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

Atevirdine CAS Registry Number: 136816-75-6 阿替韦啶

CAS Name: 1-[3-(Ethylamino)-2-pyridinyl]-4-[(5-methoxy-1H-indol-2-yl)carbonyl]piperazine
Additional Names: N-ethyl-2-[4-(5-methoxy-1H-indol-2-ylcarbonyl)-1-piperazinyl]-3-pyridinamine; 1-[5-met...
Literature References: Bisheteroarylpiperazine (BHAP) reverse transcriptase inhibitor. Prepn: D. L. Romero et al., WO 9109849 (1991 to Upjohn); and structure-activity studies: idem et al., J. Med. Chem. 37, 999 (1994). Mechanism of action study: I. W. Althaus et al., J. Biol. Chem. 268, 6119 (1993). Clinical pharmacokinetics: A. M. M. Been-Tiktak et al., Antimicrob. Agents Chemother. 39, 602 (1995). Clinical evaluation of combination with zidovudine in AIDS: R. C. Reichman et al., J. Infect. Dis. 171, 297 (1995). Clinical trial in HIV: A. M. M. Been-Tiktak et al., Antimicrob. Agents Chemother. 40, 2664 (1996).

Delavirdine CAS Registry Number: 136817-59-9 地拉韦啶

CAS Name: 1-[3-[(1-Methylethyl)amino]-2-pyridinyl]-4-[[5-[(methylsulfonyl)amino]-1H-indol-2-yl]carbonyl]piperazine
Additional Names: 1-(5-methanesulfonamido-1H-indol-2-ylcarbonyl)-4-[3-(1-methy...
Literature References: Bisheteroarylpiperazine non-nucleoside reverse transcriptase inhibitor of HIV-1. Prepn: D. L. Romero et al., WO 9109849; J. R. Palmer et al., US 5563142 (1991, 1996 both to Upjohn). Structure-activity studies: D. L. Romero et al., J. Med. Chem. 36, 1505 (1993). In vitro activity vs HIV-1: T. J. Dueweke et al., Antimicrob. Agents Chemother. 37, 1127 (1993); P. J. Pagano, K.-T. Chong, J. Infect. Dis. 171, 61 (1995). Enzyme kinetic studies: I. W. Althaus et al., Biochem. Pharmacol. 47, 2017 (1994). NMR characterization of crystalline forms: P. Gao, Pharm. Res. 15, 1425 (1998). HPLC determn in plasma: C.-L. Cheng et al., J. Chromatogr. B 769, 297 (2002). Review of discovery and development: W. J. Adams et al., in Pharm. Biotechnol., R. T. Borchardt et al., Eds. (Plenum Press, New York, 1998) pp 285-312; of clinical use in HIV infection: L. J. Scott, C. M. Perry, Drugs 60, 1411-1444 (2000).

Voacamine CAS Registry Number: 3371-85-5 老刺木胺

CAS Name: 12-Methoxy-13-[(3a)-17-methoxy-17-oxovobasan-3-yl]ibogamine-18-carboxylic acid methyl ester
Additional Names: voacanginine
Percent Composition: C 73.27%, H 7.44%, N 7.95%, O 11.35%
Literature References: Bisindole alkaloid found in Voacanga africana Stapf., V. thouarsii R. Sch., var obtusa (K. Sch.) Pichon and V. schweinfurthii Staph., Apocynaceae: Janot, Goutarel, Compt. Rend. 240, 1719 (1955); Rao, J. Org. Chem. 23, 1455 (1958); Janot, Goutarel, US 2823204 (1958 to Lab. Gobey). Identity with voacanginine: LeBarre, Gillo, Bull. Acad. R. Med. Belg. 20, 194 (1956). Cleaved by acid catalysis to voacangine: Winkler, Naturwissenschaften 48, 694 (1961). Structure: Goutarel et al., Compt. Rend. 243, 1670 (1956); Percheron, Ann. Chim. (Paris) 4, 303 (1959); Büchi et al., J. Am. Chem. Soc. 85, 1893 (1963). Review: Gorman et al. in The Alkaloids 1, J. E. Saxton, Ed. (The Chem. Soc., London, 1971) pp 242-249.

Zoledronic Acid CAS Registry Number: 118072-93-8; 165800-06-6 (monohydrate) 唑来膦酸

CAS Name: [1-Hydroxy-2-(1H-imidazol-1-yl)ethylidene]bisphosphonic acid
Additional Names: 2-(imidazol-1-yl)-1-hydroxyethane-1,1-diphosphonic acidTrademarks: Zometa (Novartis)
Percent Composit...
Literature References: Bisphosphonate antiresorptive agent. Prepn: JP Kokai 88 150291; K. A. Jaeggi, L. Wilder, US 4939130 (1988, 1990 both to Ciba-Geigy). Effect on bone metabolism: J. R. Green et al., J. Bone Miner. Res. 9, 745 (1994). Determn in plasma by enzyme inhibition assay: F. Risser et al., J. Pharm. Biomed. Anal. 15, 1877 (1997). Series of articles on pharmacology and clinical experience: Br. J. Clin. Pract. Suppl. 87, 15-22 (1996). Clinical trial in tumor-induced hypercalcemia: J. J. Body, Cancer 80, 1699 (1997); of i.v. infusion in osteoporosis: I. R. Reid et al., N. Engl. J. Med. 346, 653 (2002); in bone metastases of prostate cancer: F. Saad et al., J. Natl. Cancer Inst. 94, 1458 (2002). Review of pharmacology and therapeutic use: J.-J. Body, Expert Opin. Pharmacother. 4, 567-580 (2003).

Tiludronic Acid CAS Registry Number: 89987-06-4 替鲁膦酸

CAS Name: [[(4-Chlorophenyl)thio]methylene]bisphosphonic acid
Additional Names: ACPMD; Cl-TMBPPercent Composition: C 26.39%, H 2.85%, Cl 11.13%, O 30.13%, P 19.44%, S 10.06%
Literature References: Bisphosphonate antiresorptive agent. Prepn: J. C. Breliere et al., EP 100718; eidem, US 4876248 (1984, 1989 both to Sanofi). HPLC determn in plasma and urine: J.-P. Fels et al., J. Chromatogr. 430, 73 (1988). Determn of dissociation constants: M. Bonnery et al., Bull. Soc. Chim. Fr. 1988, 49. Symposium on pharmacology and clinical experience: Bone 17, Suppl., 471S-519S (1995). Clinical trial in Paget's disease: W. D. Fraser et al., Postgrad. Med. J. 73, 496 (1997).

Risedronic Acid CAS Registry Number: 105462-24-6 利塞膦酸

CAS Name: [1-Hydroxy-2-(3-pyridinyl)ethylidene]bisphosphonic acid
Additional Names: 2-(3-pyridinyl)-1-hydroxyethane diphosphonic acid
Percent Composition: C 29.70%, H 3.92%, N 4.95%, O 39.56...
Literature References: Bisphosphonate antiresorptive agent. Prepn: J. J. Benedict, C. M. Perkins, EP 186405; eidem, US 5583122 (1986, 1996 both to Procter Gamble). Pharmacology: W. S. S. Jee et al., Bone 14, 493 (1993). Clinical trial in Paget's disease: E. S. Siris et al., J. Bone Miner. Res. 13, 1032 (1998); in postmenopausal bone loss: L. Mortensen et al., J. Clin. Endocrinol. Metab. 83, 396 (1998). Clinical effect on reduction of fracture risk: S. T. Harris et al., J. Am. Med. Assoc. 282, 1344 (1999). Review of pharmacology and clinical efficacy: K. L. Goa, J. A. Balfour, Drugs Aging 13, 83-91 (1998).

Neridronic Acid CAS Registry Number: 79778-41-9 奈立膦酸

CAS Name: (6-Amino-1-hydroxyhexylidene)bisphosphonic acid
Percent Composition: C 26.00%, H 6.18%, N 5.05%, O 40.41%, P 22.35%
Literature References: Bisphosphonate antiresorptive agent. Prepn: J. Jary et al., BE 885139; eidem, US 4304734 (both 1981 to Vysoka Skola Chem.-Tech.); and characterization of monosodium salt: M. Neves et al., Nucl. Med. Biol. 29, 329 (2002). Crystal structure: V. M. Coiro, D. Lamba, Acta Crystallogr. C45, 446 (1989). Clinical study in Paget's disease: S. Adami et al., Clin. Exp. Rheumatol. 20, 55 (2002); in osteogenesis imperfecta: idem et al., J. Bone Miner. Res. 18, 126 (2003); in osteoporosis: V. Braga et al., Bone 33, 342 (2003).

Alendronic Acid CAS Registry Number: 66376-36-1 阿仑膦酸

CAS Name: (4-Amino-1-hydroxybutylidene)bisphosphonic acid
Additional Names: a-hydroxy-d-aminobutylidenediphosphonic acid; ABDP
Percent Composition: C 19.29%, H 5.26%, N 5.62%, O 44.96%, P 24...
Literature References: Bisphosphonate antiresorptive agent. Prepn: M. I. Kabachnik et al., Bull. Acad. Sci. USSR, 27, 374 (1978). See also: BE 903519; G. Staibano, US 4705651 (1986, 1987 both to Gentili). Improved prepn: G. R. Kieczykowski et al., J. Org. Chem. 60, 8310 (1995). Pharmacokinetics: J. H. Lin et al., Drug Metab. Dispos. 19, 926 (1991). Mechanism of action: M. Sato et al., J. Clin. Invest. 88, 2095 (1991). Determn by HPLC in urine: W. F. Kline et al., J. Chromatogr. 534, 139 (1990); by IC in pharmaceutical formulations: E. W. Tsai et al., ibid. 596, 217 (1992). Clinical evaluation in malignant hypercalcaemia: R. Rizzoli et al., Int. J. Cancer 50, 706 (1992). Clinical trial in postmenopausal osteoporosis: U. A. Liberman et al., N. Engl. J. Med. 333, 1437 (1995); in prevention of bone loss in women: D. Hosking et al., ibid. 338, 485 (1998). Clinical trial in men with osteoporosis: E. Orwoll et al., ibid. 343, 604 (2000).

Ibandronic Acid CAS Registry Number: 114084-78-5 伊班膦酸

CAS Name: [1-Hydroxy-3-(methylpentylamino)propylidene]bisphosphonic acid
Percent Composition: C 33.86%, H 7.26%, N 4.39%, O 35.08%, P 19.41%
Literature References: Bisphosphonate antiresorptive agent. Prepn: R. Gall, E. Bosies, DE 3623397; eidem, US 4927814 (1988, 1990 both to Boehringer Mann.). Inhibition of bone resorption: R. C. Mühlbauer et al., J. Bone Miner. Res. 6, 1003 (1991). Mechanism of action study: C. Vitté et al., Endocrinology 137, 2324 (1996). Clinical trial in cancer-associated hypercalcemia: M. Pecherstorfer et al., J. Clin. Oncol. 14, 268 (1996); in osteoporosis: P. Ravn et al., Bone 19, 527 (1996). Review of pharmacology and clinical efficacy: M. Dooley, J. A. Balfour, Drugs 57, 101-108 (1999); of clinical experience in osteoporosis: R. D. Chapurlat, P. D. Delmas, Expert Opin. Pharmacother. 4, 391-396 (2003); of development and therapeutic potential: L. Gennari, IDrugs 8, 155-169 (2005).

Incadronic Acid CAS Registry Number: 124351-85-5 英卡膦酸

CAS Name: [(Cycloheptylamino)methylene]bisphosphonic acid
Percent Composition: C 33.46%, H 6.67%, N 4.88%, O 33.43%, P 21.57%
Literature References: Bisphosphonate antiresorptive agent. Prepn: Y. Isomura et al., EP 325482; eidem, US 4970335 (1989, 1990 both to Yamanouchi); M. Takeuchi et al., Chem. Pharm. Bull. 41, 688 (1993). HPLC determn in plasma, urine and bone: T. Usui et al., J. Chromatogr. 584, 213 (1992). Effect on bone mineral density in dogs: H. Motoie et al., J. Bone Miner. Res. 10, 910 (1995). Toxicology: A. Okazaki et al., J. Toxicol. Sci. 20, Suppl. 1, 15 (1995). Clinical pharmacokinetics: T. Usui et al., Int. J. Clin. Pharmacol. Ther. 35, 239 (1997). Clinical evaluation in hypercalcemia of malignancy: S. Fukumoto et al., J. Clin. Endocrinol. Metab. 79, 165 (1994).