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N-((2R)-2,3-Dihydroxypropoxy)-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzamide

HCID 9826528
노트반응
기본 정보개요이름 및 식별자물성안전 및 규제화학 및 산업관련 반응화합물 노트
부분 구조 검색유사 구조 찾기

기본 정보

CAS
391210-10-9
표준 SMILES
O=C(NOC[C@H](O)CO)c1ccc(F)c(F)c1Nc1ccc(I)cc1F
InChIKey
SUDAHWBOROXANE-SECBINFHSA-N
분자식
C16H14F3IN2O4
평균 분자량
482.19 g/mol
단동위원소 질량
481.99503959

개요

PD 0325901 is a hydroxamic acid ester that is benzhydroxamic acid (N-hydroxybenzamide) in which the hydroxamic acid group has been converted to the corresponding 2,3-dihydroxypropyl ester and in which the benzene ring has been substituted at position 2 by a (2-fluoro-4-iodophenyl)amino group and at positions 3 and 4 by fluorines (the R enantiomer). It has a role as an antineoplastic agent and an EC 2.7.12.2 (mitogen-activated protein kinase kinase) inhibitor. It is a member of propane-1,2-diols, an organoiodine compound, a difluorobenzene, a secondary amino compound, a hydroxamic acid ester and a member of monofluorobenzenes.

이름 및 식별자

우선 이름
N-((2R)-2,3-Dihydroxypropoxy)-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzamide
IUPAC
N-[(2R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzamide
영어명
PD 0325901
분자식
C16H14F3IN2O4
분자량
482.19

이름 및 동의어

391210-10-9MirdametinibPD0325901PD 0325901PD-0325901N-[(2R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzamideGOMEKLIPD 32590186K0J5AK6MDTXSID0044024DTXCID8024024CHEBI:88249
이름 더 보기
Mirdametinib (PD0325901)N-[(2R)-2,3-DIHYDROXYPROPOXY]-3,4-DIFLUORO-2-[(2-FLUORO-4-IODOPHENYL)AMINO]-BENZAMIDECS-52PD 032590PD-0235901PD0325901, >=98%MEK1/2 Inhibitor III
Pd 901PD-901Benzamide, N-[(2R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-PD-03525901Benzamide, N-((2R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)-N-((2R)-2,3-Dihydroxypropoxy)-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzamidePD325901RefChem:818905

데이터베이스 식별자

CAS
391210-10-9
PubChem CID
9826528
DTXSID
DTXSID0044024

물성

구조 계산 물성

XLogP
3
극성 표면적
90.8 Ų
수소 결합 공여자 수
4
수소 결합 수용자 수
8
회전 가능 결합 수
7
무거운 원자 수
26
형식 전하
0
복잡도
465

실험 및 물리화학적 성질

DrugsPharmaceuticals -> Listed in ZINC15
Human Drugs · 4건

Breast Feeding; Lactation; Milk, Human; Antineoplastic Agents; Enzyme Inhibitors; Protein Kinase Inhibitors; MEK inhibitors

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine (Orphan designations)

FDA approved drugs -> Active ingredient

Dissociation Constants7.96

물리화학적 성질

녹는점
112 · 112-114°C
밀도
1.817 · 1.817±0.06 g/cm3(Predicted)
저장 조건
2 · 2-8°C
용해도
20 mg/mL, · DMSO: 용해성20mg/mL, 투명
물리적 상태
흰색에서 회백색 고체
산도 계수 (pKa)
13.45 · 13.45±0.20(Predicted)
색상
흰색에서 황백색까지
안정성
1 · 제공된 대로 구매일로부터 1년 동안 안정적입니다. DMSO 또는 에탄올 용액은 -20°에서 최대 3개월 동안 보관할 수 있습니다.
InChI
InChI=1S/C16H14F3IN2O4/c17-11-3-2-10(16(25)22-26-7-9(24)6-23)15(14(11)19)21-13-4-1-8(20)5-12(13)18/h1-5,9,21,23-24H,6-7H2,(H,22,25)/t9-/m1/s1

안전 및 규제

안전 정보는 참고용이며, 공급업체의 물질안전보건자료(SDS), 관련 법규 및 전문가 평가를 대체하지 않습니다.

GHS 분류

GHS Classification · 4건

Danger

H301 (97.5%): Toxic if swallowed [Danger Acute toxicity, oral]

P260, P264, P270, P273, P301+P316, P319, P321, P330, P391, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 40 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

유해성 정보

Hazard Classes and CategoriesAcute Tox. 3 (97.5%)

독성 정보

Effects During Pregnancy and Lactation◉ Summary of Use during Lactation

안전 데이터

wgk
3
ridadr
UN 2811 6.1 / PGIII
HS 번호
29242990
risk_code
25-48-50
hazard_code
T,N
safety_code
22-36/37/39-61
위험 등급
IRRITANT
스토리지 클래스
10 - Combustible liquids

화학 및 산업

약리 정보

ATC Code · 2건

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

Protein BindingHuman plasma protein binding is greater than 99%.
PharmacodynamicsIn a mouse model of NF1, oral dosing of mirdametinib inhibited ERK phosphorylation and reduced neurofibroma tumour volume and proliferation.
Mechanism of Action · 1건

NF1 is caused by the loss-of-function variants in the _NF1_ tumour suppressor gene, which encodes neurofibromin: Neurofibromin loss in tumour cells leads to dysregulated Ras signalling with hyperactivation of downstream Ras effectors, including mitogen-activated protein kinase (MAPK, MEK) and its downstream effector extracellular signal–regulated protein kinase (ERK). As the MAPK pathway regulates cellular functions such as cellular growth and senescence, dysregulation of this pathway aberrant glioblastoma cell growth. Mirdametinib is a highly selective, non-competitive inhibitor of MEK1/2. In vitro, mirdametinib inhibited kinase activity of MEK1 and MEK2 and downstream phosphorylation of ERK.

Biological Half-LifeThe mean (%CV) terminal elimination half-life is 28 h (12%).
Metabolism/MetabolitesMetabolism involves glucuronidation and oxidation via UGT (primarily UGT1A6 and UGT2B7) and carboxylesterase enzymes.
FDA Pharmacological Classification · 6건

86K0J5AK6M

MIRDAMETINIB

Established Pharmacologic Class [EPC] - Kinase Inhibitor

Mechanisms of Action [MoA] - Mitogen-Activated Protein Kinase Kinase 1 Inhibitors

Mechanisms of Action [MoA] - Mitogen-Activated Protein Kinase Kinase 2 Inhibitors

Mirdametinib is a Kinase Inhibitor. The mechanism of action of mirdametinib is as a Mitogen-Activated Protein Kinase Kinase 1 Inhibitor and Mitogen-Activated Protein Kinase Kinase 2 Inhibitor.

관련 반응

11건
반응 기록 만들기
HRID 1062295 반응식
HRID 1062295생성물로uspto-grants-2005_11
HRID 1062296 반응식
HRID 1062296생성물로uspto-grants-2005_11
HRID 1062297 반응식
HRID 1062297반응물로uspto-grants-2005_11
HRID 1062298 반응식
HRID 1062298반응물로uspto-grants-2005_11
HRID 1829093 반응식
HRID 1829093생성물로uspto-grants-2006_06
HRID 1829094 반응식
HRID 1829094생성물로uspto-grants-2006_06
HRID 1829095 반응식
HRID 1829095생성물로uspto-grants-2006_06
HRID 2218472 반응식
HRID 2218472생성물로uspto-grants-2008_08
1 / 2 페이지

화합물 노트

불러오는 중…

이 페이지에서기본 정보개요이름 및 식별자물성안전 및 규제화학 및 산업관련 반응화합물 노트
ChEMBL
CHEMBL507361
ChEBI
CHEBI:88249
UNII
86K0J5AK6M
EC Number
687-152-7
Nikkaji
J2.753.603D
InChIKey
SUDAHWBOROXANE-SECBINFHSA-N
SMILES
C(NOC[C@H](O)CO)(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F

화학적 성질

White to Off-White Solid

MeSH Pharmacological Classification
Agents that inhibit PROTEIN KINASES.
Absorption, Distribution and Excretion · 4건

The mean Cmax (%CV) at steady-state is 188 (52%) ng/mL in adults and 191 (62%) ng/mL in children. The mean AUC (%CV) at steady-state is 431 (43%) ng x h/mL in adults and 459 (46%) ng x h/mL in children. The Tmax (time to reach steady-state) is approximately six days. The mean accumulation ratio is 1.1 to 1.9. The median (min, max) Tmax is 0.8 (0.4-3) hours post-dose in tablets and 1.1 (0-4) hours post-dose in capsules. There is no data on the absolute bioavailability of mirdametinib. The effect of a high-fat, high-calorie meal on drug absorption was assessed using the geometric mean ratio (GMR%) and the 90% confidence interval (CI): The GMR was 57% (54%, 61%) for Cmax and 93% (90%, 96%) for AUCinf, indicating that a high-fat, high-calorie meal reduces Cmax but has negligible effects on drug exposure.

About 68% of mirdametinib is excreted in urine, with 0.7% of that excreted as unchanged drug. About 27% is excreted in feces, with 9% of that excreted as unchanged drug.

The mean (%CV) apparent volume of distribution is 255 L (13%). Mirdametinib penetrates the central nervous system.

The mean (%CV) apparent systemic clearance is 6.3 L/h (13%).

응용 분야

용도PD 0325901 has been used as an inhibitor in extracellular signal-regulated kinase (ERK) inhibition assay in primed induced pluripotent stem cells, RKO colorectal cancer cell line and human embryonic stem cells(hESCs).

공급사100 곳

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추가 설명 · 1건

정의ChEBI: A hydroxamic acid ester that is benzhydroxamic acid (N-hydroxybenzamide) in which the hydroxamic acid group has been converted to the corresponding 2,3-dihydroxypropyl ester and in which the benzene ring has been substituted at position by a (2-fluoro-4-iodophenyl)amino group and at positions 3 and 4 by fluorines (the R enantiomer).