Tag: 434.5373

Liver Injury with Nintedanib: A Pharmacovigilance-Pharmacokinetic Appraisal was written by Raschi, Emanuel;Fusaroli, Michele;Gatti, Milo;Caraceni, Paolo;Poluzzi, Elisabetta;De Ponti, Fabrizio. And the article was included in Pharmaceuticals in 2022.Application In Synthesis of 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide This article mentions the following:

Drug-induced liver injury (DILI) with nintedanib has emerged as an adverse event of special interest in premarketing clin. trials. We characterized DILI with nintedanib in the real world and explored the underlying pharmacol. basis. First, we assessed serious hepatic events reported to the Food and Drug Administration’s Adverse Event Reporting System by combining the disproportionality approach [reporting odds ratio (ROR) with 95% confidence interval (CI)] with individual case assessment. Demog. and clin. features were inspected (seriousness, onset, discontinuation, dechallenge/rechallenge, concomitant drugs) to implement an ad hoc causality assessment scoring system. Second, we appraised physiochem. and pharmacokinetic parameters possibly predictive of DILI occurrence. Significant disproportionality was found for nintedanib as compared to pirfenidone (N = 91; ROR = 4.77; 95% CI = 3.15-7.39). Asian population, low body weight (59 kg), and rapid DILI onset (13.5 days) emerged as clin. features. Hospitalization and discontinuation were found in a significant proportion of cases (32% and 36%, resp.). In 24% of the cases, at least two potentially hepatotoxic drugs (statins, proton pump inhibitors, antibiotics) were recorded. Causality was at least possible in 92.3% of the cases. High lipophilicity and predicted in silico inhibition of liver transporters emerged as potential pharmacokinetic features supporting the biol. plausibility. Although causality cannot be demonstrated, clinicians should consider early monitoring and medication review on a case-by-case basis. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3Application In Synthesis of 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide).

7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Application In Synthesis of 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Analysis of Drug-Drug Interaction Labeling Language and Clinical Recommendations for Newly Approved Drugs Evaluated With Digoxin, Midazolam, and S-Warfarin was written by Henderson, Lindsay M.;Steinbronn, Claire E.;Yu, Jingjing;Yeung, Catherine K.;Ragueneau-Majlessi, Isabelle. And the article was included in Clinical Therapeutics in 2021.Reference of 1211441-98-3 This article mentions the following:

To best promote drug tolerability and efficacy in the clinic, data from drug-drug interaction (DDI) evaluations and subsequent translation of the results to DDI prevention and/or management strategies must be incorporated into the US Food and Drug Administration (FDA) product labeling in a consistent manner because differences in language might result in varied interpretations. This anal. aimed to assess the consistency in DDI labeling language in New Drug Applications (NDAs). NDAs of recently approved drugs (2012-2020) that increase the exposure of digoxin, midazolam, and S-warfarin, index substrates of P-glycoprotein, cytochrome P 450 (CYP) 3A, and CYP2C9 activity, resp., were fully reviewed. Noninhibitors were also evaluated to appreciate the extent of mechanistic extrapolation in case of neg. index studies. After a systematic review of the DDI studies available in NDAs, FDA-approved labeling, and commonly used clin. tertiary resources, differences in DDI results presentation and resulting clin. recommendations were found, even for inhibitors that affect similarly the exposure of the same index substrate. Studies with neg. results were often reported in the labels without providing mechanistic interpretation, thus limiting the possible extrapolation of this information to other known substrates. The variability in language affects how the information was presented to clinicians in tertiary resources. Strategies that aim to improve the translation of mechanistic DDI index studies into consistent labeling recommendations are briefly discussed in this review. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3Reference of 1211441-98-3).

7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Reference of 1211441-98-3

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Understanding the guest binding in the cucurbit[7]uril inclusion complexes of CDK4/6 inhibitors, palbociclib, and ribociclib from a combined experimental and computational study was written by Katiyar, Dharmendra;Ahamad, Shakir;Dash, Sibananda G.;Tripathi, Sarita;Arora, Ashish;Thakur, Tejender S.. And the article was included in Journal of Molecular Structure in 2021.Reference of 1211441-98-3 This article mentions the following:

We have studied the cucurbit[7]uril inclusion complexes of two anti-cancer drugs, palbociclib and ribociclib, in the solution and solid-state with the help of exptl. and computational approaches. The formation of the cucurbit[7]uril inclusion complex, binding stoichiometry, and binding free energies in aqueous solution was determined from 1H-NMR, UV-spectroscopy and ITC studies. The binding of drugs in the ionized and unionized forms with cucurbit[7]uril was studied with the help of QTAIM anal. and free energy computations. We report the development of new co-amorphous solids of the cucurbit[7]uril inclusion complexes of drugs with enhanced thermal stability. We also report three new crystalline salt forms of palbociclib oxalate and a new DMSO solvate of ribociclib succinate dihydrate in the study. The phase interrelationship between the palbociclib oxalate forms (1a, 1b, and 1c) was established from DSC and PXRD study. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3Reference of 1211441-98-3).

7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 °C and boils at 125–130 °C. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Reference of 1211441-98-3

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Inhibition of CDK4/6 kinases causes production of aneuploid oocytes by inactivating the spindle assembly checkpoint and accelerating first meiotic progression was written by Dong, Feng;Meng, Tie-Gang;Li, Jian;Wang, Feng;Li, Yuan-yuan;Ouyang, Ying-Chun;Hou, Yi;Wang, Zhen-Bo;Schatten, Heide;Sun, Qing-Yuan. And the article was included in Biochimica et Biophysica Acta, Molecular Cell Research in 2021.COA of Formula: C23H30N8O This article mentions the following:

Cyclin D-CDK4/6 complex mediates the transition from the G1 to S phase in mammalian somatic cells. Meiotic oocytes pass through the G2/M transition and complete the first meiosis to reach maturation at the metaphase of meiosis II without intervening S phase, while Cyclin D-CDK4/6 complex is found to express during meiotic progression. Whether Cyclin D-CDK4/6 complex regulates meiotic cell cycle progression is not known. Here, we found its different role in oocyte meiosis: Cyclin D-CDK4/6 complex served as a regulator of spindle assembly checkpoint (SAC) to prevent aneuploidy in meiosis I. Inhibition of CDK4/6 kinases disrupted spindle assembly, chromosome alignment and kinetochore-microtubule attachments, but unexpectedly accelerated meiotic progression by inactivating SAC, consequently resulting in production of aneuploid oocytes. Further studies showed that the MPF activity decrease before first polar body extrusion was accelerated probably by inactivation of the SAC to promote ubiquitin-mediated cyclin B1 degradation Taken together, these data reveal a novel role of Cyclin D-CDK4/6 complex in mediating control of the SAC in female meiosis I. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3COA of Formula: C23H30N8O).

7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).COA of Formula: C23H30N8O

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Consolidation of tumorous mandibular ramus defect during denosumab treatment for rapidly progressive metastatic breast cancer was written by Friedrich, Reinhard E.;Madani, Elika. And the article was included in Anticancer Research in 2021.COA of Formula: C23H30N8O This article mentions the following:

Pharmacol. inhibition of osteoclast activity is an essential component of oncol. therapy for patients with bone metastases. In rare cases, medication-related osteonecrosis of the jaws (MRONJ) is observed MRONJ can cause bone defects not inferior to primary or metastatic jaw neoplasms. Oral examination of patients on osteoclast-inhibiting medication aims to identify risk factors at an early stage and to initiate therapy. The current focus on osteoclast-inhibiting drugs in the maxillofacial region is MRONJ. Effects of the substances other than MRONJ are rarely reported. Case Report: The female patient with metastatic breast cancer had developed extensive osteolysis of the mandibular ramus at the time of initial diagnosis. The patient was treated with denosumab. Seven months later, a significant reduction in the mandibular osteolytic zone was recorded. However, known bone metastases from other sites had increased in size during multimodal therapy, and further metastases were recorded. Conclusion: Jaw metastasis can shrink under denosumab therapy. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3COA of Formula: C23H30N8O).

7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.COA of Formula: C23H30N8O

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Overall survival with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer in the PEARL study was written by Martin, Miguel;Zielinski, Christoph;Ruiz-Borrego, Manuel;Carrasco, Eva;Ciruelos, Eva M.;Munoz, Montserrat;Bermejo, Begona;Margeli, Mireia;Csoszi, Tibor;Anton, Antonio;Turner, Nicholas;Casas, Maria I.;Morales, Serafin;Alba, Emilio;Calvo, Lourdes;de la Haba-Rodriguez, Juan;Ramos, Manuel;Murillo, Laura;Santaballa, Ana;Alonso-Romero, Jose L.;Sanchez-Rovira, Pedro;Corsaro, Massimo;Huang, Xin;Thallinger, Christiane;Kahan, Zsuzsanna;Gil-Gil, Miguel. And the article was included in European Journal of Cancer in 2022.Application of 1211441-98-3 This article mentions the following:

An earlier anal. of the PEARL phase III study showed that palbociclib plus endocrine therapy (ET) does not improve progression-free survival (PFS) over capecitabine in aromatase inhibitor-resistant, hormone receptor-pos./human epidermal growth factor receptor 2-neg. metastatic breast cancer (MBC) patients. Here, we report the final overall survival (OS) anal.Postmenopausal patients (N = 601) were randomized 1:1 to capecitabine or palbociclib plus ET (exemestane, Cohort 1; fulvestrant, Cohort 2). OS was analyzed in Cohort 2, the wild-type ESR1 population and the overall population. Addnl., we analyzed subsequent systemic therapies and explored PFS2 (time from randomization to the end of the first subsequent therapy/death).OS was 31.1 mo for palbociclib plus fulvestrant and 32.8 mo for capecitabine (adjusted hazard ratio [aHR] 1.10, 95% confidence interval [CI] 0.81-1.50, P = 0.550). In the wild-type ESR1 population, OS was 37.2 mo for palbociclib plus ET and 34.8 mo for capecitabine (aHR 1.06, 95% CI 0.81-1.37, P = 0.683). In OS analyses, no subgroup showed superiority for palbociclib plus ET over capecitabine. OS in the overall population was 32.6 mo for palbociclib plus ET and 30.9 mo for capecitabine (P = 0.995). Subsequent systemic therapy was given to 79.8% and 82.9% of patients with palbociclib plus ET and capecitabine, resp. Median PFS2 was similar between study arms (Cohort 2, P = 0.941; wild-type ESR1 population, P = 0.827). No new safety findings were observedPalbociclib plus ET did not show a statistically superior OS compared to capecitabine in MBC patients progressing on aromatase inhibitors.NCT02028507 (ClinTrials.gov), 2013-003170-27 (EudraCT). In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3Application of 1211441-98-3).

7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Application of 1211441-98-3

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Combination of miR-143 and miR-506 reduces lung and pancreatic cancer cell growth through the downregulation of cyclin-dependent kinases was written by Hossian, A. k. m. nawshad;Mackenzie, Gerardo g.;Mattheolabakis, George. And the article was included in Oncology Reports in 2021.Reference of 1211441-98-3 This article mentions the following:

Lung cancer (LC) and pancreatic cancer (PC) are the first and fourth leading causes of cancer-related deaths in the US. Deregulated cell cycle progression is the cornerstone for rapid cell proliferation, tumor development, and progression. Here, we provide evidence that a novel combinatorial miR treatment inhibits cell cycle progression at two phase transitions, through their activity on the CDK4 and CDK1 genes. Following transfection with miR-143 and miR-506, we analyzed the differential gene expression of CDK4 and CDK1, using qPCR or western blot anal., and evaluated cell cycle inhibition, apoptosis and cytotoxicity. The combinatorial miR-143/506 treatment downregulated CDK4 and CDK1 levels, and induced apoptosis in LC cells, while sparing normal lung fibroblasts. Moreover, the combinatorial miR treatment demonstrated a comparable activity to clin. tested cell cycle inhibitors in inhibiting cell cycle progression, by presenting substantial inhibition at the G1/S and G2/M cell cycle transitions. More importantly, the miR-143/506 treatment presented a broader application, effectively downregulating CDK1 and CDK4 levels, and reducing cell growth in PC cells. These findings suggest that the miR-143/506 combination acts as a promising approach to inhibit cell cycle progression for cancer treatment with minimal toxicity to normal cells. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3Reference of 1211441-98-3).

7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Reference of 1211441-98-3

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Ribociclib inhibits P-gp-mediated multidrug resistance in human epidermoid carcinoma cells was written by Zhang, Lei;Ye, Biwei;Lin, Yunfeng;Li, Yi-Dong;Wang, Jing-Quan;Chen, Zhuo;Ping, Feng-Feng;Chen, Zhe-Sheng. And the article was included in Frontiers in Pharmacology in 2022.Synthetic Route of C23H30N8O This article mentions the following:

The efficacy of cancer chemotherapy can be attenuated or abrogated by multidrug resistance (MDR) in cancer cells. In this study, we determined the effect of the CDK4/6 inhibitor, ribociclib (or LEE011), on P-glycoprotein (P-gp)-mediated MDR in the human epidermoid carcinoma MDR cell line, KB-C2, which is widely used for studying P-gpmediated MDR in cancers. The incubation of KB-C2 cells with ribociclib (3-9μM) increased the efficacy of colchicine, a substrate for P-gp. The cell expression of P-gp was downregulated at both translation and transcription levels. Furthermore, ribociclib produced a 3.5-fold increase in the basal activity of P-gp ATPase, and the concentration required to increase basal activity by 50% (EC₅₀) was 0.04μM. Docking studies indicated that ribociclib interacted with the drug-substrate binding site of P-gp. The short-term and long-term intracellular accumulation of doxorubicin greatly increased in the KB-C2 cells cocultured with ribociclib, indicating ribociclib inhibited the drug efflux activity of P-gp. The results of our study indicate that LEE011 may be a potential agent for combined therapy of the cancers with P-gp mediated MDR. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3Synthetic Route of C23H30N8O).

7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Synthetic Route of C23H30N8O

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Barriers and facilitators to taking CDK4/6 inhibitors among patients with metastatic breast cancer: a qualitative study was written by Conley, Claire C.;McIntyre, McKenzie;Pensak, Nicole A.;Lynce, Filipa;Graham, Deena;Ismail-Khan, Roohi;Lopez, Katherine;Vadaparampil, Susan T.;O’Neill, Suzanne C.. And the article was included in Breast Cancer Research and Treatment in 2022.SDS of cas: 1211441-98-3 This article mentions the following:

Most studies of adherence to treatment for breast cancer have focused on early-stage patients. Findings from these studies may not generalize to patients with metastatic breast cancer (MBC). The objective of this study was to identify barriers and facilitators of adherence to cyclin-dependent kinase 4/6 (CDK4/6) inhibitors among patients with MBC, guided by the social ecol. model (SEM). Patients with MBC (N = 25), their caregivers (N = 9), and oncol. providers (N = 13) completed semi-structured qual. interviews exploring their experiences with CDK4/6 inhibitors. Interviews were audio-recorded, transcribed verbatim, and analyzed by three raters using a combined deductive and inductive approach. Qual. anal. identified barriers and facilitators of adherence at each SEM level. Intrapersonal and interpersonal factors were most frequently discussed. Intrapersonal factors included knowledge/beliefs about CDK4/6 inhibitors, side effects, and establishing a routine. Interpersonal factors included effective communication with/coordination by the care team, support from family and friends, and information from other patients with MBC. Although less frequently discussed, policy factors (i.e., cost of CDK4/6 inhibitors) were of great concern to patients, caregivers, and providers. Barriers to adherence to CDK4/6 inhibitors exist at multiple levels. Our results underscore the potential value of a multilevel intervention (e.g., patient education, evidence-based strategies for symptom management, tips for open and assertive communication with providers, information about financial resources/support available, and so on) to support adherence in this population. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3SDS of cas: 1211441-98-3).

7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.SDS of cas: 1211441-98-3

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics