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

Flunarizine CAS Registry Number: 52468-60-7 氟桂利嗪

CAS Name: (E)-1-[Bis(4-fluorophenyl)methyl]-4-(3-phenyl-2-propenyl)piperazine
Additional Names: (E)-1-[bis(p-fluorophenyl)-methyl]-4-cinnamylpiperazine; 1-cinnamyl-4-(di-p-fluorobenzhydryl)pipe...
Literature References: Calcium channel blocker; fluorinated deriv of cinnarizine, q.v. Prepn: P. A. J. Janssen, DE 1929330 and FR 2014487; idem, US 3773939 (1970, 1970, 1973, all to Janssen). Pharmacology: L. K. Desmedt et al., Arzneim.-Forsch. 25, 1408 (1975); T. Godfraind, Eur. J. Pharmacol. 53, 273 (1979). Clinical studies: J. Schetz et al., Curr. Ther. Res. 23, 131 (1978); G. Rudofsky et al., Angiology 30, 479 (1979). Rheological effects in humans: J. D. Cree et al., ibid. 505. Mechanism of calcium blocking activity: T. Godfraind, Fed. Proc. 40, 2866 (1981). Clinical study in retinal vasculopathy: P. Nihard, Angiology 33, 37 (1982). Clinical trial in chronic cerebrovascular disorders: A. Agnoli et al., Int. J. Clin. Pharmacol. Res. 8, 189 (1988). Series of articles on absorption, distribution, excretion and metabolism: Arzneim.-Forsch. 33, 1135-1151 (1983). Review of pharmacology, toxicology and clinical studies: B. Holmes et al., Drugs 27, 6 (1984).

Gallopamil CAS Registry Number: 16662-47-8 戈洛帕米

CAS Name: a-[3-[[2-(3,4-Dimethoxyphenyl)ethyl]methylamino]propyl]-3,4,5-trimethoxy-a-(1-methylethyl)benzeneacetonitrile
Additional Names: 5-[(3,4-dimethoxyphenethyl)methylamino]-2-isopropyl-2-(...
Literature References: Calcium channel blocking agent; methoxy analog of verapamil, q.v. Prepn: F. Dengel, BE 615861; idem, US 3261859 (1962, 1966 to Knoll). Stereoselective synthesis of enantiomers: L. J. Theodore, W. L. Nelson, J. Org. Chem. 52, 1309 (1987). Pharmacology: H. Haas, E. Busch, Arzneim.-Forsch. 17, 257 (1967); eidem, ibid. 18, 401 (1968); A. Fleckenstein, ibid. 20, 1317 (1970). Clinical trial in stable angina pectoris: N. S. Khurmi et al., Am. J. Cardiol. 53, 684 (1984). Symposium on pharmacology and clinical efficacy: J. Cardiovasc. Pharmacol. 20, Suppl. 7, S1-S95 (1992). Review of pharmacokinetics and therapeutic potential in ischemic heart disease: R. N. Brogden, P. Benfield, Drugs 47, 93-115 (1994).

Gabapentin CAS Registry Number: 60142-96-3 加巴喷丁

CAS Name: 1-(Aminomethyl)cyclohexaneacetic acidTrademarks: Neurontin (Parke-Davis)
Percent Composition: C 63.13%, H 10.01%, N 8.18%, O 18.69%
Literature References: Calcium channel ligand structurally related to g-aminobutyric acid (GABA), q.v., designed to cross the blood brain barrier. Prepn: G. Satzinger et al., DE 2460891 (1976 to Gödecke); eidem, US 4024175 (1977 to Warner-Lambert). Pharmacokinetics and metabolism: K.-O. Vollmer et al., Arzneim.-Forsch. 36, 830 (1986). Clinical pharmacology: B. Saletu et al., Int. J. Clin. Pharmacol. Ther. Toxicol. 24, 362 (1986). GC determn in biological fluids: W. D. Hooper et al., J. Chromatogr. 529, 167 (1990). Clinical trial in treatment of pain in diabetic neuropathy: M. Backonja et al., J. Am. Med. Assoc. 280, 1831 (1998); in treatment of postherpetic neuralgia: M. Rowbotham et al., ibid. 1837. Review of pharmacology and clinical trials in epilepsy: B. Schmidt in Antiepileptic Drugs, R. H. Levy et al., Eds. (Raven Press, New York, 3rd ed., 1989) pp 925-935; K. L. Goa, E. M. Sorkin, Drugs 46, 409-427 (1993); of pharmacology and use in pain management: M. A. Rose, P. C. A. Kam, Anaesthesia 57, 451-462 (2002); of interactions with voltage-gated calcium channels: K. G. Sutton, T. P. Snutch, Drug Dev. Res. 54, 167-172 (2002).

Uridine 5 ¢ -Diphosphate CAS Registry Number: 58-98-0 尿苷-5’-二磷酸

CAS Name: Uridine 5'-(trihydrogen diphosphate)
Additional Names: UDP; uridine 5'-pyrophosphate; uridine-5-pyrophosphoric acid
Percent Composition: C 26.75%, H 3.49%, N 6.93%, O 47.50%, P 15....
Literature References: Can be isolated from calf's liver, thymus, and yeast. The commercial product is derived from yeast. Pentose nucleic acids (isolated from yeast) are digested with rattlesnake venom (freed of 5¢-monoesterase) and the nucleotides are separated by chromatography: Cohn, Volkin, Arch. Biochem. Biophys. 35, 465 (1952); J. Biol. Chem. 203, 319 (1953). For alternate procedures see the refs under Uridine Diphosphate Glucose. Syntheses: Chambers, J. Am. Chem. Soc. 81, 3032 (1959); Moffatt, Khorana, ibid. 83, 649 (1961).

Ajulemic Acid CAS Registry Number: 137945-48-3 (6aR,10aR)-1-羟基-6,6-二甲基-3-(2-甲基辛-2-基)-6a,7,10,10a-四氢苯并[c]色原烯-9-羧酸

CAS Name: (6aR,10aR)-3-(1,1-Dimethylheptyl)-6a,7,10,10a-tetrahydro-1-hydroxy-6,6-dimethyl-6H-dibenzo[b,d]pyran-9-carboxylic acid
Additional Names: 1',1'-dimethylheptyl-D8-tetrahydrocannabinol-1...
Literature References: Cannabinoid receptor agonist; synthetic, nonpsychoactive derivative of D9-tetrahydrocannabinol, q.v. Prepn: S. H. Burstein et al., J. Med. Chem. 35, 3135 (1992); S. H. Burstein, R. Mechoulam, WO 9401429; eidem, US 5338753 (both 1994). GC-MS determn in plasma: C. Batista et al., J. Chromatogr. B 820, 77 (2005). Binding to CB-receptors: M.-H. Rhee et al., J. Med. Chem. 40, 3228 (1997); to PPARg receptor: J. Liu et al., Mol. Pharmacol. 63, 983 (2003). Clinical evaluation in chronic neuropathic pain: M. Karst et al., J. Am. Med. Assoc. 290, 1757 (2003). Reviews of development and pharmacology: S. Burstein et al., Life Sci. 75, 1513-1522 (2004); idem, AAPS Journal 7, E143-E148 (2005); J. L. Wiley, IDrugs 8, 1002-1011 (2005).

Laurocapram CAS Registry Number: 59227-89-3 月桂氮酮

CAS Name: 1-Dodecylhexahydro-2H-azepin-2-one
Additional Names: 1-dodecylazacycloheptan-2-one; N-dodecyl-e-caprolactamTrademarks: Azone (Nelson)
Percent Composition: C 76.81%, H 12.53%, N 4.9...
Literature References: Caprolactam derivative used to enhance percutaneous absorption of physiologically active agents. Also exhibits intrinsic anti-inflammatory activity. Prepn: A. P. Swain et al., J. Org. Chem. 18, 1087 (1953). Improved synthesis: V. J. Rajadhyaksha et al., EP 95096; eidem, US 4422970 (both 1983 to Nelson). Use as skin penetrant: V. J. Rajadhyaksha, US 3989816; US 4405616 (1976, 1983 to Nelson). Anti-inflammatory activity: E. L. Nelson, US 4310525 (1982 to Nelson). Pharmacology: R. B. Stoughton, Arch. Dermatol. 118, 474 (1982). Comprehensive description: idem, Drug Dev. Ind. Pharm. 9, 725 (1983). Topical antiviral activity in vivo: M. F. Leonard et al., Chemotherapy (Basel) 33, 151 (1987).

Penciclovir CAS Registry Number: 39809-25-1 喷昔洛韦

CAS Name: 2-Amino-1,9-dihydro-9-[4-hydroxy-3-(hydroxymethyl)butyl]-6H-purin-6-one
Additional Names: 9-[4-hydroxy-3-(hydroxymethyl)but-1-yl]guanine; PCVTrademarks: Denavir (SKB); Vectavir (SKB)<...
Literature References: Carba analog of ganciclovir, q.v., active against several herpes viruses. Prepn: U. K. Pandit et al., Synth. Commun. 2, 345 (1972); R. L. Jarvest, M. R. Harnden, US 5075445 (1991 to Beecham). Synthesis: M. R. Harnden et al., J. Med. Chem. 30, 1636 (1987); J. Hannah et al., J. Heterocycl. Chem. 26, 1261 (1989). Crystal and molecular structures: M. R. Harnden et al., Nucleosides Nucleotides 9, 499 (1990). In vitro activity of enantiomers in comparison with acyclovir, q.v.: G. Abele et al., Antiviral Chem. Chemother. 2, 163 (1991); against herpes simplex viruses: A. Weinberg et al., Antimicrob. Agents Chemother. 36, 2037 (1992). Clinical pharmacokinetics: S. E. Fowles et al., Eur. J. Clin. Pharmacol. 43, 513 (1992). HPLC determn in plasma and urine: J. R. McMeekin et al., Anal. Proc. 29, 178 (1992). Review of development and antiviral activity: M. R. Harnden, Drugs Future 14, 347-358 (1989).

Loracarbef CAS Registry Number: 121961-22-6 氯碳头孢

CAS Name: (6R,7S)-7-[[(2R)-Aminophenylacetyl]amino]-3-chloro-8-oxo-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid monohydrate
Additional Names: (6R,7S)-3-chloro-7-[(R)-phenylglycinamido]-8-oxo-...
Literature References: Carbacephem analog of cefaclor, q.v. Prepn: T. Hirata et al., EP 14476; eidem, US 4708956 (1980, 1987 both to Kyowa Hakko); I. Matsukuma et al., Chem. Pharm. Bull. 37, 1239 (1989). Prepn of the crystalline monohydrate: C. E. Pasini, EP 311366 (1989 to Lilly). Enantioselective synthesis: C. C. Bodurow et al., Tetrahedron Lett. 30, 2321 (1989). Antibacterial spectrum: K. Sato et al., J. Antibiot. 42, 1844 (1989). b-Lactamase stability: R. N. Jones, A. L. Barry, Eur. J. Clin. Microbiol. 6, 570 (1987). Pharmacology in animals: T. Shetler et al., Arzneim.-Forsch. 43, 60 (1993). Pharmacokinetics in children: J. D. Nelson et al., Antimicrob. Agents Chemother. 32, 1738 (1988).

Estramustine CAS Registry Number: 2998-57-4 雌莫司汀

CAS Name: (17b)-Estra-1,3,5(10)-triene-3,17-diol 3-[bis(2-chloroethyl)carbamate]
Additional Names: estradiol 3-bis(2-chloroethyl)carbamate; estra-1,3,5(10)triene-3,17b-diol 3-[N,N-bis(2-chloroe...
Literature References: Carbamate ester linking estradiol to nor-nitrogen mustard; depolymerizes microtubules by binding to microtubule associated proteins (MAPs). Prepn: BE 646319; Fex et al., US 3299104 (1963, 1967 to AB Leo); Niculescu-Duvaz et al., J. Med. Chem. 10, 172 (1967). Clinical results: Anderes, Praxis 60, 1375 (1971); Muntzing, Nilsson, Z. Krebsforsch. Klin. Onkol. 77, 166 (1972). Review of mechanism of action: K. D. Tew, M. E. Stearns, Pharmacol. Ther. 43, 299-319 (1989); of pharmacokinetics and pharmacodynamics: A. T. Bergenheim, R. Henriksson, Clin. Pharmacokinet. 34, 163-172 (1998).

Meropenem CAS Registry Number: 96036-03-2 美罗培南

CAS Name: (4R,5S,6S)-3-[[(3S,5S)-5-[(Dimethylamino)carbonyl]-3-pyrrolidinyl]thio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
Additional Names: (1R,5S...
Literature References: Carbapenem antibiotic. Prepn: M. Sunagawa et al., EP 126587; M. Sunagawa, US 4943569 (1984, 1990 both to Sumitomo). Structure-activity study: M. Sunagawa et al., J. Antibiot. 43, 519 (1990). Crystal structure: K. Yanagi et al., Acta Crystallogr. C48, 1737 (1992). HPLC determn in serum and bronchial secretions: M. Ehrlich et al., J. Chromatogr. B 751, 357 (2001). Pharmacokinetics: R. Wise et al., Antimicrob. Agents Chemother. 34, 1515 (1990). Series of articles on antimicrobial activity, metabolism: J. Antimicrob. Chemother. 24, Suppl. A, 1-320 (1989); and clinical performance: ibid. 36, Suppl. A, 1-223 (1995). Review of clinical experience in intensive care: M. Hurst, H. M. Lamb, Drugs 59, 653-680 (2000).