Tag: 300-400

On June 23, 2016, Bradner, James; Buckley, Dennis; Winter, Georg published a patent.Computed Properties of 1216805-11-6 The title of the patent was Methods to induce targeted protein degradation through bifunctional molecules. And the patent contained the following:

The present application provides bifunctional compounds I [wherein: M = (R1)m; Y is a bond, (CH2)1-6, (CH2)0-6-O, (CH2)0-6-C(:O)NR2′, (CH2)0-6-NR2’C(:O), (CH2)0-6-NH or (CH2)0-6-NR2; X is C(:O) or C(R3)2;]. [Each R1 is independently halogen, OH, C1-6-alkyl or C1-6-alkoxy; R2 is C1-6-alkyl, C(:O)-C1-6-alkyl or C(:O)-C3-6-cycloalkyl; R2′ is H or C1-6-alkyl; each R3 is independently H or C1-3-alkyl; each R3′ is independently C1-3-alkyl;]. [Each R4is independently H or C1-3-alkyl and at least one R4 is C1-3-alkyl; or two R4, together with the carbon atom to which they are attached, form a C3-6-carbocycle or a 4-, 5- or 6-membered heterocycle comprising 1 or 2 heteroatoms selected from N and O;]. [R5 is H, deuterium, C1-3-alkyl, F or Cl; ; m is 0, 1, 2 or 3; n is 0, 1 or 2; the Linker is a group that covalently binds to the Targeting Ligand and Y; and, the Targeting Ligand binds to a targeted protein selected from EGFR, FLT3, KSR1, Raf, SMARCA2 and Ras] and II [ X1-X2 is C(R3):N or C(R3)2-C(R3)2;], or an enantiomer, diastereomer, stereoisomer, or a pharmaceutically acceptable salt thereof, which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof. Thus, dBET1 [DB-2-190-2 (III)] was prepared from JQ1 (IV) via acid hydrolysis with HCO2H and amidation with N-(4-aminobutyl)-2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamide trifluoroacetate (V·CF3CO2H) in DMF containing HATU and DIPEA. The bioactivity of III was determined [IC50 = 20 nM vs. BRD4; 85% loss of BRD4 in a human AML cell line MV4-11 an 100 nM; potent downregulation of total BRD4 in human cancer cell line SUM149 breast cancer cells (EC50 = 430 nM); showed comparable response in cell lines SUM159 and MOLM13]. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Computed Properties of 1216805-11-6

The Article related to steroid bifunctional derivative preparation induction targeted protein degradation, proliferative disorder treatment steroid bifunctional derivative, Heterocyclic Compounds (One Hetero Atom): Pyridines and other aspects.Computed Properties of 1216805-11-6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On February 8, 2007, Williams, Theresa M. published a patent.Recommanded Product: Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate The title of the patent was Preparation of heterocyclic benzodiazepine derivatives as CGRP receptor antagonists. And the patent contained the following:

The title compounds with general formula I [wherein R2 = independently H, alkyl, cycloalkyl, aryl, heteroaryl, etc.; R7 = (un)substituted alkyl, alkenyl, alkynyl cycloalkyl, etc; D = N or C(R1), where R1 = independently (un)substituted alkyl, alkenyl, alkynyl, cycloalkyl, etc.; W = O, (un)substituted NH, or (un)substituted CH2; X = C or S; Y = O, N(CN), NC(=O)NH2, etc.; and Z = (un)substituted piperidinyl, aryl, or arylamino] or pharmaceutically acceptable salts and diastereomers thereof were prepared as antagonists of calcitonin gene-related peptide (CGRP) receptors for the treatment or prevention of diseases in which the CGRP is involved, such as migraine. For example, compound II was prepared in a multi-step synthesis. I showed antagonistic activity against CGRP receptor with IC50 values of about 50 μM in native receptor binding assay, native receptor functional assay, etc. The experimental process involved the reaction of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate(cas: 883984-95-0).Recommanded Product: Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate

The Article related to preparation benzodiazepine piperidine benzene, cgrp receptor antagonist treatment human headache migraine, Heterocyclic Compounds (More Than One Hetero Atom): Diazepines and other aspects.Recommanded Product: Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On May 24, 2011, Williams, Theresa M. published a patent.HPLC of Formula: 883984-95-0 The title of the patent was Heterocyclic benzodiazepine cgrp receptor antagonists. And the patent contained the following:

Compounds of formula I:(where variables R2, R7, D, W, X, Y and Z are as described herein) which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved. The experimental process involved the reaction of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate(cas: 883984-95-0).HPLC of Formula: 883984-95-0

The Article related to preparation benzodiazepine piperidine benzene, cgrp receptor antagonist treatment human headache migraine, Heterocyclic Compounds (More Than One Hetero Atom): Diazepines and other aspects.HPLC of Formula: 883984-95-0

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On February 9, 2017, Bradner, James; Buckley, Dennis; Winter, Georg published a patent.Formula: C14H10N2O6 The title of the patent was Methods to induce targeted protein degradation through bifunctional molecules. And the patent contained the following:

The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to nucleic acids, polypeptides, cells, and methods for highly regulated, targeted degradation of proteins through the use of the bifunctional compounds A polynucleotide comprising a first nucleotide sequence encoding a first polypeptide to which a Targeting Ligand of formula I (wherein ring containing T1-T5 is (a) T1, T2, T4 = N; T3, T5 = C, or (b) T1 = N, T2 = O; T3-T5 = C; A1 is S and C=C; A2 is NH and derivatives and O; each R1 is independently C1-3 alkyl, (CH2)0-3CN, (CH2)0-3OH, etc.; R2 is H, C1-6 alkyl, (CH2)0-3heterocyclyl, etc.; R3 is independently C1-3 alkyl, (CH2)0-3CN, (CH2)0-3OH, etc.; R4 is C1-3 alkyl) is capable of binding, and a second nucleotide sequence encoding a second polypeptide, wherein the first polypeptide and the second polypeptide are linked together with a peptide bond to form a fused polypeptide, is claimed. Example compound II was prepared by acylation of N-(4-aminobutyl)-2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamide trifluoroacetate with (S)-2-(4-(4-cyanophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetic acid. Exemplified compounds I demonstrated to have potent biol. activities, e.g., binding to the protein target, mediating protein degradation, etc. (data given). The title bifunctional compounds Degron-Linker-Targeting Ligand [Degron = I (ring A = II, III; Y = a bond, O, NH, etc.; X = C(O), C(R3); X1-X2 = C(R3):N or C(R3)2C(R3)2; R1 = halo, NO2, NH2, etc.; R3 = H, alkyl optionally substituted with aryl or 5-10 membered heteroaryl; each R31 = (independently) alkyl; R4 = (independently) H or alkyl; or two R4, together with the carbon atom to which they are attached, form C(O), carbocycle, or 4-6 membered heterocycle comprising 1-2 heteroatoms selected from N and O; R5 = H, alkyl, F or Cl; n = 0-2; m = 0-3; t = 0-1); Linker = IV (p1 = 0-12; p2 = 0-12; p3 = 0-6; each W = (independently) absent, CH2, O, S, NH or NR5; Z = absent, CH2, O, NH or NR5; each R5 = (independently) alkyl; Q = absent, C(O)NH, C(O)O, etc.); Targeting Ligand = V (ring containing T1-T5 = (a) T1, T2, T4 = N; T3, T5 = C, or (b) T1 = N, T2 = O; T3-T5 = C; A1 = S or C:C; A2 = NR15 or O; nn1 = 0-2; each R11 = (independently) alkyl, (CH2)0-3CN, (CH2)0-3halogen, etc.; R12 = H, alkyl, (CH2)0-3heterocyclyl, etc.; nn2 = 0-3; each R13 = alkyl, (CH2)0-3CN, (CH2)0-3halogen, etc.; R14 = alkyl; R15 = H or alkyl); with the proviso] which act as protein degradation inducing moieties, were prepared E.g., a multi-step synthesis of VI, starting from JQ1 (VII), was described. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the title bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. Exemplified compounds I demonstrated to have potent biol. activities, e.g., binding to the protein target (e.g. BRD4), mediating protein degradation, etc. (data given). The present application also provides methods for making compounds of the application and intermediates thereof. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Formula: C14H10N2O6

The Article related to bifunctional compound preparation targeted protein degradation inducer, Heterocyclic Compounds (More Than One Hetero Atom): Diazepines and other aspects.Formula: C14H10N2O6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On August 1, 2019, Crews, Craig M.; Burslem, George; Cromm, Philipp M.; Jaime-Figueroa, Saul; Toure, Momar published a patent.Category: piperidines The title of the patent was Preparation of imide-based compounds as modulators of proteolysis and methods of use. And the patent contained the following:

The description relates to imide-based compounds of formula I, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacol. activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type. Compounds of formula I wherein L is a chem. linker: PTM is a protein target moiety that binds to at target protein or polypeptide; CLM is a cereblon E3 ubiquitin ligase binding moiety; and salts, solvates, polymorphs, and deuterated forms thereof, are claimed. Example compound II was prepared by a multistep procedure (procedure given). The invention compounds were evaluated for their protein degradation activity (data given). The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Category: piperidines

The Article related to imide preparation protein degradation proteolysis modulator, Heterocyclic Compounds (More Than One Hetero Atom): Diazepines and other aspects.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On June 24, 2016, Fournier, Jean-Francois; Clary, Laurence; Thoreau, Etienne published a patent.Quality Control of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate The title of the patent was Preparation of heterocyclic compounds as GCRP receptor antagonist and their use in medicine and in cosmetics. And the patent contained the following:

The invention relates to heterocyclic compounds of formula I and their pharmaceutically acceptable salts, and their enantiomers. The invention also relates to their use as drug, preferentially in the prevention and/or the treatment of inflammatory diseases with a component neurogene or their use as cosmetic. The compounds of this invention act like antagonists of receiver CGRP-R. Compounds of formula I wherein Y is CH2, CO, C(CH3)2 and spirocyclopropyl; R1 is (un)substituted piperidinyl, azabicyclyl, azaspirocyclyl, etc.; R2, R3 and R6 are independently H, F and Me; R4 is H, alkyl, alkenyl, alkynyl, etc.; R5 is halo, alkyl, cycloalkyl, (un)substituted Ph, etc.; and pharmaceutically acceptable salts and enantiomers thereof, are claimed. Example compound II was prepared by a multistep procedure (procedure given). The invention compounds were evaluated for their GCRP receptor antagonistic activity. From the assay, it was determined that compound II exhibited Kdapp in the range of 10 nM – 100 nM. The experimental process involved the reaction of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate(cas: 883984-95-0).Quality Control of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate

The Article related to heterocyclyl preparation gcrp receptor antagonist, Heterocyclic Compounds (More Than One Hetero Atom): Diazepines and other aspects.Quality Control of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On June 30, 2016, Fournier, Jean-Francois; Clary, Laurence; Thoreau, Etienne published a patent.COA of Formula: C19H18ClN3O4 The title of the patent was Preparation of heterocyclic compounds as GCRP receptor antagonist and their use in medicine and in cosmetics. And the patent contained the following:

The invention relates to heterocyclic compounds of formula I and their pharmaceutically acceptable salts, and their enantiomers. The invention also relates to their use as drug, preferentially in the prevention and/or the treatment of inflammatory diseases with a component neurogene or their use as cosmetic. The compounds of this invention act like antagonists of receiver CGRP-R. Compounds of formula I wherein Y is CH2, CO, C(CH3)2 and spirocyclopropyl; R1 is (un)substituted piperidinyl, azabicyclyl, azaspirocyclyl, etc.; R2, R3 and R6 are independently H, F and Me; R4 is H, alkyl, alkenyl, alkynyl, etc.; R5 is halo, alkyl, cycloalkyl, (un)substituted Ph, etc.; and pharmaceutically acceptable salts and enantiomers thereof, are claimed. Example compound II was prepared by a multistep procedure (procedure given). The invention compounds were evaluated for their GCRP receptor antagonistic activity. From the assay, it was determined that compound II exhibited Kdapp in the range of 10 nM – 100 nM. The experimental process involved the reaction of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate(cas: 883984-95-0).COA of Formula: C19H18ClN3O4

The Article related to heterocyclyl preparation gcrp receptor antagonist, Heterocyclic Compounds (More Than One Hetero Atom): Diazepines and other aspects.COA of Formula: C19H18ClN3O4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On June 24, 2022, Xu, Junyu; Li, Youbin; Zheng, Danyang; Wang, Xuesong; Wang, Yan; Tan, Yinfeng; Wang, Yong; Yang, Chenqi; Zhang, Yuchen; Guo, Tong published a patent.Related Products of 1216805-11-6 The title of the patent was Preparation method of N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)formamide derivative, and application thereof in preparation of drugs for treating and/or preventing hyperproliferative diseases. And the patent contained the following:

The title N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)formamide derivative is obtained by covalently linking T or Q and T with N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)formamide fragment, and has structural formulas as shown in claim 1, wherein Q is linking group, and is linear or branched alkylene chain composed of 1-10 CH2 or CH, and the linear or branched alkylene chain is linked with T via -NH-; and T is any one of fragments having structural formulas as shown in claim 1. The derivative has a specific structural formula as shown in claim 2, and is 2-(2,6-dioxopiperidin-3-yl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)-1,3-dioxoisoindoline-5-carboxamide. The derivative can effectively inhibit activity of human chronic myeloid leukemia cells and human gastrointestinal stromal tumor cells, and can be used in the preparation of drugs for treatment and/or prevention of hyperproliferative diseases, in particular for treatment of chronic myeloid leukemia and gastrointestinal stromal tumor. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Related Products of 1216805-11-6

The Article related to formamide pyrimidinylaminophenyl preparation hyperproliferative disease, Heterocyclic Compounds (More Than One Hetero Atom): Pyrimidines and Quinazolines and other aspects.Related Products of 1216805-11-6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On May 28, 2009, Gottschling, Dirk; Dahmann, Georg; Doods, Henri; Heimann, Annekatrin; Mueller, Stephan Georg; Rudolf, Klaus; Schaenzle, Gerhard; Stenkamp, Dirk published a patent.Synthetic Route of 883984-95-0 The title of the patent was Preparation of as pyridin-2-ones as CGRP receptor antagonists. And the patent contained the following:

Title compounds I and II [R1 = 2-oxoindoles with provisos; R2 = H, alkyl; R3 = H, alkylene, etc.; R4 = H, alkylenen, etc.; R5 = H, alkyl, benzyl, etc.;] and their pharmaceutically acceptable salts and formulations were prepared For example, deprotection of methoxypyridine III afforded claimed pyridinone IV. In CGRP receptor antagonists assays, compounds I and II exhibited Ki values ≤50 μM. The experimental process involved the reaction of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate(cas: 883984-95-0).Synthetic Route of 883984-95-0

The Article related to pyridinone preparation cgrp receptor antagonist, Heterocyclic Compounds (More Than One Hetero Atom): Pyrimidines and Quinazolines and other aspects.Synthetic Route of 883984-95-0

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On May 28, 2009, Gottschling, Dirk; Dahmann, Georg; Doods, Henri; Heimann, Annekatrin; Mueller, Stephan Georg; Rudolf, Klaus; Schaenzle, Gerhard; Stenkamp, Dirk published a patent.Synthetic Route of 883984-95-0 The title of the patent was Preparation of as 2-oxoindoles CGRP receptor antagonists. And the patent contained the following:

Title compounds I [R1 = 2-oxoindole with provisos; R2 = H, alkyl; R3 = H, alkylene, etc.; R4 = H, alkylene, etc.; U = N, N-oxide, CR5; V = N, N-oxide, CR6; X = N, N-oxide, CR7; Y = N, CR6; R5 = H, hyalo, CN, etc.; R6 = H, alkyl, etc.; R7 = H, halo, CN. etc.] and their pharmaceutically acceptable salts and formulations were prepared For example, coupling of chloropyrimide II and amine III afforded claimed oxoindole IV. In CGRP receptor antagonists assays, 4-examples of compounds I exhibited Ki values ranging from 15-535 nM. The experimental process involved the reaction of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate(cas: 883984-95-0).Synthetic Route of 883984-95-0

The Article related to oxoindole preparation cgrp receptor antagonist, Heterocyclic Compounds (More Than One Hetero Atom): Pyrimidines and Quinazolines and other aspects.Synthetic Route of 883984-95-0

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem