优秀学术报告PPT示例(Ari Koskinen)
合集下载
相关主题
- 1、下载文档前请自行甄别文档内容的完整性，平台不提供额外的编辑、内容补充、找答案等附加服务。
- 2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
- 3、如文档侵犯您的权益，请联系客服反馈,我们会尽快为您处理(人工客服工作时间：9:00-18:30)。
O CO2H
N H
O
Me O
H N Cl
N
N N
O
N OH
N O H Me
O N H
SO
Morphine
-Lactams
O
Strychnine
Br O O N Me
split
(antibiotics) Me
Me
Tagamet Progesterone (anti-ulcer)
Me O O Me N H O O Me
Ari Koskinen Laboratory of Organic Chemistry
Off Patent
December 6, 2004 Volume 82, Number 49 pp. 18-29
Ari Koskinen Laboratory of Organic Chemistry
Patents expiring
Quinine
O
O
O
O
Valium Br(tranquilizer)
Ari Koskinen Laboratory of Organic Chemistry
High Throughput Screening
Plants (500 000) Marine natural products (106) Invertebrate natural products (109) Compound libraries Structure based design Recombinant methods Peptide libraries Peptidomimetic libraries
Basis set of 100 (e.g. carbohydrates)
1004 1005 Units 10003
The problem of combinatorial synthesis is not that of making compounds, but that of finding ways to select and identify the compounds:
Combinatorial Chemistry
solid-phase organic chemistry (SPOC) combinatorial synthesis structure elucidation based on deconvolution and tagging structure-diversity automation
b
2003 data: C&EN 2003, 81 (50), 8.
Ari Koskinen Laboratory of Organic Chemistry
Market Exclusivity Times Decrease
Ari Koskinen Laboratory of Organic Chemistry
Ari Koskinen Laboratory of Organic Chemistry
$ 1.7 bn (2003) per product is spent on
R&D Stage
Synthesis/extraction
% of spendinga
11.0
16.0 6.0
% of employeesb
New Chemical Entities vs. R&D Expedinture
18 21 24 4,8 5,5 6,6 7,2 8,4 9,8 11,5 12,7 13,5 15,2 16 ,6 ,7 ,0 ,0
$ billions
60
0,70
0,60 0,50 0,40 0,30 0,20 0,10 0,00 86 87 88 89 90 91 92 93 94 95 96 97 98 99 $/No. R&D Spending $ billions New molecular entities approved by FDA Ratio: $ / No.
inhibits proliferation of KB and P388 cells protects cells infected with HIV
O N OMe OMe Br
46 43
16
OH O
9
Me HO O H A O HN I
O N 29 O
24
O O
5
33
O OH
OH
O
1
Me H H O Me O B O H MeH E OO G H C D O O Me F H OH OH H Me
One must be able to extract the information made available by library screening.
Basis set of 1000 (e.g. synthetic building blocks)
10004 10005
Ari Koskinen Laboratory of Organic Chemistry
DRUG CANDIDATE
Ari Koskinen Laboratory of Organic Chemistry
Chemical Diversity
Units 203 Library Entities 8 000
Basis set of 20 (e.g. natural amino acids)
204
160 000
3 200 000 Library Entities 1 Million 100 Million 10 Billion Library Entities 1 Billion 1 Trillion 1 Quadrillion
205
Units 1003
The number of different chemical entities, N = bx, where x = the number of steps, and b = number of different building blocks.
12.9
18.3 7.8
Biological screening/ pharmacological testing
Toxicology/safety Dosage formulation
9.6
34.5 9.6
11.6
24.3 10.3
Clinical evaluation
Process development for manufacturing/ quality control Regulatory
New Drug Development
Ari Koskinen Laboratory of Organic Chemistry
R&D By Geographic Area; 2001
Africa Americas Europe Asia-Pacific Australia Middle East Others
Phorboxazole A
Azaspiracid
causative agent for 1995 human poisonings by contaminated Irish mussels Mytilus edulis
Ari Koskinen Laboratory of Organic Chemistry
A1
O Me O
O
B
Me O
C
OH
Me MeO O O OO
H
O O
NH Me
OO O
O
F
O
O OMe
G
O O
O HO
Me
A2
O Me OH Me H MeO Me O
H
O OH
HO NO2 OA Me Me OMe
OH O O
Cl
Everninomicin 13,384-1
Callipeltoside A
3.8 9.4
4.8 10.0
Other
a
Company financed R&D in US based on 1995 figures totalling $ 11.8 bn US scientific and professional personnel totaling 34, 784 employees Source: Pharmaceutical Research & Manufacturers of America, Industry Profile 1997
Chemistry in Biomedicine and Drug Discovery
Professor Ari Koskinen Helsinki University of Technology 11.03.2005
Ari Koskinen Laboratory of Organic Chemistry
50
40 30 FDA
20 Numberapprovedby
10 0
Note: Ethical pharmaceuticals only. Expenditures worldwide by U.S.-owned research-based pharmaceutical companies
C&EN January 17, 2000, Food & Drug Administration, Pharmaceutical Research & Manufacturers of America: PhRMA Annual Survey 2000. Ari Koskinen Laboratory of Organic Chemistry
Development pipeline
Ari Koskinen Laboratory of Organic Chemistry
Top 10 Therapies
December 6, 2004 Volume 82, Number 49 pp. 18-29
Ari Koskinen Laboratory of Organic Chemistry
Chemical Strategies in Drug Development
Isolation
Structure based synthesis
HO
wk.baidu.com
Rational Drug Design
H RCO N NMe S N
O H
N H
O OMe
O HO
Design based on Chemical Diversity N CN NHH N
Top 10 Products
December 6, 2004 Volume 82, Number 49 pp. 18-29
Ari Koskinen Laboratory of Organic Chemistry
Mergers
December 6, 2004 Volume 82, Number 49 pp. 18-29
December 6, 2004 Volume 82, Number 49 pp. 18-29
Ari Koskinen Laboratory of Organic Chemistry
Promising New Drugs
December 6, 2004 Volume 82, Number 49 pp. 18-29
Ari Koskinen Laboratory of Organic Chemistry
Drug Development Paradigms
Traditional Approach
Clinical/preclinical Observations
Disease model
Studies on pathophysiology
in vivo
LEAD
in vivo
Rational Approach
Disease gene
in vitro or in vivo in vitro
Validated target
Transgenic animals
LEAD
design
Ari Koskinen Laboratory of Organic Chemistry
Ari Koskinen Laboratory of Organic Chemistry
Diversity of Drug Structures
Natural Products as Drug Leads
O Me MeO DO Me OH O OH Me OMe
EO
OMeO Me Cl HO Cl
Drug Development Paradigms
TARGET IDENTIFICATION
General combinatorial libraries Biased combinatorial libraries
LEAD GENERATION
LEAD OPTIMIZATION
Structural chemistry
N H
O
Me O
H N Cl
N
N N
O
N OH
N O H Me
O N H
SO
Morphine
-Lactams
O
Strychnine
Br O O N Me
split
(antibiotics) Me
Me
Tagamet Progesterone (anti-ulcer)
Me O O Me N H O O Me
Ari Koskinen Laboratory of Organic Chemistry
Off Patent
December 6, 2004 Volume 82, Number 49 pp. 18-29
Ari Koskinen Laboratory of Organic Chemistry
Patents expiring
Quinine
O
O
O
O
Valium Br(tranquilizer)
Ari Koskinen Laboratory of Organic Chemistry
High Throughput Screening
Plants (500 000) Marine natural products (106) Invertebrate natural products (109) Compound libraries Structure based design Recombinant methods Peptide libraries Peptidomimetic libraries
Basis set of 100 (e.g. carbohydrates)
1004 1005 Units 10003
The problem of combinatorial synthesis is not that of making compounds, but that of finding ways to select and identify the compounds:
Combinatorial Chemistry
solid-phase organic chemistry (SPOC) combinatorial synthesis structure elucidation based on deconvolution and tagging structure-diversity automation
b
2003 data: C&EN 2003, 81 (50), 8.
Ari Koskinen Laboratory of Organic Chemistry
Market Exclusivity Times Decrease
Ari Koskinen Laboratory of Organic Chemistry
Ari Koskinen Laboratory of Organic Chemistry
$ 1.7 bn (2003) per product is spent on
R&D Stage
Synthesis/extraction
% of spendinga
11.0
16.0 6.0
% of employeesb
New Chemical Entities vs. R&D Expedinture
18 21 24 4,8 5,5 6,6 7,2 8,4 9,8 11,5 12,7 13,5 15,2 16 ,6 ,7 ,0 ,0
$ billions
60
0,70
0,60 0,50 0,40 0,30 0,20 0,10 0,00 86 87 88 89 90 91 92 93 94 95 96 97 98 99 $/No. R&D Spending $ billions New molecular entities approved by FDA Ratio: $ / No.
inhibits proliferation of KB and P388 cells protects cells infected with HIV
O N OMe OMe Br
46 43
16
OH O
9
Me HO O H A O HN I
O N 29 O
24
O O
5
33
O OH
OH
O
1
Me H H O Me O B O H MeH E OO G H C D O O Me F H OH OH H Me
One must be able to extract the information made available by library screening.
Basis set of 1000 (e.g. synthetic building blocks)
10004 10005
Ari Koskinen Laboratory of Organic Chemistry
DRUG CANDIDATE
Ari Koskinen Laboratory of Organic Chemistry
Chemical Diversity
Units 203 Library Entities 8 000
Basis set of 20 (e.g. natural amino acids)
204
160 000
3 200 000 Library Entities 1 Million 100 Million 10 Billion Library Entities 1 Billion 1 Trillion 1 Quadrillion
205
Units 1003
The number of different chemical entities, N = bx, where x = the number of steps, and b = number of different building blocks.
12.9
18.3 7.8
Biological screening/ pharmacological testing
Toxicology/safety Dosage formulation
9.6
34.5 9.6
11.6
24.3 10.3
Clinical evaluation
Process development for manufacturing/ quality control Regulatory
New Drug Development
Ari Koskinen Laboratory of Organic Chemistry
R&D By Geographic Area; 2001
Africa Americas Europe Asia-Pacific Australia Middle East Others
Phorboxazole A
Azaspiracid
causative agent for 1995 human poisonings by contaminated Irish mussels Mytilus edulis
Ari Koskinen Laboratory of Organic Chemistry
A1
O Me O
O
B
Me O
C
OH
Me MeO O O OO
H
O O
NH Me
OO O
O
F
O
O OMe
G
O O
O HO
Me
A2
O Me OH Me H MeO Me O
H
O OH
HO NO2 OA Me Me OMe
OH O O
Cl
Everninomicin 13,384-1
Callipeltoside A
3.8 9.4
4.8 10.0
Other
a
Company financed R&D in US based on 1995 figures totalling $ 11.8 bn US scientific and professional personnel totaling 34, 784 employees Source: Pharmaceutical Research & Manufacturers of America, Industry Profile 1997
Chemistry in Biomedicine and Drug Discovery
Professor Ari Koskinen Helsinki University of Technology 11.03.2005
Ari Koskinen Laboratory of Organic Chemistry
50
40 30 FDA
20 Numberapprovedby
10 0
Note: Ethical pharmaceuticals only. Expenditures worldwide by U.S.-owned research-based pharmaceutical companies
C&EN January 17, 2000, Food & Drug Administration, Pharmaceutical Research & Manufacturers of America: PhRMA Annual Survey 2000. Ari Koskinen Laboratory of Organic Chemistry
Development pipeline
Ari Koskinen Laboratory of Organic Chemistry
Top 10 Therapies
December 6, 2004 Volume 82, Number 49 pp. 18-29
Ari Koskinen Laboratory of Organic Chemistry
Chemical Strategies in Drug Development
Isolation
Structure based synthesis
HO
wk.baidu.com
Rational Drug Design
H RCO N NMe S N
O H
N H
O OMe
O HO
Design based on Chemical Diversity N CN NHH N
Top 10 Products
December 6, 2004 Volume 82, Number 49 pp. 18-29
Ari Koskinen Laboratory of Organic Chemistry
Mergers
December 6, 2004 Volume 82, Number 49 pp. 18-29
December 6, 2004 Volume 82, Number 49 pp. 18-29
Ari Koskinen Laboratory of Organic Chemistry
Promising New Drugs
December 6, 2004 Volume 82, Number 49 pp. 18-29
Ari Koskinen Laboratory of Organic Chemistry
Drug Development Paradigms
Traditional Approach
Clinical/preclinical Observations
Disease model
Studies on pathophysiology
in vivo
LEAD
in vivo
Rational Approach
Disease gene
in vitro or in vivo in vitro
Validated target
Transgenic animals
LEAD
design
Ari Koskinen Laboratory of Organic Chemistry
Ari Koskinen Laboratory of Organic Chemistry
Diversity of Drug Structures
Natural Products as Drug Leads
O Me MeO DO Me OH O OH Me OMe
EO
OMeO Me Cl HO Cl
Drug Development Paradigms
TARGET IDENTIFICATION
General combinatorial libraries Biased combinatorial libraries
LEAD GENERATION
LEAD OPTIMIZATION
Structural chemistry