其它产品项目整合

项目整合的本质是一项集合成方法学、反应工程学与过程分析技术于一体的系统工程。其核心逻辑可以概括为以下几点：源头优选：利用如N-硝胺化学等底层方法学突破，从分子层面颠覆传统高成本、高污染路线。过程强化：依托连续流技术，攻克有机金属试剂应用、光化学反应放大等“不可能”任务，实现高危工艺的本质安全。系统集成：整合“反应-淬灭-分离”全流程，利用微流控与在线分析技术，消除批次间的差异，实现药品制造的连续化与智能化。当前，中间体工艺研发正在经历从“经验驱动”向“数据驱动”的转变。AI辅助路线设计、自动化高通量筛选与连续制造平台的结合，将使得“分子结构与最优工艺路径”之间的映射关系逐渐清晰。未来的竞争优势，将属于那些能够将底层化学创新与先进工程技术进行无缝整合的研发体系。
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其它产品项目整合

Dideoxyadenosine CAS Registry Number: 4097-22-7 2',3'-二脱氧腺苷

CAS Name: 2',3'-Dideoxyadenosine
Additional Names: 6-amino-9-(2',3'-dideoxy-b-D-glycero-pentofuranosyl)purine; DDA; ddAdo
Percent Composition: C 51.06%, H 5.57%, N 29.77%, O 13.60%
Literature References: Purine nucleoside analog with antiviral (retrovirus) activity. Prepn: M. J. Robins, R. K. Robins, J. Am. Chem. Soc. 86, 3585 (1964); G. L. Tong et al., J. Org. Chem. 30, 2854 (1965); J. R. McCarthy et al., J. Am. Chem. Soc. 88, 1549 (1966). In vitro inhibition of bacterial DNA synthesis: L. Toji, S. S. Cohen, Proc. Natl. Acad. Sci. USA 63, 871 (1969). Antibacterial activity in mice: G. Beskid et al., Antimicrob. Agents Chemother. 19, 424 (1981). Inhibition of in vitro infectivity of HIV-1 virus: H. Mitsuya, S. Broder, Proc. Natl. Acad. Sci. USA 83, 1911 (1986). HPLC determn in biological fluids: P. A. Blau et al., J. Chromatogr. 420, 1 (1987). Metabolism by cloned human T-cells: D. A. Cooney et al., Biochem. Pharmacol. 36, 1765 (1987).

Acadesine CAS Registry Number: 2627-69-2 阿卡地辛

CAS Name: 5-Amino-1-b-D-ribofuranosyl-1H-imidazole-4-carboxamide
Additional Names: 5-amino-4-imidazolecarboxamide ribonucleoside; AICA-riboside
Trademarks: Arasine (Gensia); Protara (Gensia)...
Literature References: Purine nucleoside analog. Prototype adenosine regulating agent; enhances endogenous adenosine levels in ischemic tissue. Biosynthesis, isoln, and characterization: G. R. Greenberg, E. L. Spilman, J. Biol. Chem. 219, 411 (1956). Chemical synthesis: J. Baddiley et al., Proc. Chem. Soc. London 1957, 149; J. P. Ferris et al., J. Org. Chem. 50, 747 (1985); T. Saito et al., Chem. Pharm. Bull. 42, 2263 (1994). Pharmacology: Z.-Q. Zhao et al., Cardiovasc. Res. 29, 495 (1995). Antiplatelet activity: D. A. Bullough et al., J. Clin. Invest. 94, 1524 (1994). Disposition and metabolism: R. Dixon et al., J. Clin. Pharmacol. 33, 955 (1993). HPLC determn in plasma: L.-S. Chen et al., J. Liq. Chromatogr. 18, 1451 (1995). Review of pharmacology: K. Mullane, M. Young, Drug Dev. Res. 28, 336-343 (1993); of development: K. Mullane et al., Trends Cardiovasc. Med. 3, 227-234 (1993). Meta-analysis of clinical trials in coronary artery bypass graft surgery: D. T. Mangano et al., J. Am. Med. Assoc. 277, 325-332 (1997).

Ribavirin CAS Registry Number: 36791-04-5 利巴韦林

CAS Name: 1-b-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide
Additional Names: RTCA; tribavirinTrademarks: Copegus (Roche); Rebetol (Schering-Plough); Viramid (Alfa); Virazide (Valeant); Viraz...
Literature References: Purine nucleoside analog; inhibits inosine monophosphate dehydrogenase (IMPDH). Prepn: J. T. Witkowski, R. Robins, DE 2220246; eidem, US 3798209 (1972, 1974 both to ICN); J. T. Witkowski et al., J. Med. Chem. 15, 1150 (1972); eidem, J. Carbohydr. Nucleosides Nucleotides 5, 363 (1978). Regioselective synthesis: Y. Ito et al., Tetrahedron Lett. 1979, 2521. NMR study: G. P. Kreishman et al., J. Am. Chem. Soc. 94, 5894 (1972). Crystal structure: P. Prusiner, M. Sundaralingam, Nature New Biol. 244, 116 (1973). Teratogenicity study: D. M. Kochhar et al., Toxicol. Appl. Pharmacol. 52, 99 (1980). Review of antiviral activity: R. W. Sidwell et al., Pharmacol. Ther. 6, 123-146 (1979); of clinical experience: H. Fernandez et al., Eur. J. Epidemiol. 2, 1-14 (1986); of molecular modes of action: J. L. Patterson, R. Fernandez-Larsson, Rev. Infect. Dis. 12, 1139-1146 (1990). Clinical trial in infants with respiratory syncytial viral infection: C. B. Hall et al., N. Engl. J. Med. 308, 1443 (1983); in combination with interferon alfa-2b in hepatitis C: O. Reichard et al., Lancet 351, 83 (1998).

Vidarabine CAS Registry Number: 5536-17-4 阿糖腺苷

CAS Name: 9-b-D-Arabinofuranosyl-9H-purine-6-amine monohydrate
Additional Names: 9-b-D-arabinofuranosyladenine monohydrate; arabinosyladenine; adenine arabinoside; spongoadenosine; ara-ATradema...
Literature References: Purine nucleoside first synthesized as a potential anticancer agent: Lee et al., J. Am. Chem. Soc. 82, 2648 (1960); Reist et al., J. Org. Chem. 27, 3274 (1962); Glaudemans, Fletcher, ibid. 28, 3004 (1963); Reist et al., ibid. 29, 3725 (1964). Fermentation process using a strain of Streptomyces antibioticus: GB 1159290; J. D. Howells, A. Ryder, US 3616208 (1969, 1971 both to Parke, Davis). Crystal and molecular structure: Bunick, Voet, Acta Crystallogr. 30B, 1641 (1974). Series of articles on antiviral activity: Antimicrob. Agents Chemother. 1968, 136-179. Toxicity study: S. M. Kurtz et al., ibid. 180. HPLC determn in plasma and urine: W. P. McCann et al., ibid. 28, 265 (1985). Clinical trial in immunocompromised patients: R. J. Whitley et al., J. Infect. Dis. 165, 450 (1992). Book: Adenine Arabinoside: An Antiviral Agent, D. Paven-Langston et al., Eds. (Raven Press, New York, 1975) xviii + 425 pp. Review of pharmacology and clinical experience: R. A. Buchanan, F. Hess, Pharmacol. Ther. 8, 143-171 (1980). Comprehensive description: W. Hong et al., Anal. Profiles Drug Subs. 15, 647-672 (1986).

Piroctone CAS Registry Number: 50650-76-5 吡罗克酮

CAS Name: 1-Hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridinone
Percent Composition: C 70.85%, H 9.77%, N 5.90%, O 13.48%
Literature References: Pyridone deriv related structurally to ciclopirox, q.v. Prepn: G. Lohaus, W. Dittmar, DE 2, DE 214608 corresp to US 3972888 (1973, 1976 both to Hoechst); eidem, Arzneim.-Forsch. 31, 1311 (1981). Evaluation of efficacy as anti-dandruff agent: E. Futterer, J. Soc. Cosmet. Chem. 32, 327 (1981).

Uridine 5 ¢ -Triphosphate CAS Registry Number: 63-39-8 尿苷-5'-三磷酸

CAS Name: Uridine 5'-(tetrahydrogen triphosphate)
Additional Names: UTP
Percent Composition: C 22.33%, H 3.12%, N 5.79%, O 49.57%, P 19.19%
Literature References: Pyrimidine analog of ATP. Activates chloride channels in epithelial cells; increases ciliary beat frequency and induces degranulation of goblet cells in airway epithelia. Also effects inflammatory cell function and vascular reactivity. Isoln from rabbit muscle: Lipton et al., J. Am. Chem. Soc. 75, 5450 (1953). Synthesis: Kenner et al., J. Chem. Soc. 1954, 2288; Hall, Khorana, J. Am. Chem. Soc. 76, 5056 (1954). Review of bioactivity mediated by nucleotide receptors: S. E. O'Connor, Life Sci. 50, 1657-1664 (1992). Clinical effect on chloride secretion in cystic fibrosis: M. R. Knowles et al., Am. J. Respir. Crit. Care Med. 151, S65 (1995); on mucociliary clearance in combination with amiloride, q.v.: W. D. Bennett et al., ibid. 153, 1796 (1996).

Decitabine CAS Registry Number: 2353-33-5 地西他滨

CAS Name: 4-Amino-1-(2-deoxy-b-erythro-pentofuranosyl)-1,3,5-triazin-2(1H)-one
Additional Names: 5-aza-2'-deoxycytidineTrademarks: Dacogen (SuperGen)
Percent Composition: C 42.10%, H 5.30%, ...
Literature References: Pyrimidine analog that inhibits DNA methylation and induces differentiation of leukemic cells. Prepn: J. Pliml, F. Sorm, Collect. Czech. Chem. Commun. 29, 2576 (1964); A. Piskala, F. Sorm, in Nucleic Acid Chemistry Part 1 (Wiley, New York, 1978) pp 443-449. Improved synthesis: J. Ben-Hattar, J. Jiricny, Nucleosides Nucleotides 6, 393 (1987). Chemical stability in soln: K.-T. Lin et al., J. Pharm. Sci. 70, 1228 (1981). HPLC determn in plasma: eidem, J. Chromatogr. 345, 162 (1985). Clinical trial in chronic myelogenous leukemia: H. M. Kantarjian et al., Cancer 98, 522 (2003). Review of pharmacology and mechanism of action: R. L. Momparler, Pharmacol. Ther. 30, 287-299 (1985); idem et al., Leukemia 11, Suppl. 1, 1-6 (1997); of clinical experience: B. T. Hennessy et al., Expert. Opin. Invest. Drugs 12, 1985-1993 (2003).

Zalcitabine CAS Registry Number: 7481-89-2 2',3'-二脱氧胞苷

CAS Name: 2',3'-Dideoxycytidine
Additional Names: dideoxycytidine; ddCyd
Trademarks: Hivid (Roche)
Percent Composition: C 51.18%, H 6.20%, N 19.89%, O 22.72%
Literature References: Pyrimidine nucleoside analog with antiviral activity. Prepn: J. P. Horwitz et al., J. Org. Chem. 32, 817 (1967); R. Marumoto, M. Honjo, Chem. Pharm. Bull. 22, 128 (1974). Prepn and structure-activity study: T.-S. Lin et al., J. Med. Chem. 30, 440 (1987). In vitro inhibition of viral DNA synthesis: P. C. van der Vliet, M. M. Kwant, Biochemistry 20, 2628 (1981); of HIV-1 virus replication: H. Mitsuya, S. Broder, Proc. Natl. Acad. Sci. USA 83, 1911 (1986). Phosphorylation by human cells: D. A. Cooney et al., Biochem. Pharmacol. 35, 2065 (1986). Metabolism by human cells: M. C. Starnes, Y. Cheng, J. Biol. Chem. 262, 988 (1987). Potential application in acquired immunodeficiency syndrome (AIDS): E. De Clercq, J. Med. Chem. 29, 1561 (1986).

Zidovudine CAS Registry Number: 30516-87-1 齐多夫定

CAS Name: 3'-Azido-3'-deoxythymidine
Additional Names: azidothymidine; AZTTrademarks: Retrovir (GSK)
Percent Composition: C 44.94%, H 4.90%, N 26.21%, O 23.95%
Literature References: Pyrimidine nucleoside analog; reverse transcriptase inhibitor. Prepn: J. P. Horwitz et al., J. Org. Chem. 29, 2076 (1964); R. P. Glinski et al., ibid. 38, 4299 (1973). See also: J. L. Rideout et al., US 4724232 (1988 to Burroughs Wellcome). Total synthesis: C. K. Chu et al., Tetrahedron Lett. 29, 5349 (1988). In vitro antiviral and antitumor activity: E. De Clercq et al., Biochem. Pharmacol. 29, 1849 (1980); vs HIV-1 virus: H. Mitsuya et al., Proc. Natl. Acad. Sci. USA 82, 7096 (1985). Clinical pharmacokinetics: R. W. Klecker et al., Clin. Pharmacol. Ther. 41, 407 (1987). Toxicology studies: K. M. Ayers, Am. J. Med. 85, Suppl. 2A, 186 (1988). Comprehensive description: M. L. Sethi, Anal. Profiles Drug Subs. 20, 729-765 (1991). Review of clinical experience: G. X. McLeod, S. M. Hammer, Ann. Intern. Med. 117, 487-501 (1992); in prevention of perinatal HIV transmission: R. Sperling, Infect. Dis. Obstet. Gynecol. 6, 197-203 (1998).

Pyrithiobac CAS Registry Number: 123342-93-8 2-氯-6-(4,6-二甲氧嘧啶-2-硫基)苯甲酸

CAS Name: 2-Chloro-6-[(4,6-dimethoxy-2-pyrimidinyl)thio]benzoic acidPercent Composition: C 47.78%, H 3.39%, Cl 10.85%, N 8.57%, O 19.59%, S 9.81%
Literature References: Pyrimidinylsalicylic acid herbicide for use in cotton; acetolactate synthase inhibitor. Prepn: Y. Saito et al., EP 315889; eidem, US 4923501 (1989, 1990 both to Kumiai Chem. Ind.; Ihara Chem. Ind.). Field trials in cotton: J. W. Keeling et al. Weed Technol. 7, 930 (1993). Mechanism of action: T. Shimizu et al., J. Pestic. Sci. 19, 59 (1994). Comprehensive description: S. Takahashi et al., Brighton Crop Prot. Conf. - Weeds 1991, 57-62.