PHYSICAL PARAMETERS FOR BRAIN UPTAKE - OPTIMIZING LOG-P, LOG-D AND PKA OF THA

被引：21

作者：

DESAI, MC

THADEIO, PF

LIPINSKI, CA

LISTON, DR

SPENCER, RW

WILLIAMS, IH

机构：

[1] Central Research Division, Pfizer Inc., Groton

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1991年 / 1卷 / 08期

关键词：

D O I：

10.1016/S0960-894X(00)80267-X

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Two positions on the acetylcholinesterase (AChE) inhibitor, 9-amino-1,2,3,4-tetrahydroacridine (THA), have been identified which can be modified to vary log P, log D and pK(a) values. Most importantly, these changes can be carried out without altering its AChE activity.

引用

页码：411 / 414

页数：4

共 12 条

[1]

CLARKE FH, 1987, J PHARM SCI, V8, P611

[2]

DESAI MC, 1989, TETRAHEDRON LETT, V29, P5223

[3] A NEW AND RAPID COLORIMETRIC DETERMINATION OF ACETYLCHOLINESTERASE ACTIVITY [J].

ELLMAN, GL ;

COURTNEY, KD ;

ANDRES, V ;

FEATHERSTONE, RM .

BIOCHEMICAL PHARMACOLOGY, 1961, 7 (02) :88-&

[4]

Greig N. H., 1989, IMPLICATIONS BLOOD B, V1, P311

[5] HYDROPHOBICITY AND CENTRAL-NERVOUS-SYSTEM AGENTS - ON THE PRINCIPLE OF MINIMAL HYDROPHOBICITY IN DRUG DESIGN [J].

HANSCH, C ;

BJORKROTH, JP ;

LEO, A .

JOURNAL OF PHARMACEUTICAL SCIENCES, 1987, 76 (09) :663-687

[6] EFFECTS OF AMIRIDIN ON AMBULATORY ACTIVITY AND DISCRETE SHUTTLE AVOIDANCE-RESPONSE IN MICE [J].

KURIBARA, H .

FOLIA PHARMACOLOGICA JAPONICA, 1986, 88 (04) :299-307

[7] CORRELATION OF BRAIN LEVELS OF 9-AMINO-1,2,3,4-TETRAHYDROACRIDINE (THA) WITH NEUROCHEMICAL AND BEHAVIORAL-CHANGES [J].

NIELSEN, JA ;

MENA, EE ;

WILLIAMS, IH ;

NOCERINI, MR ;

LISTON, D .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1989, 173 (01) :53-64

[8] ACETYLCHOLINESTERASE - ENZYME STRUCTURE, REACTION DYNAMICS, AND VIRTUAL TRANSITION-STATES [J].

QUINN, DM .

CHEMICAL REVIEWS, 1987, 87 (05) :955-979

[9] USE OF DISTRIBUTION COEFFICIENTS IN QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS [J].

SCHERRER, RA ;

HOWARD, SM .

JOURNAL OF MEDICINAL CHEMISTRY, 1977, 20 (01) :53-58

[10]

SHUTSKE GM, 1989, J MED CHEM, V32, P1850

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