, Erik Alphie; Wager, Travis T.; Hayward, Matthew Merrill published a patent.Reference of Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate The title of the patent was 6,7-Dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide compounds as PDE4 inhibitors and their preparation. And the patent contained the following:

The invention is directed to PDE4B inhibitors of formula Ior a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising the compounds, methods of treatment using the compounds, and methods of preparing the compounds Compounds of formula I wherein R1 is (un)substituted C3-8 cycloalkyl, (un)substituted C6-10 aryl, (un)substituted 5- to 10-membered heteroaryl, etc.; R2 and R3 are independently H, (un)substituted C1-6 alkyl, (un)substituted C3-8 cycloalkyl, (un)substituted C6-10 aryl, etc.; n is 0, 1, 2 and 3; each R4 is independently halo, CN, OH, SF5, NO2, etc.; and pharmaceutically acceptable salts thereof, are claimed. Example compound II was prepared by cross-coupling of azetidin-1-yl(3-bromo-6,7-dihydro-5H-pyrazolo[5,1-b]oxazin-2-yl)methanol with 4-chloro-2-methylphenylboronic acid. The invention compounds were evaluated for their PDE4 inhibitory activity. From the assay, it was determined that compound II exhibited IC50 values of 211 nM, 241 nM and 653 nM towards PDE4B1, PDE4A3 and PDE4C1, resp. 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).Reference of Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate

The Article related to pyrazolooxazinecarboxamide preparation pde4 inhibitor, Heterocyclic Compounds (More Than One Hetero Atom): Oxazines (Including Morpholine) and other aspects.Reference of Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate

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

On February 18, 2021, Abela, Alexander Russell; Anderson, Corey Don; Bookser, Brett C.; Busch, Brett B.; Clemens, Jeremy J.; Cleveland, Thomas; Coon, Timothy Richard; Frieman, Bryan; Ghirmai, Senait G.; Gulevich, Anton V.; Hadida Ruah, Sara Sabina; Ishihara, Yoshihiro; Khatuya, Haripada; McCartney, Jason; Miller, Mark Thomas; Paraselli, Prasuna; Pierre, Fabrice; Termin, Andreas; Swift, Sara E.; Uy, Johnny; Vogel, Carl V.; Zhou, Jinglan; Grootenhuis, Peter published a patent.SDS of cas: 215610-30-3 The title of the patent was Macrocycles as modulators of cystic fibrosis transmembrane conductance regulator and preparation. And the patent contained the following:

This disclosure provides compounds of formula I as modulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), pharmaceutical compositions containing at least one such modulator, methods of treatment of cystic fibrosis using such modulators and pharmaceutical compositions, and processes for making such modulators. Compound I, wherein ring A is a Ph, indole, 5-membered hetereoaryl ring, etc.; ring B is Ph, pyridinyl and pyrimidinyl ring; X is O, NH and N(C1-6 alkyl); each R1 is independently C1-6 alkyl, C1-6 alkoxyl,C1-6 haloalkyl; m is 0, 1, 2, 3 and 4; each R2 is independently halo, cyano, (un)substituted C1-6 alkyl; n is 0, 1 and 2; R0 is H, halo, cyano, etc.; each R3 is (un)substituted C1-6 alkyl and two R3 are joined to form C3-6 cycloaklyl ring; Z is a divalent linker (L)r wherein r is 1, 2, 3, 4, 5 and 6; each L is independently C(R8)(R9), O, NRb, etc.; each R8 and R9 is independently H, halo, C1-6 haloalkyl, etc.; and tautomers, deuterated derivatives and pharmaceutically acceptable salts thereof, are claimed. Compound II was prepared using a multi-step procedure (procedure given). Compound II was tested for CFTR modulatory activity giving an EC50 of <1μM. Compounds of the invention were tested for their CFTR modulatory activity (data given). The experimental process involved the reaction of 5-Methoxy-1H-pyrazole(cas: 215610-30-3).SDS of cas: 215610-30-3

The Article related to macrocycle preparation cftr modulator cystic fibrosis, Heterocyclic Compounds (More Than One Hetero Atom): Eight- and Higher-Membered Rings and other aspects.SDS of cas: 215610-30-3

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

On November 11, 2021, Tang, Xinxing; Horan, Joshua Courtney; Mente, Scot Richard; Pelish, Henry Efrem; Shair, Matthew D.; Tangpeerachaikul, Anupong published a patent.Formula: C4H6N2O The title of the patent was Preparation of heteroaromatic macrocyclic ether chemotherapeutic agents for treatment of cancer. And the patent contained the following:

Disclosed are heterocyclic heteroaromatic macrocyclic ether compounds of formula I useful alone or in combination addnl. tyrosine kinase inhibitors for the treatment or prevention of cancer. Compounds of formula I [wherein Q = CH or N; Z = CR5 or N; X = 5-membered heteroarylene, comprising 1 to 3 heteroatoms selected from N, O, and S, wherein the 5-membered heteroarylene is substituted with 0, 1, or 2 occurrences of R2, with proviso; Y = 5- to 6-membered heteroarylene, comprising 1 to 3 heteroatoms selected from N, O, and S, wherein the heteroarylene is substituted with 0, 1, or 2 occurrences of R3; R1 = H, Me, and hydroxymethyl; each R2 and R3 independently = H, CN, halo, C1-4alkoxy, etc.; R4 and R5 independently = H or F] and pharmaceutically acceptable salts and pharmaceutical compositions thereof, are claimed and exemplified. Example compound II was prepared from a multistep synthesis (preparation given). Exemplified I were evaluated for inhibition of mutant and wild-type ROS1 and ALK kinases from which II demonstrated apparent inhibitory constants of <50 nM for each kinase. The experimental process involved the reaction of 5-Methoxy-1H-pyrazole(cas: 215610-30-3).Formula: C4H6N2O

The Article related to heteroaromatic macrocyclic ether preparation cancer ros1 alk kinase inhibitor, Heterocyclic Compounds (More Than One Hetero Atom): Eight- and Higher-Membered Rings and other aspects.Formula: C4H6N2O

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

On November 11, 2021, Horan, Joshua Courtney; Mente, Scot Richard; Pelish, Henry Efrem; Shair, Matthew D.; Tang, Xinxing; Tangpeerachaikul, Anupong published a patent.Related Products of 215610-30-3 The title of the patent was Preparation of heteroaromatic macrocyclic ether chemotherapeutic agents for treatment of cancer. And the patent contained the following:

Disclosed are heterocyclic heteroaromatic macrocyclic ether compounds of formula I useful alone or in combination addnl. tyrosine kinase inhibitors for the treatment or prevention of cancer. Compounds of formula I [wherein Q = CH or N; Z = CR5 or N; X = 5-membered heteroarylene, comprising 1 to 3 heteroatoms selected from N, O, and S, wherein the 5-membered heteroarylene is substituted with 0, 1, or 2 occurrences of R2, with proviso; Y = 5- to 6-membered heteroarylene, comprising 1 to 3 heteroatoms selected from N, O, and S, wherein the heteroarylene is substituted with 0, 1, or 2 occurrences of R3; R1 = H, Me, and hydroxymethyl; each R2 and R3 independently = H, CN, halo, C1-4alkoxy, etc.; R4 and R5 independently = H or F] and pharmaceutically acceptable salts and pharmaceutical compositions thereof, are claimed and exemplified. Example compound II was prepared from a multistep synthesis (preparation given). Exemplified I were evaluated for inhibition of mutant and wild-type ROS1 and ALK kinases from which II demonstrated apparent inhibitory constants of <50 nM for each kinase. The experimental process involved the reaction of 5-Methoxy-1H-pyrazole(cas: 215610-30-3).Related Products of 215610-30-3

The Article related to heteroaromatic macrocyclic ether preparation cancer ros1 alk kinase inhibitor, Heterocyclic Compounds (More Than One Hetero Atom): Eight- and Higher-Membered Rings and other aspects.Related Products of 215610-30-3

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

On January 16, 2020, Brace, Gareth Neil; Brookings, Daniel Christopher; Foulkes, Gregory; Lecomte, Fabien Claude published a patent.Name: 1-(Tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylic acid The title of the patent was Spirocyclic indane analogs as IL-17 modulators and their preparation. And the patent contained the following:

A series of substituted spirocyclic indane derivatives of formula I, and analogs thereof, being potent modulators of human IL-17 activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including inflammatory and autoimmune disorders. Compounds of formula I wherein ring A is C3-9 cycloalkyl, C3-7 heterocycloalkyl and C4-9 heterobicycloalkyl; B is CR2 and N; D is CR3 and N; E is CR4 and N; XY is OCY1Y2, NHSO2 and derivatives, CO2, etc.; R1 is (un)substituted C1-6 alkyl, (un)substituted C3-9 cycloalkyl, (un)substituted aryl, (un)substituted heteroaryl, etc.; R2, R3 and R4 H, halo, CN, C1-6 alkyl, etc.; Y1 is H, halo, CN, CF3, etc.; Y2 is H, halo and C1-6 alkyl; and N-oxides as pharmaceutically acceptable salts thereof, are claimed. Example compound II was prepared by amidation of lithium 2-cyclooctyl-2-(3-methylisoxazole-4-carboxamido)acetate with spiro[indene-1,4′-oxane]-5-amine. The invention compounds were evaluated for their IL-17 modulatory activity (some data given). The experimental process involved the reaction of 1-(Tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylic acid(cas: 1340372-11-3).Name: 1-(Tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylic acid

The Article related to spirocyclic indane preparation il17 modulator, Heterocyclic Compounds (One Hetero Atom): Spiro Compounds With One Hetero Atom In Each Ring and other aspects.Name: 1-(Tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylic acid

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

On December 24, 2008, Sprott, Kevin; Talley, John Jeffrey; Pearson, James Philip; Milne, Todd G. published a patent.Formula: C9H7N3O2 The title of the patent was Indole derivatives as FAAH inhibitors and their preparation and use in the treatment of diseases. And the patent contained the following:

Indole derivatives of formula I that are useful for treating pain, inflammation and other conditions are described. Certain of the compounds are benzyl derivatives and others are benzoyl derivatives The compounds are substituted at least at the 3 position of the indole. Compounds of formula I wherein each V, W, X, Y, Z, J, K, L and M are independently N and C; each P1 – P6 are independently N and C; each Q1 – Q6 are independently N and C; A and A’ are independently OH, and (un)substituted C1-3 alkoxy; AA’ taken together to form =O, =NOH, and =NOMe, etc.; dashed bonds indicated single and double bonds; R2 is halo, OH, NO2, (un)substituted C1-5 alkyl, (un)substituted C1-5 alkoxy, etc.; each of R4 – R17 is absent when bonded to N; each one of R4 – R17 is H, halo, NO2, CN, CO2H, OH, etc.; and pharmaceutically acceptable salts thereof, are claimed. Example compound II was tested for its FAAH inhibitory activity. From the assay, it was determined that compound II exhibited IC50 valued of < 1 μM. The experimental process involved the reaction of 1-(Pyridin-3-yl)-1H-pyrazole-4-carboxylic acid(cas: 1014631-89-0).Formula: C9H7N3O2

The Article related to indole preparation faah inhibitor treatment disease, Heterocyclic Compounds (One Hetero Atom): Indoles, Indolizines, Carbazoles, and Other Arenopyrroles and other aspects.Formula: C9H7N3O2

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

Xu, Juan; Zhao, Xinyu; Kang, Congmin published an article in 2018, the title of the article was Improved synthesis of pyrazolo[1,5-a]pyridine-3-carboxylic acid derivatives.Product Details of 143803-93-4 And the article contains the following content:

Pyrazolo[1,5-a]pyridine-3-carboxylate derivatives were obtained from 1,3-dipolar cycloaddition reaction with Et propynoate and N-aminopyridine sulfate synthesized by the reactions of substituted pyridines and hydroxyamine-O-sulfonic acid. They were further treated with 30% NaOH aqueous solution to give corresponding substituted pyrazolo[1,5-a]pyridine-3-carboxylic acid derivatives In this method, N-aminopyridine sulfate was directly put into the next reaction, which eliminated the step of converting sulfate into iodine salt in the traditional method and solved the problem that the iodine salt was difficult to precipitate N-aminopyridine sulfate and Et propynoate were dissolved in water and N,N-dimethylformamide, resp., and then mixed to increase the solubility of reactants. Six compounds (4a∼4f) were successfully synthesized with yields of 88%∼93%. The method is mild and easy to process and has low cost as a new process for mass production The experimental process involved the reaction of 4-Methylpyrazolo[1,5-a]pyridine-3-carboxylic acid(cas: 143803-93-4).Product Details of 143803-93-4

The Article related to pyrazolopyridine carboxylic acid derivative synthesis, Industrial Organic Chemicals, Leather, Fats, and Waxes: Manufacture Of Industrial Organic Chemicals and other aspects.Product Details of 143803-93-4

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

On February 14, 2008, Talley, John Jeffrey; Sprott, Kevin; Pearson, James Philip; Milne, G. Todd; Schairer, Wayne; Yang, Jing Jing; Kim, Charles; Barden, Timothy; Lundigran, Regina; Mermerian, Ara; Currie, Mark G. published a patent.Synthetic Route of 1014631-89-0 The title of the patent was Indole compounds for treating pain, inflammation and other conditions. And the patent contained the following:

The title indoles such as I [V, W, X, Y, Z, J, K, L and M = N or C; P1-P6 = N or C; Q1-Q5 = N or C; A and A1 = OH or (un)substituted alkoxy; or A and A1 taken together = O, N(OH), N(OMe); or A and A1 together with the carbon atom to which they are attached form a cyclic ketal containing a total of 4 or 5 carbon atoms which can be optionally substituted; R2 = halo, OH, NO2, etc.; R4-R17 = absent, H, halo, NO2, etc.; with the provisos] that are useful for treating pain, inflammation and other conditions are described. Certain of the compounds I are benzyl derivatives and others are benzoyl derivatives The compounds I are substituted at least at the 3 position of the indole. General synthetic methods for the preparation of compounds I are described. E.g., a multistep synthesis of {1-[(5-chlorothien-2-yl)carbonyl]-6-fluoro-5-hydroxy-2-methyl-1H-indole-3-yl}acetic acid, starting from 3-fluoro-4-methoxyaniline, was given. Pharmaceutical composition comprising the compound I is disclosed. The experimental process involved the reaction of 1-(Pyridin-3-yl)-1H-pyrazole-4-carboxylic acid(cas: 1014631-89-0).Synthetic Route of 1014631-89-0

The Article related to indole preparation analgesic antiinflammatory faah dao related disorder treatment, Heterocyclic Compounds (One Hetero Atom): Indoles, Indolizines, Carbazoles, and Other Arenopyrroles and other aspects.Synthetic Route of 1014631-89-0

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