Dexmethylphenidate is metabolised to the inactive metabolite ritalinic acid by carboxylesterase 1A1 in the liver. Other minor pathways metabolise dexmethylphenidate to the inactive metabolites 6-oxo-methylphenidate and p-hydroxy-methylphenidate which are de-esterified and conjugated into other unknown metabolites.
参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 美国食品药品监督管理局批准的药物标签用于研究药物诱导的肝损伤，《药物发现今日》，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按人类发展药物诱导肝损伤风险排名的最大参考药物清单。《药物发现今日》2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
Taking dexmethylphenidate with or without food does not affect patients in a clinically relevant way. 90% of an oral dose is absorbed but as a result of hepatic first pass metabolism, oral bioavailability of dexmethylphenidate is 23% compared to l-methylphenidate with an oral bioavailability of 5%. Maximum concentration is generally reached in 1-1.5 hours.
[EN] SERDEXMETHYLPHENIDATE CONJUGATES, COMPOSITIONS AND METHODS OF USE THEREOF [FR] CONJUGUÉS DE SERDEXMÉTHYLPHÉNIDATE, ET COMPOSITIONS ET MÉTHODES D'UTILISATION ASSOCIÉES
[EN] A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN AGENT CYTOTOXIQUE À UNE MOLÉCULE DE LIAISON CELLULAIRE AVEC DES LIEURS RAMIFIÉS
申请人：HANGZHOU DAC BIOTECH CO LTD
公开号：WO2020257998A1
公开（公告）日：2020-12-30
Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.
[EN] CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES<br/>[FR] DÉRIVÉ DE DIMÈRE DE PYRROLOBENZODIAZÉPINE RÉTICULÉ (PBD) ET SES CONJUGUÉS
申请人：HANGZHOU DAC BIOTECH CO LTD
公开号：WO2020006722A1
公开（公告）日：2020-01-09
A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.
[EN] PROCESSES USEFUL FOR THE SYNTHESIS OF (R)-1-{2-[4'-(3-METHOXYPROPANE-1-SULFONYL)-BIPHENYL-4-YL]-ETHYL}-2-METHYL-PYRROLIDINE<br/>[FR] PROCÉDÉS UTILES POUR LA SYNTHÈSE DE LA (R)-1-{2-[4'-(3-MÉTHOXYPROPANE-1-SULFONYL)-BIPHÉNYL-4-YL]-ÉTHYL}-2-MÉTHYL-PYRROLIDINE
申请人：ARENA PHARM INC
公开号：WO2009128907A1
公开（公告）日：2009-10-22
Processes useful for making a pharmaceutically useful compound according to Formula (I), forms of such a compound, and intermediates useful in such processes are described.
根据公式（I）制备药用化合物的有用过程，以及该化合物的形式和在这些过程中有用的中间体被描述。
Carbon-linked substituted piperidines and derivatives thereof useful as histamine H3 antagonists
申请人：Aslanian G. Robert
公开号：US20070010513A1
公开（公告）日：2007-01-11
Disclosed are compounds of the formula
or a pharmaceutically acceptable salt thereof, wherein:
M
1
and M
3
are CH or N;
M
2
is CH, CF or N;
Y is —C(═O)—, —C(═S)—, —(CH
2
)
q
—, —C(═NOR
7
)— or —SO
1-2
—; Z is a bond or optionally substituted alkylene or alkenylene;
R
1
is H, alkyl, alkenyl, or optionally substituted cycloalkyl, aryl, heteroaryl, heterocycloalkyl or a group of the formula:
where ring A is a monoheteroaryl ring;
R
1
is optionally substituted alkyl, alkenyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl; and the remaining variables are as defined in the specification; compositions and methods of treating allergy-induced airway responses, congestion, obesity, metabolic syndrome nonalcoholic fatty liver disease, hepatic steatosis, nonalcoholic steatohepatitis, cirrhosis, hepatacellular carcinoma or cognition deficit disorders using said compounds, alone or in combination with other agents.
Phenoxypiperidines and analogs thereof useful as histamine H3 antagonists
申请人：Mutahi W. Mwangi
公开号：US20070167435A1
公开（公告）日：2007-07-19
Disclosed are compounds of the formula
or a pharmaceutically acceptable salt or solvate thereof, wherein: M is CH or N; U and W are each CH, or one of U and W is CH and the other is N;
X is a bond, alkylene, —C(O)—, —C(N—OR
5
)—, —C(N—OR
5
)—CH(R
6
)—, —CH(R
6
)—C(N—OR
5
)—, —O—, —OCH
2
—, —CH
2
O— or —S(O)
0-2
—;
Y is —O—, —(CH
2
)
2
—, —C(═O)—, —C(═NOR
7
)— or —SO
0-2
—; Z is a bond, optionally substituted alkylene or alkylene interrupted by a heteroatom or heterocyclic group;
R
1
is optionally substituted alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocycloalkyl, or benzimidazolyl or a derivative thereof;
R
2
is optionally substituted alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl or heterocycloalkyl; and the remaining variables are as defined in the specification; compositions and methods for treating an allergy-induced airway response, congestion, diabetes, obesity, an obesity-related disorder, metabolic syndrome and a cognition deficit disorder using said compounds, alone or in combination with other agents.
