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新药研发案例研究 明星药物如何从实验室走向市场

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新药研发案例研究 明星药物如何从实验室走向市场

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《新药研发案例研究——明星药物如何从实验室走向市场》是我国新药研发参考书中颇具特色的一本学术专著,作者均系在一线从事药物化学研究教学的骨干,在执笔撰写的领域有自己多年的研究心得。作者首次从学术高度结合市场规律,以案例研究形式深度剖析了26种具有代表性的药物能成为当时或至今仍是明星药物的内在原因,是国内第一本此类专著。
Content Description

作为“十二五”国家重点图书《高等药物化学》的姊妹篇,本书首次从学术高度结合市场规律,以案例研究形式深度剖析了26种具有代表性的药物能成为当时或至今仍是明星药物的内在原因。书中对所选的这些明星药物除了有关背景和研发历程的学术性介绍外,更突出了在整个研发过程中的亮点、关键节点,包括最后成为上市新药的各种学术、技术、管理和医药法规的诸多因素和推动力。并对每种药物研发全过程进行总结,归纳出经验和教训,作为今后的借鉴。
本书可供我国药学界、化学界和生物医学界的师生、科研人员,各级药政和企业管理人员及资深科学家学习参考。
Catalogue

第1章新药研发的实用策略1
11新药研发现状和困境2
12新药研发的实用策略4
13结束语12
参考文献13
第2章阿司匹林(Aspirin)14
21阿司匹林的早期发现史15
22近50年阿司匹林研究的进展22
23阿司匹林为何能百年长寿32
参考文献35
第3章沙利度胺(Thalidomide)40
31早期“反应停”事件41
32沙利度胺致畸作用机制及新发现43
33沙利度胺治疗领域的拓展44
34沙利度胺的化学与制剂研究47
35沙利度胺研发的教训和启示50
参考文献53
第4章阿伐他汀(Atorvastatin)56
41他汀类降脂药物的作用机制57
42他汀类药物的发现和发展58
43阿伐他汀的研究开发——从模仿创新到同类最佳60
44阿伐他汀的商业开发——从第五到第一,再到史上最畅销药71
45阿伐他汀成功的启示74
参考文献75
第5章埃索美拉唑(Esomeprazole)79
51胃酸分泌的背景知识80
52质子泵抑制剂的研发历程82
53埃索美拉唑成功上市的启示95
参考文献96
第6章乙溴替丁(Ebrotidine)99
61组胺受体与消化道溃疡100
62乙溴替丁的研发过程102
63乙溴替丁的药理特点及临床应用109
64乙溴替丁的药代动力学及体内代谢113
65乙溴替丁的肝毒性和撤回114
66乙溴替丁的专利情况115
67乙溴替丁的研发启示116
参考文献117
第7章美托洛尔(Metoprolol)121
71肾上腺素能阻滞剂122
72β肾上腺素受体的分类及功能122
73β受体阻滞剂的研究123
74美托洛尔的合成工艺研究128
75美托洛尔缓释片的工艺研究130
76美托洛尔的药代动力学研究131
77美托洛尔与高血压134
78美托洛尔的其他临床应用135
79美托洛尔的不良反应138
710美托洛尔研发过程的启示138
参考文献139
第8章氨氯地平(Amlodipine)142
81高血压病及其治疗药物143
82钙离子通道阻滞剂143
83氨氯地平的发现145
84氨氯地平的合成工艺与手性拆分148
85氨氯地平临床前药理研究152
86氨氯地平临床研究154
87氨氯地平的联合用药157
88氨氯地平成功上市的启示158
参考文献159
第9章赖诺普利(Lisinopril)162
91高血压病及其发病机制163
92血管紧张素转换酶及其抑制剂164
93赖诺普利的发现166
94赖诺普利的合成工艺研究169
95赖诺普利的tACE晶体复合物研究171
96赖诺普利的临床前药理学研究173
97赖诺普利的药代动力学研究176
98赖诺普利的其他临床应用178
99赖诺普利的不良反应179
910赖诺普利成功的启示180
参考文献181
第10章氟西汀(Fluoxetine)183
101抑郁症及其发病机制184
102抑郁症的药物治疗185
103氟西汀的发现及其抗抑郁活性研究188
104氟西汀的其他临床效应195
105氟西汀的不良反应196
106氟西汀成功上市的启示197
参考文献198
第11章奥氮平(Olanzapine)201
111非经典抗精神病药物202
112奥氮平的研发历程——从实验室到临床204
113奥氮平上市后的开发——从品牌药到仿制药210
114奥氮平研发成功的启示213
参考文献214
第12章吡格列酮(Pioglitazone)217
121糖尿病和现有治疗药物218
122噻唑烷二酮类胰岛素增敏剂219
123吡格列酮的发现220
124噻唑烷二酮类药物的作用机制228
125吡格列酮的临床研究229
126吡格列酮的安全性230
127从PPARγ激动剂到选择性PPARγ调节剂232
128吡格列酮开发成功的启示233
参考文献234
第13章左氧氟沙星(Levofloxacin)237
131喹诺酮类抗菌药物238
132左氧氟沙星的发现242
133左氧氟沙星成功上市的启示250
参考文献251
第14章利奈唑胺(Linezolid)253
141抗菌药的研究背景和医学需要254
142唑烷酮类抗菌药研究的起源256
143唑烷酮类抗菌药的结构毒性关系和结构活性关系258
144唑烷酮的合成工艺及进一步结构优化260
145利奈唑胺的选定和作用机理265
146利奈唑胺的药物动力学和临床使用267
147第一个合成的唑烷酮抗菌药上市的意义和启示269
参考文献270
第15章普瑞巴林(Pregabalin)273
151癫痫及其发病机理274
152抗癫痫药物的作用机制275
153作用于钙离子通道α2δ亚基的抗惊厥药物——普瑞巴林的发现275
154普瑞巴林的临床研究及安全性评价280
155作用于钙离子通道α2δ亚基药物的研究进展283
156普瑞巴林成功的启示285
参考文献286
第16章西地那非(Sildenafil)291
161研究背景292
162西地那非的发现与活性研究293
163西地那非与男性阴茎勃起障碍296
164西地那非与肺动脉高压299
165西地那非的其他临床效应300
166西地那非与PDE5结合模式分析301
167其他选择性PDE5抑制剂302
168西地那非所引发的思考和借鉴303
参考文献304
第17章多奈哌齐(Donepezil)308
171阿尔茨海默症及其发病机理309
172中枢胆碱能假说与乙酰胆碱酯酶抑制剂310
173多奈哌齐的发现310
174多奈哌齐临床前药理研究317
175多奈哌齐的临床研究319
176多奈哌齐与靶标的相互作用321
177外消旋体多奈哌齐成功上市的启示323
参考文献324
第18章塞来考昔(Celecoxib)328
181研究背景329
182从概念到新药的发现334
183塞来考昔的专利纠纷343
184选择性COX2抑制剂的其他作用及隐忧344
185塞来考昔的其他临床应用345
186塞来考昔研发的启示345
参考文献346
第19章多西他赛(Docetaxel)349
191前言350
192多西他赛的前身——紫杉醇351
193多西他赛的发现361
194多西他赛的临床前药理研究365
195多西他赛的临床研究368
196紫杉烷类化合物的构效关系及最新研发进展372
197多西他赛的研发启示376
参考文献378
第20章伊马替尼(Imatinib)382
201肿瘤药物研发的现状及趋势383
202酪氨酸激酶为抗肿瘤药物的重要靶标385
203伊马替尼的发现历程385
204伊马替尼的作用靶标和机理390
205伊马替尼的临床实验及药代动力学研究397
206伊马替尼在治疗多种肿瘤及其他疾病方面的应用402
207伊马替尼的耐药性及对策403
208讨论与展望406
参考文献407
第21章氯吡格雷(Clopidogrel)413
211氯吡格雷的发现——从实验室到病房之路414
212氯吡格雷的作用机制及临床研究420
213氯吡格雷药物相互作用423
214漫漫研发路上的小风波425
215氯吡格雷的最新进展426
216氯吡格雷研发的启示427
参考文献428
第22章蒿甲醚(Artemether)432
221疟疾及抗疟药物433
222青蒿及青蒿素的发现435
223蒿甲醚的合成及抗疟活性研究446
224蒿甲醚研发的启示449
参考文献450
第23章地氯雷他定(Desloratadine)454
231过敏性鼻炎与抗组胺药物455
232从氯雷他定到地氯雷他定457
233地氯雷他定的安全性评价462
234地氯雷他定的临床前药理研究466
235地氯雷他定的临床药动学研究467
236地氯雷他定临床应用469
237地氯雷他定成功上市的启示470
参考文献471
第24章他莫西芬(Tamoxifen)475
241研究背景476
242非甾体类抗雌激素药物476
243他莫西芬的专利481
244他莫西芬与乳腺癌482
245他莫西芬的其他临床效应485
246选择性雌激素受体调节剂489
247他莫西芬成功的启示490
参考文献492
第25章奥司他韦(Oseltamivir)495
251背景496
252流感病毒497
253神经氨酸酶抑制剂研究501
254奥司他韦与神经氨酸酶复合物晶体结构分析509
255奥司他韦临床研究509
256奥司他韦成功上市及市场效益510
257奥司他韦研发启示510
参考文献511
第26章雷特格韦(Raltegravir)513
261逆转录病毒的生命周期和药物干预靶标514
262HIV1整合酶的结构和功能515
263芳基二酮酸类整合酶抑制剂的发现和机理研究516
264雷特格韦的选定和成药性优化517
265雷特格韦的临床前药理研究525
266雷特格韦的临床应用及前景527
267雷特格韦:从HCV多聚酶抑制剂到HIV整合酶抑制剂的启示530
参考文献532
第27章克唑替尼(Crizotinib)536
271癌症的个体化治疗537
272受体酪氨酸激酶(RTK)作为癌症靶点538
273克唑替尼的研发540
274克唑替尼的临床前药理研究548
275克唑替尼的临床研究550
276克唑替尼与靶标的相互作用554
277克唑替尼成功上市的启示556
参考文献557
中文索引563
英文索引573
Introduction

我国的创新药物研究发展迅速,医药工业正处于从仿制药为主向自主创新转变的关键时期。创新药物研究是多学科交叉的研究领域,涉及化学、药理学、生物学、信息和计算机科学等多学科的知识和技术,具有研究周期长、投入大、风险高的显著特点。至今国内还没有一部专著或教材全面地阐述创新药物研发所涉及的学术、技术、管理和研发人员之直觉与灵感等诸多因素对创新药物研究的作用和贡献。
为了提高我国创新药物研究的效率、降低研发风险,非常有必要借鉴一些有标志性的重要药物的研发经验和教训,让研发人员全面了解新药研发的规律,帮助他们更好更快地开展新药研发。因此,挑选在新药发展史上具有重要影响的明星或代表性药物,将它们作为案例,总结这些药物从活性化合物发现到成功上市的经验和教训,无疑将会对培养一流的创新药物研发和组织管理人才、推动我国创新药物研究产生深远的影响。
白东鲁和沈竞康教授主编的《新药研发案例研究——明星药物如何从实验室走向市场》一书,选取了药物发展史上具有代表性的26个明星或重磅炸弹式药物作为典型案例,系统地总结了这些药物成功上市的经验和教训,重点描述了这些药物研发过程中的亮点、关键节点和促成最后上市的各种学术、技术、管理和医药法规的诸多因素和推动力,介绍了研发人员的直觉与灵感在药物研究中的作用。该书的编写具有鲜明的特色,除了详细介绍了活性化合物的发现、结构优化研究过程及后期开发情况外,每章都列出了该药研发的大事记,并在最后一节对所论述药物的研发全过程作了总结和讨论,指出了经验和教训。毫无疑问,这些知识是无法从教科书或课堂上学习获得的,该书将成为新药研发人员全方位了解新药研发的难度和关键因素,掌握新药研发规律的重要参考读物。
该书选材具有显著的代表性,章节编排独具匠心,图文并茂,文字可读性强,填补了国内新药研究领域该类参考书的空白,是一本不可多得的好书。我觉得它和《高等药物化学》(化学工业出版社,2011)构成了新药研究专著中的“姊妹篇”,一个偏重理论和基础,一个偏重实际和应用,相信两者结合可以给读者更多的收获和启迪。我衷心希望该书能够促进我国创新药物研究人才的培养,推进我国创新药物研发事业快速发展,使我国早日成为创新药物研究强国。

陈凯先
2014年5月于上海

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Gift card deals are special offers for selected products;

The gift card deals will automatically be activated if a customer uses gift card balance at check out and the balance is sufficient to pay for the total price of the shopping cart products with gift card deals;

You will not be able to activate the gift card deals if you choose other payment methods besides gift card. The products will be purchased at their normal prices;

If your account balance is not enough to pay for the products with gift card deals, you can choose to reload your gift card balance by clicking on the Reload button at either shopping cart page or check out page;

Products that have gift card deals can be recognized by a special symbol showing 'GC Deal';

For any additional questions or concerns, please contact our customer service;

Yamibuy reserves the right of final interpretation.

Sold by Yami

Service Guarantee

Yami Free Shipping over $49
Yami Easy Returns
Yami Ships from United States

Shipping

  • United States

    Standard Shipping is $5.99 (Excluding Alaska & Hawaii). Free on orders of $49 or more.

    Local Express is $5.99 (Available in Parts of CA, NJ, MA & PA). Free on orders of $49 or more.

    2-Day Express (Includes Alaska & Hawaii) starts at $19.99.

Return Policy

Yami is committed to provide our customers with a peace of mind when purchasing from us. Most items shipped from Yamibuy.com can be returned within 30 days of receipt of shipment (For Food, Beverages, Snacks, Dry Goods, Health supplements, Fresh Grocery and Perishables Goods, within 7 days of receipt of shipment due to damages or quality issues; To ensure that every customer receives safe and high-quality products, we do not provide refunds or returns for beauty products once they have been opened or used, except in the case of quality issues; Some products may have different policies or requirements associated with them, please see below for products under special categories, or contact Yami Customer Service for further assistance).
Thank you for your understanding and support.

Learn More

Sold by Yami

Terms and Conditions of Yami E-Gift Card

If you choose “Redeem automatically” as your delivery method, your gift card balance will be reload automatically after your order has been processed successfully;

If you choose “Send to Email”as your delivery method, the card number and CVV will be sent to the email address automatically;

Any user can use the card number and CVV to redeem the gift card, please keep your gift card information safely. If you have any trouble receiving email, please contact Yami customer service;

Yami gift card can be used to purchase both Yami owned or Marketplace products;

Yami gift card will never expire;

Yami gift card balance does not have to be used up at once;

All rights reserved by Yami.

Return Policy

Gift card that has already been consumed is non-refundable.

Sold by JD@CHINA

Service Guarantee

Yami Free Shipping over $49
Yami Easy Returns
Yami Ships from United States

Shipping

  • United States

    Standard Shipping is $5.99 (Excluding Alaska & Hawaii). Free on orders of $49 or more.

    Local Express is $5.99 (Available in Parts of CA, NJ, MA & PA). Free on orders of $49 or more.

    2-Day Express (Includes Alaska & Hawaii) starts at $19.99.

Return Policy

You may return product within 30 days upon receiving the product. Items returned must be new in it's original packing, including the original invoice for the purchase. Customer return product at their own expense.

Sold by JD@CHINA

Service Guarantee

Yami Cross-store Free Shipping over $69
Yami 30-days Return

Yami-China FC

Yami has a consolidation warehouse in China which collects multiple sellers’ packages and combines to one order. Our Yami consolidation warehouse will directly ship the packages to your door. Cross-store free shipping over $69.

Return Policy

You may return products within 30 days upon receiving the products. Sellers take responsibilities for any wrong shipment or missing items. Packing needs to be unopened for any other than quality issues return. We promise to pack carefully, but because goods are taking long journey to destinations, simple damages to packaging may occur. Any damages not causing internal goods quality problems are not allowed to return. If you open the package and any quality problem is found, please contact customer service within three days after receipt of goods.

Shipping Information

Yami Consolidation Service Shipping Fee $9.99(Free shipping over $69)

Sellers in China will ship their orders within 1-2 business days once the order is placed. Packages are sent to our consolidation warehouse in China and combined there. Our Yami consolidation warehouse will directly ship the packages to you via UPS. The average time for UPS to ship from China to the United States is about 10 working days and it can be traced using the tracking number. Due to the pandemic, the delivery time may be delayed by about 5 days. The package needs to be signed by the guest. If the receipt is not signed, the customer shall bear the risk of loss of the package.

Sold by JD@CHINA

Service Guarantee

Free shipping over 69
Genuine guarantee

Shipping

Yami Consolidated Shipping $9.99(Free shipping over $69)


Seller will ship the orders within 1-2 business days. The logistics time limit is expected to be 7-15 working days. In case of customs clearance, the delivery time will be extended by 3-7 days. The final receipt date is subject to the information of the postal company.

Yami Points information

All items are excluding from any promotion or points events on Yamibuy.com

Return Policy

You may return product within 30 days upon receiving the product. Items returned must be new in it's original packing, including the original invoice for the purchase. Customer return product at their own expense.

Yami

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Jingdong book

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Jingdong book